Synthesis of Bioactive Speciosins G and P from Hexagonia speciosa

The first total synthesis of speciosins P and G, previously isolated from Hexagonia speciosa, is reported. These compounds have been synthesized by Sonogashira coupling from readily available starting materials. Siccayne was also synthesized from the same starting material in two steps along with a number of other derivatives. The compounds were tested in the wheat coleoptile bioassay. The most active compound was the intermediate 18, followed by 29 and 17. The structural requirements for activity in these compounds are the presence of methoxy groups in the aromatic ring and a formyl or hydroxy group in the side chain

Ecthyma gangrenosum: a report of eight cases

Abstract: Ecthyma gangrenosum is a rare skin infection classically associated with Pseudomonas aeruginosa. We performed a retrospective study of all cases diagnosed with ecthyma gangrenosum from 2004-2010 in a university hospital in Mexico (8 cases, 5 female patients and 3 male patients, ages between 4 months and 2 years). The most common risk factor for ecthyma gangrenosum is neutropenia in immunocompromised patients. In previously healthy patients, immunological evaluation is important to rule out underlying immunodeficiency. Ecthyma gangrenosum in healthy patients has a high mortality rate and early diagnosis and aggressive antibiotic treatment is imperative as it can improve patients’ prognosis. Keywords: Ecthyma; Pseudomonas; Pseudomonas aeruginosa; Pseudomonas infection

Intercellular Trafficking of Gold Nanostars in Uveal Melanoma Cells for Plasmonic Photothermal Therapy

Efficient plasmonic photothermal therapies (PPTTs) using non-harmful pulse laser irradiation at the near-infrared (NIR) are a highly sought goal in nanomedicine. These therapies rely on the use of plasmonic nanostructures to kill cancer cells while minimizing the applied laser power density. Cancer cells have an unsettled capacity to uptake, retain, release, and re-uptake gold nanoparticles, thus offering enormous versatility for research. In this work, we have studied such cell capabilities for nanoparticle trafficking and its impact on the effect of photothermal treatments. As our model system, we chose uveal (eye) melanoma cells, since laser-assisted eye surgery is routinely used to treat glaucoma and cataracts, or vision correction in refractive surgery. As nanostructure, we selected gold nanostars (Au NSs) due to their high photothermal efficiency at the near-infrared (NIR) region of the electromagnetic spectrum. We first investigated the photothermal effect on the basis of the dilution of Au NSs induced by cell division. Using this approach, we obtained high PPTT efficiency after several cell division cycles at an initial low Au NS concentration (pM regime). Subsequently, we evaluated the photothermal effect on account of cell division upon mixing Au NS-loaded and non-loaded cells. Upon such mixing, we observed trafficking of Au NSs between loaded and non-loaded cells, thus achieving effective PPTT after several division cycles under low irradiation conditions (below the maximum permissible exposure threshold of skin). Our study reveals the ability of uveal melanoma cells to release and re-uptake Au NSs that maintain their plasmonic photothermal properties throughout several cell division cycles and re-uptake. This approach may be readily extrapolated to real tissue and even to treat in situ the eye tumor itself. We believe that our method can potentially be used as co-therapy to disperse plasmonic gold nanostructures across affected tissues, thus increasing the effectiveness of classic PPTT

Synthesis, antibacterial and antifungal activities of naphthoquinone derivatives: a structure–activity relationship study

The synthesis of 1,4-naphthoquinone derivatives is of great interest since these compounds exhibit strong activity as antimalarial, antibacterial, antifungal and anticancer agents. A series of 50 naphthoquinone derivatives was synthesized and evaluated for antibacterial and antifungal activity against Escherichia coli, Pseudomonas aeruginosa, Enterococcus faecalis, Staphylococcus aureus, Candida krusei, Candida parapsilosis and Cryptococcus neoformans using the broth microdilution method. The Candida species were the most susceptible microorganisms. Halogen derivatives of 1,4-naphthoquinone presented strong activity, e.g., 2-bromo-5-hydroxy-1,4-naphthoquinone, which exhibited inhibition at an MIC of 16 lg/ mL in S. aureus, and 2-chloro-5,8-dihydroxy-1,4-naphthoquinone, with an MIC of 2 lg/mL in C. krusei. These compounds showed higher activity against fungi, but the antibacterial activities were very low. The study of structure–activity relationships is very important in the search for new antimicrobial drugs due to the limited therapeutic arsenal

Tag-SNP analysis of the GFI1-EVI5-RPL5-FAM69 risk locus for multiple sclerosis

A recent genome-wide association study conducted by the International Multiple Sclerosis Genetic Consortium (IMSGC) identified, among others, a number of putative multiple sclerosis (MS) susceptibility variants at position 1p22. Twenty-one SNPs positively associated with MS were located at the GFI-EVI5-RPL5-FAM69A locus. In this study, we performed an analysis and fine mapping of this locus, genotyping eight Tag-SNPs in 732 MS patients and 974 controls from Spain. We observed an association with MS in three of eight Tag-SNPs: rs11804321 (P=0.008, OR=1.29; 95% CI1.08-1.54), rs11808092 (P=0.048, OR=1.19; 95% CI1.03-1.39) and rs6680578 (P=0.0082, OR=1.23; 95% CI1.07-1.41). After correcting for multiple comparisons and using logistic regression analysis to test the addition of each SNP to the most associated SNPs, we observed that rs11804321 alone was sufficient to model the association. This Tag-SNP captures two SNPs in complete linkage disequilibrium (r2= 1), both located within the 17th intron of the EVI5 gene. Our findings agree with the corresponding data of the recent IMSGC study and present new genetic evidence that points to EVI5 as a factor of susceptibility to MS. © 2010 Macmillan Publishers Limited All rights reserved.Financial support for the study was provided by the Ministerio de Ciencia e Innovación-Fondos Feder (Grant SAF2009–11491) and Junta de Andalucía (P07-CVI-02551) to A. Alcina, and by Fondo de Investigación Sanitaria (PI081636) to F. Matesanz. María Fedetz is a holder of a fellowship from Fundación IMABIS. Dorothy Ndagire is a holder of AECI-Ministerio de Asuntos Exteriores fellowship.Peer Reviewe

Evidence‐based treatment for gynoid lipodystrophy: A review of the recent literature

Resumen La lipodistrofia ginoide (LDG) es una alteracion estructural, inflamatoria y bioquımica del tejido subcutaneo que causa modificaciones topograficas en la piel. Conocida comunmente como “celulitis”, la LDG afecta hasta a 90% de las mujeres, practicamente en todas las etapas de la vida, iniciando en la pubertad. Se trata de una condicion que afecta considerablemente la calidad de vida de quien la padece. Es motivo frecuente de consulta aunque las pacientes recurren a tratamientos empıricos, improvisados, sin bases ni evidencia cientıfica, los cuales desmotivan y producen frustracion no solo por su falta de resultados, sino por complicaciones derivadas de dichos tratamientos. Un grupo de expertos de diversas especialidades involucradas en el manejo de este problema presenta en este artıculo el resultado de una busqueda bibliografica sistematica y de la discusion consensuada de la evidencia obtenida de diversos tratamientos disponibles actualmente. El analisis se dividio en tratamientos topicos, tratamientos sistemicos, tratamientos no invasivos y tratamientos mınimamente invasivos

Cuentos del Olivar

En este apasionante viaje tenemos las puertas abiertas para todo aquel que se quiera sumar, ya sea trabajando en pos de la difusión de la cultura ligada al olivo o disfrutando de lecturas como las que se recogen en este libro, que seguro les depara un sabroso disfrute y les descubre una cultura del olivar que tiene a sus espaldas varios milenios de historia. Les deseo que paladeen cada uno de estos relatos, que conforman un excelente aperitivo literario.Área de Historia del Art

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality