Discriminating unifloral honey from a dioecious mass flowering tree of Brazilian seasonally dry tropical forest through pollen spectra: consequences of honeybee preference for staminate flowers

International audienceMyracrodruon urundeuva (“aroeira”) is a dioecious tree of the seasonally dry tropical forest (SDTF) of Brazil and source of a unique unifloral honey. To discriminate this honey by its pollen spectra, we compared melissopalynological analysis of reference honey samples with those of other samples collected in the SDTF belt. Reference honeys had on average 99% of aroeira pollen, while the other honey samples averaged 84% of this pollen. We used the receiver operating characteristic (ROC) curve, applied here for the first time in honey analysis, for determining the cut-off value of at least 93% of Myracrodruon pollen in a sample for classifying unifloral aroeira honey. The over-representation of aroeira pollen in this honey reflects that honeybees visited ten times as many staminate flowers as pistillate flowers. We conclude that unifloral aroeira honey has uniform pollen spectra, as a byproduct of the preference of honeybees for staminate flowers

Effect of rapamycin on immunity induced by vector-mediated dystrophin expression in mdx skeletal muscle

Duchenne muscular dystrophy (DMD) is caused by mutations in the dystrophin gene. Therapeutic gene replacement of a dystrophin cDNA into dystrophic muscle can provide functional dystrophin protein to the tissue. However, vector-mediated gene transfer is limited by anti-vector and anti-transgene host immunity that causes rejection of the therapeutic protein. We hypothesized that rapamycin (RAPA) would diminish immunity due to vector-delivered recombinant dystrophin in the adult mdx mouse model for DMD. To test this hypothesis, we injected limb muscle of mdx mice with RAPA-containing, poly-lactic-co-glycolic acid (PLGA) microparticles prior to dystrophin gene transfer and analyzed treated tissue after 6 weeks. RAPA decreased host immunity against vector-mediated dystrophin protein, as demonstrated by decreased cellular infiltrates and decreased anti-dystrophin antibody production. The interpretation of the effect of RAPA on recombinant dystrophin expression was complex because of an effect of PLGA microparticles.National Institutes of Health (U.S.) (F31-NS056780-01A2)National Center for Research Resources (U.S.) (KL2 RR024154)United States. Army Medical Research and Materiel Command (grant W81XWH-05-1-0334

Hubble Space Telescope Observations of UV Oscillations in WZ Sagittae During the Decline from Outburst

We present a time series analysis of Hubble Space Telescope observations of WZ Sge obtained in 2001 September, October, November and December as WZ Sge declined from its 2001 July superoutburst. Previous analysis of these data showed the temperature of the white dwarf decreased from ~29,000 K to ~18,000 K. In this study we binned the spectra over wavelength to yield ultraviolet light curves at each epoch that were then analyzed for the presence of the well-known 27.87 s and 28.96 s oscillations. We detect the 29 s periodicity at all four epochs, but the 28 s periodicity is absent. The origin of these oscillations has been debated since their discovery in the 1970s and competing hypotheses are based on either white dwarf non-radial g-mode pulsations or magnetically-channelled accretion onto a rotating white dwarf. By analogy with the ZZ Ceti stars, we argue that the non-radial g-mode pulsation model demands a strong dependence of pulse period on the white dwarf's temperature. However, these observations show the 29 s oscillation is independent of the white dwarf's temperature. Thus we reject the white dwarf non-radial g-mode pulsation hypothesis as the sole origin of the oscillations. It remains unclear if magnetically-funnelled accretion onto a rapidly rotating white dwarf (or belt on the white dwarf) is responsible for producing the oscillations. We also report the detection of a QPO with period ~18 s in the September light curve. The amplitudes of the 29 s oscillation and the QPO vary erratically on short timescales and are not correlated with the mean system brightness nor with each other.Comment: 20 pages, 3 figures, 1 table; accepted for publication in Ap

Theoretical study of structural and electronic trends of sulfonylurea herbicides family

The sulfonylurea herbicide family has beenextensively studied using computational techniques. The moststable conformer structures of the 34 molecules analyzed ingaseous, aqueous, and octanol phases have been determined. Thestudy employed CREST conformational search methods alongwith the CENSO script to explore all possible conformationalstructures. Additional evaluations conducted at the B3LYP-D3/6-311+G(d,p) level have enabled the identification of intramolecularstability patterns across the various compounds. It has beendiscovered that stability is primarily determined by two factors:intramolecular hydrogen bonding involving an NH group adjacentto the sulfonyl group with either N donors or the nearby carbonylgroup and potential π−π interactions between the aromatic rings ofthe molecules. These have been characterized through QTAIM and NCI population analyses. Furthermore, with the goal ofdeveloping predictive models for the physicochemical properties of pesticides that include the sulfonylurea family, a statisticalanalysis among the different properties of the studied molecules has been conducted. Significant correlations have been foundbetween various properties, predicting a promising future for the prediction of characteristics that could assist laboratories inselecting among different pesticidesPDC2021-121203-I00, Y2020/EMT-629

Efficacy and Safety of Viltolarsen in Boys With Duchenne Muscular Dystrophy: Results From the Phase 2, Open-Label, 4-Year Extension Study

Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations, resulting in absence of functional dystrophin protein. Viltolarsen, an exon 53 skipping therapy, significantly increased dystrophin levels in patients with DMD. Presented here are completed study results of \u3e 4 years of functional outcomes in viltolarsen-treated patients compared to a historical control group (Cooperative International Neuromuscular Research Group Duchenne Natural History Study [CINRG DNHS]). Objective: To evaluate the efficacy and safety of viltolarsen for an additional 192 weeks in boys with DMD. Methods: This phase 2, open-label, 192-week long-term extension (LTE) study (NCT03167255) evaluated the efficacy and safety of viltolarsen in participants aged 4 to \u3c 10 years at baseline with DMD amenable to exon 53 skipping. All 16 participants from the initial 24-week study enrolled into this LTE. Timed function tests were compared to the CINRG DNHS group. All participants received glucocorticoid treatment. The primary efficacy outcome was time to stand from supine (TTSTAND). Secondary efficacy outcomes included additional timed function tests. Safety was continuously assessed. Results: For the primary efficacy outcome (TTSTAND), viltolarsen-treated patients showed stabilization of motor function over the first two years and significant slowing of disease progression over the following two years compared with the CINRG DNHS control group which declined. Viltolarsen was well tolerated, with most reported treatment-emergent adverse events being mild or moderate. No participants discontinued drug during the study. Conclusions: Based on the results of this 4-year LTE, viltolarsen can be an important treatment strategy for DMD patients amenable to exon 53 skipping

The TREAT-NMD advisory committee for therapeutics (TACT): an innovative de-risking model to foster orphan drug development

Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community's chances of successfully bringing new rare disease drugs to registration and ultimately to marke

Walking and cycling, as active transportation, and obesity factors in adolescents from eight countries

© The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.Background: Evidence has shown that active transportation decreases obesity rates, but considering walking or cycling as separate modes could provide additional information on the health benefits in adolescents. This study aimed to examine the associations between walking and cycling as form active transportation and obesity indicators in Latin American adolescents. Methods: Population-based study with 671 adolescents (mean age: 15.9 [standard deviation: 0.8] years) from eight countries participating in the Latin American Study of Nutrition and Health/Estudio Latino Americano Nutrition y Salud (ELANS). Walking and cycling for active transportation were measured using the International Physical Activity Questionnaire long version. Body mass index, waist circumference, neck circumference, and relative fat mass were used as obesity indicators. Associations were estimated using logistic regression models for the pooled data adjusted for country, sex, age, socio-economic levels, race/ethnicity, leisure-time physical activity and energy intake. Results: Mean time spent walking and cycling was 22.6 (SD: 33.1) and 5.1 (SD: 24.1) min/day, respectively. The median values were 12.8 (IQR: 4.2; 25.7) and 0 (IQR: 0; 6.2) for walking and cycling. Participants reporting ≥ 10 min/week of walking or cycling for active transportation were 84.2% and 15.5%, respectively. Costa Rica (94.3% and 28.6%) showed the highest prevalence for walking and cycling, respectively, while Venezuela (68.3% and 2.4%) showed the lowest prevalence. There was no significant association between walking for active transportation and any obesity indicator. In the overall sample, cycling for ≥ 10 min/week was significantly associated with a lower likelihood of overweight/obesity based on BMI (OR: 0.86; 95%CI: 0.88; 0.94) and waist circumference (OR: 0.90; 95%CI: 0.83; 0.97) adjusted for country, sex, age, socio-economic level, race/ethnicity, leisure-time physical activity and energy intake compared to cycling for < 10 min/week. There were no significant associations between cycling for active transportation and neck circumference as well as relative fat mass. Conclusions: Cycling for active transportation was negatively associated with obesity indicators, especially body mass index and waist circumference. Programs for promoting cycling for active transportation could be a feasible strategy to tackle the high obesity rates in adolescents in Latin America.info:eu-repo/semantics/publishedVersio

Metabolic recovery after weight loss surgery is reflected in serum microRNAs.

Funder: Ministerio de Educación, Cultura y Deporte - SpainFunder: Fondation Leducq; FundRef: http://dx.doi.org/10.13039/501100001674Funder: Marie Skłodowska-Curie Innovative Training Network TRAIN-HEARTFunder: National Institute of Health ResearchINTRODUCTION: Bariatric surgery offers the most effective treatment for obesity, ameliorating or even reverting associated metabolic disorders, such as type 2 diabetes. We sought to determine the effects of bariatric surgery on circulating microRNAs (miRNAs) that have been implicated in the metabolic cross talk between the liver and adipose tissue. RESEARCH DESIGN AND METHODS: We measured 30 miRNAs in 155 morbidly obese patients and 47 controls and defined associations between miRNAs and metabolic parameters. Patients were followed up for 12 months after bariatric surgery. Key findings were replicated in a separate cohort of bariatric surgery patients with up to 18 months of follow-up. RESULTS: Higher circulating levels of liver-related miRNAs, such as miR-122, miR-885-5 p or miR-192 were observed in morbidly obese patients. The levels of these miRNAs were positively correlated with body mass index, percentage fat mass, blood glucose levels and liver transaminases. Elevated levels of circulating liver-derived miRNAs were reversed to levels of non-obese controls within 3 months after bariatric surgery. In contrast, putative adipose tissue-derived miRNAs remained unchanged (miR-99b) or increased (miR-221, miR-222) after bariatric surgery, suggesting a minor contribution of white adipose tissue to circulating miRNA levels. Circulating levels of liver-derived miRNAs normalized along with the endocrine and metabolic recovery of bariatric surgery, independent of the fat percentage reduction. CONCLUSIONS: Since liver miRNAs play a crucial role in the regulation of hepatic biochemical processes, future studies are warranted to assess whether they may serve as determinants or mediators of metabolic risk in morbidly obese patients

Evolution of costs of inflammatory bowel disease over two years of follow-up

Background: With the increasing use of anti-TNF therapy in inflammatory bowel disease (IBD), a shift of costs has been observed with medication costs replacing hospitalization and surgery as major cost driver. We aimed to explore the evolution of IBD-related costs over two years of follow-up. Methods and Findings: In total 1,307 Crohn's disease (CD) patients and 915 ulcerative colitis (UC) patients were prospectively followed for two years by three-monthly web-based questionnaires. Changes of healthcare costs, productivity costs and out-of-pocket costs over time were assessed using mixed model analysis. Multivariable logistic regression analysis was used to identify costs drivers. In total 737 CD patients and 566 UC were included. Total costs were stable over two years of follow-up, with annual total costs of € 7,835 in CD and € 3,600 in UC. However, within healthcare costs, the proportion of anti-TNF therapy-related costs increased from 64% to 72% in CD (p<0.01) and from 31% to 39% in UC (p < 0.01). In contrast, the proportion of hospitalization costs decreased from 19% to 13% in CD (p<0.01), and 22% to 15% in UC (p < 0.01). Penetrating disease course predicted an increase of healthcare costs (adjusted odds ratio (adj. OR) 1.95 (95% CI 1.02-3.37) in CD and age <40 years in UC (adj. OR 4.72 (95% CI 1.61-13.86)). Conclusions: BD-related costs remained stable over two years. However, the proportion of anti-TNFrelated healthcare costs increased, while hospitalization costs decreased. Factors associated with increased costs were penetrating disease course in CD and age <40 in UC