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Muscular dystrophies (MD) are a group of hereditary diseases marked by progressive muscle loss, leading to weakness and degeneration of skeletal muscles. These conditions often result from structural defects in the Dystrophin–Glycoprotein Complex (DGC), as seen in Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD). Since MDs currently have no cure, research has focused on identifying potential therapeutic targets to improve patients’ quality of life. In this study, skeletal muscle tissue samples from DMD and BMD patients, as well as non-dystrophic controls, were analyzed using label-free mass spectrometry (MS/MS) to characterize the proteomic profile of these conditions and identify biomarkers for differential diagnosis. In-silico analysis revealed that dystrophic muscle tissues are linked to biological processes related to cellular energy metabolism, including oxidation of organic compounds, energy production, and cellular respiration. Enrichment of functions associated with cell structure and RNA binding was also observed, including cytoskeletal protein binding and RNA binding. The human phenotypes most related to the proteomic signature were abnormal circulating metabolites, muscle physiology, and weakness. Quantitative analysis identified significant changes in proteins associated with sarcomere organization and protein ubiquitination, such as myomesin, myozenin, and E3 ubiquitin-protein ligase rififylin, suggesting these as potential therapeutic targets.

Autologous hematopoietic stem cell transplantation (ASCT) improves survival in multiple myeloma (MM). However, many individuals are unable to collect optimal CD34 + hematopoietic stem and progenitor cell (HSPC) numbers with granulocyte colony-stimulating factor (G-CSF) mobilization. Motixafortide is a novel cyclic-peptide CXCR4 inhibitor with extended in vivo activity. The GENESIS trial was a prospective, phase 3, double-blind, placebo-controlled, multicenter study with the objective of assessing the superiority of motixafortide + G-CSF over placebo + G-CSF to mobilize HSPCs for ASCT in MM. The primary endpoint was the proportion of patients collecting ≥6 × 10 6 CD34 + cells kg –1 within two apheresis procedures; the secondary endpoint was to achieve this goal in one apheresis. A total of 122 adult patients with MM undergoing ASCT were enrolled at 18 sites across five countries and randomized (2:1) to motixafortide + G-CSF or placebo + G-CSF for HSPC mobilization. Motixafortide + G-CSF enabled 92.5% to successfully meet the primary endpoint versus 26.2% with placebo + G-CSF (odds ratio (OR) 53.3, 95% confidence interval (CI) 14.12–201.33, P  < 0.0001). Motixafortide + G-CSF also enabled 88.8% to meet the secondary endpoint versus 9.5% with placebo + G-CSF (OR 118.0, 95% CI 25.36–549.35, P  < 0.0001). Motixafortide + G-CSF was safe and well tolerated, with the most common treatment-emergent adverse events observed being transient, grade 1/2 injection site reactions (pain, 50%; erythema, 27.5%; pruritis, 21.3%). In conclusion, motixafortide + G-CSF mobilized significantly greater CD34 + HSPC numbers within two apheresis procedures versus placebo + G-CSF while preferentially mobilizing increased numbers of immunophenotypically and transcriptionally primitive HSPCs. Trial Registration: ClinicalTrials.gov , NCT03246529 The phase 3 GENESIS trial reports the superiority of the novel CXCR4 inhibitor motixafortide with G-CSF in mobilizing hematopoietic progenitor cells for autologous stem cell transplantation in multiple myeloma.

Endometriosis is a chronic inflammatory disease that occurs in women of reproductive age. Much of the treatment involves hormone therapy that suppresses the proliferation of endometriosis lesions. Objective To compare discontinuation rates of pharmacological treatment with estrogen-progestins and progestins medications. The secondary objective is to evaluate the main side effects of these drugs in patients with endometriosis. Methods This retrospective study analyzed data from 330 patients who attended the Hospital of the State Public Servant of São Paulo from August 1999 to September 2020 and received pharmacological treatment for endometriosis. The data were obtained by review of the files of medical appointments with specialized staff. Results The median treatment time was 18 months, ranging from 1 to 168 months, and 177 patients interrupted the proposed treatment. The combined contraceptives with estrogens and progestins were significantly linked to treatment interruption, with a relative risk of 1,99 ( p  = 0,005). The most important side effects that resulted in treatment interruption were pain persistence ( p  = 0,043), weight gain ( p  = 0,017) and spotting ( p  < 0,001).

Inadequate management conditions can impair the welfare of captive-bred horses. Understanding individuals’ viewpoints and the factors influencing their decisions about adopting or avoiding certain practices may provide insights into their motivations and decision-making processes. This is particularly relevant in the equestrian community, where equine practitioners and enthusiasts often engage in harmful practices. We explored the beliefs, knowledge, and attitudes of equine practitioners and enthusiasts about horse welfare and the barriers that prevent them from employing better management practices that are essential to promoting horses’ welfare. The study consisted of in-depth semi-structured interviews conducted in person with 31 individuals directly involved in the equestrian environment in Brazil. Responses were analyzed through thematic analysis with a data-driven deductive approach. Participants’ beliefs, knowledge and attitudes to horse welfare were divided into three themes. The first theme, “Let the horse be a horse”, captured participants’ perceptions about how physical and mental aspects related to the nature and welfare of horses. The second theme, “Everyone does it like that”, includes the social norms that influence decisions about the practices that impact on the welfare of the horses. The third theme, “Beyond utopia: how and why horses are managed the way they are”, covered barriers that participants perceived as impediments to the use of best practices for the welfare of horses. While participants demonstrated awareness of welfare issues and acknowledged factors that negatively impact horses, there was a notable discrepancy between this knowledge and the implementation of improved management practices. This could be explained by several perceived barriers to implementing management practices that could enhance horse welfare, including lack of financial resources, limited physical space, shortage of qualified labor, time constraints, inadequate tools, and insufficient knowledge. Additionally, we identified deeply rooted social norms within the equestrian community and culturally established practices that limit approaches to horse welfare. Participants underscored the influence of these norms and different interpretations of “letting the horse be a horse” based on the horse’s value and purpose. Concerning low-value horses, the primary justifications for stall housing and concentrated feeding were linked to elevated costs involved in spatial demands and labor; in contrast, for high-value horses used in performance and aesthetics, the arguments shifted to potential benefits to the horses’ well-being. From an ethical perspective, ideally, individuals should refrain from owning horses if they cannot ensure the animals’ welfare. Additionally, if the equestrian community neglects public attitudes towards animal welfare, it risks eroding its social license.

Abstract The study aimed to analyze the spatial distribution and factors associated with oral cancer mortality in the 2009-2019 period in the municipalities of Ceará, Brazil. This ecological study of oral cancer deaths used distribution analysis, autocorrelation, and spatial regression. The oral cancer mortality rate has spatial autocorrelation. In the geographically weighted regression analysis, a negative relationship was observed between mortality and the number of households with access to the sewage system (β = -0.001) and the mean number of people per household (β = -5.947). We observed a positive relationship between mortality and percentage of oral health coverage in Primary Health Care (β = 0.021), number of people living in the rural area of the municipality (β = 0.0001), Municipal Human Development Index (β = 40.417), and aging rate (β = 1.169). We can conclude that the influence on the mortality risk showed spatial clusters that require priority in public policies that impact oral cancer morbimortality. Resumo O estudo objetivou analisar a distribuição espacial e fatores associados à mortalidade por câncer de boca no período de 2009-2019 nos municípios do Ceará, no Brasil. Trata-se de um estudo ecológico dos óbitos por câncer de boca utilizando análise de distribuição, autocorrelação e regressão espacial. O coeficiente de mortalidade por câncer de boca possui autocorrelação espacial. Na análise de regressão geograficamente ponderada, observou-se relação negativa entre mortalidade e número de moradias com acesso à rede de esgoto (β = -0,001) e média de pessoas por domicílio (β = -5,947). Observou-se relação positiva entre mortalidade e percentual de cobertura de saúde bucal na Atenção Primária à Saúde (β = 0,021), número de pessoas que vivem na zona rural do município (β = 0,0001), Índice de Desenvolvimento Humano Municipal (β = 40,417) e taxa de envelhecimento (β = 1,169). Pode-se concluir que a influência sobre o risco de mortalidade evidenciou aglomerados espaciais que requerem prioridade em políticas públicas que impactem na morbimortalidade por câncer de boca.

Recent changes in the epidemiology of meningococcal have been reported and meningococcal group W (MenW) has become the third most prevalent group isolated in Brazil in the last 10 years. In this study we have developed a conjugate vaccine for MenW using a modified reductive amination conjugation method through a covalent linkage between periodate-oxidized MenW non-O-acetylated polysaccharide and hydrazide-activated monomeric tetanus toxoid. Process control of bulks was done by physicochemical analysis including polysaccharide and protein quantification, high performance liquid chromatography – size exclusion chromatography, capillary electrophoresis, and hydrogen nuclear magnetic resonance. Conjugate bulks were best produced with concentration of polysaccharide twice as high as protein, at room temperature, and pH approximately 6.0. A scaled-up bulk (100 mg scale) was formulated and inoculated intramuscularly in mice in a dose–response study (0.1, 0.5, 1.0 and 10.0 µg of polysaccharide/dose). The immunogenicity of conjugate bulks was determined by serum bactericidal assay and ELISA assays of serum from immunized mice. ELISA and SBA titers revealed high titers of IgG and demonstrated the functionality of the antibodies produced in all doses studied 15 days after the third dose. However, significant differences were observed among them by ELISA. In conclusion, this study established the best conditions to produce MenW conjugate bulks and showed the efficacy of the obtained conjugate bulk in induce a good immune response in mice. Further experiments will need to be done to scale up the conjugation reaction and then allow the use of this conjugate in clinical trials.

Objectives The objective of this study was to assess the impact of the COVID-19 pandemic, after 2 years, on mammographic screening in Brazil evaluating BIRADS® results, breast cancer diagnosis rates, and breast cancer stage. Study Design This was an ecological observational study based on retrospective data from Brazil’s mammographic screening program from 2015 to 2023. Methods Data were obtained from the national screening database DATASUS – SISCAN (Cancer System Information) and retrieved in March 2024. Inclusion criteria comprised completeness of mammogram data (incomplete records were excluded), female participants aged 50 to 69 years, and mammograms exclusively performed for screening purposes. The study analyzed the number of mammograms conducted during the specified period, focusing on BIRADS® test results. Results Out of 23,851,371 mammograms performed between 2015 and 2023, 15,000,628 were included for analysis. A significant reduction of 39.6% in mammograms was observed in 2020 compared to 2019, followed by a 12.6% decrease in 2021. Notably, a substantial rise in BIRADS categories 4 and 5 examinations was seen post-pandemic. Breast cancer staging analysis revealed a shift towards more advanced stages (III and IV) diagnosed post-pandemic, suggesting potential delays in detection and diagnosis. Conclusions In conclusion, the study highlighted significant discrepancies in mammographic screenings and breast cancer diagnosis rates over 9 years. The pandemic reflected significant influence on the timing and stage at diagnosis, suggesting potential delays in detection and diagnosis that resulted in later identification of more advanced disease stages.

Manganese (Mn) toxicity is a very common soil stress around the world, which is responsible for low soil fertility. This manuscript evaluates the effect of the endophytic bacterium Pseudomonas sp. Q1 on different rhizobial-legume symbioses in the absence and presence of Mn toxicity. Three legume species, Cicer arietinum (chickpea), Trifolium subterraneum (subterranean clover), and Medicago polymorpha (burr medic) were used. To evaluate the role of 1-aminocyclopropane-1-carboxylate (ACC) deaminase produced by strain Q1 in these interactions, an ACC deaminase knockout mutant of this strain was constructed and used in those trials. The Q1 strain only promoted the symbiotic performance of Rhizobium leguminosarum bv. trifolii ATCC 14480T and Ensifer meliloti ATCC 9930T, leading to an increase of the growth of their hosts in both conditions. Notably, the acdS gene disruption of strain Q1 abolished the beneficial effect of this bacterium as well as causing this mutant strain to act deleteriously in those specific symbioses. This study suggests that the addition of non-rhizobia with functional ACC deaminase may be a strategy to improve the pasture legume–rhizobial symbioses, particularly when the use of rhizobial strains alone does not yield the expected results due to their difficulty in competing with native strains or in adapting to inhibitory soil conditions.

The aim of this study was to evaluate the effect of association of forage cactus meal (CM) and cunhã hay (CH) on carcass traits, meat quality, and fatty acid (FA) profile of goats. Twenty-four goats were finished on diets composed with the association of CM and CH (83% CH + 17% CM, 67% CH + 33% CM, or 50% CH + 50% CM), corresponding to 60% of the total diet; the remainder was composed of 10% elephant grass and 30% concentrate. The control treatment consisted of 70% elephant grass and 30% concentrate. Carcass yield and commercial cut weight were higher in the animals fed CH and CM at any concentration (P < 0.05). Animals fed with intermediate and high CM content resulted in meat with better proportions of unsaturated FA (P = 0.0281), desirable FA (P = 0.0024), omega 6/omega 3 ratio (P = 0.0340), and hypo-/hypercholesterolemic index (P = 0.0140). The inclusion of CH and CM provided carcass yield and FA profile more favorable for consumer market and human health.

The aim of this study was to evaluate the effect of adding different concentrations of either urea or NaOH in dehydrated acerola (Malpighia emarginata) fruit residue (DAFR) on chemical composition, in vitro rumen degradability, and gas and methane production. A completely randomized design was used with the following seven treatments: control, without chemical treatment, or pretreatment of DAFR with urea or NaOH at 20, 40, or 60 g/kg dry matter (DM). DM degradability and gas and methane production of DAFR were evaluated by semi-automated in vitro gas production technique. DAFR treated with urea or NaOH at concentrations of 40 and 60 g/kg DM decreased its neutral detergent fiber (P = 0.0115) and lignin (P < 0.0001) content, and this reduction was greater with the highest concentration (60 g/kg DM). In all tested concentrations, urea and NAOH were effective to increase the DM effective degradability of DAFR compared with the control treatment, although treatments with a concentration of 60 g/kg DM presented the highest values (P < 0.0001). Treatment of DAFR with NaOH or urea at 60 g/kg DM promotes greater lignin solubilization and DM degradability and lower gas and methane production in in vitro rumen fermentation.