Corrigendum to “Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy” [Neuromuscular Disorders, Vol. 30 (6) 2020, 492-502] (Neuromuscular Disorders (2020) 30(6) (492–502), (S0960896620301188), (10.1016/j.nmd.2020.05.002))

This article reported on the results from a phase 2 trial of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619). The manuscript also provided results on two secondary endpoints for magnetic resonance imaging (MRI), muscle volume and muscle volume index. The authors regret that, following publication of the results and in preparation for a separate publication on MRI results from this trial, the MRI images were reviewed and segmentation errors were identified. As a result, the team worked to (1) Perform a rigorous quality inspection of all analysed data; (2) Identify cases where there were incorrect segmentations; (3) correct segmentation errors; (4) Re-analyse all data with correct segmentation. Using the updated MRI data, the MMRM analysis showed there was a change in the significance of secondary endpoints evaluating Thigh Muscle Volume and Muscle Volume Index. No significant differences between treatment groups in muscle volume measures were found in the original analysis. These results have not altered the overall interpretation of the study results but do necessitate revisions to the article. These data confirm that the trial design and execution adequately tested the hypothesis that myostatin inhibition would slow or delay the loss of function in patients with Duchenne muscular dystrophy (DMD). The increase in muscle volume observed by MRI in patients with DMD treated with domagrozumab is in accordance with mechanism of action for domagrozumab, which targets myostatin, a negative regulator of muscle growth. The increase in muscle volume did not lead to a clinical benefit in patients with DMD. The primary endpoint (4 stair climb) did not meet statistical significance, nor did the other functional tests. The study was terminated due to lack of efficacy. Full details of the needed revisions are as follows: 1. In the results section 3.6 (page 8, second paragraph), we reported no significant differences in mean percent change from baseline between domagrozumab and placebo for both muscle volume and muscle volume index. This paragraph was replaced with the following text: “There was a significant difference between domagrozumab and placebo in the mean percent change from baseline in thigh muscle volume at Week 17 (difference 2.945%, P=0.0087) and Week 49 (differences 4.087%, P=0.0298), and in muscle volume index at Week 33 (difference 2.612%, P=0.0376) and Week 49 (differences3.208%, P=0.0411).” 2. In the discussion (page 9), the following sentence, “Although neither muscle volume nor muscle volume index measures were statistically significant in this study, they are both consistent with a potential anabolic effect.” was replaced with, “The increase in muscle volume observed on MRI in patients with DMD treated with domagrozumab, is in accordance with mechanism of action for this compound which targets myostatin, a negative regulator of muscle growth. However, the increase in muscle volume did not lead to a clinical benefit (improved function) in patients with DMD.” 3. In view of the correction to the Results section, this is now reflected in the abstract which has changed to read: “There were no significant between-group differences in secondary clinical endpoints, except for the thigh muscle volume and muscle volume index measures (P\u3c0.05).” The authors would like to apologise for any inconvenience caused

Impact of volatile phenols and their precursors on wine quality and control measures of Brettanomyces/Dekkera yeasts

Volatile phenols are aromatic compounds and one of the key molecules responsible for olfactory defects in wine. The yeast genus Brettanomyces is the only major microorganism that has the ability to covert hydroxycinnamic acids into important levels of these compounds, especially 4-ethylphenol and 4-ethylguaiacol, in red wine. When 4-ethylphenols reach concentrations greater than the sensory threshold, all wine’s organoleptic characteristics might be influenced or damaged. The aim of this literature review is to provide a better understanding of the physicochemical, biochemical, and metabolic factors that are related to the levels of p-coumaric acid and volatile phenols in wine. Then, this work summarizes the different methods used for controlling the presence of Brettanomyces in wine and the production of ethylphenols

A new method for the detection of early contamination of red wine by Brettanomyces bruxellensis using Pseudomonas putida 4-ethylphenol methylene hydroxylase (4-EPMH)

Brettanomyces/Dekkera bruxellensis is a cause of major concern for the winemaking industry worldwide. If a slight presence of this spoilage yeast in red wine adds a Brett character, a strong contamination has irreversible and detrimental effects on the organoleptic qualities due to the production of volatile phenols such as 4-ethylphenol. Time is a key factor in the treatment of B. bruxellensis contaminations. Nowadays, the diagnostic and quantification resources available are time consuming and too expensive, making them either inadequate or inaccessible to most of the winemakers. This study was focused on a new, easy to use, inexpensive method that could allow winemakers to directly detect B. bruxellensis contamination in red wine at an early stage, hence, reducing wine spoilage. In this work, the ability of Pseudomonas putida 4-ethylphenol methylene hydroxylase was tested in order to catabolize the 4-ethylphenol and to elaborate an enzymatic assay with the purpose of detecting early contaminations by B. bruxellensis in red wine. We have developed a colorimetric enzymatic assay, based on the redox state of the 4-ethylphenol methylene hydroxylase co-factor, cytochrome C, that can detect and quantify low concentrations of 4-ethylphenol. The range of concentrations detected is well below the level detectable by the human nose. Combined to an enrichment step, this method allows the detection of B. bruxellensis at an initial concentration of less than 10 cells per ml

Hyperandrogenism in female athletes with functional hypothalamic amenorrhea: a distinct phenotype

Asma Javed,1 Rahul Kashyap,2 Aida N Lteif1 1Pediatric and Adolescent Medicine, Division of Pediatric Endocrinology Mayo Clinic, Rochester, MN, USA; 2Department of Anesthesia and Critical Care Medicine, Mayo Clinic, Rochester, MN, USA Objective: To compare the reproductive, metabolic, and skeletal profiles of young athletic women with functional hypothalamic amenorrhea (FHA) as well as clinical or biochemical hyperandrogenism (FHA-EX+HA) with body mass index matched women with FHA due to exercise (FHA-EX) or anorexia nervosa (FHA-AN) alone.Design: Retrospective cohort study.Setting: Tertiary care teaching hospital.Population: Adolescents and young women, 15–30 years of age, diagnosed with FHA along with concurrent signs of hyperandrogenism (n=22) and body mass index matched control groups consisting of 22 women in each group of FHA-EX and FHA-AN. Main outcomes: 1) Reproductive hormone profile: luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone, pelvic ultrasound features. 2) Metabolic function and skeletal health markers: fasting glucose, cholesterol, number of stress fractures and bone mineral density as assessed by spine dual-energy X-ray absorptiometry z scores. Results: FHA-EX+HA group was older at diagnosis compared to the other groups with a median (interquartile range [IQR]) age of 22 (18.75–25.25) years versus (vs) 17.5 (15.75–19) for FHA-EX; (P<0.01) and 18 (16–22.25) years for FHA-AN (P=0.01). There were no differences among the groups based on number of hours of exercise per week, type of physical activity or duration of amenorrhea. Median (IQR) LH/FSH ratio was higher in FHA-EX+HA than both other groups, 1.44 (1.03–1.77) vs 0.50 (0.20–0.94) for FHA-EX and 0.67 (0.51–0.87) for FHA-AN (P<0.01 for both). Total testosterone concentrations were not different among the groups. Median (IQR) fasting serum glucose concentration was higher in FHA-EX+HA vs FHA-EX, 88.5 mg/dL (82.8–90 mg/dL) vs 83.5 mg/dL (78.8–86.3 mg/dL) (P=0.01) but not different from FHA-AN (P=0.31). Percentage of women with stress fractures was lower in FHA-EX+HA (4.5%) as compared to both FHA-EX (27.3%) and FHA-AN (50%); P=0.04 and 0.01 respectively. The LH/FSH ratio was weakly positively associated with serum glucose (adjusted r2=0.102; P=0.01) as well as with dual-energy X-ray absorptiometry spine score (adjusted r2=0.191; P=0.04) in the entire cohort.Conclusion: In a small cohort of female athletes with hyperandrogenism, a distinct reproductive hormone profile consisting of higher LH to FHS ratio may be associated with adverse metabolic health markers but improved skeletal health. Keywords: functional hypothalamic amenorrhea, hyperandrogenism, polycystic ovary syndrome, young athlete

Phosphoric acid production by attacking phosphate rock with recycled hexafluosilicic acid

International audienc

Population biology of the little gulper shark Centrophorus uyato in Lebanese waters

International audienceA total of 38 individuals of the heavily exploited little gulper shark Centrophorus uyato were collected from Lebanese coastal waters using bottom longlines and trammel nets of different meshes at depths ranging from 115 to 600 m between May 2013 and February 2014. Their total lengths were between 45 and 94 cm and their total mass was from 870 to 6700 g. The sex ratio was not significantly different from 1:1, with 20 males and 18 females, but bathymetric sexual segregation occurred. Catch per net setting (CNS) was used as a relative abundance index to detect spatial distribution; trammel nets showed largest CNS ranging from 4·9 to 5·45 kg per unit effort in the north and south, at depths from 120 to 200 m, during spring and summer. The mass-length relationships demonstrated negative allometric growth (b < 3) (males: MT  = 0.3585LT2·071 , r2  = 0·94; females: MT  = 0.0239LT2·735 , r2  = 0·64). The condition factor as well as the gonado-somatic and hepato-somatic indices of C. uyato in the study area were also calculated. The results are discussed in relation to the distribution, growth and reproduction as well as the management of C. uyato