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Dillenia indica (Linn.) has been reported by several biological activities, including anti-inflammatory, antioxidant, antidiabetic, anti-hyperglycemic, antiproliferative, antimutagenic, anticholinesterase, and antimicrobial. In Brazilian traditional medicine, the fruits of D. indica have been used to treat general topical pain and inflammation, but with no scientific validation. Thus, aiming to study its chemical constitution and antinociceptive properties, the crude extract (CE) and fractions obtained from the fruits of D. indica were submitted to an in vivo pharmacological evaluation and a dereplication study by LC-MS/MS analysis, assisted by the Global Natural Product Social Molecular Networking (GNPS). The oral antinociceptive activity of the fruits of D. indica and the possible participation of the opioid and cannabinoid systems were demonstrated in the formalin-induced nociception model. The chemical dereplication study led us to identify several known chemical constituents, including flavonoids, such as caffeoylmalic acid, naringenin, quercetin, and kaempferol. According to literature data, our results are compatible with significant antinociceptive and anti-inflammatory activities. Therefore, the flavonoid constituents of the fruits of D. indica are probably responsible for its antioxidant, anti-inflammatory, and antinociceptive effects mediated by both opioid and cannabinoid systems, confirming its folk use in the treatment and relief of pain.

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ABSTRACT Purpose: to characterize the actions of vocal health promotion and/or prevention of vocal disorders applied to voice professionals. Methods: a scoping review following the PRISMA-ScR guidelines in SciELO and PubMed databases was conducted. Articles that had as participants voice professionals without concomitant vocal treatment, that described proposals for health promotion or vocal disorders prevention, published between 2010 and 2023, were included. They were grouped into categories and data were presented descriptively. Literature Review: eighteen articles with artistic and non-artistic voice professionals, mostly teachers, were included. Most of the studies focused on healthy voices, aiming at primary prevention. Many articles presented guidance on vocal hygiene and health and used resources such as vocal enhancement, voice workshop, voice amplifiers and apps. All the articles positively mentioned their results, especially with regard to self-perception in relation to voice, vocal quality and quality of life, awareness of positive and harmful practices to the voice. Conclusion: the proposals contemplated different levels of prevention, but most focused on primary prevention, including vocally healthy participants; all articles indicated positive results in voice self-perception, voice quality and quality of life, and awareness of positive and harmful voice practices.

RESUMO Objetivo: caracterizar as ações de promoção de saúde vocal e/ou prevenção de distúrbios vocais aplicadas em profissionais da voz. Métodos: foi conduzida uma revisão de escopo seguindo as diretrizes do PRISMA-ScR nas bases de dados SciELO e PubMed. Foram incluídos artigos que tivessem como participantes profissionais da voz sem tratamento vocal concomitante, que descrevessem propostas de promoção da saúde ou prevenção de distúrbios vocais, publicados entre 2010 e 2023. Os artigos foram agrupados em categorias e os dados apresentados de forma descritiva. Revisão da Literatura: foram incluídos 18 artigos com profissionais da voz artística e não-artística, em sua maioria professores. A maior parte dos estudos tinha como foco vozes saudáveis, visando a prevenção primária. Muitos artigos apresentaram orientações sobre higiene e saúde vocal e utilizaram recursos como aprimoramento vocal, oficina de voz, amplificadores de voz e aplicativos. Todos os artigos mencionam resultados benéficos, principalmente no que se refere à autopercepção em relação a voz, qualidade vocal e de vida, conscientização de práticas positivas e prejudiciais à voz. Conclusão: as propostas contemplaram diferentes níveis de prevenção, mas a maioria tinha como foco a prevenção primária, incluindo participantes vocalmente saudáveis; todos os artigos indicaram resultados favoráveis na autopercepção em relação à voz, qualidade vocal e de vida e conscientização de práticas benéficas e prejudiciais à voz.

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The scientific information regarding staphylococci in procyonids is scarce. Hence, the aim of this study was to evaluate the frequency, distribution, and pattern of antimicrobial resistance of staphylococcal species isolated from free-roaming coatis (Nasua nasua) in an urban park in Belo Horizonte, Minas Gerais, Brazil. Rectal swabs from 55 free-living coatis were plated onto mannitol salt agar for isolating staphylococci, and species were identified using matrix-assisted laser desorption/ionization-time of flight mass spectrometry, polymerase chain reaction (PCR) of nuc, and sequencing of 16S rRNA and rpoB when needed. Antimicrobial susceptibility was investigated using the disk diffusion method, and the presence of the mecA gene was investigated by PCR. A total of 72.7% of the animals tested positive for staphylococci. Nine different species were identified, and Staphylococcus intermedius (60.4%) and S. delphini (20.9%) were the most frequently isolated species. Most of the isolates were susceptible to most of the antimicrobials evaluated, with a resistance pattern seen for penicillin (13.9%). One isolate was multidrug-resistant (MDR). The present study suggests that coatis are natural hosts of S. intermedius and S. delphini and, despite living in a heavily anthropized environment, the Staphylococcus spp. isolates showed a low incidence of drug resistance.

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Melanoma is considered the most aggressive form of skin cancer, showing high metastatic potential and persistent high mortality rates despite the introduction of immunotherapy and targeted therapies. Thus, it is important to identify new drug candidates for melanoma. The design of hybrid molecules, with different pharmacophore fragments combined in the same scaffold, is an interesting strategy for obtaining new multi-target and more effective anticancer drugs. We designed nine hybrid compounds bearing piperine and chlorogenic acid pharmacophoric groups and evaluated their antitumoral potential on melanoma cells with distinct mutational profiles SK-MEL-147, CHL-1 and WM1366. We identified the compound named PQM-277 (3a) to be the most cytotoxic one, inhibiting mitosis progression and promoting an accumulation of cells in pro-metaphase and metaphase by altering the expression of genes that govern G2/M transition and mitosis onset. Compound 3a downregulated FOXM1, CCNB1, CDK1, AURKA, AURKB, and PLK1, and upregulated CDKN1A. Molecular docking showed that 3a could interact with the CUL1-RBX1 complex, which activity is necessary to trigger molecular events essential for FOXM1 transactivation and, in turn, G2/M gene expression. In addition, compound 3a effectively induced apoptosis by increasing BAX/BCL2 ratio. Our findings demonstrate that 3a is an important antitumor candidate prototype and support further investigations to evaluate its potential for melanoma treatment, especially for refractory cases to BRAF/MEK inhibitors.

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Abstract Introduction The acoustic analysis of speech (measurements of the fundamental frequency and formant frequencies) of different vowels produced by speakers with the Angle class II, division 1, malocclusion can provide information about the relationship between articulatory and phonatory mechanisms in this type of maxillomandibular disproportion. Objectives To investigate acoustic measurements related to the fundamental frequency (F0) and formant frequencies (F1 and F2) of the oral vowels of Brazilian Portuguese (BP) produced by male speakers with Angle class II, division 1, malocclusion (study group) and compare with men with Angle class I malocclusion (control group). Methods In total, 60 men (20 with class II, 40 with class I) aged between 18 and 40 years were included in the study. Measurements of F0, F1 and F2 of the seven oral vowels of BP were estimated from the audio samples containing repetitions of carrier sentences. The statistical analysis was performed using the Student t-test and the effect size was calculated. Results Significant differences (p-values) were detected for F0 values in five vowels ([e], [i], [o], [o] and [u]), and for F1 in vowels [a] and [ɔ], with high levels for class II, division 1. Conclusion Statistical differences were found in the F0 measurements with higher values in five of the seven vowels analysed in subjects with Angle class II, division 1. The formant frequencies showed differences only in F1 in two vowels with higher values in the study group. The data suggest that data on voice and speech production must be included in the protocol's assessment of patients with malocclusion.

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Introduction The acoustic analysis of speech (measurements of the fundamental frequency and formant frequencies) of different vowels produced by speakers with the Angle class II, division 1, malocclusion can provide information about the relationship between articulatory and phonatory mechanisms in this type of maxillomandibular disproportion. Objectives To investigate acoustic measurements related to the fundamental frequency (F0) and formant frequencies (F1 and F2) of the oral vowels of Brazilian Portuguese (BP) produced by male speakers with Angle class II, division 1, malocclusion (study group) and compare with men with Angle class I malocclusion (control group). Methods In total, 60 men (20 with class II, 40 with class I) aged between 18 and 40 years were included in the study. Measurements of F0, F1 and F2 of the seven oral vowels of BP were estimated from the audio samples containing repetitions of carrier sentences. The statistical analysis was performed using the Student t -test and the effect size was calculated. Results Significant differences ( p -values) were detected for F0 values in five vowels ([e], [i], [ᴐ], [o] and [u]), and for F1 in vowels [a] and [ᴐ], with high levels for class II, division 1. Conclusion Statistical differences were found in the F0 measurements with higher values in five of the seven vowels analysed in subjects with Angle class II, division 1. The formant frequencies showed differences only in F1 in two vowels with higher values in the study group. The data suggest that data on voice and speech production must be included in the protocol's assessment of patients with malocclusion.

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A male adult ocelot (Leopardus pardalis) kept under human care developed anuria, which progressed to death. Grossly, the urinary bladder was markedly dilated and filled with red discolored urine containing blood clots. In addition, the animal had a hepatoid cell adenoma adjacent to the urethra, which likely caused partial urethral occlusion. Microscopically, there was a predominantly neutrophilic, fibrinous and hemorrhagic urethritis, cystitis, and pyelonephritis with intralesional gram-positive cocci. Microbiologic culture followed by MALDI-TOF MS analysis resulted in the identification of isolates from the urine and urethra as Staphylococcus felis.(AU)

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Staphylococcus pseudintermedius is a major commensal bacterium of the skin and mucosae of dogs and an opportunistic agent responsible for several clinical infections, such as pyoderma, otitis, and surgical wound infections. The emergence of methicillin-resistant S. pseudintermedius (MRSP) has become a problem of great concern in veterinary and human medicine because it is multidrug resistant (MDR) and can also infect humans. This study aimed to identify the occurrence of Staphylococcus spp. in infected patients and investigate the antimicrobial resistance profiles and molecular structure of MRSP isolates. Samples were obtained from two different veterinary clinics; suggestive colonies were submitted to matrix-assisted laser desorption ionization-time of flight (MALDI-ToF) mass spectrometry and confirmed at the species level by polymerase chain reaction (PCR). Sequencing of the 16S rRNA and rpoB genes were used in selected samples that were not identified by MALDI-ToF and by the species-specific PCR. Antimicrobial susceptibility and PCR detection of mecA were performed. MRSP isolates were subjected to multilocus sequence typing. Of all the clinical staphylococci (n = 131), 98 (74.8%) were identified as S. pseudintermedius. Multidrug resistance (resistance to ≥3 classes of antimicrobials) was observed in 63.2% of S. pseudintermedius isolates, and 24.5% of S. pseudintermedius isolates were methicillin-resistant. Half of the MRSP isolates were isolated from surgical site infections. Among the ten sequence types (ST) identified, nine were novel. ST71 was the most prevalent and associated with resistance to fluoroquinolones. Prior antimicrobial therapy, hospitalization, and surgical site infections seemed to be risk factors for MRSP acquisition. The present study showed a high rate of MDR staphylococci in infected dogs. MRSP was isolated from different clinical conditions, mainly surgical site infections. Additionally, this is the first study to extensively investigate the population structure of MRSP in Brazil, which revealed the dispersion of CC71 and nine novel ST. These findings raise concerns for both animal and human health due to the zoonotic potential of this species and limited therapeutic options available for MRSP infections.

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The practice of feeding dogs raw meat-based diets (RMBDs) is growing in several countries, and the risks associated with the ingestion of pathogenic and antimicrobial-resistant Escherichia coli in dogs fed these diets are largely unknown. We characterized E. coli strains isolated from dogs fed either an RMBD or a conventional dry feed, according to the phylogroup, virulence genes, and antimicrobial susceptibility profiles of the bacteria. Two hundred and sixteen E. coli strains were isolated. Dogs fed RMBDs shed E. coli strains from the phylogroup E more frequently and were positive for the E. coli heat-stable enterotoxin 1-encoding gene. Isolates from RMBD-fed dogs were also frequently positive for multidrug-resistant E. coli isolates including extended-spectrum beta-lactamase (ESBL) producers. Whole-genome sequencing of seven ESBL-producing E. coli strains revealed that they predominantly harbored blaCTX-M-55, and two strains were also positive for the colistin-resistant gene mcr-1. These results suggest that feeding an RMBD can affect the dog's microbiota, change the frequency of certain phylogroups, and increase the shedding of diarrheagenic E. coli. Also, feeding an RMBD seemed to be linked with the fecal shedding of multidrug-resistant E. coli, including the spread of strains harboring mobilizable colistin resistance and ESBL genes. This finding is of concern for both animal and human health.

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Nowadays, neurodegenerative diseases (NDs), such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a great challenge in different scientific fields, such as neuropharmacology, medicinal chemistry, molecular biology and medicine, as all these pathologies remain incurable, with high socioeconomic impacts and high costs for governmental health services. Due to their severity and multifactorial pathophysiological complexity, the available approved drugs for clinic have not yet shown adequate effectiveness and exhibited very restricted options in the therapeutic arsenal; this highlights the need for continued drug discovery efforts in the academia and industry. In this context, natural products, such as curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) have been recognized as important sources, with promising chemical entities, prototype models and starting materials for medicinal organic chemistry, as their molecular architecture, multifunctional properties and single chemical diversity could facilitate the discovery, optimization and development of innovative drug candidates with improved pharmacodynamics and pharmacokinetics compared to the known drugs and, perhaps, provide a chance for discovering novel effective drugs to combat NDs. In this review, we report the most recent efforts of medicinal chemists worldwide devoted to the exploration of curcumin (1), resveratrol (2) and cannabidiol (CBD, 3) as starting materials or privileged scaffolds in the design of multi-target directed ligands (MTDLs) with potential therapeutic properties against NDs, which have been published in the scientific literature during the last 10 years of research and are available in PubMed, SCOPUS and Web of Science databases.

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