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PURPOSE: Prostate cancer (PCa) is the leading cause of death among men in 48 countries. Genetic alterations play a significant role in PCa carcinogenesis. For the hypothesis of this research, five unique polymorphisms (SNP) were investigated in different genes that showed to be associated in different ways with PCa: rs4430796, rs2735839, rs4792311, rs12329760, and rs28931588, respectively for the genes HNF1B, KLK3, ELAC2, TMPRSS2-ERG, and CTNNB1. PATIENTS AND METHODS: Blood samples from 426 subjects were evaluated: 290 controls (161 females and 129 males) and 136 PCa patients. SNP were determined by real-time polymerase chain reaction. TaqMan SNP genotyping assay. In the control samples, the SNPs were defined in association with the self-reported ethnicity, and in 218 control samples with markers with ancestry indicators. The genes were in Hardy-Weinberg equilibrium. One hundred and seventy control samples were matched by ethnicity for comparison with the PCa samples. RESULTS: The G allele at rs28931588 was monomorphic in both patients and controls studied. Significant differences were observed in allelic and genotypic frequencies between the control and Pca samples in rs2735839 (KLK3; p = 0.002 and χ2 = 8.73 and p = 0.01, respectively), by the global frequency and in the dominant model rs2735839_GG (odds ratio [OR] = 0.51, p = 0.02). AA and GA genotypes at rs4792311 (ELAC2) were more frequent in patients with Gleason 7(4 + 3), 8, and 9 (n = 37%-59.7%) compared to patients with Gleason 6 and 7(3 + 4) (n = 26%-40.0%) conferring a protective effect on the GG genotype (OR = 0.45, p = 0.02). The same genotype showed an OR = 2.71 (p = 0.01) for patients with low severity. The HNF1B-KLK3-ELAC2-TMPRSS2-ERG haplotypes: GAAT, AAAT, GAGT, and AAGT were more frequent in patients with Pca with OR ranging from 4.65 to 2.48. CONCLUSIONS: Higher frequencies of risk alleles were confirmed in the SNPs, KLK3 rs2735839_A, ELAC2 rs4792311_A, and TMPRSS2 rs12329760_T in patients with Pca. Rs2735839_A was associated with risk of Pca and rs4792311_A with severity and Gleason score of 7(4 + 3) or greater. There is a need for careful observation of rs2735839 and rs4792311 in association with the prostatic biopsy due to the increased risk of Pca.
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Antígeno Prostático Específico , Neoplasias da Próstata , Masculino , Humanos , Calicreínas/genética , Predisposição Genética para Doença , Neoplasias da Próstata/patologia , Genótipo , Polimorfismo de Nucleotídeo Único , Regulador Transcricional ERG/genética , Fator 1-beta Nuclear de Hepatócito/genética , Proteínas de Neoplasias , beta Catenina/genéticaRESUMO
BACKGROUND: Quantitative flow ratio (QFR) and myocardial perfusion scintigraphy (MPS) are utilized for assessing coronary artery disease (CAD) significance. We aimed to analyze their concordance and prognostic impact. AIMS: We aimed to analyze the concordance between QFR and MPS and their risk stratification. METHODS: Patients with invasive coronary angiography and MPS were categorized as concordant if QFR ≤ 0.80 and summed difference score (SDS) ≥ 4 or if QFR > 0.80 and SDS < 4; otherwise, they were discordant. Concordance was classified by coronary territory involvement: total (three territories), partial (two territories), poor (one territory), and total discordance (zero territories). Leaman score assessed coronary atherosclerotic burden. RESULTS: 2010 coronary territories (670 patients) underwent joint QFR and MPS analysis. MPS area under the curve for QFR ≤ 0.80 was 0.637. Concordance rates were total (52.5%), partial (29.1%), poor (15.8%), and total discordance (2.6%). Most concordance occurred in patients without significant CAD or with single-vessel disease (89.5%), particularly without MPS perfusion defects (91.5%). Leaman score (odds ratio [OR]: 0.839, 95% confidence interval [CI]: 0.805-0.875, p < 0.001) and MPS perfusion defect (summed stress score [SSS] ≥ 4) (OR: 0.355, 95% CI: 0.211-0.596, p < 0.001) were independent predictors for discordance. After 1400 days, no significant difference in death/myocardial infarction was observed based on MPS assessment, but Leaman score, functional Leaman score, and average QFR identified higher risk patients. CONCLUSIONS: MPS showed good overall accuracy in assessing QFR significance but substantial discordance existed. Predictors for discordance included higher atherosclerotic burden and MPS perfusion defects (SSS ≥ 4). Leaman score, QFR-based functional Leaman score, and average QFR provided better risk stratification for all-cause death and myocardial infarction than MPS.
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Angiografia Coronária , Doença da Artéria Coronariana , Vasos Coronários , Imagem de Perfusão do Miocárdio , Valor Preditivo dos Testes , Humanos , Imagem de Perfusão do Miocárdio/métodos , Feminino , Masculino , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/fisiopatologia , Doença da Artéria Coronariana/mortalidade , Pessoa de Meia-Idade , Idoso , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/fisiopatologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Reprodutibilidade dos Testes , Circulação Coronária , Índice de Gravidade de Doença , Tomografia Computadorizada de Emissão de Fóton Único , Reserva Fracionada de Fluxo Miocárdico , Fatores de TempoRESUMO
BACKGROUND: Guide catheter extensions (GCEs) increase support and facilitate equipment delivery, but aggressive instrumentation may be associated with a higher risk of complications. AIM: Our aim was to assess the impact of GCEs on procedural success and complications in patients submitted to chronic total occlusion (CTO) percutaneous coronary intervention (PCI). METHODS: We analyzed data from the multicenter LATAM CTO Registry. Procedural success was defined as <30% residual stenosis and TIMI 3 distal flow. Major adverse cardiac and cerebrovascular events (MACCE) was defined as the composite of all-cause death, myocardial infarction, target vessel revascularization, and stroke. Propensity score matching (PSM) was used to compare outcomes with and without GCE use. RESULTS: From August 2010 to August 2021, 3049 patients were included. GCEs were used in 438 patients (14.5%). In unadjusted analysis, patients in the GCE group were older and had more comorbidities. The median J-CTO score and its components were higher in the GCE group. After PSM, procedural success was higher with GCE use (87.7% vs. 80.5%, p = 0.007). The incidence of coronary perforation (odds ratio [OR]: 1.46, 95% confidence interval [CI]: 0.78-2.71, p = 0.230), bleeding (OR: 1.99, 95% CI: 0.41-2.41, p = 0.986), in-hospital death (OR: 1.39, 95% CI: 0.54-3.62, p = 0.495) and MACCE (OR: 1.07, 95% CI: 0.52-2.19, p = 0.850) were similar in both groups. CONCLUSION: In a contemporary, multicenter cohort of patients undergoing CTO PCI, GCEs were used in older patients, with more comorbidities and complex anatomy. After PSM, GCE use was associated with higher procedural success, and similar incidence of adverse outcomes.
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Oclusão Coronária , Intervenção Coronária Percutânea , Idoso , Humanos , Catéteres , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/terapia , Oclusão Coronária/etiologia , Mortalidade Hospitalar , Intervenção Coronária Percutânea/efeitos adversos , Resultado do TratamentoRESUMO
Bioactive compounds derived from secondary metabolism in animals have refined selectivity and potency for certain biological targets. The superfamily Dendrobatoidea is adapted to the dietary sequestration and secretion of toxic alkaloids, which play a role in several biological activities, and thus serve as a potential source for pharmacological and biotechnological applications. This article constitutes a scoping review to understand the trends in experimental research involving bioactive alkaloids derived from Dendrobatoidea based upon scientometric approaches. Forty-eight (48) publications were found in 30 journals in the period of 60 years, between 1962 and 2022. More than 23 structural classes of alkaloids were cited, with 27.63% for batrachotoxins, 13.64% for pyridinics, with an emphasis on epibatidine, 16.36% for pumiliotoxins, and 11.82% for histrionicotoxins. These tests included in vivo (54.9%), in vitro (39.4%), and in silico simulations (5.6%). Most compounds (54.8%) were isolated from skin extracts, whereas the remainder were obtained through molecular synthesis. Thirteen main biological activities were identified, including acetylcholinesterase inhibitors (27.59%), sodium channel inhibitors (12.07%), cardiac (12.07%), analgesic (8.62%), and neuromuscular effects (8.62%). The substances were cited as being of natural origin in the "Dendrobatidae" family, genus "Phyllobates," "Dendrobates," and seven species: Epipedobates tricolor, Phyllobates aurotaenia, Oophaga histrionica, Oophaga pumilio, Phyllobates terribilis, Epipedobates anthonyi, and Ameerega flavopicta. To date, only a few biological activities have been experimentally tested; hence, further studies on the bioprospecting of animal compounds and ecological approaches are needed.
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Alcaloides , Peçonhas , Animais , Acetilcolinesterase , Anuros/metabolismo , Batraquiotoxinas/química , Alcaloides/química , Alcaloides/metabolismoRESUMO
Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide in the parabrachial nucleus (CGRPPBN neurons) relay sensory signals that contribute to satiation and pain-induced fear behaviour, but it is unclear how they encode these distinct processes. Here, by recording calcium transients in vivo from individual neurons in mice, we show that most CGRPPBN neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). The same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating. CGRPPBN neurons are also activated during consumption of novel foods or by an auditory cue that has previously been paired with electrical footshocks. Correspondingly, silencing of CGRPPBN neurons attenuates the expression of food neophobia and conditioned fear responses. Therefore, in addition to transducing primary sensory danger signals, CGRPPBN neurons promote affective-behavioural states that limit harm in response to potential threats.
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Aprendizagem da Esquiva/fisiologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Medo/fisiologia , Neurônios/metabolismo , Núcleos Parabraquiais/citologia , Animais , Sinalização do Cálcio , Condicionamento Clássico/fisiologia , Dieta Hiperlipídica , Eletrochoque , Medo/psicologia , Resposta ao Choque Térmico , Lipopolissacarídeos/farmacologia , Masculino , Rememoração Mental/fisiologia , Camundongos , Dor/psicologia , Núcleos Parabraquiais/fisiologia , Prurido , Resposta de Saciedade/fisiologiaRESUMO
Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.
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Infecções Urinárias , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Infecções Urinárias/imunologia , Infecções Urinárias/terapia , Animais , Humanos , Camundongos , Escherichia coli , Feminino , Extratos Celulares/farmacologia , Extratos Celulares/uso terapêutico , Lisados BacterianosRESUMO
Risk and uncertainty are central concepts of decision neuroscience. However, a comprehensive review of the literature shows that most studies define risk and uncertainty in an unclear fashion or use both terms interchangeably, which hinders the integration of the existing findings. We suggest uncertainty as an umbrella term that comprises scenarios characterized by outcome variance where relevant information about the type and likelihood of outcomes may be somewhat unavailable (ambiguity) and scenarios where the likelihood of outcomes is known (risk).These conceptual issues are problematic for studies on the temporal neurodynamics of decision-making under risk and ambiguity, because they lead to heterogeneity in task design and the interpretation of the results. To assess this problem, we conducted a state-of-the-art review of ERP studies on risk and ambiguity in decision-making. By employing the above definitions to 16 reviewed studies, our results suggest that: (a) research has focused more on risk than ambiguity processing; (b) studies assessing decision-making under risk often implemented descriptive-based paradigms, whereas studies assessing ambiguity processing equally implemented descriptive- and experience-based tasks; (c) descriptive-based studies link risk processing to increased frontal negativities (e.g., N2, N400) and both risk and ambiguity to reduced parietal positivities (e.g., P2, P3); (d) experience-based studies link risk to increased P3 amplitudes and ambiguity to increased frontal negativities and the LPC component; (e) both risk and ambiguity processing seem to be related with cognitive control, conflict monitoring, and increased cognitive demand; (f) further research and improved tasks are needed to dissociate risk and ambiguity processing.
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BACKGROUND: Low areal bone mineral density (BMD), increased fracture risk and altered bone remodeling have been described among stone formers (SFs), but the magnitude of these findings differs by age, sex, menopausal status and urinary calcium (uCa). This study aimed to investigate volumetric BMD (vBMD), bone microarchitecture and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in young SFs, irrespective of calciuria, further distinguishing trabecular from cortical compartments. METHODS: HR-pQCT/FEA was performed at the distal tibia (DT) and distal radius (DR) in 106 SFs (57 males and 49 premenopausal females; median age 37 years) and compared with 106 non-SFs (NSFs) retrieved from an existing database, matched for age, sex and body mass index (BMI). Biochemical/hormonal serum and urinary parameters were obtained from SFs. RESULTS: SFs exhibited significantly lower trabecular number (TbN) and higher trabecular separation (TbSp) than NSFs at both anatomical sites and lower cortical porosity in the DR. In a subgroup analysis separated by sex, female SFs presented significantly lower TbvBMD, relative bone volume fraction (BV/TV) and TbN and higher TbSp than NSFs at both sites, while male SFs showed significantly lower stiffness and failure load. Multivariate analysis showed TbN to be independently associated with sex and BMI at both sites and with uCa at the DR. CONCLUSIONS: The present findings suggest that bone disease represents an early event among SFs, associated at least in part with calcium excretion and mainly characterized by trabecular bone microarchitecture impairment, especially among women, but with reduced bone strength parameters in men.
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Doenças Ósseas Metabólicas , Cálculos Renais , Feminino , Masculino , Humanos , Adulto , Densidade Óssea , Estudos Transversais , Cálcio , Absorciometria de FótonRESUMO
Cosmocercoides Wilkie, 1930 are gastrointestinal parasites commonly found in amphibians and reptiles, with 4 species reported from the Neotropical region. In the present study, a new species of Cosmocercoides, namely Cosmocercoides amapari n. sp. is described using integrated approaches such as light and scanning microscopy, and DNA sequencing of the mitochondrial cytochrome c oxidase subunit 1 gene. The specimens were collected from the large intestine of 3 species of hylid frogs in Amapá, Brazil. The new species can be distinguished from its congeners by morphological traits, including the pattern of caudal papillae, absence of the gubernaculum, 2 poorly sclerotized spicules, presence of lateral alae and somatic papillae along the body. In addition, our molecular analyses and phylogenetic reconstructions strongly support the status of the new taxon, which clustered poorly with a large clade of Cosmocerca spp. Cosmocercoides amapari n. sp. is the 29th species of the genus, the 5th from the Neotropical region, the third reported in Brazil, the second described from the Amazon region and the first belonging to the Neotropical region with molecular data.
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Ascaridídios , Nematoides , Parasitos , Animais , Brasil , Filogenia , Anuros/parasitologia , Ascaridídios/genética , Ascaridídios/anatomia & histologiaRESUMO
Maintaining energy homeostasis requires coordinating physiology and behavior both on an acute timescale to adapt to rapid fluctuations in caloric intake and on a chronic timescale to regulate body composition. Hypothalamic agouti-related peptide (AgRP)-expressing neurons are acutely activated by caloric need, and this acute activation promotes increased food intake and decreased energy expenditure. On a longer timescale, AgRP neurons exhibit chronic hyperactivity under conditions of obesity and high dietary fat consumption, likely due to leptin resistance; however, the behavioral and metabolic effects of chronic AgRP neuronal hyperactivity remain unexplored. Here, we use chemogenetics to manipulate Gq signaling in AgRP neurons in mice to explore the hypothesis that chronic activation of AgRP neurons promotes obesity. Inducing chronic Gq signaling in AgRP neurons initially increased food intake and caused dramatic weight gain, in agreement with published data; however, food intake returned to baseline levels within 1 wk, and body weight returned to baseline levels within 60 d. Additionally, we found that, when mice had elevated body weight due to chronic Gq signaling in AgRP neurons, energy expenditure was not altered but adiposity and lipid metabolism were both increased, even under caloric restriction. These findings reveal that the metabolic and behavioral effects of chronic Gq signaling in AgRP neurons are distinct from the previously reported effects of acute Gq signaling and also of leptin insensitivity.
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Proteína Relacionada com Agouti/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Obesidade/metabolismo , Adiposidade/efeitos dos fármacos , Animais , Peso Corporal , Restrição Calórica , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Energia , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Feminino , Homeostase/efeitos dos fármacos , Hipotálamo/metabolismo , Leptina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/metabolismo , Obesidade/fisiopatologia , Transdução de Sinais , Aumento de Peso/efeitos dos fármacosRESUMO
Shellfish-growing areas in rural catchments are occasionally affected by elevated faecal contamination from diffuse sources and may be subject to frequent harvest closures/classification downgrades. We combined traditional risk management methods based on sanitary surveys and monitoring of Escherichia coli in seawater and shellfish with faecal source tracking, bacterial source apportionment, and hydrometeorological modelling to determine the causes of elevated E. coli concentrations contributing to harvest closures in Papanui Inlet (Aotearoa New Zealand). These multiple lines of evidence were used to inform a weight of evidence assessment of bacterial contamination in the inlet. Ruminant livestock was estimated to contribute 80% of the faecal coliform loading. Concentrations of E. coli in seawater were low (≤ 87 MPN 100 ml-1) whilst concentrations in tuaki/cockles/little neck clams (Austrovenus stutchburyi) occasionally exceeded the "Approved" classification limit (230 MPN 100 g-1). The most frequent positive genetic markers in seawater were the seagull (Catellicoccus marimammalium) (54% of seawater samples), and in shellfish, the bovine and seagull markers (both 12.5% of shellfish samples). Solar radiation was negatively correlated with E. coli in tuaki. We found that the growing area is affected by faecal inputs from animal and, to a lesser extent, human (septic tank discharges) sources which elevate contamination to levels detectable in tuaki but not in seawater, particularly in the summer months. The innovative approach can enhance the management of shellfish-growing areas affected by intermittent contamination and enables more targeted action to reduce pollution to improve shellfish water quality.
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Bivalves , Escherichia coli , Animais , Bovinos , Humanos , Monitoramento Ambiental , Microbiologia da Água , Frutos do Mar/microbiologia , Bactérias , Fezes/microbiologia , Qualidade da ÁguaRESUMO
In this study, the genomes of two lytic bacteriophages, vB_EcoS-phiEc3 and vB_EcoS-phiEc4, were sequenced and characterized using bioinformatics approaches. Whole-genome analysis showed that both phages belonged to the Kagunavirus genus, Guernseyvirinae subfamily and Siphoviridae family. Moreover, their genomes had 45, 288 bp and 44,540 bp, and G + C content of 48.42% and 50.04%, respectively. The genome of vB_EcoS-phiEc3 harbored 80 protein coding sequences (CDSs), whereas vB_EcoS-phiEc4 harbored 75 CDSs. Among them, 50 CDSs in vB_EcoS-phiEc3 and 44 CDSs in vB_EcoS-phiEc4 were considered as functional genes. Their lytic activity against multidrug-resistant uropathogenic Escherichia coli (UPEC) strains, as well as the absence of antibiotic resistance genes, lysogenic and virulence genes, enable vB_EcoS-phiEc3 and vB_EcoS-phiEc4 as a safe therapy option against UPEC infections.
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Bacteriófagos , Infecções por Escherichia coli , Siphoviridae , Escherichia coli Uropatogênica , Bacteriófagos/genética , Genoma Viral , Humanos , Siphoviridae/genética , Escherichia coli Uropatogênica/genéticaRESUMO
OBJECTIVES: To evaluate the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) in patients with and without prior coronary artery bypass graft (CABG) surgery. BACKGROUND: Data on the outcomes of CTO PCI in patients with versus without CABG remains limited and with scarce representation from developing regions like Latin America. METHODS: We evaluated patients undergoing CTO PCI in 42 centers participating in the LATAM CTO registry between 2008 and 2020. Statistical analyses were stratified according to CABG status. The outcomes of interest were technical and procedural success and in-hospital major adverse cardiac and cerebrovascular events (MACCE). RESULTS: A total of 1662 patients were included (n = 1411 [84.9%] no-CABG and n = 251 [15.1%] prior-CABG). Compared with no-CABG, those with prior-CABG were older (67 ± 11 vs. 64 ± 11 years; p < 0.001), had more comorbidities and lower left ventricular ejection fraction (52.8 ± 12.8% vs. 54.4 ± 11.7%; p = 0.042). Anatomic complexity was higher in the prior-CABG group (J-CTO score 2.46 ± 1.19 vs. 2.10 ± 1.22; p < 0.001; PROGRESS CTO score 1.28 ± 0.89 vs. 0.91 ± 0.85; p < 0.001). Absence of CABG was associated with lower risk of technical and procedural failure (OR: 0.60, 95% CI: 0.43-0.85 and OR: 0.58, 95% CI: 0.40-0.83, respectively). No significant differences in the incidence of in-hospital MACCE (3.8% no-CABG vs. 4.4% prior-CABG; p = 0.766) were observed between groups. CONCLUSION: In a contemporary multicenter CTO-PCI registry from Latin America, prior-CABG patients had more comorbidities, higher anatomical complexity, lower success, and similar in-hospital adverse event rates compared with no-CABG patients.
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Oclusão Coronária , Intervenção Coronária Percutânea , Doença Crônica , Angiografia Coronária , Ponte de Artéria Coronária/efeitos adversos , Oclusão Coronária/diagnóstico por imagem , Oclusão Coronária/cirurgia , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Sistema de Registros , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Função Ventricular EsquerdaRESUMO
Topical formulations composed of API-pure crystals have been increasingly studied, especially in regards to the impact of particle size in penetration efficiency. Less attention, however, has been devoted to the solid-state properties of drugs delivered to the skin. In this study, we address the effect of formulation composition on the crystal form existing in topical products. Dapsone (DAP) gel formulations were prepared by mixing an organic solution containing DAP with an aqueous solution containing polymers and preservatives. The organic solvent was chosen as ethoxydiglycol (DEGEE), polyethylene glycol (PEG), or 1-methyl-2-pirrolidone (MPR) to assess the impact of composition on DAP crystal form. Such solvent variations resulted in different particulate matter. In terms of crystalline nature, the presence of DEGEE in formulations induced the crystallization of DAP hydrate, while PEG cocrystal and a mixture of hydrate and MPR solvate crystallized from the same amounts of PEG and MPR, respectively. Microscopic analysis of the gels showed heterogeneous particles with different characteristics. The behavior of gels after application to the skin was also tested. Interestingly, the different formulations seemed to accumulate in different regions of the skin. This could be the result of the effect of vehicle composition/excipients on the characteristics of the skin, such as hydration. The site-specific accumulation, however, was more pronounced in crystal-loaded gels as opposed to blank formulations. These results indicate that future studies should consider the effect of formulation composition on the API crystal form landscape as part of the strategies used to successfully target drug delivery to the skin.
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Dapsona , Excipientes , Sistemas de Liberação de Medicamentos , Excipientes/química , Géis , Polietilenoglicóis , Pele , SolventesRESUMO
PURPOSE: To understand the anomalous behavior of Saquinavir Mesylate (SQVM) in sodium decyl sulfate (SDS) medium during a dissolution test through a crystallographic analysis of the crystal obtained. As a result, it will be possible to elucidate its crystal structure and carry out a complete solid-state characterization of the API. METHODS: The solid form obtained was characterized by a structural analysis through X-ray single crystal and powder diffraction. The crystallographic structures of the new salt and the SQVM were compared. In addition, a complete solid-state characterization of SQVM raw material was carried out by techniques such as diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS), Raman spectroscopy, scanning electron microscopy and a dissolution method. RESULTS: A new salt consisting of SQVM and SDS was crystallized and its crystal structure was elucidated and reported herein for the first time. The anionic part of SDS interacts with the cationic segment of SQVM to obtain a new salt designated as SQV-DS, which precipitates. The main difference between the two structures occurs in the c-axis expansion, which increases from 15.966 (5) to 21.1924 (14), respectively. CONCLUSIONS: Some of the strategies to enhance the dissolution rate of poorly aqueous soluble APIs include the use of surfactants such as SDS in the dissolution medium, as well as in the formulated products. However, there have been constant reports of a dissolution rate slowdown by some surfactants. The interaction mechanisms between the APIs and the dissolution medium containing surfactants need to be carefully investigated in current pharmaceutical formulations. Graphical Abstract.
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Saquinavir , Sódio , Varredura Diferencial de Calorimetria , Preparações Farmacêuticas , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Sulfatos , Difração de Raios XRESUMO
Rhabdias Stiles and Hassal, 1905 comprises approximately 90 species of parasitic lung nematodes of amphibians and reptiles that have a wide distribution, with 21 species occurring in the Neotropics. In the present study, we describe Rhabdias waiapi n. sp. found parasitizing the lungs of the anuran species Pristimantis chiastonotus from the Amazon Biome in the Amapá State, Northern Brazil. The new species is characterized by having an elongated body, expansions of the cuticular inflation in the anterior end that become more discrete along the body, an anterior end with a slight constriction at the level of the esophageal apex with four rounded subapical elevations of the body wall, six lips, four near the edge of the oral opening and two more distant lateral ones, and a gradually tapering elongated tail. In addition, molecular analyses and phylogenetic reconstructions were made, with sequences from the coding region of the mitochondrial cytochrome c oxidase subunit I gene. Those results strongly support the status of the new taxon, which formed a poorly supported clade with Rhabdias sp. 5 from Anolis brasiliensis from Northeast Brazil. Rhabdias waiapi n. sp. is the 19th species of the genus described in the Neotropics for amphibians, the 10th in Brazil, the second described from hosts of the family Strabomantidae from the Neotropical region, and the first amphibian nematode species described in the Amapá State.
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Nematoides , Parasitos , Animais , Anuros , Brasil , Pulmão , FilogeniaRESUMO
This paper reviews recent literature on the abundance and distribution of faecal indicator bacteria and pathogens in shellfish production areas in the state of Santa Catarina, on the subtropical coast of Brazil. This state supplies > 95% of the national production of shellfish. Microbiological monitoring data were mapped using GIS and the results compared with those from other countries. Coastal human population is the main predictive parameter for faecal bacteria in the production areas. Temporal variations of the bacteria can also be predicted by solar radiation and rainfall. The prevalence of pathogens such as hepatitis A virus, human norovirus, Salmonella spp. and Vibrio spp. does not differ substantially from that in developed countries. The information reported here can be used to inform development of microbiological risk profiles for shellfish production areas.
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Aquicultura , Monitoramento Ambiental , Frutos do Mar , Brasil , Países em Desenvolvimento , Meio Ambiente , Monitoramento Ambiental/métodos , Fezes/microbiologia , Humanos , Prevalência , Frutos do Mar/microbiologia , Frutos do Mar/virologiaRESUMO
A new uniform distribution model, generalized powered uniform distribution (GPUD), which is based on incorporating the parameter k into the probability density function (pdf) associated with the power of random variable values and includes a powered mean operator, is introduced in this paper. From this new model, the shape properties of the pdf as well as the higher-order moments, the moment generating function, the model that simulates the GPUD and other important statistics can be derived. This approach allows the generalization of the distribution presented by Jayakumar and Sankaran (2016) through the new GPUD ( J - S ) distribution. Two sets of real data related to COVID-19 and bladder cancer were tested to demonstrate the proposed model's potential. The maximum likelihood method was used to calculate the parameter estimators by applying the maxLik package in R. The results showed that this new model is more flexible and useful than other comparable models.
RESUMO
BACKGROUND: Developing countries struggle to diagnose and treat ST-segment elevation myocardial infarction (STEMI) patients in a timely manner, and subsequent outcomes are suboptimal. METHODS: The Latin America Telemedicine Network (LATIN) functioned between 2013 to present in four countries-Brazil, Colombia, Mexico, and Argentina. A Hub and Spoke platform was developed to expand access to >100 million population for STEMI care. Patients were triaged at spokes that included small clinics and primary health care centers in remote South American locations. Three telemedicine command sites provided immediate 24/7 electrocardiogram diagnosis and teleconsultation of the STEMI process at 355 centers in four countries. RESULTS: LATIN Spokes (n = 313) screened up to 30,000 patients per month, and a total of 780,234 patients over the study period. Telemedicine experts diagnosed 8395 (1·1%) with STEMI, of which a total of 3872 (46·1%) were urgently treated at 47 Hubs. A total of 3015 patients (78%) were reperfused with percutaneous coronary intervention. Time-to-telemedicine diagnosis averaged 3·5 min. Average door-to-balloon time improved from 120 to 48 min during the study period and overall STEMI mortality was 5·2%. INTERPRETATION: Telemedicine transcends boundaries and enables access to millions of patients for STEMI care. With this initiative, LATIN has created a template for reducing disparities in STEMI management between developed and developing countries.
Assuntos
Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Telemedicina , Eletrocardiografia , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Resultado do TratamentoRESUMO
OBJECTIVES: This article aimed to compare the outcomes after hybrid revascularization with conventional coronary artery bypass grafting (CABG) surgery. BACKGROUND: The concept of hybrid coronary revascularization combines the advantages of CABG and percutaneous coronary intervention to improve the treatment of patients with complex multivessel disease. METHODS: The Myocardial hybrid revascularization versus coronary artERy bypass GraftING for complex triple-vessel disease-MERGING study is a pilot randomized trial that allocated 60 patients with complex triple-vessel disease to treatment with hybrid revascularization or conventional CABG (2:1 ratio). The primary outcome was the composite of all-cause death, myocardial infarction, stroke, or unplanned repeat revascularization at 2 years. RESULTS: Clinical and anatomical characteristics were similar between groups. After a mean follow-up of 802 ± 500 days, the primary endpoint rate was 19.3% in the hybrid arm and 5.9% in the CABG arm (p = NS). The incidence of unplanned revascularization increased over time in both groups, reaching 14.5 versus 5.9% in the hybrid and in the CABG groups, respectively (p = .4). Of note, in the hybrid group, there were no reinterventions driven by the occurrence of stent restenosis. CONCLUSIONS: Hybrid myocardial was feasible but associated with increasing rates of major adverse cardiovascular events during 2 years of clinical follow-up, while the control group treated with conventional surgery presented with low rates of complications during the same period. In conclusion, before more definitive data arise, hybrid revascularization should be applied with careful attention in practice, following a selective case-by-case indication.