Genome-wide analysis in Drosophila reveals diet-by-gene interactions and uncovers diet-responsive genes.

Genetic and environmental factors play a major role in metabolic health. However, they do not act in isolation, as a change in an environmental factor such as diet may exert different effects based on an individual's genotype. Here, we sought to understand how such gene-diet interactions influenced nutrient storage and utilization, a major determinant of metabolic disease. We subjected 178 inbred strains from the Drosophila genetic reference panel (DGRP) to diets varying in sugar, fat, and protein. We assessed starvation resistance, a holistic phenotype of nutrient storage and utilization that can be robustly measured. Diet influenced the starvation resistance of most strains, but the effect varied markedly between strains such that some displayed better survival on a high carbohydrate diet (HCD) compared to a high-fat diet while others had opposing responses, illustrating a considerable gene × diet interaction. This demonstrates that genetics plays a major role in diet responses. Furthermore, heritability analysis revealed that the greatest genetic variability arose from diets either high in sugar or high in protein. To uncover the genetic variants that contribute to the heterogeneity in starvation resistance, we mapped 566 diet-responsive SNPs in 293 genes, 174 of which have human orthologs. Using whole-body knockdown, we identified two genes that were required for glucose tolerance, storage, and utilization. Strikingly, flies in which the expression of one of these genes, CG4607 a putative homolog of a mammalian glucose transporter, was reduced at the whole-body level, displayed lethality on a HCD. This study provides evidence that there is a strong interplay between diet and genetics in governing survival in response to starvation, a surrogate measure of nutrient storage efficiency and obesity. It is likely that a similar principle applies to higher organisms thus supporting the case for nutrigenomics as an important health strategy.

Outcomes of an Emergency Department Observation Unit-Based Pathway for the Treatment of Uncomplicated Vaso-occlusive Events in Sickle Cell Disease.

STUDY OBJECTIVE: This was a prospective, pre-post, 13-year observational study documenting the multiyear implementation of an observation unit sickle cell pathway for patients with uncomplicated vaso-occlusive events. METHODS: The sickle cell pathway begins with rapid triage to identify patients with uncomplicated vaso-occlusive events for immediate transfer to the observation unit and initiation of patient-controlled analgesia followed by repeated evaluations of pain and identification of other complications. Data were abstracted from the electronic medical record or observation unit database. The sickle cell pathway was initiated in April 2006. Major revisions of it were carried out in June 2009 (physician evaluation occurs in sickle cell pathway and only patient-controlled analgesia administration of medications) and October 2010 (multidisciplinary management and individual dosing). RESULTS: Annual ED visits ranged between 287 and 528. The preimplementation hospital admission rate was 33% (123/368), 3-day return rate 16% (60/368), and 30-day return rate 67% (248/368). Refinements to the sickle cell pathway have resulted in a decrease in admission rate to 20% (258/1276); 3-day return rate, to 3.6% (46/1,276); and 30-day return rate, to 41% (525/1,276) for the past 3 years. CONCLUSION: The use of a sickle cell pathway for the treatment of uncomplicated vaso-occlusive events has been effective in providing rapid treatment and reducing hospital admissions. However, it was not only the intervention and its refinement that made the sickle cell pathway successful. With the Consolidated Framework for Implementation Research, it was discerned that outer setting factors of organizational commitment to the care of patients with SCD, inner setting factors of learning climate and leadership engagement, individuals, and process contributed to the success of the sickle cell pathway.

Insulin signaling requires glucose to promote lipid anabolism in adipocytes.

Adipose tissue is essential for metabolic homeostasis, balancing lipid storage and mobilization based on nutritional status. This is coordinated by insulin, which triggers kinase signaling cascades to modulate numerous metabolic proteins, leading to increased glucose uptake and anabolic processes like lipogenesis. Given recent evidence that glucose is dispensable for adipocyte respiration, we sought to test whether glucose is necessary for insulin-stimulated anabolism. Examining lipogenesis in cultured adipocytes, glucose was essential for insulin to stimulate the synthesis of fatty acids and glyceride-glycerol. Importantly, glucose was dispensable for lipogenesis in the absence of insulin, suggesting that distinct carbon sources are used with or without insulin. Metabolic tracing studies revealed that glucose was required for insulin to stimulate pathways providing carbon substrate, NADPH, and glycerol 3-phosphate for lipid synthesis and storage. Glucose also displaced leucine as a lipogenic substrate and was necessary to suppress fatty acid oxidation. Together, glucose provided substrates and metabolic control for insulin to promote lipogenesis in adipocytes. This contrasted with the suppression of lipolysis by insulin signaling, which occurred independently of glucose. Given previous observations that signal transduction acts primarily before glucose uptake in adipocytes, these data are consistent with a model whereby insulin initially utilizes protein phosphorylation to stimulate lipid anabolism, which is sustained by subsequent glucose metabolism. Consequently, lipid abundance was sensitive to glucose availability, both during adipogenesis and in Drosophila flies in vivo Together, these data highlight the importance of glucose metabolism to support insulin action, providing a complementary regulatory mechanism to signal transduction to stimulate adipose anabolism.

Physical characteristics of nano-Hydroxyapatite Pickering-emulsions and their adjuvant activity on the antibody response towards the Bothros asper snake venom.

Emulsions are crucial in the treatment of snake bites to bust the antibody response of the inmunogen. The widely used Freund's emulsion typically combines 50/50 water-oil (W/O) phase. However, its use is limited because it is associated with tissue damage. We formulated and characterized a Pickering Emulsion 70/30 (W/O) that uses a chemically modified hydrophobic hydroxyapatite as surfactant. This Pickering emulsion has similar rheologic behavior to Freund's emulsion 50/50, but with lower oil and surfactant concentration. Evaluation of cell recruitment, antibody response and adhering tissue in mice immunized with B. asper of Pacific venom and treated with Freund's and Pickering 70/30 emulsions resulted in similar adjuvant activity (only 18% lower in Pickering 70/30 emulsion). However, Pickering 70/30 emulsions minimized negative side effects in the host animals and showed better ease of flow that favors injection of the host. Our results open up room for optimization and improvement of Pickering emulsion based on modified nanoparticles for medical applications.

Thermal effusivity measurement of conventional and organic coffee oils via photopyroelectric technique.

In this work, oil samples extracted from organic and conventional coffee beans were studied. A fatty acids profile analysis was done using gas chromatography and physicochemical analysis of density and acidity index to verify the oil purity. Additionally, Mid-Infrared Fourier Transform Photoacoustic Spectroscopy (FTIR-PAS) aided by Principal Component Analysis (PCA) was used to identify differences between the intensities of the absorption bands related to functional groups. Thermal effusivity values between 592±3 and 610±4Ws1/2m-2K-1 were measured using the photopyroelectric technique in a front detection configuration. The acidity index was between 1.11 and 1.27% and the density changed between 0.921 and 0.94g/mL. These variables, as well as the extraction yield between 12,6 and 14,4%, showed a similar behavior than that observed for the thermal effusivity, demonstrating that this parameter can be used as a criterion for discrimination between oil samples extracted from organic and conventional coffee beans.

Chemically driven tetragonal-to-monoclinic polymorphic transformation in retrieved ZTA femoral heads from dual mobility hip implants.

Two short-term (two and nine months) retrieved zirconia-toughened alumina (ZTA) femoral heads and nine pristine femoral heads from the same manufacturer have been investigated with respect to their surface stability by means of confocal Raman spectroscopy. Quantitative estimations of monoclinic volume fraction have been carried out in both non-wear and main wear zones of the retrieved heads, which invariantly showed high volume fractions of monoclinic polymorph. In-depth (sub-surface) profiles, non-destructively collected in the main wear zones with the Raman probe in confocal configuration, indeed confirmed that polymorphic transformation was extended down to 100µm below the bearing surface of the femoral heads. Acceleration of tetragonal-to-monoclinic transformation rate leads to unexpectedly high fractions of monoclinic phase within very short-term in-vivo exposures. Phase transformation in-vivo is much more marked than what one could actually predict according to simply simulating a hydrothermal environment in-vitro and could not be simply ascribed to the mechanical stress fields generated during normal service at the bearing surface. Instead, the chemical consequences of metal contamination on the ZTA femoral head surface are shown to play the most detrimental role in phase destabilization.

Mindfulness en Pediatría: el proyecto "Creciendo con atención y consciencia plena" / Mindfulness in Pediatrics: the "Growing with mindfulness" project

Distintos estudios sugieren que la atención y consciencia plena mindfulness tiene, entre otros, el beneficio potencial de mejorar la atención de los niños y las habilidades sociales, la reducción de ansiedad ante los exámenes y la mejora en mantener la calma. Promovido desde el espacio grupal "De jóvenes a jóvenes" y fruto de la colaboración entre nuestro centro de salud y el colegio Emperador Fernando de Alcalá de Henares (Madrid), está en marcha, desde octubre de 2012, el proyecto "Creciendo con atención y consciencia plena", que trata de educar para la salud a través de la atención y consciencia plena (mindfulness). El proyecto obtiene en 2013 el Primer Premio semFYC a Proyectos de Actividades Comunitarias en Atención Primaria. El objetivo principal es aprender a gestionar nuestras capacidades de control sobre nuestra salud desde la atención y consciencia plena, y a relacionarnos de forma empática con las personas, sin juzgarlas, desde la aceptación y la no exigencia (exigir es desresponsabilizar al otro, yendo en contra de su empoderamiento para la salud). En la evaluación continua del proyecto se están observando en los participantes aumento de la empatía, mejora de las relaciones, reducción de la ansiedad y de los síntomas de déficit de atención e hiperactividad y mejora del rendimiento académico (AU)

Several studies suggest that mindfulness has, among others, potential to improve the attention of children and social skills, reducing test anxiety and improving the ability to keep calm. The "Growing with mindfulness" project is promoted by the group "From youth to youth" and a product of the collaboration between our health center and the Emperador Fernando's school of Alcalá de Henares (Madrid). It is underway since October 2012. This project seeks to educate health through the mindfulness. The project obtained in 2013 the First Prize in the semFYC Projects in Community Activities in Primary Care. The main objective is to learn to manage our capabilities of control over our health from the mindfulness and relate empathetically to people without judging, from acceptance and no demand (demand is taking responsibility to the other, going against empowerment for health). Participants increased empathy, improving relationships, reducing anxiety and symptoms of attention deficit hyperactivity disorder and improving academic performance are being observed in the continuous assessment of the project

Effects of chloroformic extracts from washed and unwashed papaya seeds (Carica papaya) on the sperm concentration of dogs.

Papaya seeds (Carica papaya Linn) have been found to have a significant effect on sperm characteristics in some mammals, including humans, but no studies have investigated the effects on dogs. In the present study, a significant decrease in sperm concentration was observed in a group of dogs treated with extracts from washed papaya seeds, but no decrease was observed in the group of dogs treated with non-washed seeds. An important effect of extract components from washed seeds such as fatty acids is probably involved in the reduction of sperm production because of Sertoli cell damage, as has been suggested for langur monkeys. Dilution of the active components in the non-washed papaya seeds or interference with some of the components may reduce the expected effect on spermatogenesis. This first report on the effects of a chloroformic extract of papaya seeds in dogs suggests that an increased dose is necessary to achieve azoospermia.

Perfil del usuario derivado desde Atención Primaria a una Unidad de Salud Mental / No disponible

Objetivo: la recogida y análisis de los datos de laactividad asistencial de una Unidad de Salud Mentaldeberían proporcionar elementos de reflexión para laplanificación de los Servicios y la formación de los profesionales.Resultados: en nuestro caso hemos analizado variablessociodemográficas y clínicas de los 1.224 casosnuevos atendidos durante el año 2008, siendo los datosmás llamativos la elevada proporción de mujeres (el70% de los casos) y la diferencia en la incidencia de losdiagnósticos según procedencia, edad o género.Conclusión: el perfil del usuario que acude a nuestroequipo de salud mental es una mujer, casada o en pareja,de 25 a 35 años, de nivel socioeconómico medio yprocedencia urbana que consulta por padecer un trastornoafectivo o de ansiedad(AU)

Objectives: the gathering and analysis of data relatingto the type of patients of a Mental Health Unit provideus with information which should be taken intoaccount as regards service planning and the formationof doctors.Results: we have analyzed socio-demographic andclinical variables of 1.224 new cases treated during2008. The most relevant data gathered refer to the higherproportion of female patients (70% of the cases) andthe difference of diagnoses depending on their provenance,age or gender.Conclusions: the most common profile of a patientseeking medical care in our Mental Health Unit is thatof a married woman, 25 to 35 years old, from a mediumsocio-economical level and with an urban provenance,affected by an affective or anxiety disorder(AU)

Activity of taraxasteryl acetate on inflammation and heat shock protein synthesis.

Pluchea sagittalis whole plant dichloromethane extract showed inhibitory activity in several inflammatory models: rat hind paw-edema, mice ear edema, and air-pouch rat granuloma. The extract inhibited the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in stimulated human neutrophils. It also showed inhibitory effect on heat shock protein 72 (hsp72) synthesis in stimulated neutrophils, while it had opposite effects on unstimulated cells. The triterpene taraxasteryl acetate was obtained from the dichloromethane extract by bioassay directed isolation, being active against induced ROS and RNS production in human neutrophils. In mice ear edema (induced by phorbol-12-mirystate-13-acetate, croton oil and arachidonic acid), taraxasteryl acetate showed a topical anti-inflammatory activity similar to the extract, but at 1/20 of the dose. The same ratio was observed for the inhibition of hsp72 production in stimulated human neutrophils. In unstimulated monocytes and neutrophils, taraxasteryl acetate showed a higher stimulating activity of hsp72 production than the extract, involving different mechanisms in each cell type. To our knowledge, taraxasteryl acetate is the first natural product for which a dual effect on the hsp response is reported.

Activity of plant extracts on the respiratory burst and the stress protein synthesis.

Aqueous, methanol and dichloromethane extracts from Artemisia copa, Baccharis grisebachii, Baccharis incarum, Baccharis latifolia, Mutisia kurtzii and Pluchea sagittalis, plants used in the Traditional Medicine of South America, are studied for activity on the respiratory burst and the inducible heat shock protein of 72 kD (hsp72) synthesis. Activity on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as on hsp72 synthesis was measured by flow cytometry in human neutrophils. Cells were stimulated using hydrogen peroxide, phorbol-12-myristate-13-acetate (PMA) or formyl-methionyl-leucyl-phenylalanine (FMLP) for ROS generation, and sodium nitroprusside (SNP) or PMA in the presence of calmodulin inhibitor W-13 for RNS. The production of hsp72 was induced by heat, PMA, H2O2 and SNP. The best inhibitory activity was shown by the dichloromethane extracts of Baccharis grisebachii and Pluchea sagittalis that were active in all the assays. The aqueous extract of Pluchea sagittalis was also active in most assays. The aqueous extract from Mutisia kurtzii caused a clear increase of the hsp72 production and showed prooxidant activity.

Heterotheca inuloides: anti-inflammatory and analgesic effect.

Heterotheca inuloides Cass. (Asteraceae) is used in the traditional medicine of Mexico. The aqueous extract obtained from the flowers of H. inuloides was assessed for anti-inflammatory activity by carrageenan-induced edema test. At 100 mg/kg, i.p, it produced 29% inhibition of inflammation. Ethyl ether (HI-1), butanol (HI-2) and aqueous fraction (HI-3) were obtained from the aqueous extract. The biological assay, by carrageenan-induced edema test, gave the following values (% inhibition): HI-1, 19.9; HI-2, 58.0 and HI-3, 30.0. HI-2 was significantly more effective than HI-1 and HI-3. The dose-effect curve of HI-2 was obtained and the calculated ED50 was 29.7 (22.5-39.2) mg/kg. The peritoneal examination after the treatment with HI-2 showed that the anti-inflammatory action of H. inuloides was not due to an irritating effect at the injection site. At 50-100 mg/kg, i.p., HI-2 inhibited inflammation induced by dextran (38.9-68.1% inhibition) and arachidonic acid (0-33.9%). No effect was observed at the same doses for zymosan or C16-paf-induced edema. In addition, HI-2 reduced abdominal constrictions in mice following injection of acetic acid: at 50-100 mg/kg, it gave 73.8-78.2% inhibition. The ulcerogenic assay showed that ulcer indices after HI-2 i.p. treatment were 0.5 +/- 0.5 at 50 mg/kg and 1.2 +/- 0.4 at 100 mg/kg. The results showed related anti-inflammatory activity and the analgesic effect of HI-2.

Xanthophyll biosynthesis. Cloning, expression, functional reconstitution, and regulation of beta-cyclohexenyl carotenoid epoxidase from pepper (Capsicum annuum).

Pepper (Capsicum annuum) beta-cyclohexenyl xanthophyll epoxidase cDNA was cloned and the corresponding enzyme overexpressed and purified from Escherichia coli, for investigation of its catalytic activity. The recombinant protein did not directly accept NADPH for epoxidation of cyclohexenyl carotenoids, nor did it operate according to a peroxygenase-based mechanism. Instead, the reducing power of NADPH was transferred to the epoxidase via reduced ferredoxin as shown by reconstitution of epoxidase activity in the presence of NADPH, ferredoxin oxidoreductase, and ferredoxin. Bacterial rubredoxin could be substituted for ferredoxin. The pepper epoxidase acted specifically on the beta-ring of xanthophylls such as beta-cryptoxanthin, zeaxanthin, and antheraxanthin. The proposed reaction mechanism for epoxidation involves the formation of a transient carbocation. This characteristic allows selective inhibition of the epoxidase activity by different nucleophilic diethylamine derivatives, p-dimethylaminobenzenediazonium fluoroborate and N,N-dimethyl-2-phenylaziridinium. It was also shown that the epoxidase gene was up-regulated during oxidative stress and when chloroplasts undergo differentiation into chromoplasts in pepper fruit.

Anti-inflammatory and analgesic activity of Baccharis trimera: identification of its active constituents.

The butanolic fraction (BT-II) derived from the aqueous crude extract was prepared from aerial parts of Baccharis trimera and assessed in anti-inflammatory, analgesia, and ulcerogenesis models. Intraperitoneal pretreatment with lyophilized BT-II, at doses ranging from 40 to 100 mg/kg, markedly inhibited carrageenan- and dextran-induced inflammation (70.4-90.8% and 25.7-71.3%, respectively) and weakly decreased C16-paf- and arachidonic acid-induced swelling (24.9-36.7% and 0-30.6%, respectively). No effect was observed, at the same doses, on zymosan-induced edema. The intraperitoneal examination indicates that the anti-phlogistic action of BT-II was not due to an irritating effect at the injection site. Besides, BT-II reduced abdominal constrictions in mice following injection of acetic acid: at 50 mg/kg, it gave 67.4% inhibition and, at 100 mg/kg, 95.1%. The ulcerogenic assay showed that the incidence of ulcers after BT-II i.p. treatment was 2/6 at 50 mg/kg and 6/6 at 100 mg/kg. Ulcerogenic indices were 1.3 +/- 0.5 and 2.7 +/- 0.8, respectively. These results indicate that B.trimera shows strong anti-inflammatory and analgesic properties which seem to be due, at least partly, to the inhibition of prostaglandin biosynthesis. The chromatographic separation of BT-II monitored by bio-assay (carrageenan-induced edema test in mice) was carried out. The active constituents were found to be mainly saponins in which echinocystic acid (or its enantiomer) is the major aglycone, and also rutin.

Molecular identification of zeaxanthin epoxidase of Nicotiana plumbaginifolia, a gene involved in abscisic acid biosynthesis and corresponding to the ABA locus of Arabidopsis thaliana.

Abscisic acid (ABA) is a plant hormone which plays an important role in seed development and dormancy and in plant response to environmental stresses. An ABA-deficient mutant of Nicotiana plumbaginifolia, aba2, was isolated by transposon tagging using the maize Activator transposon. The aba2 mutant exhibits precocious seed germination and a severe wilty phenotype. The mutant is impaired in the first step of the ABA biosynthesis pathway, the zeaxanthin epoxidation reaction. ABA2 cDNA is able to complement N.plumbaginifolia aba2 and Arabidopsis thaliana aba mutations indicating that these mutants are homologous. ABA2 cDNA encodes a chloroplast-imported protein of 72.5 kDa, sharing similarities with different mono-oxigenases and oxidases of bacterial origin and having an ADP-binding fold and an FAD-binding domain. ABA2 protein, produced in Escherichia coli, exhibits in vitro zeaxanthin epoxidase activity. This is the first report of the isolation of a gene of the ABA biosynthetic pathway. The molecular identification of ABA2 opens the possibility to study the regulation of ABA biosynthesis and its cellular location.

Anti-inflammatory action of Pluchea sagittalis: involvement of an antioxidant mechanism.

Pluchea sagittalis, (Lam.) Cabr., a popular medicinal herb grown in South America, was studied for anti-inflammatory and antioxidant activities. The anti-edema action of P. sagittalis aqueous extract was assayed in different models of inflammation: 1) the mouse ear edema test induced by arachidonic acid and croton oil; 2) the rat hind-paw edema test produced by several inflammatory inductors: carrageenan, dextran, zymosan, platelet-activating factor (PAF) and arachidonic acid; 3) a subacute model based on the rat carrageenan air-pouch granuloma test. Blood leukocyte free radical production was measured by flow cytometry with 2',7'-dichlorofluorescin diacetate (DCFH-DA) in vivo, in rats with induced air-pouch granuloma, and in a model in vitro. stimulating leukocytes with hydrogen peroxide. The aqueous extract of P. sagittalis showed a marked anti-inflammatory effect in both ear edema tests, dextran and carrageenan hind-paw edemas and carrageenan air-pouch model. It also had a potent antioxidant activity in blood leukocytes, both in vivo and in vitro. Our results correlate the reduction of free radical production with the anti-inflammatory effect of this plant.

Cardiac fulguration, a new alternative therapy for atrioventricular nodal reentrant tachycardia.

Ten patients underwent endocardial catheter ablation of the atrioventricular junction for atrioventricular nodal reentrant tachycardias. Unipolar cathodic discharges at the distal electrode were administered against an external plate. Bipolar His and atrial deflections showed a mean of 0.15 mv and 0.5 mv respectively. Mean total energy used per patient was 195 J (range: 50-750), with a mean number of ablating discharges of 2.0 per patient, (range: 1-5). Complete atrioventricular block was achieved, but conduction reappeared in all except one patient, after a mean interval of 19.9 min. Electrophysiological evaluation was assessed 3-8 days after ablation. Sustained atrioventricular nodal reentrant tachycardias were no longer inducible in any patient. Retrograde conduction was abolished in six, and was slow and decremental in four. First-degree atrioventricular block, with intranodal delay was diagnosed in six, with an AH interval that ranged from 240 to 130 ms. Mean cycle length for appearance of Wenckebach atrioventricular block was 390 ms after ablation. One patient developed complete atrioventricular block after two discharges of 50 J, another required a repeat ablation for recurrence of intranodal tachycardia and also developed complete anterograde block in a new session of ablation with a 150 J discharge. In these two patients permanent pacing was needed. Eight patients were cured after a mean follow-up of 20 months. Less energy and fewer discharges should be administered to abolish functional dissociation of the atrioventricular node, without complete interruption of anterograde conduction.

Treatment of portal systemic encephalopathy: standard and new treatments.

The management of hepatic encephalopathy should be considered accordingly with the precipitating factor and the type of encephalopathy. Ideally the therapeutic approach must be useful for both acute and chronic forms of encephalopathy. Current treatment of hepatic encephalopathy consists of certain well-established measures attempting to identify and treat the precipitating factors, and to reduce the intestinal nitrogenous compounds formation and absorption by dietary restriction or bowel-cleansing with catartics or antibiotics such as neomycin, metronidazol, etc. This review describes briefly several therapeutic modalities.