Severe Allergy as a Chronic Inflammatory Condition From a Systems Biology Perspective.

Persistent and unresolved inflammation is a common underlying factor observed in several and seemingly unrelated human diseases, including cardiovascular and neurodegenerative diseases. Particularly, in atopic conditions, acute inflammatory responses such as those triggered by insect venom, food or drug allergies possess also a life-threatening potential. However, respiratory allergies predominantly exhibit late immune responses associated with chronic inflammation, that can eventually progress into a severe phenotype displaying similar features as those observed in other chronic inflammatory diseases, as is the case of uncontrolled severe asthma. This review aims to explore the different facets and systems involved in chronic allergic inflammation, including processes such as tissue remodelling and immune cell dysregulation, as well as genetic, metabolic and microbiota alterations, which are common to other inflammatory conditions. Our goal here was to deepen on the understanding of an entangled disease as is chronic allergic inflammation and expose potential avenues for the development of better diagnostic and intervention strategies.

External urology consultation quality at a third-level public hospital in Mexico.

INTRODUCTION: Patient satisfaction is the degree of conformity with the healthcare they receive. It is real evidence and one of the most important factors in determining the effectiveness and quality of healthcare systems. OBJECTIVE: To identify the quality of care in the Urology outpatient department of a third-level hospital. MATERIALS AND METHODS: The NHS (National Health Service) 2018 quality of care questionnaire with 11 sections, 133 items, and duration of approximately 25min was randomly administered to 250 patients attending Urology outpatients at a third-level public hospital in Mexico. RESULTS: According to responses, 92% (n=230) knew the reason for the consultation. 64.8% (n=162) had a consultation with the same physician by whom they were initially seen. The longest reported hospital wait time before being seen was more than 2h in 29.6% (n=74). As for consultation time, 212 patients responded and the duration was 11-20min in 52.8% (n=112). Finally, 33.2% (n=83) considered the quality of service to be good. CONCLUSIONS: The use of the NHS 2018 survey in the Urology service at a third-level public hospital in Mexico is feasible, since we managed to obtain a significant and continuous improvement in all its indicators which is satisfactory for all.

Microbiome and Allergy: New Insights and Perspectives.

The role of the microbiome in the molecular mechanisms underlying allergy has become highly relevant in recent years. Studies are increasingly suggesting that altered composition of the microbiota, or dysbiosis, may result in local and systemic alteration of the immune response to specific allergens. In this regard, a link has been established between lung microbiota and respiratory allergy, between skin microbiota and atopic dermatitis, and between gut microbiota and food allergy. The composition of the human microbiota is dynamic and depends on host-associated factors such as diet, diseases, and lifestyle. Omics are the techniques of choice for the analysis and understanding of the microbiota. Microbiota analysis techniques have advanced considerably in recent decades, and the need for multiple approaches to explore and comprehend multifactorial diseases, including allergy, has increased. Thus, more and more studies are proposing mechanisms for intervention in the microbiota. In this review, we present the latest advances with respect to the human microbiota in the literature, focusing on the intestinal, cutaneous, and respiratory microbiota. We discuss the relationship between the microbiome and the immune system, with emphasis on allergic diseases. Finally, we discuss the main technologies for the study of the microbiome and interventions targeting the microbiota for prevention of allergy.

Neurobehcet, a propósito de un caso / Neurobechet, about a case

El neurobehcet (NB) es una manifestación poco frecuente y grave de la enfer-medad de Behcet (EB) con diferentes formas de presentación según el aérea del sistema nervioso que se vea afectada. Se presenta el caso de una paciente de sexo femenino de 38 años de edad con historia de larga data de psicosis de posible cau-sa orgánica. Durante su última hospitalización por deterioro funcional y cognitivo se rescata el antecedente de úlceras orales y genitales y un episodio previo de es-cleritis. Se complementa el estudio con punción lumbar, resonancia y angioreso-nancia nuclear magnética de cerebro y antígeno de histocompatibilidad los cuales sugieren el diagnóstico de NB. Se trata con corticoides e inmunosupresores, pero a pesar de mejoría en el líquido cefalorraquídeo no hay mejoría clínica, que se presume sería consecuencia de lo tardío del diagnóstico y tratamiento.

Neurobehcet (NB) is a rare and serious manifestation of Behcet's disease (EB), with different forms of presentation depending on the area of the nervous system involved. A clinical case of a 38-year-old female patient with a long-standing his-tory of psychosis of possible organic cause is presented. During her last hospital-ization due to functional and cognitive impairment the history of oral and genital ulcers and a previous episode of scleritis is obtained. The study is complemented with a lumbar puncture, magnetic resonance, magnetic nuclear angioresonance of the brain and histocompatibility antigen which suggests the diagnosis of NB. It is treated with corticosteroids and immunosuppressants, but despite improve-ment in cerebrospinal fluid there is no clinical improvement, which is presumed to be a consequence of the late diagnosis and treatment.

Effects of preoperative dexamethasone on postoperative pain, nausea, vomiting and respiratory function in women undergoing conservative breast surgery for cancer: Results of a controlled clinical trial.

The objective was to evaluate whether preoperative administration of dexamethasone improved postoperative nausea and vomiting (PONV), pain and respiratory function tests in women undergoing conservative surgery for breast cancer. This was a controlled clinical trial conducted between June 2013 and October 2014. Eighty patients were evaluated. Patients received a preoperative dose of 8 mg of dexamethasone (n = 40) or placebo (n = 40). The data on PONV and pain intensity was obtained and forced spirometry tests were performed, 1 hr before and at 1, 6, 12 and 24 hr after surgery. Any use of additional analgesic/antiemetic drugs was recorded. Patients were followed until 30 days after surgery for any surgical or medical complications. The pain intensity was lower in the treatment group for all periods; PONV was lower at 6, 12 and 24 hr; Additional analgesics/antiemetics were required less frequently (all p < .05). Both groups exhibited a restrictive ventilatory pattern immediately after surgery, which was reversed in the following hours. However, spirometric values were higher in the dexamethasone group. There were no pulmonary or metabolic complications after surgery. Our conclusions were that dexamethasone significantly reduced the incidences of PONV, pain and improved respiratory parameters, and reduced the need for additional postoperative analgesic and antiemetic drugs.

Allergic asthma: an overview of metabolomic strategies leading to the identification of biomarkers in the field.

Allergic asthma is a prominent disease especially during childhood. Indoor allergens, in general, and particularly house dust mites (HDM) are the most prevalent sensitizers associated with allergic asthma. Available data show that 65-130 million people are mite-sensitized world-wide and as many as 50% of these are asthmatic. In fact, sensitization to HDM in the first years of life can produce devastating effects on pulmonary function leading to asthmatic syndromes that can be fatal. To date, there has been considerable research into the pathological pathways and structural changes associated with allergic asthma. However, limitations related to the disease heterogeneity and a lack of knowledge into its pathophysiology have impeded the generation of valuable data needed to appropriately phenotype patients and, subsequently, treat this disease. Here, we report a systematic and integral analysis of the disease, from airway remodelling to the immune response taking place throughout the disease stages. We present an overview of metabolomics, the management of complex multifactorial diseases through the analysis of all possible metabolites in a biological sample, obtaining a global interpretation of biological systems. Special interest is placed on the challenges to obtain biological samples and the methodological aspects to acquire relevant information, focusing on the identification of novel biomarkers associated with specific phenotypes of allergic asthma. We also present an overview of the metabolites cited in the literature, which have been related to inflammation and immune response in asthma and other allergy-related diseases.

Stress barriers controlling lateral migration of magma revealed by seismic tomography.

Understanding how monogenetic volcanic systems work requires full comprehension of the local and regional stresses that govern magma migration inside them and why/how they seem to change from one eruption to another. During the 2011-2012 El Hierro eruption (Canary Islands) the characteristics of unrest, including a continuous change in the location of seismicity, made the location of the future vent unpredictable, so short term hazard assessment was highly imprecise. A 3D P-wave velocity model is obtained using arrival times of the earthquakes occurred during that pre-eruptive unrest and several latter post-eruptive seismic crises not related to further eruptions. This model reveals the rheological and structural complexity of the interior of El Hierro volcanic island. It shows a number of stress barriers corresponding to regional tectonic structures and blocked pathways from previous eruptions, which controlled ascent and lateral migration of magma and, together with the existence of N-S regional compression, reduced its options to find a suitable path to reach the surface and erupt.

Factors Associated with Health-Related Quality of Life in Mexican Lupus Patients Using the LupusQol.

INTRODUCTION: Health-related quality of life (HRQOL) is affected by numerous clinical variables, including disease activity, damage, fibromyalgia, depression and anxiety. However, these associations have not yet been described in Mexican patients with systemic lupus erythematosus (SLE). OBJECTIVE: To evaluate the relationship between disease activity, damage, depression and fibromyalgia and HRQOL measured by the LupusQoL-instrument in Mexican patients with SLE. METHODS: A cross-sectional study was conducted in women fulfilling the 1997 ACR classification criteria for SLE. HRQOL was evaluated using a disease-specific instrument for SLE, the LupusQoL (validated for the Spanish-speaking population). Patients were evaluated clinically to determine the degree of disease activity and damage using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and Systemic Lupus International Collaborating Clinics-Damage Index (SLICC), respectively. Fibromyalgia and depression were assessed using the ACR criteria and the CES-D scale, respectively. The relationship between HRQOL and these variables was measured using Spearman's rank correlation coefficient and linear regression analysis. RESULTS: A total of 138 women with SLE, age 40.3±11 years, disease duration 8.8±6.4 years, with disease activity in 51.4%, depression in 50%, damage in 43% and fibromyalgia in 19.6% were included. Poorer HRQOL correlated with depression (r = -0.61; p< 0.005), fibromyalgia (r = -0.42; p< 0.005), disease activity (r = -0.37; p < 0.005) and damage (r = -0.31; p < 0.005). In the multivariate linear regression analysis, damage (ß = -3.756, p<0.005), fibromyalgia (ß = -0.920, p<0.005), depression (ß = -0.911, p<0.005) and disease activity (ß = -0.911, p<0.005) were associated with poor HRQOL. CONCLUSION: SLE disease activity, damage, fibromyalgia and depression were associated with poor HRQOL in our sample of Mexican SLE patients.

Genetic ancestry in relation to the metabolic response to a US versus traditional Mexican diet: a randomized crossover feeding trial among women of Mexican descent.

BACKGROUND/OBJECTIVES: Certain populations with a large proportion of indigenous American (IA) genetic ancestry may be evolutionarily adapted to traditional diets high in legumes and complex carbohydrates, and may have a detrimental metabolic response to US diets high in refined carbohydrates and added sugars. We tested whether IA ancestry modified the metabolic response to a US versus traditional Mexican diet in a controlled dietary intervention. SUBJECTS/METHODS: First and second generation Mexican immigrant women (n=53) completed a randomized crossover feeding trial testing the effects of a US versus traditional Mexican diet. The metabolic response to the diets was measured by fasting serum concentrations of glucose, insulin, insulin-like growth factor-1 (IGF-1), IGF-binding protein-3 (IGFBP-3), adiponectin, C-reactive protein, interleukin-6 and computed homeostasis model assessment for insulin resistance (HOMAIR). Blood collected at baseline was used for genotyping, and estimation of African, European and IA ancestries with the use of 214 ancestry informative markers. RESULTS: The genetic ancestral background was 56% IA, 38% European and 6% African. Women in the highest IA ancestry tertile (>62%) were shorter in height, less educated and less acculturated to the US lifestyle, and tended to have higher waist-to-hip ratio compared with women in the middle and lowest IA ancestry tertiles, respectively. Compared with the US diet, the traditional Mexican diet tended to reduce glucose, insulin, IGF-1, IGFBP-3 and HOMAIR among women in the middle IA ancestry group (IA ancestry ⩽45-62%), whereas having no effect on biomarkers related to inflammation. CONCLUSIONS: We observed modest interactions between IA ancestry and the metabolic response to a US versus traditional Mexican diet among Mexican immigrant women.

Trombosis venosa cerebral en una paciente puérpera con preeclampsia con datos de severidad / Cerebral venous thrombosis in a post-partum patient with preeclampsia with signs of severity

Resumen ANTECEDENTES: la trombosis venosa cerebral es infrecuente, pero con mayor incidencia durante la gestación y el puerperio. OBJETIVO: revisar la bibliografía más reciente y proponer una opción de tratamiento de la paciente con trombosis venosa cerebral durante el puerperio. CASO CLÍNICO: paciente de 30 años de edad, con antecedente de dos embarazos y dos cesáreas. En el séptimo día de puerperio tuvo edema de miembros inferiores, cifras tensionales elevadas, cefalea y alteraciones visuales. Con el tratamiento antihipertensivo con nifedipino y neuroprotección con sulfato de magnesio se logró el control de la hipertensión, aunque persistieron la cefalea y los síntomas de visión borrosa y diplopía. La resonancia magnética reportó: trombosis venosa de seno transverso lateral izquierdo. Con el tratamiento anticoagulante hubo disminución importante de los síntomas neurológicos. CONCLUSIONES: puesto que la preeclampsia y la eclampsia pueden ocultar los síntomas de la trombosis venosa cerebral, es importante tener siempre en mente ambos padecimientos para el diagnóstico y tratamiento oportuno de uno y otro.

Abstract BACKGROUND: cerebral venous thrombosis is infrequent, but with the highest incidence during pregnancy and puerperium. OBJECTIVE: to review the most recent bibliography and propose a treatment option for the patient with cerebral venous thrombosis during puerperium. CLINICAL CASE: a 30 year old patient with a history of two pregnancies and two Cesarean sections. On the seventh day of puerperium she presented edema of the lower limbs, high blood pressure, headache and visual disorders. Antihypertensive treatment with nifedipine and neuroprotection with magnesium sulfate, hypertension was controlled although the headache and blurry vision and double vision symptoms persisted. The MRI results reported: venous thrombosis of the left lateral transverse sinus. With anticoagulant treatment there was significant decrease of neurological symptoms. CONCLUSIONS: since preeclampsia and eclampsia can hide symptoms of cerebral venous thrombosis, it is important to always consider both conditions for the timely diagnosis and treatment of both.

Population Fluctuation of Ceratitis capitata (Diptera: Tephritidae) as a Function of Altitude in Eastern Guatemala.

Population fluctuations of Ceratitis capitata (Wiedemann) were evaluated over a period of 12 mo in four altitudinal strata (400-750, 750-1,100, 1,100-1,450, and 1,450-1,800 meters above sea level, masl) in Eastern Guatemala. Within each altitudinal range, sampling plots were established in coffee plantations and adjacent areas, in which Jackson traps were set and baited with Trimedlure. Coffee berries and other host fruits were collected. Population density was lowest at the 400-750 masl stratum and highest at 1,450-1,800 masl. At every altitudinal range, the fluctuations of the pest were associated mainly with the availability of ripe coffee berries as a primary host. From 750-1,450 masl, the pest was also associated with the availability of sweet orange and mandarins in commercial and backyard orchards. The highest densities of the pest were recorded in the dry season. Citrus were the main alternate host where ripe coffee berries were not available. This knowledge on population dynamics of C. capitata will contribute to develop more effective area-wide pest management strategies including the use of sterile insects, natural enemies, and bait sprays.

Fasting and postprandial regulation of the intracellular localization of adiponectin and of adipokines secretion by dietary fat in rats.

BACKGROUND/OBJECTIVE: Dietary fat sources modulate fasting serum concentration of adipokines, particularly adiponectin. However, previous studies utilized obese animals in which adipose tissue function is severely altered. Thus, the present study aimed to assess the postprandial regulation of adipokine secretion in nonobese rats that consumed high-fat diet (HFD) composed of different types of fat for a short time. METHODS: The rats were fed a control diet or a HFD containing coconut, safflower or soybean oil (rich in saturated fatty acid, monounsaturated fatty acid or polyunsaturated fatty acid, respectively) for 21 days. The serum concentrations of adiponectin, leptin, retinol, retinol-binding protein-4 (RBP-4), visfatin and resistin were determined at fasting and after refeeding. Adiponectin multimerization and intracellular localization, as well as the expression of endoplasmic reticulum (ER) chaperones and transcriptional regulators, were evaluated in epididymal white adipose tissue. RESULTS: In HFD-fed rats, serum adiponectin was significantly decreased 30 min after refeeding. With coconut oil, all three multimeric forms were reduced; with safflower oil, only the high-molecular-weight (HMW) and medium-molecular-weight (MMW) forms were decreased; and with soybean oil, only the HMW form was diminished. These reductions were due not to modifications in mRNA abundance or adiponectin multimerization but rather to an increment in intracellular localization at the ER and plasma membrane. Thus, when rats consumed a HFD, the type of dietary fat differentially affected the abundance of endoplasmic reticulum resident protein 44 kDa (ERp44), sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ (PPARγ) mRNAs, all of which are involved in the post-translational processing of adiponectin required for its secretion.Leptin, RBP-4, resistin and visfatin serum concentrations did not change during fasting, whereas modest alterations were observed after refeeding. CONCLUSIONS: The short-term consumption of a HFD affected adiponectin localization in adipose tissue, thereby decreasing its secretion to a different magnitude depending on the dietary fat source. Evaluating the fasting serum concentration of adipokines was not sufficient to identify alterations in their secretion, whereas postprandial values provided additional information as dynamic indicators.

Manejo y administración de hemoderivados por personal de enfermería en un hospital de segundo nivel / Handling and management of blood-derived products by the nursing staff in a second level hospital

Introducción: El manejo y administración de hemoderivados es una actividad que realiza el personal de enfermería, por lo cual es de gran importancia tener presente que un uso inadecuado de éstos puede tener consecuencias graves en los pacientes, siendo fundamental el buen desempeño del personal de enfermería para la práctica segura. Objetivo: Evaluar el desempeño de enfermería en el manejo y administración de hemoderivados en un hospital de segundo nivel. Métodos: Estudio de diseño transversal. Se incluyeron enfermeras durante el 1º Enero al 30 junio del 2013. Se utilizó un instrumento validado que consta de 4 criterios con 27 ítems de respuestas dicotómicas para identificar el desempeño en el manejo y ministración de hemoderivados. La población fue dividida por categoría contractual. Análisis estadístico: prueba Chi-cuadrada y/ exacta de Fisher. Resultados: Se incluyeron un total de 110 observaciones a personal de enfermería que administró hemoderivados. Se obtuvo un índice de eficiencia global parcial (IEG) parcial a excelente de 64.5%. No se encontró asociación en el turno (p=0.16), servicio (p=0.31) y/o categoría contractual (p=0.25). Los porcentajes de excelente en el IEF fueron bajos (por turno: matutino y nocturno de 10 y 13 respectivamente, medicina interna y cirugía general 5 y 7%, y conforme a la categoría contractual, la enfermera general obtuvo en excelente sólo el 7.5%). Conclusiones: Nuestros resultados nos alertan para implantar programas de capacitación a enfermeras, para otorgar atención de calidad, disminuyendo los riesgos que comprometan la vida del paciente.

Introduction: Handling and managing blood-derived products is a nursing staff activity and thus, it is very important to keep in mind that an inadequate handling of these products can have serious consequences on patients. Therefore, a safe practice from the nursing staff is fundamental. Objective: To assess the nursing performance related to the handling and management of blood-derived products in a second level hospital. Methods: A transversal study design. Nurses were observed from January 1 to June 30, of 2013. A validated instrument with 27 dichotomy-items, and based on 4 criteria, to assess the handling and management of blood-derived products was used. The population was divided by contractual category. Statistical analysis: Chi square and/or Fisher exact test. Results: A total of 110 observations to the nursing staff handling and managing blood-derived products were included. An index of global efficiency (IGE) of partial to excellent of 64.5% was obtained. No associations were found with shift (p=.16), service (p=.31) and/or contractual category (p=.25). The percentages of excellent in the IEF were low (per shift: morning and night of 10 and 13 respectively; per service: internal medicine and general surgery 5 and 7%, and according to the contractual category, overall excellent nurse obtained only 7.5%). Conclusions: Our results encourage us to foster training programs for nurses in order to enhance the quality of care and also decrease the life risks on the patients.

A pilot study of plasma metabolomic patterns from patients treated with ketamine for bipolar depression: evidence for a response-related difference in mitochondrial networks.

BACKGROUND AND PURPOSE: (R,S)-ketamine produces rapid and significant antidepressant effects in approximately 65% of patients suffering from treatment-resistant bipolar depression (BD). The genetic, pharmacological and biochemical differences between ketamine responders and non-responders have not been identified. The purpose of this study was to employ a metabolomics approach, a global, non-targeted determination of endogenous metabolic patterns, to identify potential markers of ketamine response and non-response. EXPERIMENTAL APPROACH: Plasma samples from 22 BD patients were analyzed to produce metabolomic patterns. The patients had received ketamine in a placebo-controlled crossover study and the samples were obtained 230 min post-administration at which time the patients were categorized as responders or non-responders. Matching plasma samples from the placebo arm of the study were also analysed. During the study, the patients were maintained on either lithium or valproate. KEY RESULTS: The metabolomic patterns were significantly different between the patients maintained on lithium and those maintained on valproate, irrespective of response to ketamine. In the patients maintained on lithium, 18 biomarkers were identified. In responders, lysophosphatidylethanolamines (4) and lysophosphatidylcholines (9) were increased relative to non-responders. CONCLUSIONS AND IMPLICATIONS: The results indicate that the differences between patients who respond to ketamine and those who do not are due to alterations in the mitochondrial ß-oxidation of fatty acids. These differences were not produced by ketamine administration. The data indicate that pretreatment metabolomics screening may be a guide to the prediction of response and a potential approach to the individualization of ketamine therapy.

Health related quality of life in Mexican women with systemic lupus erythematosus: a descriptive study using SF-36 and LupusQoL(C).

The LupusQoL© questionnaire is a disease-specific health related quality of life (HRQOL) instrument for adults with systemic lupus erythematosus (SLE). The Short Form-36 (SF-36) is a generic instrument that captures the physical, psychological, and social impact. We conducted a descriptive study of women aged ≥ 18 years attending our Lupus Clinic. HRQOL was assessed by applying the LupusQoL© and SF-36. Lupus activity was measured using the Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and chronic damage using the Systemic Lupus Collaborative Clinics Damage Index (SDI). Data were analyzed using descriptive statistics, the chi-square test and Pearson's product moment correlation coefficient. A total of 127 patients were included with a mean age of 40.5 ± 12.6 years. The mean disease duration was 8.2 ± 5.6 years, the mean disease activity score was 2.4 ± 3.0, and the mean SDI score 0.77 ± 1.06. The mean SF-36 score was 58.1 ± 21.1 and the mean LupusQoL© score was 69 ± 22.7. The correlation between global scores of the SF-36 and LupusQoL© was rho = 0.73 (p < 0.001). The correlation between lupus disease activity and the SF-36 and the LupusQoL© was -0.26 (p = 0.003) and -0.25 (p = 0.004), respectively. The correlation between the SDI and the SF-36 and the LupusQoL© was -0.28 (p = 0.001) and -0.38 (p < 0.0001), respectively. In conclusions: both LupusQoL© and SF-36 were useful instruments in assessing HRQOL in Mexican lupus female patients. The usefulness of the LupusQoL© should be evaluated in lupus patients with moderate to severe disease activity.

Soy protein isoflavones differentially regulate liver X receptor isoforms to modulate lipid metabolism and cholesterol transport in the liver and intestine in mice.

AIMS/HYPOTHESIS: Liver X receptor (LXR)α regulates the genes involved in cholesterol, fatty acid and glucose metabolism. Soy protein (SP) consumption reduces the hepatic accumulation of cholesterol and triacylglycerol, and improves insulin sensitivity. However, it is not known whether these effects are mediated via LXRα. We therefore investigated whether the consumption of SP regulates metabolic changes in cholesterol metabolism and insulin sensitivity via LXRα. METHODS: Wild-type (WT) and Lxrα(-/-) (Lxrα, also known as Nr1h3) mice were fed an SP diet with or without cholesterol for 28 days. The expression of LXRα target genes was measured in liver and intestine, as were hepatic lipid content and faecal bile acid concentration. Oral glucose and insulin tolerance tests were also performed. Hepatocytes were used to study the effect of isoflavones on LXR activity. RESULTS: The livers of WT and Lxrα(-/-) mice fed an SP high-cholesterol diet showed less steatosis than those fed casein. The SP diet increased the expression of the ATP-binding cassette (ABC) sub-family genes Abca1, Abcg5 and Abcg8 in the liver and intestine, as well as increasing total faecal bile acid excretion and insulin sensitivity in WT mice compared with mice fed a casein diet. However, these effects of SP were not observed in Lxrα(-/-) mice. The SP isoflavone, genistein, repressed the activation of LXRα target genes by T0901317, whereas it stimulated the activation of LXRß target genes. The AMP-activated protein kinase inhibitor, compound C, had the opposite effects to those of genistein. CONCLUSIONS/INTERPRETATION: Our results suggest that SP isoflavones stimulate the phosphorylation of LXRα or LXRß, resulting in different biological effects for each LXR isoform.

Messinian salinity crisis regulated by competing tectonics and erosion at the Gibraltar arc.

The Messinian salinity crisis (5.96 to 5.33 million years ago) was caused by reduced water inflow from the Atlantic Ocean to the Mediterranean Sea resulting in widespread salt precipitation and a decrease in Mediterranean sea level of about 1.5 kilometres due to evaporation. The reduced connectivity between the Atlantic and the Mediterranean at the time of the salinity crisis is thought to have resulted from tectonic uplift of the Gibraltar arc seaway and global sea-level changes, both of which control the inflow of water required to compensate for the hydrological deficit of the Mediterranean. However, the different timescales on which tectonic uplift and changes in sea level occur are difficult to reconcile with the long duration of the shallow connection between the Mediterranean and the Atlantic needed to explain the large amount of salt precipitated. Here we use numerical modelling to show that seaway erosion caused by the Atlantic inflow could sustain such a shallow connection between the Atlantic and the Mediterranean by counteracting tectonic uplift. The erosion and uplift rates required are consistent with previous mountain erosion studies, with the present altitude of marine sediments in the Gibraltar arc and with geodynamic models suggesting a lithospheric slab tear underneath the region. The moderate Mediterranean sea-level drawdown during the early stages of the Messinian salinity crisis can be explained by an uplift of a few millimetres per year counteracted by similar rates of erosion due to Atlantic inflow. Our findings suggest that the competition between uplift and erosion can result in harmonic coupling between erosion and the Mediterranean sea level, providing an alternative mechanism for the cyclicity observed in early salt precipitation deposits and calling into question previous ideas regarding the timing of the events that occurred during the Messinian salinity crisis.