Methylene blue? Therapeutic alternative in the management of septic shock refractory to norepinephrine

Introduction: Methylene blue is receiving special interest in perioperative and intensive care of patients with distributive shock due to its ability to block the action of nitric oxide and to antagonize deep vasodilation. Objective: The objective is to illustrate the use of the methylene blue, summarizing the perioperative management of a case with secondary vasoplegic syndrome due to a norepinephrine refractory septic shock and the response to methylene blue, reviewing the latest evidence of this therapeutic alternative. In practice:We describe the case of a 60-year-old man, paraplegic, with septic shock due to a long evolution decubitus pressure ulcer. After two hours of surgery, the patient remained with hemodynamic deterioration despite high doses of vasopressin (3 IU/hour) and norepinephrine (2 µg/kg /min), therefore methylene blue was administered with two intravenous bolus doses of 50 mg without adverse effects. After half an hour hemodynamic improvement was evidenced, allowing to decrease norepinephrine infusion and normalizing blood pressure. Finally, debridement of necrotic tissue, amputation and disarticulation of left coxofemoral joint was performed with subsequent transfer to the ICU and discharge to the spinal cord injury ward twenty eight days later. Conclusions: As it has been demonstrated in our patient, methylene blue is a therapeutic alternative to manage patients with persistent hypotension despite the use of various vasopressors during the management of vasoplegic syndrome secondary to septic shock

Macroevolutionary dynamics of nectar spurs, a key evolutionary innovation.

Floral nectar spurs are widely considered a key innovation promoting diversification in angiosperms by means of pollinator shifts. We investigated the macroevolutionary dynamics of nectar spurs in the tribe Antirrhineae (Plantaginaceae), which contains 29 genera and 300-400 species (70-80% spurred). The effect of nectar spurs on diversification was tested, with special focus on Linaria, the genus with the highest number of species. We generated the most comprehensive phylogeny of Antirrhineae to date and reconstructed the evolution of nectar spurs. Diversification rate heterogeneity was investigated using trait-dependent and trait-independent methods, and accounting for taxonomic uncertainty. The association between changes in spur length and speciation was examined within Linaria using model testing and ancestral state reconstructions. We inferred four independent acquisitions of nectar spurs. Diversification analyses revealed that nectar spurs are loosely associated with increased diversification rates. Detected rate shifts were delayed by 5-15 Myr with respect to the acquisition of the trait. Active evolution of spur length, fitting a speciational model, was inferred in Linaria, which is consistent with a scenario of pollinator shifts driving diversification. Nectar spurs played a role in diversification of the Antirrhineae, but diversification dynamics can only be fully explained by the complex interaction of multiple biotic and abiotic factors.This work was supported by the Marie Curie Intra-European Fellowship LINARIA-SPECIATION (FP7-PEOPLE-2013-IEF, reference 624396), an Isaac Newton Trust Research Grant (Trinity College, Cambridge), a Juan de la Cierva fellowship to M.F.-M. (Spanish Ministry of Economy and Competitivity, reference IJCI-2015-23459) and a Generalitat Valenciana postdoctoral grant to A.J. (Ministry of Education, Culture and Sport, reference BEST/2014/264)

An experience beyond continuous assessment activities: virtual tour to the medieval medicinal plant garden of the Pedralbes monastery

El grupo de innovación docente integrado por profesores del área de Botánica (GIBAF) de la Universidad de Barcelona (UB) se plantea cada curso el diseño de nuevas actividades acreditativas en el marco de la evaluación continuada. Se presenta la experiencia llevada a cabo durante el curso 2008- 09 en la asignatura Botánica Farmacéutica. El objetivo ha sido implicar durante un semestre a los estudiantes en la autoría de un proyecto tutorizado de inmediata utilidad y clara perdurabilidad, más allá de su utilidad acreditativa. Como recurso se ha utilizado el Jardín de Plantas Medicinales del Monasterio de Pedralbes y se ha firmado un convenio de colaboración docente entre la UB y el Instituto de Cultura de Barcelona. Los estudiantes han realizado el trabajo utilizando la plataforma Moodle del Campus virtual de la UB en cinco etapas que han incluido la confección de unas fichas que se han ido modificando en función de las diversas retroacciones de los profesores. Al inicio de la actividad, se facilitó a los estudiantes el cronograma completo de la actividad, la pauta para su realización, así como un total de 18 recursos bibliográficos de uso obligado. Finalmente, a través de GoogleSites, se ha realizado una web que permite realizar un paseo virtual por el jardín, documentando de forma referenciada para las 50 plantas medicinales su nomenclatura, descripción botánica, distribución, usos (históricos, actuales y futuros) y toxicidad. El resultado de la actividad fue presentado en un acto público en el Monasterio de Pedralbes y puede consultarse en: http://sites.google.com/site/jardimedievalpedralbes/The group of teaching innovation in the area of Botany (GIBAF), University of Barcelona (UB), is raised each year to design new accreditation activities under continuous evaluation framework. We present the experience carried out during the academic year 2008-09 in the course of Pharmaceutical Botany. The aim has been to involve students for a semester in the authorship of a tutored project immediately useful and of easy permanence, beyond its assessment proving usefulness. The Medicinal Plants Garden of the Monastery of Pedralbes has been used as a resource and a collaboration agreement has been signed between the UB faculty and the Institute of Culture of Barcelona. The students have developed the work using the Moodle platform CampusvirtualUB into five stages which included preparation of files by students that have been modified in some steps following the various feedbacks from teachers. At the beginning of the activity, students were provided with a complete schedule of activities, the schedule for its implementation, and a total of 18 forced-use library resources. Finally, through Google sites, a website has been implemented, allowing for a virtual tour of the garden, documenting by referenced literature 50 medicinal plants for their nomenclature, botanical description, distribution, uses (historical, current and future) and toxicity. The result of the activity was presented at a public ceremony in the Monastery of Pedralbes and is available at: http://sites.google.com/site/jardimedievalpedralbes/Este trabajo ha sido parcialmente financiado con un Ajut per a Projectes d'Innovació Docent (2006PID-UB/11) de la Universidad de Barcelona

Lipid-lowering response in subjects with the p.(Leu167del) mutation in the APOE gene

Background and aims: The aim of this work was to compared the effect of lipid lowering drugs among familial hypercholesterolemia (FH) subjects with a functional mutation in LDLR (LDLR FH) and FH with the p.(Leu167del) mutation in APOE. Methods: We retrospectively selected all adults with the p.(Leu167del) mutation on lipid-lowering treatment (n = 22) attending the Lipid Unit at the Hospital Miguel Servet. Age and sex matched LDLR FH from the same Unit were randomly selected as a control group (n = 44). Results: The mean percentage reduction in LDLc was significantly higher in the p.(Leu167del) carriers (-52.1%) than in the LDLR FH (-39.7%) (p = 0.040) when on high intensity statins. Similar differences between groups were observed in non-HDLc -49.4% and -36.4%, respectively (p = 0.030). Conclusions: Subjects with p.(Leu167del) mutation have a higher lipid-lowering response to statins with or without ezetimibe than LDLR FH. This supports the use of genetics for a more efficient management of FH

Economic impact of improving patient safety using Sugammadex for routine reversal of neuromuscular blockade in Spain

Background: Neuromuscular blocking (NMB) agents are often administered to facilitate tracheal intubation and prevent patient movement during surgical procedures requiring the use of general anesthetics. Incomplete reversal of NMB, can lead to residual NMB, which can increase the risk of post-operative pulmonary complications. Sugammadex is indicated to reverse neuromuscular blockade induced by rocuronium or vecuronium in adults. The aim of this study is to estimate the clinical and economic impact of introducing sugammadex to routine reversal of neuromuscular blockade (NMB) with rocuronium in Spain. Methods: A decision analytic model was constructed reflecting a set of procedures using rocuronium that resulted in moderate or deep NMB at the end of the procedure. Two scenarios were considered for 537, 931 procedures using NMB agents in Spain in 2015: a scenario without sugammadex versus a scenario with sugammadex. Comparators included neostigmine (plus glycopyrrolate) and no reversal agent. The total costs for the healthcare system were estimated from the net of costs of reversal agents and overall cost offsets via reduction in postoperative pneumonias and atelectasis for which incidence rates were based on a Spanish real-world evidence (RWE) study. The model time horizon was assumed to be one year. Costs were expressed in 2019 euros (€) and estimated from the perspective of a healthcare system. One-way sensitivity analysis was carried out by varying each parameter included in the model within a range of +/- 50%. Results: The estimated budget impact of the introduction of sugammadex to the routine reversal of neuromuscular blockade in Spanish hospitals was a net saving of €57.1 million annually. An increase in drug acquisition costs was offset by savings in post-operative pulmonary events, including 4806 post-operative pneumonias and 13, 996 cases of atelectasis. The total cost of complications avoided was €70.4 million. All parameters included in the model were tested in sensitivity analysis and were favorable to the scenario with sugammadex. Conclusions: This economic analysis shows that sugammadex can potentially lead to cost savings for the reversal of rocuronium-induced moderate or profound NMB compared to no reversal and reversal with neostigmine in the Spanish health care setting. The economic model was based on data obtained from Spain and from assumptions from clinical practice and may not be valid for other countries

Glycerol kinase deficiency in adults: Description of 4 novel cases, systematic review and development of a clinical diagnostic score

Background and aims: Glycerol kinase deficiency (GKD) is a rare genetic disorder characterized by hyperglycerolemia and glyceroluria, which could be misdiagnosed as a moderate to severe hypertriglyceridemia (HTG). We aimed to describe four novel cases of GKD, to complete a systematic review of all cases of isolated GKD published so far, and to develop a suspicion clinical diagnostic score for GKD. Methods: We reported four cases with suspicion of GKD and compared their phenotype with 584 males with triglycerides (TG) > 300 mg/dL, selected as control group (HTG non-GKD). The GK gene was sequenced in all cases. Lipoprotein particle concentrations were measured in all cases with GKD. The systematic review involved a PubMed, Cochrane and Scopus databases search to identify anthropometric and biochemical characteristics of all described cases with GKD. Results: The systematic review retrieved a total of 15 articles involving 39 subjects with GKD. GKD cases reported a history of high TG levels resistant to lipid-lowering therapy. Compared to GKD subjects (n = 43), HTG non-GKD subjects (n = 584) showed significantly higher BMI, total cholesterol, non-HDL cholesterol and gamma-glutamyltransferase, significantly lower HDL cholesterol and TG, and higher prevalence of diabetes. The proposed diagnostic score was significantly higher in GKD than in HTG non-GKD subjects. Conclusions: This is the first systematic review that compiles all GKD cases reported to date including 4 novel cases, and examine the differential GKD phenotype compared to other types of HTG. The proposed score would have a broad utility in clinical practice to avoid unwarranted lipid lowering treatment in GKD patients

A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0–700 μM). Colostrum co-treated with DEX was executed at 0.1–5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis

Restoration of european habitats in mainland, Portugal, using commercial seed mixtures. Considerations for its management and conservation

Permanent mountain pastures include meadows and other perennial pastures of high ecological, economic, cultural and scenic value. Increasing desertification limits the maintenance and conservation of its biodiversity and the associated landscape mosaic. A restoration experiment in permanent high altitude grasslands in Beira Alta (Centre East (CE) mainland Portugal) was made, by sowing adequate cultivars of existing grass and legume species. The main objectives addressed were: (1) comparison of floristic composition between reference communities included in the previous habitats and the improved communities; (2) evaluation of the success of sowing adequate cultivars of autochthonous species; (3) evaluation of the establishment of target species in terms of the maintenance of floristic composition of reference. The experiment was carried out in 2014 on nine farms situated in Beira Alta (Guarda District) and the phytosociological method was applied in the floristic surveys. The sown species with highest percentage of soil cover were Trifolium subterraneum, Lolium multiflorum, Ornithopus sativus and Trifolium vesiculosum. In the priority habitat 6220 it was observed a re-establishment of many species in their original composition and a high cover of several cultivars of Trifolium subterraneum. These results highlight the importance of using cultivars of autochthonous species in the improvement of altitude pasturesinfo:eu-repo/semantics/publishedVersio

Regioselective Synthesis of Benzimidazolones via Cascade C–N Coupling of Monosubstituted Ureas

A direct method for the regioselective construction of benzimidazolones is reported wherein a single palladium catalyst is employed to couple monosubstituted urea substrates with differentially substituted 1,2-dihaloaromatic systems. In this method, the catalyst is able to promote a cascade of two discrete chemoselective C–N bond-forming processes that allows the highly selective and predictable formation of complex heterocycles from simple, readily available starting materials.National Institutes of Health (U.S.) (Award GM58160)National Institutes of Health (U.S.) (Award GM099817)Lanxess CorporationMassachusetts Institute of Technology. Undergraduate Research Opportunities Progra