Pregnancy outcome in women with Gaucher disease type 1 who had unplanned pregnancies during eliglustat clinical trials

Gaucher disease type 1 (GD1) is an inherited lysosomal storage disorder caused by deficient enzymatic activity of acid β-glucosidase, resulting in accumulation of its substrate glucosylceramide, leading to debilitating visceral, hematologic, and skeletal manifestations. Women with GD1 are at increased risk for complications during pregnancy, delivery, and postpartum. Treatment with enzyme replacement therapy is generally recommended before and during pregnancy to reduce risks. Eliglustat, an oral substrate-reduction therapy, is a first-line treatment for adults with GD1 adults who have extensive, intermediate, or poor CYP2D6-metabolizer phenotypes (>90% of patients). We report on pregnancy outcomes among women in eliglustat trials who had unplanned pregnancies and female partners of men in the trials. In four phase 2 and 3 eliglustat trials of 393 adults with GD1, women of childbearing potential were required to use contraception, have monthly pregnancy tests, and discontinue eliglustat promptly if pregnant. In phase 2 and 3 trials, 18 women had 19 pregnancies, resulting in 14 healthy infants from 13 pregnancies (one set of twins), three elective terminations, one ectopic pregnancy, one spontaneous abortion, and one in utero death. Median estimated eliglustat exposure duration during pregnancy was 38 days. In phase 1 trials (non-GD1 subjects), one woman had a spontaneous abortion. Partners of 16 eliglustat-treated men with GD1 had 18 pregnancies, all resulting in healthy infants. Eliglustat is not approved during pregnancy due to limited data. Guidelines for clinicians and patients with GD that address use of eliglustat in women of childbearing potential are needed

A new silverleaf inducing biotype of Bemisia tabaci (Hemiptera: Aleyrodidae) Ms, indigenous for the islands of the South West Indian Ocean

Following the first detection of tomato yellow leaf curl virus (TYLCV) from Réunion (700 km east of Madagascar) in 1997 and the upsurge of Bemisia tabaci (Gennadius) on vegetable crops, two genetic types of B. tabaci were distinguished using RAPD¿PCR and cytochrome oxidase I (COI) gene sequence comparisons. One type was assigned to biotype B and the other was genetically dissimilar to the populations described elsewhere and was named Ms, after the Mascarenes Archipelago. This new genetic type forms a distinct group that is sister to two other groups, one to which the B biotype is a member and one to which the Q biotype belongs. The Ms biotype is thought to be indigenous to the region as it was also detected in Mauritius, the Seychelles and Madagascar. Both B and Ms populations of B. tabaci induced silverleaf symptoms on Cucurbita sp., and were able to acquire and transmit TYLCV. Taken together these results indicate that the Ms genetic type should be considered a new biotype of B. tabac

Skeletal improvement in patients with Gaucher disease type 1: a phase 2 trial of oral eliglustat

Objective: Eliglustat is an investigational oral substrate reduction therapy for Gaucher disease type 1 (GD1). Its skeletal effects were evaluated by prospective monitoring of bone mineral density (BMD), fractures, marrow infiltration by Gaucher cells, focal bone lesions, and infarcts during an open-label, multi-site, single-arm phase 2 trial (NCT00358150). Materials and methods Institutional review board approval and patient informed consent were obtained. Eliglustat (50 or 100 mg) was self-administered by mouth twice daily; 19 patients completed 4 years of treatment. All were skeletally mature (age range, 18–55 years). DXA and MRI assessments were conducted at baseline and annually thereafter. X-rays were obtained annually until month 24, and then every other year. Results: Lumbar spine BMD increased significantly (p = 0.02; n = 15) by a mean (SD) of 9.9 % (14.2 %) from baseline to year 4; corresponding T-scores increased significantly (p = 0.01) from a mean (SD) of −1.6 (1.1) to −0.9 (1.3). Mean femur T-score remained normal through 4 years. Femur MRI showed that 10/18 (56 %) patients had decreased Gaucher cell infiltration compared to baseline; one patient with early improvement had transient worsening at year 4. There were no lumbar spine or femoral fractures and no reported bone crises during the study. At baseline, 8/19 (42 %) patients had focal bone lesions, which remained stable, and 7/19 (37 %) patients had bone infarctions, which improved in one patient by year 2. At year 4, one new asymptomatic, indeterminate bone lesion was discovered that subsequently resolved. Conclusions: Eliglustat may be a therapeutic option for treating the skeletal manifestations of GD1

Ice-sheet configuration in the CMIP5/PMIP3 Last Glacial Maximum experiments

We describe the creation of a data set describing changes related to the presence of ice sheets, including ice-sheet extent and height, ice-shelf extent, and the distribution and elevation of ice-free land at the Last Glacial Maximum (LGM), which were used in LGM experiments conducted as part of the fifth phase of the Coupled Modelling Intercomparison Project (CMIP5) and the third phase of the Palaeoclimate Modelling Intercomparison Project (PMIP3). The CMIP5/PMIP3 data sets were created from reconstructions made by three different groups, which were all obtained using a model-inversion approach but differ in the assumptions used in the modelling and in the type of data used as constraints. The ice-sheet extent in the Northern Hemisphere (NH) does not vary substantially between the three individual data sources. The difference in the topography of the NH ice sheets is also moderate, and smaller than the differences between these reconstructions (and the resultant composite reconstruction) and ice-sheet reconstructions used in previous generations of PMIP. Only two of the individual reconstructions provide information for Antarctica. The discrepancy between these two reconstructions is larger than the difference for the NH ice sheets, although still less than the difference between the composite reconstruction and previous PMIP ice-sheet reconstructions. Although largely confined to the ice-covered regions, differences between the climate response to the individual LGM reconstructions extend over the North Atlantic Ocean and Northern Hemisphere continents, partly through atmospheric stationary waves. Differences between the climate response to the CMIP5/PMIP3 composite and any individual ice-sheet reconstruction are smaller than those between the CMIP5/PMIP3 composite and the ice sheet used in the last phase of PMIP (PMIP2)

South West Indian Ocean islands tomato begomovirus populations represent a new major monopartite begomovirus group

Biological and molecular properties of Tomato leaf curl Madagascar virus isolates from Morondova and Toliary (ToLCMGV-[Tol], -[Mor]), Tomato leaf curl Mayotte virus isolates from Dembeni and Kahani (ToLCYTV-[Dem], -[Kah]) and a Tomato yellow leaf curl virus isolate from Réunion (TYLCV-Mld[RE]) were determined. Full-length DNA components of the five isolates from Madagascar, Mayotte and Réunion were cloned and sequenced and, with the exception of ToLCMGV-[Tol], were shown to be both infectious in tomato and transmissible by Bemisia tabaci. Sequence analysis revealed that these viruses had genome organizations of monopartite begomoviruses and that both ToLCMGV and ToLCYTV belong to the African begomoviruses but represent a distinct monophyletic group that we have tentatively named the South West islands of the Indian Ocean (SWIO). All of the SWIO isolates examined were apparently complex recombinants. None of the sequences within the recombinant regions closely resembled that of any known non-SWIO begomovirus, suggesting an isolation of these virus population

Occurrence of an isolate of maize stripe virus on sorghum in India

A disease characterised by chlorotic stripes and bands, named sorghum stripe disease (SStD), was observed on sorghum in India with an incidence of less than 0.5% to nearly 10%. The affected plants were dwarfed and had poor or no panicle formation. This disease could be transmitted by the delphacid planthopper Peregrinus maidis to sorghum but not to Brachiaria eruciformis; Cenchrus ciliaris; Chloris barbata; Dichantium annulatum; Dichantium aristatum; Digitaria ciliaris: Dinebra retroflexa; Echinocloa colona; Eleusine coracana; Pennisetum glaucum; Pennisetum violaceum; Setaria pallida Fusca; Triticum aestivum and Zea mays. Sorghum stripe disease was shown to be caused by a tenuivirus serologically related to maize stripe virus (MStV). Virus particles were filamentous, less than 10 nm in width. The purified virus preparation contained only one polypeptide of 34 500 D. Eight species of nucleic acids, four ssRNA of 1.21, 0.87, 0.73, 0.47 ± 106D and four dsRNA of 2.43, 1.69, 1.40, 0.71 ± 106D, were extracted from purified virus preparations. When the four dsRNA were denatured, they migrated along with the four ssRNA species indicating that dsRNA contained duplex RNA of same molecular weight as the four ssRN A. In enzyme-linked immunosorbent assay and in electro-blot immunoassay it was evident that MStV-Sorg was serologically more closely related to the MStV isolates from Florida, Reunion and Venezuela than to a RStV isolate from Japan. The virus was named MStV-Sorg to distinguish it from MStV which readily infects maize. This is the first report of occurrence of a tenuivirus in the Indian subcontinent