Cytotoxic and Antifungal Activities of 5-Hydroxyramulosin, a Compound Produced by an Endophytic Fungus Isolated from Cinnamomum mollisimum

An endophytic fungus isolated from the plant Cinnamomum mollissimum was investigated for the bioactivity of its metabolites. The fungus, similar to a Phoma sp., was cultured in potato dextrose broth for two weeks, followed by extraction with ethyl acetate. The crude extract obtained was fractionated by high-performance liquid chromatography. Both crude extract and fractions were assayed for cytotoxicity against P388 murine leukemic cells and inhibition of bacterial and fungal pathogens. The bioactive extract fraction was purified further and characterized by nuclear magnetic resonance, mass spectral and X-ray crystallography analysis. A polyketide compound, 5-hydroxyramulosin, was identified as the constituent of the bioactive fungal extract fraction. This compound inhibited the fungal pathogen Aspergillus niger (IC50 1.56 μg/mL) and was cytotoxic against murine leukemia cells (IC50 2.10 μg/mL). 5-Hydroxyramulosin was the major compound produced by the endophytic fungus. This research suggests that fungal endophytes are a good source of bioactive metabolites which have potential applications in medicine

Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study

Background Urine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children. Methods We prospectively recruited children (aged ≤15 years) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa, between March 1, 2009, and April 30, 2012. We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral fl ow assay and ELISA, with mycobacterial culture of two induced sputum samples as the reference standard. Positive cultures were identifi ed by acid-fast staining and tested to confi rm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid. Findings 535 children (median age 42·5 months, IQR 19·1–66·3) had urine and two induced specimens available for testing. 89 (17%) had culture-confi rmed tuberculosis and 106 (20%) had HIV. The lateral fl ow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48·3% (95% CI 37·6–59·2), specifi city of 60·8% (56·1–65·3), and an area under the receiver operating characteristic curve of 0·53 (0·46–0·60) for children without HIV and 0·64 (0·51–0·76) for children with HIV. ELISA had poor sensitivity in children without HIV (sensitivity 3·0%, 95% CI 0·4–10·5) and children with HIV (0%, 0·0–14·3); overall specifi city was 95·7% (93·4–97·4). Interpretation Urine lipoarabinomannan tests have insuffi cient sensitivity and specifi city to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population

Maternal iron deficiency perturbs embryonic cardiovascular development in mice.

Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene-environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women

Maternal iron deficiency perturbs embryonic cardiovascular development in mice

Funder: Novo Nordisk; doi: https://doi.org/10.13039/501100004191Funder: National Heart Foundation of Australia (Heart Foundation); doi: https://doi.org/10.13039/501100001030Funder: NSW Health; doi: https://doi.org/10.13039/501100009287Funder: Oxford University | John Fell Fund, University of Oxford (John Fell OUP Research Fund); doi: https://doi.org/10.13039/501100004789Funder: The Federated FoundationAbstract: Congenital heart disease (CHD) is the most common class of human birth defects, with a prevalence of 0.9% of births. However, two-thirds of cases have an unknown cause, and many of these are thought to be caused by in utero exposure to environmental teratogens. Here we identify a potential teratogen causing CHD in mice: maternal iron deficiency (ID). We show that maternal ID in mice causes severe cardiovascular defects in the offspring. These defects likely arise from increased retinoic acid signalling in ID embryos. The defects can be prevented by iron administration in early pregnancy. It has also been proposed that teratogen exposure may potentiate the effects of genetic predisposition to CHD through gene–environment interaction. Here we show that maternal ID increases the severity of heart and craniofacial defects in a mouse model of Down syndrome. It will be important to understand if the effects of maternal ID seen here in mice may have clinical implications for women

Polyketide and benzopyran compounds of an endophytic fungus isolated from C innamomum mollissimum: biological activity and structure

Objective: To study bioactivity and compounds produced by an endophytic Phoma sp. fungus isolated from the medicinal plant Cinnamomum mollissimum. Methods: Compounds produced by the fungus were extracted from fungal broth culture with ethyl acetate. This was followed by bioactivity profiling of the crude extract fractions obtained via high performance liquid chromatography. The fractions were tested for cytotoxicity to P388 murine leukemic cells and antimicrobial activity against bacteria and pathogenic fungi. Compounds purified from active fractions which showed antibacterial, antifungal and cytotoxic activities were identified using capillary nuclear magnetic resonance analysis, mass spectrometry and admission to AntiMarin database. Results: Three known compounds, namely 4-hydroxymellein, 4,8-dihydroxy-6-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one and 1-(2,6-dihydroxyphenyl) ethanone, were isolated from the fungus. The polyketide compound 4-hydroxymellein showed high inhibitory activity against P388 murine leukemic cells (94.6%) and the bacteria Bacillus subtilis (97.3%). Meanwhile, 4,8-dihydroxy-6-methoxy-3-methyl-3,4-dihydro-1H-isochromen-1-one, a benzopyran compound, demonstrated moderate inhibitory activity against P388 murine leukemic cells (48.8%) and the fungus Aspergillus niger (56.1%). The second polyketide compound, 1 (2,6-dihydroxyphenyl) ethanone was inactive against the tested targets. Conclusions: These findings demonstrate the potential of endophytes as producers of pharmacologically important compounds, including polyketides which are major secondary metabolites in fungi

Evidence-based practice in speech-language pathology curricula: a scoping study

This scoping study investigated how evidence-based practice (EBP) principles are taught in Australian speech-language pathology (SLP) teaching and learning contexts. It explored how Australian SLP university programs: (1) facilitate student learning about the principles of EBP in academic and clinical settings, and (2) self-evaluate their curricula in relation to EBP. The research involved two surveys. Survey 1 respondents were 131 academic staff, program coordinators, and on-campus and off-campus clinical educators. This survey gathered information about EBP teaching and learning in SLP programs as well as future EBP curriculum plans. Survey 2 investigated how clinical educators incorporated EBP into the way they taught clinical decision-making to students. Surveys responses from 85 clinical educators were analysed using descriptive and nonparametric statistics and thematic grouping of open-ended qualitative responses. Both surveys revealed strengths and gaps in integrating EBP into Australian SLP curricula. Perceived strengths were that respondents were positive about EBP, most had EBP training and access to EBP resources. The perceived gaps included the academic staff’s perceptions of students’ understanding and application of EBP, respondents’ understanding of research methodologies, communication and collaboration between academic staff and clinical educators, and a lack of explicit discussion by clinical educators and students of EBP in relation to clients

Urine lipoarabinomannan testing for diagnosis of pulmonary tuberculosis in children: a prospective study

Background: Urine tests for mycobacterial lipoarabinomannan might be useful for point-of-care diagnosis of tuberculosis in adults with advanced HIV infection, but have not been assessed in children. We assessed the accuracy of urine lipoarabinomannan testing for the diagnosis of pulmonary tuberculosis in HIV-positive and HIV-negative children. Methods: We prospectively recruited children (aged ≤15 years) who presented with suspected tuberculosis at a primary health-care clinic and paediatric referral hospital in South Africa, between March 1, 2009, and April 30, 2012. We assessed the diagnostic accuracy of urine lipoarabinomannan testing with lateral flow assay and ELISA, with mycobacterial culture of two induced sputum samples as the reference standard. Positive cultures were identified by acid-fast staining and tested to confirm Mycobacterium tuberculosis and establish susceptibility to rifampicin and isoniazid. Findings: 535 children (median age 42·5 months, IQR 19·1–66·3) had urine and two induced specimens available for testing. 89 (17%) had culture-confirmed tuberculosis and 106 (20%) had HIV. The lateral flow lipoarabinomannan test showed poor accuracy against the reference standard, with sensitivity of 48·3% (95% CI 37·6–59·2), specificity of 60·8% (56·1–65·3), and an area under the receiver operating characteristic curve of 0·53 (0·46–0·60) for children without HIV and 0·64 (0·51–0·76) for children with HIV. ELISA had poor sensitivity in children without HIV (sensitivity 3·0%, 95% CI 0·4–10·5) and children with HIV (0%, 0·0–14·3); overall specificity was 95·7% (93·4–97·4). Interpretation: Urine lipoarabinomannan tests have insufficient sensitivity and specificity to diagnose HIV-positive and HIV-negative children with tuberculosis and should not be used in this patient population. Funding: US National Institutes of Health, the National Health Laboratory Services Research Trust, the Medical Research Council of South Africa, and the Wellcome Trust

Maternal iron deficiency perturbs embryonic cardiovascular development in mice

From mouse experiments, the authors link iron deficiency in mothers with cardiovascular defects and increased retinoic acid signalling in their offspring, and giving iron early in pregnancy can prevent most defects