Biocatalytic and antimetastatic studies of the marine cembranoids sarcophine and 2-epi-16-deoxysarcophine

The soft coral Sarcophyton glaucum is a rich resource of several bioactive cembranoids. Sarcophytol A (1) and sarcophine (2) are cembranoid diterpenes reported from this soft coral and extensively investigated for their cancer chemopreventive properties. This study aimed at investigating the antimetastatic potential of the major cembranoids, sarcophine (2) and 2-epi-16-deoxysarcophine (3), from the Red Sea soft coral S. glaucum. Biocatalytic transformation of 3 using Rhizopus stolonifer ATCC 6227a and Absidia spinosa ATCC 6648 afforded four new metabolites, 5-7 and 9, along with the known 9α-hydroxysarcophine (8). Sarcophine, 2-epi-16-deoxysarcophine, and metabolites 5-9 revealed significant antimetastatic activity against the highly metastatic mouse melanoma cell line (B16B15b). Cembranoids demonstrate a great potential for further development as antimetastatic agents. © 2006 American Chemical Society and American Society of Pharmacognosy

Clinical and genetic assessment of pediatric patients with Gaucher’s disease in Upper Egypt

Background: Gaucher’s disease (GD) is an autosomal recessive genetic disorder that results from pathogenic mutations of GBA gene encoding the enzyme glucocerebrosidase (acid b-glucosidase). Of the approximately 300 mutations associated with GD, 4 accounts for the majority of mutations seen in GD patients: N370S, L444P, 84 GG and IVS2+1.Aim: Establishing and providing, clinical and molecular backgrounds of pediatric patients with GD in Upper Egypt.Subjects and methods: The present study is a cross sectional study, carried out on 26 pediatric patients with GD. They were recruited from the pediatric outpatient clinics and inpatients Pediatric departments of Assiut and Qena University hospitals, Upper Egypt. Clinical evaluation and mutation analysis using commercially available strip assay kit after PCR amplification of the target gene were done for all included GD patients.Results: Consanguinity between patients’ parents was present in 73.1% of the included patients. 76.9% of included patients were of type 1 GD, while 23.1% were of type 3 GD and none of our patients was classified as type 2 GD. The main frequent clinical presentations of GD in this study were hepatosplenomegaly (88.5%); pallor (76.9%); abdominal distension (61.5%) and musculoskeletal involvement (37.1%). Neurological abnormalities of type 3 GD included in this study were squint, seizures and delayed mental development. Five different genotypes were detected, homozygous for the mutation L444P, homozygous for the mutation N370S, heterozygous for the mutations N370S and rec Ncil, heterozygous for IVS2 +1 and rec NciI, heterozygous for L444P and IVS2 +1. Conclusions: Non-neuropathic type 1 and type 3 GD were the only clinical types found in the present study. The most common mutant alleles found in this study were L444P and N370S

Total Synthesis of Eleuthoside A; Application of Rh-Catalyzed Intramolecular Cyclization of Diazonaphthoquinone

The first total synthesis of (±)-eleutherol and eleuthoside A, the natural cytotoxic substances extracted from medicinal Indonesian plant, is described. First, the synthesis of (±)-eleutherol has been ­accomplished in nine steps starting from bromo methoxy aldehyde with the aid of diazo-transfer chemistry approach. Second, a metal-­catalyzed intramolecular cyclization reaction of the corresponding ­diazonaphthoquinone led to the desired eleuotherol, which served as a precursor to eleuthoside A. Then, several glycosidation routes, using different glucosyl donors, were experimented to reach effective O-glycosidation of eleutherol. The only successful strategy involved Koenigs–Knorr glycosidation using peracetyl glycosyl bromide in the presence of Ag2O and quinoline. This strategy furnished our desired acetylated glycoside of β-configuration, regioselectively. Finally, deacetylation and successive separation of diastereomers were conducted to give eleuthoside A

Alternatively spliced transcripts and novel pseudogenes of the Plasmodium falciparum resistance-associated locus pfcrt detected in East African malaria patients.

OBJECTIVES: Polymorphisms in the lysosomal transporter encoded by the pfcrt gene directly impact on Plasmodium falciparum susceptibility to aminoquinolines. The Lys76Thr mutation is the critical change conferring chloroquine resistance in vitro and in vivo, but always occurs with additional non-synonymous changes in the pfcrt coding sequence. We sought to better describe pfcrt polymorphisms distal to codon 76. METHODS: Small-volume samples (≤ 500 μL) of parasite-infected blood collected directly from malaria patients presenting for treatment in Sudan and Tanzania were immediately preserved for RNA extraction. The pfcrt locus was amplified from cDNA preparations by nested PCR and sequenced directly to derive full-length mRNA sequences. RESULTS: In one of two sites in Sudan, two patients were found with an unorthodox spliced form of pfcrt mRNA in which two exons were skipped, but it was not possible to test for the presence of the putative protein products of these aberrant transcripts. Genomic DNA sequencing from dried blood spots collected in parallel confirmed the presence of spliced pfcrt pseudogenes in a minority of parasite isolates. Full-length cDNA from conventionally spliced mRNA molecules in all study sites demonstrated the existence of a variety of pfcrt haplotypes in East Africa, and thus provides evidence of intragenic recombination. CONCLUSIONS: The presence of pseudogenes, although unlikely to have any direct public health impact, may confound results obtained from simple genotyping methods that consider only codon 76 and the adjacent residues of pfcrt

Electrical power output prediction of combined cycle power plants using a recurrent neural network optimized by waterwheel plant algorithm

It is difficult to analyze and anticipate the power output of Combined Cycle Power Plants (CCPPs) when considering operational thermal variables such as ambient pressure, vacuum, relative humidity, and temperature. Our data visualization study shows strong non-linearity in the experimental data. We observe that CCPP energy production increases linearly with temperature but not pressure. We offer the Waterwheel Plant Algorithm (WWPA), a unique metaheuristic optimization method, to fine-tune Recurrent Neural Network hyperparameters to improve prediction accuracy. A robust mathematical model for energy production prediction is built and validated using anticipated and experimental data residuals. The residuals’ uniformity above and below the regression line suggests acceptable prediction errors. Our mathematical model has an R-squared value of 0.935 and 0.999 during training and testing, demonstrating its outstanding predictive accuracy. This research provides an accurate way to forecast CCPP energy output, which could improve operational efficiency and resource utilization in these power plants

Burden of musculoskeletal disorders in the Eastern Mediterranean Region, 1990–2013: findings from the Global Burden of Disease Study 2013

Moradi-Lakeh M, Forouzanfar MH, Vollset SE, et al. Burden of musculoskeletal disorders in the Eastern Mediterranean Region, 1990–2013: findings from the Global Burden of Disease Study 2013. Annals of the Rheumatic Diseases. 2017;76(8):annrheumdis-2016-210146

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London