HPLC-based activity profiling for GABAA receptor modulators from the traditional Chinese herbal drug Kushen (Sophora flavescens root). PUMID/DOI：DOI: 10.1007/s11030-010-9297-7 Mol Divers. 2011 May;15(2):361-72. An EtOAc extract from the roots of Sophora flavescens (Kushen) potentiated γ-aminobutyric acid (GABA)-induced chloride influx in Xenopus oocytes transiently expressing GABA(A) receptors with subunit composition, α (1) β (2) γ (2S). HPLC-based activity profiling of the extract led to the identification of 8-lavandulyl flavonoids, kushenol I, sophoraflavanone G, (-)-kurarinone, and kuraridine as GABA(A) receptor modulators. In addition, a series of inactive structurally related flavonoids were characterized. Among these, kushenol Y (4) was identified as a new natural product. The 8-lavandulyl flavonoids are first representatives of a novel scaffold for the target. Acyl secoiridoids and antifungal constituents from Gentiana macrophylla. PUMID/DOI：9397205 Phytochemistry. 1996 Jul;42(5):1305-13. LC-UV-mass spectrometry and bioassay co-directed fractionation of an aqueous acetone extract of the roots of Gentiana macrophylla gave three new chromene derivatives and two novel and six known secoiridoids, along with kurarinone, kushenol I, beta-sitosterol, stigmasterol, daucosterol, beta-sitosterol-3-O-gentiobioside, alpha-amyrin, oleanolic acid, isovitexin, gentiobiose and methyl 2-hydroxy-3-(1-beta-D-glucopyranosyl)oxybenzoate. The structures of the new products were established from spectral and chemical evidence as 2-methoxyanofinic acid and macrophyllosides A-D. The six known secoiridoids were gentiopicroside, sweroside, 6'-O-beta-D-glucosylgentiopicroside, 6'-O-beta-D-glucosylsweroside, trifloroside and rindoside. The new acid (2-methoxyanofinic acid), its methyl ester, kurarinone and kushenol I were shown to be active against the plant pathogenic fungus Cladosporium cucumerinum. The methyl ester and kurarinone inhibited also the growth of the human pathogenic yeast Candida albicans. Structure-activity relationships were studied. Thus, addition of a methoxyl group to the benzene nucleus of anofinic acid (2,2-dimethyl-2H-1-benzopyran-6-carboxylic acid) increased the antifungal activity remarkably whereas glycosylation at the carboxylic moiety was found to remove the activity. Esterification of the new acid induced its activity against C. albicans, but decreased its growth inhibition properties against C. cucumerinum. Hydroxylation of kurarinone at the 3 beta-position removed its activity against C. albicans and decreased the inhibition of C. cucumerinum. In addition, the chemotaxonomic significance of the identified constituents is discussed.
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To identify factors predictive of mortality in patients admitted to the ICU with tuberculosis (TB)/HIV coinfection in the Manaus, Amazon Region.
This was a retrospective cohort study of TB/HIV coinfected patients over 18 years of age who were admitted to an ICU in the city of Manaus, Brazil, between January of 2011 and December of 2014. Sociodemographic, clinical, and laboratory variables were assessed. To identify factors predictive of mortality, we employed a Cox proportional hazards model.
During the study period, 120 patients with TB/HIV coinfection were admitted to the ICU. The mean age was 37.0 ± 11.7 years. Of the 120 patients evaluated, 94 (78.3%) died and 62 (66.0%) of those deaths having occurred within the first week after admission. Data on invasive mechanical ventilation (IMV) and ARDS were available for 86 and 67 patients, respectively Of those 86, 75 (87.2%) underwent IMV, and, of those 67, 48 (71.6%) presented with ARDS. The factors found to be independently associated with mortality were IMV (p = 0.002), hypoalbuminemia (p = 0.013), and CD4 count < 200 cells/mm3 (p = 0.002). Conclusions: A high early mortality rate was observed among TB/HIV coinfected ICU patients. The factors predictive of mortality in this population were IMV, hypoalbuminemia, and severe immunosuppression.
Mycobacterium tuberculosis, Critical care, Respiration, artificial, Acquired immunodeficiency syndrome
Predictors of mortality among intensive care unit patients coinfected with tuberculosis and HIV
Marcia Danielle Ferreira, 1 , 2 Cynthia Pessoa das Neves, 1 , 3 Alexandra Brito de Souza, 3 Francisco Beraldi-Magalhães, 1 , 3 Giovanni Battista Migliori, 4 Afranio Lineu Kritski, 5 and Marcelo Cordeiro-Santos 1 ,
The primary aim of this study was to develop an assessment of the fundamental, combined, and complex movement skills required to support childhood physical literacy. The secondary aim was to establish the feasibility, objectivity, and reliability evidence for the assessment.
An expert advisory group recommended a course format for the assessment that would require children to complete a series of dynamic movement skills. Criterion-referenced skill performance and completion time were the recommended forms of evaluation. Children, 8-12 years of age, self-reported their age and gender and then completed the study assessments while attending local schools or day camps. Face validity was previously established through a Delphi expert (n = 19, 21% female) review process. Convergent validity was evaluated by age and gender associations with assessment performance. Inter- and intra-rater (n = 53, 34% female) objectivity and test-retest (n = 60, 47% female) reliability were assessed through repeated test administration.
Median total score was 21 of 28 points (range 5-28). Median completion time was 17 s. Total scores were feasible for all 995 children who self-reported age and gender. Total score did not differ between inside and outside environments (95% confidence interval (CI) of difference: −0.7 to 0.6; p = 0.91) or with/without footwear (95%CI of difference: −2.5 to 1.9; p = 0.77). Older age (p < 0.001, η2 = 0.15) and male gender (p < 0.001, η2 = 0.02) were associated with a higher total score. Inter-rater objectivity evidence was excellent (intraclass correlation coefficient (ICC) = 0.99) for completion time and substantial for skill score (ICC = 0.69) for 104 attempts by 53 children (34% female). Intra-rater objectivity was moderate (ICC = 0.52) for skill score and excellent for completion time (ICC = 0.99). Reliability was excellent for completion time over a short (2-4 days; ICC = 0.84) or long (8-14 days; ICC = 0.82) interval. Skill score reliability was moderate (ICC = 0.46) over a short interval, and substantial (ICC = 0.74) over a long interval. Conclusion The Canadian Agility and Movement Skill Assessment is a feasible measure of selected fundamental, complex and combined movement skills, which are an important building block for childhood physical literacy. Moderate-to-excellent objectivity was demonstrated for children 8-12 years of age. Test-retest reliability has been established over an interval of at least 1 week. The time and skill scores can be accurately estimated by 1 trained examiner.
Agility course, Children, Dynamic motor skill, Locomotor skill, Object manipulation, Population assessment
Canadian Agility and Movement Skill Assessment (CAMSA): Validity, objectivity, and reliability evidence for children 8-12 years of age
Patricia E. Longmuir,a,b,* Charles Boyer,a Meghann Lloyd,c Michael M. Borghese,a,d Emily Knight,a Travis J. Saunders,a,e Elena Boiarskaia,f Weimo Zhu,f and Mark S. Tremblaya,b
Although the tonsils contribute to first line immunity against foreign pathogens in the upper aero-digestive tract, the association of tonsillectomy with the risk of deep neck infection remains unclear. The aim of this study was to assess the incidence rate and risk of deep neck infection among patients who had undergone a tonsillectomy.
This retrospective cohort study evaluated all patients who had undergone tonsillectomy between 2001 and 2009 as identified from the Taiwan National Health Insurance Research Database. For each post-tonsillectomy patient, 10 age-, sex-, and index date-matched controls without a history of tonsillectomy were randomly selected. Cox Proportional hazard model and propensity score model were performed to evaluate the association between tonsillectomy and deep neck infection after adjusting for demographic and clinical data.
There were 34 (71.6 cases per 100,000 person-years) and 174 (36.6 cases per 100,000 person-years) patients that developed deep neck infection in the tonsillectomized and comparison cohorts, respectively. After adjusting for covariates, patients who had undergone a tonsillectomy had a 1.71-fold greater risk of deep neck infection by both Cox proportional hazard model (95% confidence interval, 1.13-2.59) and propensity score model (95% confidence interval, 1.10-2.66). This association was not altered regardless of the indication for tonsillectomy (i.e. chronic/recurrent tonsillitis or sleep apnea/hypertrophy of tonsil) (p = 0.9797).
Based on our review of a nationwide cohort study we identified that the risk of deep neck infection is significantly increased among patients who have undergone a tonsillectomy. Additional research is needed to explore the possible mechanisms behind these findings.
Tonsillectomy and the Risk for Deep Neck Infection—A Nationwide Cohort Study
Ying-Piao Wang, 1 , 2 , 3 Mao-Che Wang, 2 , 4 Hung-Ching Lin, 1 , 3 Kuo-Sheng Lee, 1 , 3 and Pesus Chou 2 ,* Salomon Amar, Academic Editor