Mechanisms and drug therapy of pulmonary hypertension at high altitude.

Abstract Scherrer, Urs, Yves Allemann, Emrush Rexhaj, Stefano F. Rimoldi, and Claudio Sartori. Mechanisms and drug therapy of pulmonary hypertension at high altitude. High Alt Med Biol 14:126-133, 2013.-Pulmonary vasoconstriction represents a physiological adaptive mechanism to high altitude. If exaggerated, however, it is associated with important morbidity and mortality. Recent mechanistic studies using short-term acute high altitude exposure have provided insight into the importance of defective vascular endothelial and respiratory epithelial nitric oxide (NO) synthesis, increased endothelin-1 bioavailability, and overactivation of the sympathetic nervous system in causing exaggerated hypoxic pulmonary hypertension in humans. Based on these studies, drugs that increase NO bioavailability, attenuate endothelin-1 induced pulmonary vasoconstriction, or prevent exaggerated sympathetic activation have been shown to be useful for the treatment/prevention of exaggerated pulm9onary hypertension during acute short-term high altitude exposure. The mechanisms underpinning chronic pulmonary hypertension in high altitude dwellers are less well understood, but recent evidence suggests that they differ in some aspects from those involved in short-term adaptation to high altitude. These differences have consequences for the choice of the treatment for chronic pulmonary hypertension at high altitude. Finally, recent data indicate that fetal programming of pulmonary vascular dysfunction in offspring of preeclampsia and children generated by assisted reproductive technologies represents a novel and frequent cause of pulmonary hypertension at high altitude. In animal models of fetal programming of hypoxic pulmonary hypertension, epigenetic mechanisms play a role, and targeting of these mechanisms with drugs lowers pulmonary artery pressure. If epigenetic mechanisms also are operational in the fetal programming of pulmonary vascular dysfunction in humans, such drugs may become novel tools for the treatment of hypoxic pulmonary hypertension.

Nissanim - 1-25

Sisällys/Contents: 1. ¿Andersen: ham-Mal¿ak. Targum: ¿Abi¿asap. 2. ¿Andersen: Be-¿aharit-jam. 3. ¿Andersen: Tippat ham-majim. & ha-Hol. 4-5. Andersen: Perah qatan. 6. H. Lewe: Perah nipla¿. & Qeren hash-shemesh. 7-8. Maqs Nordo: Siah hash-shoshannim. Targum: Sh.L. Gordon. 9. P. ¿Awwirpuk: ¿Ateret haz-zahab. 10. ¿A. Terje: he-Halil han-nipla¿. Targum: P. ¿Awwirpuk. 11-15. Ma¿asijjot liladim. Targum: Shelomo Berman. 16. Mika Josep Berditshevsqi: Ma¿asijjot we-¿aggadot. 17-18. Herodot: Hekal ra¿meses. ¿al jede: ¿A-S. 19. J.V. Levner: hab-Kotel ham-ma¿arabi. 20. ¿A.L. Ja¿aqubovis: ¿Abraham hak-Kaspi. 21-22. Sha¿ul Tshernihovsqi: Shirim. 23-25. Jishaq J. Qassenelson. Shirim.

El diálogo entre Caronte y el ánima de Pedro Luis Farnesio: un libro abierto.

En septiembre de 1547 asesinaron a Pedro Luis Farnesio, duque de Parma y de Piacenza, hijo del papa Paulo III...

Formação de cálculo uretral ao redor de um corpo estranho: relato de um caso

Os cálculos uretrais primários são raros no ocidente. O seu desenvolvimento freqüentemente está associado a alterações prévias do fluxo urinário, como divertículos uretrais, áreas de estenose ou corpos estranhos impactados. Os autores relatam um caso de um paciente de 77 anos de idade que se apresentou com queixa de retenção urinária aguda e dor na região genital. O diagnóstico de uretrolitíase foi feito e, mediante estudos radiográficos, um objeto estranho, cilindro de madeira, foi identificado no interior do cálculo.

The Influence of Age and Sex on Genetic Associations with Adult Body Size and Shape: A Large-Scale Genome-Wide Interaction Study.

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR<5%) age-specific effects, of which 11 had larger effects in younger (<50y) than in older adults (≥50y). No sex-dependent effects were identified for BMI. For WHRadjBMI, we identified 44 loci (27 previously established for main effects, 17 novel) with sex-specific effects, of which 28 showed larger effects in women than in men, five showed larger effects in men than in women, and 11 showed opposite effects between sexes. No age-dependent effects were identified for WHRadjBMI. This is the first genome-wide interaction meta-analysis to report convincing evidence of age-dependent genetic effects on BMI. In addition, we confirm the sex-specificity of genetic effects on WHRadjBMI. These results may provide further insights into the biology that underlies weight change with age or the sexually dimorphism of body shape.

Impact of Study Design on Reported Incidences of Acute Mountain Sickness: A Systematic Review.

AIMS: Published incidences of acute mountain sickness (AMS) vary widely. Reasons for this variation, and predictive factors of AMS, are not well understood. We aimed to identify predictive factors that are associated with the occurrence of AMS, and to test the hypothesis that study design is an independent predictive factor of AMS incidence. We did a systematic search (Medline, bibliographies) for relevant articles in English or French, up to April 28, 2013. Studies of any design reporting on AMS incidence in humans without prophylaxis were selected. Data on incidence and potential predictive factors were extracted by two reviewers and crosschecked by four reviewers. Associations between predictive factors and AMS incidence were sought through bivariate and multivariate analyses for different study designs separately. Association between AMS incidence and study design was assessed using multiple linear regression. RESULTS: We extracted data from 53,603 subjects from 34 randomized controlled trials, 44 cohort studies, and 33 cross-sectional studies. In randomized trials, the median of AMS incidences without prophylaxis was 60% (range, 16%-100%); mode of ascent and population were significantly associated with AMS incidence. In cohort studies, the median of AMS incidences was 51% (0%-100%); geographical location was significantly associated with AMS incidence. In cross-sectional studies, the median of AMS incidences was 32% (0%-68%); mode of ascent and maximum altitude were significantly associated with AMS incidence. In a multivariate analysis, study design (p=0.012), mode of ascent (p=0.003), maximum altitude (p<0.001), population (p=0.002), and geographical location (p<0.001) were significantly associated with AMS incidence. Age, sex, speed of ascent, duration of exposure, or history of AMS were inconsistently reported and therefore not further analyzed. CONCLUSIONS: Reported incidences and identifiable predictive factors of AMS depend on study design.

Aineettomien pääomaerien tunnistaminen ja hyväksikäyttö strategiatyössä

Tässä tutkimuksessa tutkittiin keinoja tunnistaa organisaation aineeton pääoma ja yhdistää se strategiatyöhön. Aineettomien pääomien tunnistamisen yhteydessä tutkittiin myös sitä, miten on mahdollista tunnistaa juuri strategisesti merkittävät aineettomat pääomat. Tutkimuksen teoreettinen osuus toteutettiin kirjallisuuskatsauksena. Tutkimuksen empiirinen osuus toteutettiin case-tutkimuksena käyttäen menetelminä osallistuvaa havainnointia kahden työpajan aikana ja kyselylomaketta. Tutkimus oli haasteellinen toteuttaa johtuen aihe-alueen laajuudesta ja teorioiden päällekkäisyydestä sekä aihepiirin vieraudesta tutkimukseen osallistuneille. Analyysi, tulokset ja johtopäätökset perustuivat tutkijan omiin tulkintoihin. Tulkintoja tehtiin analysoimalla case-tutkimuksen aikana kerättyjä aineistoja ja vertaamalla case-tutkimuksen tuloksia teoriaan. Case-tutkimus osoitti, että aineettoman pääoman tunnistamisen ja strategiaan yhdistämisen tueksi tarvitaan toimivia työkaluja. Huolimatta toimivistakin työkaluista, on aineettoman pääoman erien tunnistaminen haastavaa eikä ydinkompetenssien tunnistaminen välttämättä onnistu täysin objektiivisesti. Myös aineettoman pääoman yhdistäminen strategiaan on aiemmin asiaan perehtymättömälle vaikeaa. Tutkimus todisti, että aineettoman pääoman rakenteen ja hyväksikäytön tutkimusta tulee jatkaa jotta voidaan kehittää toimivia ja helppokäyttöisiä työkaluja aineettoman pääoman johtamisen tueksi.

Antimycobacterial and cytotoxicity activity of synthetic and natural compounds

Antimycobacterial and cytotoxicity activity of synthetic and natural compounds. Secondary metabolites from Curvularia eragrostidis and Drechslera dematioidea, Clusia sp. floral resin, alkaloids from Pilocarpus alatus, salicylideneanilines, piperidine amides, the amine 1-cinnamylpiperazine and chiral pyridinium salts were assayed on Mycobacterium tuberculosis H37Rv. N-(salicylidene)-2-hydroxyaniline was the most effective compound with a minimal inhibitory concentration (MIC) of 8 µmol/L. Dihydrocurvularin was moderately effective with a MIC of 40 µmol/L. Clusia sp. floral resin and a gallocatechin-epigallocatechin mixture showed MIC of 0.02 g/L and 38 µmol/L, respectively. The cytotoxicity was evaluated for N-(salicylidene)-2-hydroxyaniline, curvularin, dihydrocurvularin and Clusia sp. floral resin, and the selectivity indexes were > 125, 0.47, 0.75 and 5, respectively.

Validação de método analítico para determinar a migração de ε-caprolactama das embalagens para alimentos gordurosos

ε-Caprolactam (CAP) is a monomer of nylon 6 used as food packaging for bologna sausage, turkey blanquettes, fowl breast, pâtés and ham luncheon meat. After polymerization a part of the monomer can remain in the packaging and migrate into the food. The aim of this work was develop and validate a single laboratory method to determine CAP in ethanol 95% that simulates fatty food characteristics. Thus, linear range was 2 to 32 mg/L of CAP, detection and quantification limits were 0.83 and 1.63 mg/L, respectively. Repeatability showed Hor Rat values lower than 2 while recovery range was 97.5 to 106.5%. The method was considered adequate for purpose.

Formas de interação de três bairros periféricos com o Parque Municipal das Mangabeiras, Belo Horizonte, Minas Gerais

Este estudo teve como objetivo verificar se as diferenças no padrão socioeconômico dos habitantes de bairros adjacentes ao Parque Municipal das Mangabeiras - PARMA levariam a diferenças na interação dos moradores de cada bairro com essa área. Para tanto, foram analisadas respostas de 30 moradores de cada um dos três bairros imediatamente limítrofes ao PARMA, em Belo Horizonte, capital do Estado de Minas Gerais, os quais responderam a questionários semi-abertos, avaliaram a interação da comunidade com o Parque e com o ambiente e o seu comportamento de conservação. O objetivo geral do estudo foi dar subsídios ao Plano de Educação Ambiental do Parque das Mangabeiras, sendo o específico verificar se as diferenças socioeconômicas influem na interação do morador do entorno com o Parque. Durante as análises dos resultados, observou-se que as três comunidades diferiram em relação à freqüência nos programas e projetos do Parque, em relação às desvantagens causadas pela proximidade do PARMA e em relação à importância do Parque, fato corroborado pelas análises estatísticas. No tocante às demais questões, apesar de não terem sido verificadas diferenças estatisticamente significativas, observaram-se diferenças qualitativas nas respostas dadas pelos moradores.