Background: Duchenne muscular dystrophy (DMD) is caused by DMD gene mutations. Delandistrogene moxeparvovec is an investigational gene transfer therapy, developed to address the underlying cause of DMD. We report findings from Part 1 (52 weeks) of the two-part EMBARK trial (NCT05096221). Methods: Key inclusion criteria: Ambulatory patients aged ≥4-<8 years with a confirmed DMD mutation within exons 18–79 (inclusive); North Star Ambulatory Assessment (NSAA) score >16 and <29 at screening. Eligible patients were randomized 1:1 to intravenous delandistrogene moxeparvovec (1.33×1014 vg/kg) or placebo. The primary endpoint was change from baseline in NSAA total score to Week 52. Results: At Week 52 (n=125), the primary endpoint did not reach statistical significance, although there was a nominal difference in change from baseline in NSAA total score in the delandistrogene moxeparvovec (2.6, n=63) versus placebo groups (1.9, n=61). Key secondary endpoints (time to rise, micro-dystrophin expression, 10-meter walk/run) demonstrated treatment benefit in both age groups (4-5 and 6-7 years; p<0.05).There were no new safety signals, reinforcing the favorable and manageable safety profile observed to date. Conclusions: Based on the totality of functional assessments including the timed function tests, treatment with delandistrogene moxeparvovec indicates beneficial modification of disease trajectory.

Ultra-processed plant-based foods, such as plant-based burgers, have gained in popularity. Particularly in the out-of-home (OOH) environment, evidence regarding their nutritional profile and environmental sustainability is still evolving. Plant-based burgers available at selected OOH sites were randomly sampled in Amsterdam, Copenhagen, Lisbon and London. Plant-based burgers (patty, bread and condiment) (n 41) were lab analysed for their energy, macronutrients, amino acids and minerals content per 100 g and serving and were compared with reference values. For the plant-based burgers, the median values per 100 g were 234 kcal, 20·8 g carbohydrates, 3·5 g dietary fibre and 12·0 g fat, including 0·08 g TFS and 2·2 g SFA. Protein content was 8·9 g/100 g, with low protein quality according to amino acid composition. Median Na content was 389 mg/100 g, equivalent to 1 g salt. Compared with references, the median serving provided 31% of energy intake based on a 2000 kcal per day and contributed to carbohydrates (17–28%), dietary fibre (42%), protein (40%), total fat (48%), SFA (26%) and Na (54%). One serving provided 15–23% of the reference values for Ca, K and Mg, while higher contributions were found for Zn, Mn, P and Fe (30–67%). The ultra-processed plant-based burgers provide protein, dietary fibre and essential minerals and contain relatively high levels of energy, Na and total fats. The amino acid composition indicated low protein quality. The multifaceted nutritional profile of plant-based burgers highlights the need for manufacturers to implement improvements to better support healthy dietary habits, including reducing energy, Na and total fats.

The objective was to evaluate energy partitioning and predict the relationship between metabolizable energy (ME) and digestible energy (DE) in hair sheep fed tropical diets at three feeding levels (maintenance, intermediate and high). To evaluate the energy partition, a database with 114 records (54 non-castrated males and 60 females) from comparative slaughter studies was used. To estimate the ratio ME:DE, 207 observations (74 non-castrated males and 133 females) were used from six studies in a multi-study approach, two indirect calorimetry studies (n = 93) and four comparative slaughter (n = 114), using a mixed model and study as random effect. A simple linear regression equation of the ME against DE was fitted to predict the efficiency of DE to ME conversion. Gas losses were greatest (P < 0.05) for animals fed at maintenance level (7.92% of gross energy intake). The variations of energy losses in the urine were 2.64, 2.06 and 2.08%; faecal losses were 34.37, 37.80 and 36.91% for maintenance, intermediary and high level of feeding, respectively. The regression analysis suggested a strong linear relationship between ME and DE, generating the model ME (MJ/day) = −0.1559 (±0.07525) + 0.8503 (±0.005864) × DE (MJ/day). This study highlights the importance of the relationship ME:DE. Equation/factor 0.85 presented herein is alternative that could be used for the calculation of ME from DE in feedlot diets tropical. In conclusion, we suggest that for hair sheep fed tropical diets the conversion factor 0.85 is more adequate to predict ME from DE.

Background: SMA affects individuals with a broad age range and spectrum of disease severity. Risdiplam (EVRYSDI®) is a centrally and peripherally distributed, oral SMN2 pre-mRNA splicing modifier. Methods: SUNFISH is a multicenter, two-part, randomized, placebo-controlled, double-blind study in patients with Types 2/3 SMA. Part 1 assessed the safety, tolerability and pharmacokinetics/pharmacodynamics of different risdiplam dose levels in patients with Types 2/3 SMA. Part 2 assessed the efficacy and safety of the selected dose of risdiplam versus placebo in Type 2 and non-ambulant Type 3 SMA. In Part 2, participants were treated with risdiplam or placebo for 12 months, then received risdiplam in a blinded manner until month 24. At month 24, patients were offered the opportunity to enter the open-label extension phase. Results: Change from baseline in MFM32 total score (Part 2- primary endpoint) in patients treated with risdiplam versus placebo was met at month 12. These increases in motor function were sustained in the second and third year after risdiplam treatment. Here we present 4-year efficacy and safety data from SUNFISH. Conclusions: SUNFISH is ongoing and will provide further long-term efficacy and safety data of risdiplam in a broad population of individuals with SMA.

Preantral to early antral follicles transition is a complex process regulated by endocrine and paracrine factors, as well as by a precise interaction among oocyte, granulosa cells and theca cells. Understanding the mechanisms that regulate this step of folliculogenesis is important to improve in vitro culture systems, and opens new perspectives to use oocytes from preantral follicles for assisted reproductive technologies. Therefore, this review aims to discuss the endocrine and paracrine mechanisms that control granulosa cell proliferation and differentiation, formation of the antral cavity, estradiol production, atresia, and follicular fluid production during the transition from preantral to early antral follicles. The strategies that promote in vitro growth of preantral follicles are also discussed.

Fifty years of deforestation in the Arc of Deforestation have put at risk species survival, ecosystem services and the stability of biogeochemical cycles in Amazonia, with global repercussions. In response, we need to understand the diversity, distribution and abundance of flagship species groups, such as primates, which can serve as umbrella species for broad biodiversity conservation strategies and help mitigate climate change. Here we identify the range, suitable habitat areas and population size of Vieira's titi monkey Plecturocebus vieirai and use it as an emblematic example to discuss biodiversity conservation and climate change mitigation in one of the largest deforestation frontiers. Our findings show that deforestation for agriculture and cattle-ranching expansion is the major threat to P. vieirai and is responsible for present (56%) and projected (14%) reductions in habitat area and population size. We also found that human-driven climate change affects the P. vieirai niche negatively, triggering habitat degradation and further population decline even inside protected areas. Primate watching can be a profitable alternative to forest exploitation on private, public or Indigenous lands in the Arc of Deforestation and is a way to shift the traditional, predatory extraction of natural resources from Amazonia towards sustainable land use based on biodiversity conservation at local, regional and global scales, local people's welfare and climate change mitigation. New models of land use and income generation are required to protect the unique natural and human heritages of the Arc of Deforestation and the life-supporting ecosystem services and products provided by Amazonia.

The purpose of this study was to evaluate the quality of Marandu grass (Brachiaria brizantha) haylage according to different dry matter (DM) contents in storage. The design adopted was completely randomized with four treatments and five replications. The treatments were DM contents of the plant at the moment of storage (in natura, 30–40, 40–50 and 50–60% DM). The analyses to assess the quality of the haylage were performed after 90 days of storage. The chemical composition, microbiological population, gas quantification, pH, N-NH3, volatile fatty acids, soluble carbohydrates (CHO) and the aerobic stability were evaluated. The means were compared through the Tukey's test and linear regression. The treatment with 50–60% DM presented the highest DM and CHO contents which were 563.8 and 42.0 g/kg, respectively. There was a higher presence of oxygen in the haylage of in natura material, which was 4.8%. There was no difference between treatments for the population of lactic acid bacteria; however, the treatment with 50–60% DM had the highest concentration of enterobacteria. The haylage with 30–40% DM and 50–60% DM presented high concentrations of acetic acid. There was no break in aerobic stability for any treatment within 120 h after opening the bales. There was a smaller amount of N-NH3 in treatments with 40–50% DM and 50–60% DM. The Marandu grass with a DM content of 50–60% for haylage making demonstrated better quality characterization of conserved forage.

Cactus pear is an important species for animal feeding in the regions of dry climate. There is no information on the fertilization with coated urea in the cultivation of cactus pear under rainfed conditions in the savannah region. The aim of the current study was to evaluate the forage potential of Nopalea cochenillifera variety Doce in yellow latosol under rainfed conditions in the Brazilian savannah, comparing the fertilization with urea and coated urea in different levels. A randomized block design was adopted, in a 2 × 4 × 2 factorial scheme, with the factors corresponding to two sources of nitrogen (urea and urea coated with polymers, N+), four levels of nitrogen (0, 60, 120 and 240 kg/ha/year) and two harvests (year I and year II). The plants were evaluated after 1 year of growth, in each year of evaluation, regarding the characteristics of growth, production, chemical and mineral composition and nutritional value. The level of 240 kg/ha provided higher emission of cladodes per plant (17.33 and 18.17), respectively, for N+ and urea. The highest nitrogen use efficiency was found in the level of 60 kg N/ha (142 kg/ha/year). NFC values were 3.5 g/kg dry matter (DM) higher when the cactus pear was fertilized with urea in year I and 5.4 g/kg DM in year II. The use of conventional urea promoted better results of agronomic and nutritional characteristics of the cactus pear, under rainfed regime, when compared to the use of urea coated with polymers.

Zn deficiency compromises its biological functions, its effect on the immune system and its antiviral activity, increasing vulnerability to infectious diseases. This narrative review aims at presenting and discussing functional aspects and possible mechanisms involved in the potential role of Zn in the immune response and antiviral activity for coronavirus infectious disease-19 (COVID-19) prevention and control. The searches were conducted in PubMed and Science Direct databases, using clinical trials, experimental studies in animals and humans, case–control studies, case series, letters to the editor, and review articles published in English, without restrictions on year of publication. Search approach was based on using the terms: ‘zinc’, ‘COVID-19’, ‘antiviral agents’, ‘immunologic factors’ and ‘respiratory tract infections’. Literature shows the importance of Zn as an essential mineral immunomodulator with relevant antiviral activity in the body. Thus, although there is still a scarcity of studies evaluating Zn supplementation in patients with COVID-19, the results on the topic show the necessity of controlling Zn mineral deficiency, as well as maintaining its homoeostasis in the body in order to strengthen the immune system and improve the prevention of highly complex viral infections, such as that of the COVID-19.

The seminal characteristics of Moenkhausia oligolepis are described. Three males were induced with a single dose of carp pituitary. Semen was collected 6 h after induction, and diluted in dibasic sodium phosphate extender solution. For motility analysis, 1 µl of diluted semen was added to 10 µl of distilled water to achieve gamete activation. The average duration of total motility was 76.67 s; while the average sperm motility rate at intervals of 15 s was 95.3, 85.3, 59.6, 31.7, 13.0, 4.6 and 1.2%. To determine sperm concentration in samples, 0.5 μl of semen was diluted with 500 μl of glutaraldehyde. An aliquot of 10 μl of this dilution was utilized for cell counting. An average count of 4.97 × 109 ± 3.46 sperm/ml was obtained. Morphological analyses were performed using eosin–nigrosine dye; 20.33% of the sperm were observed to be dead. Live sperm, comprising the other 79.67%, had an average length of approximately 30 µm, with a head diameter of 4.488 ± 0.7 µm; and a flagella plus mid-piece length of 26.071 ± 12.4 µm. Of those sperm, 69% had a normal morphology, while 31% had primary and secondary abnormalities. The observed abnormality rate did not have a detrimental effect on artificial fertilization potential for the species. The description of the seminal characteristics of a species is one of the most important sets of information required for artificial reproduction of fish in captivity. It also contributes significantly to the total biological knowledge of the studied species.

The current study aimed to select the strains of lactic acid bacteria (LAB) isolated from forage cactus plants and silage and assess their effects on silage fermentation and aerobic stability. Forty wild isolates from plant and cactus silage, classified as LAB, were evaluated for metabolite production and identified by 16S ribosomal DNA sequencing. These wild isolates were identified as Lactobacillus plantarum, Weissella cibaria, Weissella confusa and Weissella paramesenteroides and the LAB populations differed among the silage. The use of microbial inoculants did not influence gas or effluent losses in forage cactus silage. The silage inoculated with the microbial strain GP15 showed the highest number of LAB populations. The amounts of water-soluble carbohydrates (WSC) and ammonia nitrogen differed among the silage. The silage inoculated with the GP1 strain presented the highest WSC. Populations of enterobacteria and yeasts and moulds were below the minimum detection limit (<2.0 log cfu/g silage) in all the silage studied. The predominant action of inoculants was to maximize dry matter recovery of the silage, which could be the criterion adopted to select the strains of LAB for use as inoculants in Opuntia silage.

Ensuring appropriate review, approval, and oversight of research involving animals becomes increasingly complex when researchers collaborate across multiple sites. In these situations, it is important that the division of responsibilities is clear and that all involved parties share a common understanding. The National Institutes of Health Office of Laboratory Animal Welfare and the United States Department of Agriculture Animal Plant Health Inspection Service require an Institutional Animal Care and Use Committee (IACUC) to review the care and use of animals in research, and both agree that it is acceptable for one IACUC to review the work taking place at multiple institutions. With this in mind, several Harvard-affiliated hospitals and academic centers developed the Master Reciprocal Institutional Agreement for Animal Care and Use (Master IACUC Agreement) to support collaboration, decrease administrative burden, increase efficiencies, reduce duplicative efforts, and ensure appropriate protections for animals used in research. Locally, the Master IACUC Agreement has fostered greater collaboration and exchange while ensuring appropriate review and oversight of research involving animals. As multisite animal protocols become more prevalent, this Agreement could provide a model for a distributed, national network of IACUC reliance.

Reducing the risk of human immunodeficiency virus type 1 (HIV-1) transmission is still a public health priority. The development of effective control strategies relies on the quantification of the effects of prophylactic and therapeutic measures in disease incidence. Although several assays can be used to estimate HIV incidence, these estimates are limited by the poor performance of these assays in distinguishing recent from long-standing infections. To address such limitation, we have developed an assay to titrate p24-specific IgG3 antibodies as a marker of recent infection. The assay is based on a recombinant p24 protein capable to detect total IgG antibodies in sera using a liquid micro array and enzyme-linked immunosorbent assay. Subsequently, the assay was optimised to detect and titrate anti-p24 IgG3 responses in a panel of sequential specimens from seroconverters over 24 months. The kinetics of p24-specific IgG3 titres revealed a transient peak in the 4 to 5-month period after seroconversion. It was followed by a sharp decline, allowing infections with less than 6 months to be distinguished from older ones. The developed assay exhibited a mean duration of recent infection of 144 days and a false-recent rate of ca. 14%. Our findings show that HIV-1 p24-specific IgG3 titres can be used as a tool to evaluate HIV incidence in serosurveys and to monitor the efficacy of vaccines and other transmission control strategies.