ATX-101 for reduction of submental fat: A phase III randomized controlled trial

BackgroundATX-101, an injectable form of deoxycholic acid, causes adipocytolysis when injected subcutaneously into fat.ObjectiveWe sought to evaluate the efficacy and safety of ATX-101.MethodsIn this phase III trial (REFINE-2), adults dissatisfied with their moderate or severe submental fat (SMF) were randomized to ATX-101 or placebo. Coprimary end points, evaluated at 12 weeks after last treatment, were composite improvements of 1 or more grades and 2 or more grades in SMF observed on both the validated Clinician- and Patient-Reported SMF Rating Scales. Other end points included magnetic resonance imaging–based assessment of submental volume, assessment of psychological impact of SMF, and additional patient-reported outcomes.ResultsAmong those treated with ATX-101 or placebo (n = 258/treatment group), 66.5% versus 22.2%, respectively, achieved a composite improvement of 1 or more grades (Mantel-Haenszel risk ratio 2.98; 95% confidence interval 2.31-3.85) and 18.6% versus 3.0% achieved a composite improvement of 2 or more grades in SMF (Mantel-Haenszel risk ratio 6.27; 95% confidence interval 2.91-13.52; P < .001 for both). Those treated with ATX-101 were more likely to achieve submental volume reduction confirmed by magnetic resonance imaging, greater reduction in psychological impact of SMF, and satisfaction with treatment (P < .001 for all). Overall, 85.7% of adverse events in the ATX-101 group and 76.9% in the placebo group were localized to the injection site.LimitationsFollow-up was limited to 44 weeks.ConclusionATX-101 is an alternative treatment for SMF reduction

Duration of wrinkle correction following repeat treatment with Juvéderm hyaluronic acid fillers

Many patients elect to have repeat treatments with hyaluronic acid dermal fillers to maintain wrinkle correction, but the clinical performance of these products after repeat treatments has not been formally assessed. The primary objective of this study was to evaluate the effectiveness of Juvéderm injectable gel (Juvéderm Ultra, Juvéderm Ultra Plus, and Juvéderm 30) through 1 year after repeat treatment of nasolabial folds (NLFs) that were previously treated with Juvéderm or Zyplast 6–9 months prior to the repeat treatment. Upon completion of the pivotal IDE clinical trial for Juvéderm, five of the original 11 study sites were selected to participate in an extended follow-up evaluation, and a total of 80 subjects were enrolled. For the Juvéderm-treated NLFs in each treatment group, the median injection volume was 1.5–1.6 mL for initial treatment but only 0.5–0.6 mL for the repeat treatment (p < 0.0001). Mean Investigator-assigned NLF severity scores on a scale of 0–4 for the Juvéderm-treated NLFs improved from 2.5–2.7 (moderate to severe) at baseline to 1.2–1.5 (mild) just prior to repeat treatment (>24 weeks) and 0.7–0.9 (mild) at 4 weeks after repeat treatment. At 48 weeks post-repeat treatment, the mean NLF scores were 1.1–1.3 (mild), and 78–90% of subjects were considered responders (≥1 point improvement). Thus, subjects sustained a total of 18–21 months of wrinkle correction with a repeat treatment at 6–9 months and needed substantially less filler (60% less) for repeat treatment than for initial treatment, indicating that retreatment at this timepoint may be beneficial to patients

Craters, Boulders and Regolith of (101955) Bennu Indicative of an Old and Dynamic Surface

Small, kilometre-sized near-Earth asteroids are expected to have young and frequently refreshed surfaces for two reasons: collisional disruptions are frequent in the main asteroid belt where they originate, and thermal or tidal processes act on them once they become near-Earth asteroids. Here we present early measurements of numerous large candidate impact craters on near-Earth asteroid (101955) Bennu by the OSIRIS-REx (Origins, Spectral Interpretation, Resource Identification, and Security- Regolith Explorer) mission, which indicate a surface that is between 100 million and 1 billion years old, predating Bennu's expected duration as a near-Earth asteroid. We also observe many fractured boulders, the morphology of which suggests an influence of impact or thermal processes over a considerable amount of time since the boulders were exposed at the surface. However, the surface also shows signs of more recent mass movement: clusters of boulders at topographic lows, a deficiency of small craters and infill of large craters. The oldest features likely record events from Bennu's time in the main asteroid belt

ELOVL6 Genetic Variation Is Related to Insulin Sensitivity: A New Candidate Gene in Energy Metabolism

BACKGROUND: The elongase of long chain fatty acids family 6 (ELOVL6) is an enzyme that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. ELOVL6 is expressed in lipogenic tissues and it is regulated by sterol regulatory element binding protein 1 (SREBP-1). OBJECTIVE: We investigated whether ELOVL6 genetic variation is associated with insulin sensitivity in a population from southern Spain. DESIGN: We undertook a prospective, population-based study collecting phenotypic, metabolic, nutritional and genetic information. Measurements were made of weight and height and the body mass index (BMI) was calculated. Insulin resistance was measured by homeostasis model assessment. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by gas chromatography. Five SNPs of the ELOVL6 gene were analyzed by SNPlex. RESULTS: Carriers of the minor alleles of the SNPs rs9997926 and rs6824447 had a lower risk of having high HOMA_IR, whereas carriers of the minor allele rs17041272 had a higher risk of being insulin resistant. An interaction was detected between the rs6824447 polymorphism and the intake of oil in relation with insulin resistance, such that carriers of this minor allele who consumed sunflower oil had lower HOMA_IR than those who did not have this allele (P = 0.001). CONCLUSIONS: Genetic variations in the ELOVL6 gene were associated with insulin sensitivity in this population-based study

The nature and origin of Charon's smooth plains

Charon displays extensive plains that cover the equatorial area and south to the terminator on the sub-Pluto hemisphere observed by New Horizons. We hypothesize that these plains are a result of Charon's global extension and early subsurface ocean yielding a large cryoflow that completely resurfaced this area leaving the plains and other features that we observe today. The cryoflow consisted of ammonia-rich material, and could have resurfaced this area either by cryovolcanic effusion similar to lunar maria emplacement or a mechanism similar to magmatic stoping where lithospheric blocks foundered. Geological observations, modeling of possible flow rheology, and an analysis of rille orientations support these hypotheses

Novel Primate-Specific Genes, RMEL 1, 2 and 3, with Highly Restricted Expression in Melanoma, Assessed by New Data Mining Tool

Melanoma is a highly aggressive and therapy resistant tumor for which the identification of specific markers and therapeutic targets is highly desirable. We describe here the development and use of a bioinformatic pipeline tool, made publicly available under the name of EST2TSE, for the in silico detection of candidate genes with tissue-specific expression. Using this tool we mined the human EST (Expressed Sequence Tag) database for sequences derived exclusively from melanoma. We found 29 UniGene clusters of multiple ESTs with the potential to predict novel genes with melanoma-specific expression. Using a diverse panel of human tissues and cell lines, we validated the expression of a subset of three previously uncharacterized genes (clusters Hs.295012, Hs.518391, and Hs.559350) to be highly restricted to melanoma/melanocytes and named them RMEL1, 2 and 3, respectively. Expression analysis in nevi, primary melanomas, and metastatic melanomas revealed RMEL1 as a novel melanocytic lineage-specific gene up-regulated during melanoma development. RMEL2 expression was restricted to melanoma tissues and glioblastoma. RMEL3 showed strong up-regulation in nevi and was lost in metastatic tumors. Interestingly, we found correlations of RMEL2 and RMEL3 expression with improved patient outcome, suggesting tumor and/or metastasis suppressor functions for these genes. The three genes are composed of multiple exons and map to 2q12.2, 1q25.3, and 5q11.2, respectively. They are well conserved throughout primates, but not other genomes, and were predicted as having no coding potential, although primate-conserved and human-specific short ORFs could be found. Hairpin RNA secondary structures were also predicted. Concluding, this work offers new melanoma-specific genes for future validation as prognostic markers or as targets for the development of therapeutic strategies to treat melanoma

New Frontiers-class Uranus Orbiter: Exploring the feasibility of achieving multidisciplinary science with a mid-scale mission

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Publisher Correction: Craters, boulders and regolith of (101955) Bennu indicative of an old and dynamic surface

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Evidence for widespread hydrated minerals on asteroid (101955) Bennu

Early spectral data from the Origins, Spectral Interpretation, Resource Identification, and Security-Regolith Explorer (OSIRIS-REx) mission reveal evidence for abundant hydrated minerals on the surface of near-Earth asteroid (101955) Bennu in the form of a near-infrared absorption near 2.7 µm and thermal infrared spectral features that are most similar to those of aqueously altered CM-type carbonaceous chondrites. We observe these spectral features across the surface of Bennu, and there is no evidence of substantial rotational variability at the spatial scales of tens to hundreds of metres observed to date. In the visible and near-infrared (0.4 to 2.4 µm) Bennu’s spectrum appears featureless and with a blue (negative) slope, confirming previous ground-based observations. Bennu may represent a class of objects that could have brought volatiles and organic chemistry to Earth