Does the traditional medicinal use of Leonurus cardiaca L. as specified by the European Medicines Agency (EMA) monographs reflect documented historical use and current research? A content analysis.

Abstract: AIMS: To investigate the documented historical uses of Leonurus cardiaca in order to assess the traditional uses as outlined in the European Medicines Agency (EMA) monograph. METHODS: Content analysis was used for coding and analysing data. Raw data was extracted from source texts into a framework. Data was then translated and coded for comparison and discussion. KEY FINDINGS: The EMA monograph was justified in its recommendation for the indications of nervous tension and cardiac complaints.Gynaecological uses, along with a number of other uses, frequently featured in historical texts but were not present in the EMA monograph. Posology was difficult to ascertain as ranges varied widely; however the EMA recommended a higher dose of liquid extract than historical texts suggested. Safety information was difficult to establish. Several factors had an impact on the results including translation and coding challenges, scarcity and plagiarism of texts, authentication of motherwort and difficulties associated with data mining. CONCLUSION: While EMA indications appeared frequently throughout source texts, motherwort appeared to have uses beyond what the EMA monograph suggests. Lack of recent research into motherwort's gynaecological uses may have contributed to the omission of these uses on the EMA monograph. This suggests that the EMA monograph does not fully reflect documented historical use. RECOMMENDATIONS: Gynaecological use shows promise and may warrant further investigation with additional gynaecological studies recommended. Additional research may be required in order to decipher texts using a different system of medical belief. A greater number of sources and further analysis of posology advised

Effect of burimamide on histamine- and pentagastrin-stimulated acid and pepsin secretion in the pig

Burimamide, a specific histamine H2-receptor antagonist, is an effective inhibitor of histamine and pentagastrinstimulated gastric acid secretion in the innervated pig stomach. Pepsin secretion, and acid secretion from denervated gastric pouches, were not significantly depressed by burimamide in the dose used in this study. Atropine inhibited pentagastrin- but not histaminestimulated gastric acid secretion from the innervated and denervated portions of the pig stomach.S. Afr. Med. J., 48, 1985 (1974)

Horizontal gene transfer to a defensive symbiont with a reduced genome in a multipartite beetle microbiome

Symbiotic mutualisms of bacteria and animals are ubiquitous in nature, running a continuum from facultative to obligate from the perspectives of both partners. The loss of functions required for living independently but not within a host gives rise to reduced genomes in many symbionts. Although the phenomenon of genome reduction can be explained by existing evolutionary models, the initiation of the process is not well understood. Here, we describe the microbiome associated with the eggs of the beetle Lagria villosa, consisting of multiple bacterial symbionts related to Burkholderia gladioli, including a reduced-genome symbiont thought to be the exclusive producer of the defensive compound lagriamide. We show that the putative lagriamide-producing symbiont is the only member of the microbiome undergoing genome reduction and that it has already lost the majority of its primary metabolism and DNA repair pathways. The key step preceding genome reduction in the symbiont was likely the horizontal acquisition of the putative lagriamide lga biosynthetic gene cluster. Unexpectedly, we uncovered evidence of additional horizontal transfers to the symbiont's genome while genome reduction was occurring and despite a current lack of genes needed for homologous recombination. These gene gains may have given the genome-reduced symbiont a selective advantage in the microbiome, especially given the maintenance of the large lga gene cluster despite ongoing genome reduction. IMPORTANCE Associations between microorganisms and an animal, plant, or fungal host can result in increased dependence over time. This process is due partly to the bacterium not needing to produce nutrients that the host provides, leading to loss of genes that it would need to live independently and to a consequent reduction in genome size. It is often thought that genome reduction is aided by genetic isolation-bacteria that live in monocultures in special host organs, or inside host cells, have less access to other bacterial species from which they can obtain genes. Here, we describe exposure of a genome-reduced beetle symbiont to a community of related bacteria with nonreduced genomes. We show that the symbiont has acquired genes from other bacteria despite going through genome reduction, suggesting that isolation has not yet played a major role in this case of genome reduction, with horizontal gene gains still offering a potential route for adaptation

China’s dash for gas : local challenges and global consequences

The recent 2017–18 “dash for gas” captured global attention, but also exposed critical failings in China’s gas market. The 2019 lull imposed by the Government reflects the need to address local challenges. This paper analyzes the prospects for demand growth and assesses the various ways in which that demand can be met. There is considerable uncertainty surrounding demand growth, with cost competitiveness being the determining factor. Equally, although China has significant natural gas reserves, they are largely unconventional and present significant geological and technical challenges; with domestic production growth failing to keep pace as demand import dependence increases. China’s gas imports are met by pipeline gas from Central Asia and Myanmar and Liquified Natural Gas (LNG) from avariety of countries. The Power of Siberia pipeline started deliveries of Russian in late 2019. However, plans to expand Central Asian imports have disappointed and China may agree to asecond pipeline from Russia or increase its LNG imports. Asimple “gas balance model” is used in the final discussion and conclusions to explore future developments and their consequences for global gas security

Endovascular repair of an inflammatory abdominal aortic aneurysm complicated by aortoduodenal fistulation with an unusual presentation

AbstractAortoenteric fistulation (AEF) is a well-documented late complication of open abdominal aortic aneurysm (AAA) repair, occurring in between 0.4% and 4% of cases. In the absence of an anastomosis, AEF is likely to be rare after endovascular aneurysm repair (EVAR) and has only recently been described in the literature as a result of mechanical stent failure or migration. We present the case of a 61-year-old man who underwent EVAR for an AAA with a “nonspecific” periaortic inflammatory mass. Six months postoperatively, an AEF developed, presenting with metastatic sepsis followed by septic infective thromboembolization to his right leg, and amputation was necessary. His stent was well positioned and mechanically intact. We emphasize the need for vigilance about the risk of AEF when adopting an endovascular approach to repair the AAA with a nonspecific periaortic inflammatory mass and highlight the need for awareness about the unusual septic manifestations of AEF. (J Vasc Surg 2001;33:874-9.

Definitions of Metabolic Health and Risk of Future Type 2 Diabetes in BMI Categories: A Systematic Review and Network Meta-analysis.

OBJECTIVE: Various definitions of metabolic health have been proposed to explain differences in the risk of type 2 diabetes within BMI categories. The goal of this study was to assess their predictive relevance. RESEARCH DESIGN AND METHODS: We performed systematic searches of MEDLINE records for prospective cohort studies of type 2 diabetes risk in categories of BMI and metabolic health. In a two-stage meta-analysis, relative risks (RRs) specific to each BMI category were derived by network meta-analysis and the resulting RRs of each study were pooled using random-effects models. Hierarchical summary receiver operating characteristic curves were used to assess predictive performance. RESULTS: In a meta-analysis of 140,845 participants and 5,963 incident cases of type 2 diabetes from 14 cohort studies, classification as metabolically unhealthy was associated with higher RR of diabetes in all BMI categories (lean RR compared with healthy individuals 4.0 [95% CI 3.0-5.1], overweight 3.4 [2.8-4.3], and obese 2.5 [2.1-3.0]). Metabolically healthy obese individuals had a high absolute risk of type 2 diabetes (10-year cumulative incidence 3.1% [95% CI 2.6-3.5]). Current binary definitions of metabolic health had high specificity (pooled estimate 0.88 [95% CI 0.84-0.91]) but low sensitivity (0.40 [0.31-0.49]) in lean individuals and satisfactory sensitivity (0.81 [0.76-0.86]) but low specificity (0.42 [0.35-0.49]) in obese individuals. However, positive (0.4) likelihood ratios were consistent with insignificant to small improvements in prediction. CONCLUSIONS: Although individuals classified as metabolically unhealthy have a higher RR of type 2 diabetes compared with individuals classified as healthy in all BMI categories, current binary definitions of metabolic health have limited relevance to the prediction of future type 2 diabetes.The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. This work was supported by the Netherlands Organization for Scientific Research (NWO), and the Medical Research Council UK (grant no. MC_U106179471). A.A. is supported by a Rubicon grant from the NWO (Project no. 825.13.004).This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes Care. The American Diabetes Care Association (ADA), publisher of Diabetes Care, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes Care in print and online at http://care.diabetesjournals.org

Replication of LDL SWAs hits in PROSPER/PHASE as validation for future (pharmaco)genetic analyses

<p><b>Background:</b> The PHArmacogenetic study of Statins in the Elderly at risk (PHASE) is a genome wide association study in the PROspective Study of Pravastatin in the Elderly at risk for vascular disease (PROSPER) that investigates the genetic variation responsible for the individual variation in drug response to pravastatin. Statins lower LDL-cholesterol in general by 30%, however not in all subjects. Moreover, clinical response is highly variable and adverse effects occur in a minority of patients. In this report we first describe the rationale of the PROSPER/PHASE project and second show that the PROSPER/PHASE study can be used to study pharmacogenetics in the elderly.</p> <p><b>Methods:</b> The genome wide association study (GWAS) was conducted using the Illumina 660K-Quad beadchips following manufacturer's instructions. After a stringent quality control 557,192 SNPs in 5,244 subjects were available for analysis. To maximize the availability of genetic data and coverage of the genome, imputation up to 2.5 million autosomal CEPH HapMap SNPs was performed with MACH imputation software. The GWAS for LDL-cholesterol is assessed with an additive linear regression model in PROBABEL software, adjusted for age, sex, and country of origin to account for population stratification.</p> <p><b>Results:</b> Forty-two SNPs reached the GWAS significant threshold of p = 5.0e-08 in 5 genomic loci (APOE/APOC1; LDLR; FADS2/FEN1; HMGCR; PSRC1/CELSR5). The top SNP (rs445925, chromosome 19) with a p-value of p = 2.8e-30 is located within the APOC1 gene and near the APOE gene. The second top SNP (rs6511720, chromosome 19) with a p-value of p = 5.22e-15 is located within the LDLR gene. All 5 genomic loci were previously associated with LDL-cholesterol levels, no novel loci were identified. Replication in WOSCOPS and CARE confirmed our results.</p> <p><b>Conclusion:</b> With the GWAS in the PROSPER/PHASE study we confirm the previously found genetic associations with LDL-cholesterol levels. With this proof-of-principle study we show that the PROSPER/PHASE study can be used to investigate genetic associations in a similar way to population based studies. The next step of the PROSPER/PHASE study is to identify the genetic variation responsible for the variation in LDL-cholesterol lowering in response to statin treatment in collaboration with other large trials.</p&gt

Polymorphisms in the Lipoprotein Lipase and Hepatic Lipase Genes and Plasma Lipid Values in the Czech Population

Summary We have determined the genotypes of two common polymorphisms in the lipoprotein lipase (S447X) and hepatic lipase (-480C/T) genes in a cohort of 285 representative selected Czech probands (131 male and 154 female), examined in 1988 and reinvestigated in 1996. The genotype distributions of both polymorphisms were in Hardy-Weinberg equilibrium and did not differ between male and female subjects. The rare allele frequency of the lipoprotein lipase polymorphism did not differ significantly from the other European populations. Compared to the German populations, the frequency of the hepatic lipase -480T allele was significantly higher in the Czech group (20% vs. 36%, p<0.0001). There were no significant associations between the lipoprotein lipase gene variants and lipid parameters measured either in 1988, or in 1996 or with changes of lipid parameters over the 8-year period. The carriers of the T-480 allele of the hepatic lipase polymorphism were found to have higher HDL cholesterol levels (p=0.02). However, this difference was confined to female subjects only. The male carriers of the -480T allele had higher concentrations of total cholesterol (p=0.03) as compared to CC-480 subjects. Both associations were observed in 1996 only. In the Slavic Czech population, a common polymorphism in the hepatic lipase gene (-480C/T), but not in the lipoprotein lipase gene (S447X), is a significant determinant of plasma HDL cholesterol in females and plasma total cholesterol in males and indicates the importance of gender-associated effects in the genetic determinations of plasma lipids