A novel combination of CYP51A mutations confers pan-azole resistance in aspergillus fumigatus

The treatment of invasive and chronic aspergillosis involves triazole drugs. Its intensive use has resulted in the selection of resistant isolates, and at present, azole resistance in Aspergillus fumigatus is considered an emerging threat to public health worldwide. The aim of this work is to uncover the molecular mechanism implicated in the azole resistance phenotype of three Aspergillus fumigatus clinical strains isolated from an Argentinian cystic fibrosis patient under long-term triazole treatment. Strain susceptibilities were assessed, and CYP51A gene sequences were analyzed. Two of the studied Aspergillus fumigatus strains harbored the TR34- L98H allele. These strains showed high MIC values for all tested triazoles (>16.00μg/ml, 1.00 μg/ml, 1.00 μg/ml, and 2.00 μg/ml for itraconazole, isavuconazole, posaconazole, and voriconazole, respectively). The third strain had a novel amino acid change (R65K) combined with the TR34-L98H mutations. This new mutation combination induces a pan-azole MIC augment compared with TR34-L98H mutants (>16 μg/ml, 4.00μg/ml, 4.00μg/ml, and 8.00μg/ml for itraconazole, isavuconazole, posaconazole, and voriconazole, respectively). The strain harboring the TR34-R65K-L98H allele showed no inhibition halo when voriconazole susceptibility was evaluated by disk diffusion. The effect of these mutations in the azole-resistant phenotype was confirmed by gene replacement experiments. Transformants harboring the TR34-L98H and TR34-R65KL98H alleles mimicked the azole-resistant phenotype of the clinical isolates, while the incorporation of the TR34-R65K and R65K alleles did not significantly increase azole MIC values. This is the first report of the TR34-L98H allele in Argentina. Moreover, a novel CYP51A allele (TR34-R65K-L98H) that induces a pan-azole MIC augment is described.Fil: Macedo, Daiana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; ArgentinaFil: Brito Devoto, Tomás. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Pola, Santiago. Universidad de Buenos Aires; ArgentinaFil: Finquelievich, Jorge L.. Universidad de Buenos Aires; ArgentinaFil: Cuestas, María Luján. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones en Microbiología y Parasitología Médica. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones en Microbiología y Parasitología Médica; ArgentinaFil: Garcia Effron, Guillermo. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas; Argentin

Plan de negocio para la creación de una empresa que brinde un servicio basado en una plataforma de interacción humana dentro de un metaverso enfocado en el sector corporativo

El trabajo se centra en el desarrollo del proyecto para una plataforma de trabajo remoto en el metaverso, con la idea de cubrir las carencias de la no presencialidad y facilitar el desarrollo de habilidades para los empleados. La plataforma de metaverso ha sido diseñada desde el enfoque de microservicios para garantizar un rendimiento deseado. Se han utilizado diferentes herramientas para definir correctamente el público objetivo y poder así centrarse en las necesidades de este y crear un proyecto viable e innovador

Classification system for cardiorespiratory fitness based on a sample of the Brazilian population

Background: Peak oxygen consumption (VO2peak) is an important prognostic marker and its classification helps the cardiologist in the therapeutic decision-making process. The most commonly used cardiorespiratory fitness (CRF) classification has not been validated for the Brazilian population. Objective: To elaborate a CRF classification using a Brazilian sample and to compare it with the American Heart Association (AHA), Cooper and UNIFESP classifications. Methods: A total of 6,568 healthy subjects were analyzed through cardiopulmonary exercise testing (CPET). They were distributed by sex and the following age groups (years): 7-12, 13-19, 20-79 (per decades) and > 80 years. After measurement of the VO2peak, participants were distributed into quintiles of CRF in very poor, poor, moderate, high and very high (AEMA Table). The CRF classifications by AEMA, AHA, Cooper, and UNIFESP were compared using the Wilcoxon, Kappa and concordance percentages. Results: VO2peak presented an inverse and moderate correlation with age considering both sexes (R = -0.488, p < 0.001). All paired comparisons between CRF classification systems showed differences (p < 0.001) and disagreement percentage - AEMA versus AHA (k = 0.291, 56.7%), AEMA versus Cooper (k = 0.220, 62.4%) and AEMA versus UNIFESP (k = 0.201, 63.9 %). Conclusion: The AEMA table showed important discrepancies in the classification of CRF when compared to other tables widely used in our setting. Because it was obtained from a large sample of the Brazilian population, the AEMA table should be preferred over other classification systems in our population

Papel da extensão universitária para formação jurídica: visita ao Castelo Alto de Xangô

O presente trabalho objetiva apresentar discussão acerca da importância da extensão universitária para a formação dos estudantes de Direito, bem como da imersão destes no universo das religiões de matriz africana, de forma a capacitar os futuros operadores do Direito para o melhor exercício da profissão, despidos de estereótipos e preconceitos relacionados ao Candomblé. A metodologia utilizada foi multi-métodos; técnica de coleta de dados: aula de campo, questionário, revisão bibliográfica e entrevista semiestruturada. Como análise de dados, utilizou-se uma abordagem teórica e empírica das vivências. Por suporte teórico, o texto valeu-se de Severino (2017), Costa (2021), Caputo e Passos (2007), Gil (1999), Villani e Nascimento (2003), entre outros. Os resultados revelam que a experiência promoveu uma apreciação do Candomblé e destacou a importância da transmissão oral de conhecimento para a compreensão dos estudantes, bem como foi basilar para a desconstrução de preconceitos e ampliação do alcance universitário para formação de ponte sólida entre sociedade/universidade com os terreiros inseridos diretamente nesse processo

Pyoderma gangrenosum after trauma to the dorsum of the hand

Introduction: Cullen’s postoperative gangrene, also called pyoderma gangrenosum (PG) or sterile neutrophilic abscess, was first described in the medical literature by Cullen in 1924. Later Brusting et al., in 1930, described PG in more detail. Objective: To report a rare case of pyoderma gangrenosum (PG) in an extraneous limb that was triggered by blunt trauma to the dorsum of the hand. Discussion: A histopathological exam is not sufficient to diagnose PG, Therefore, a PG diagnosis is based on clinical evidence. The clinical presentation is variable and includes rare bullous, pustular and vegetative forms. Other rare forms of PG occur at sites of pathergy (20-30%), periostomal skin, the dorsum of the hand, the head and neck. PG can also be multisystemic and paraneoplastic. Conclusion: The appearance of sudden-onset PG is rare in the dorsum of the hand. It is important to classify PG’s clinical forms, and to establish associations between PG and underlying pathologies. It is also very important to avoid surgery during early PG. The many drugs used to treat PG, and the multiple patient responses, demonstrate the difficulty of standardizing treatment. Physicians may have to use an empirical approach to select the appropriate drug for each patient

Antibacterial composite membranes of polycaprolactone/gelatin loaded with zinc oxide nanoparticles for guided tissue regeneration

The bacterial colonization of absorbable membranes used for guided tissue regeneration (GTR), as well as their rapid degradation that can cause their rupture, are considered the major reasons for clinical failure. To address this, composite membranes of polycaprolactone (PCL) and gelatin (Gel) loaded with zinc oxide nanoparticles (ZnO-NPs; 1, 3 and 6 wt% relative to PCL content) were fabricated by electrospinning. To fabricate homogeneous fibrillar membranes, acetic acid was used as a sole common solvent to enhance the miscibility of PCL and Gel in the electrospinning solutions. The effects of ZnO-NPs in the physico-chemical, mechanical and in vitro biological properties of composite membranes were studied. The composite membranes showed adequate mechanical properties to offer a satisfactory clinical manipulation and an excellent conformability to the defect site while their degradation rate seemed to be appropriate to allow successful regeneration of periodontal defects. The presence of ZnO-NPs in the composite membranes significantly decreased the planktonic and the biofilm growth of the Staphylococcus aureus over time. Finally, the viability of human osteoblasts and human gingival fibroblasts exposed to the composite membranes with 1 and 3 wt% of ZnO-NPs indicated that those membranes are not expected to negatively influence the ability of periodontal cells to repopulate the defect site during GTR treatments. The results here obtained suggest that composite membranes of PCL and Gel loaded with ZnO-NPs have the potential to be used as structurally stable GTR membranes with local antibacterial properties intended for enhancing clinical treatments

Pododermatite séptica em bovinos: evolução clínica da fase inicial

This study aimed to describe the clinical signs of the initial phase of septic pododermatitis in thirty female girolando bovines under the same handling care from different farms in State of Goiás. Following the diagnosis, they were submitted to daily clinical examination of the hoofs during fifteen days. It was considered as the end of the initial phase the presence of fistula in interdigital space or when the observation time over. It was observed the farm's soil type and the period of the year (if rainy and dryness). During the disease evolution, edema and pain increased in progressive order until skin disruption and fistula formation. In 73,33%, the illness envolved the hind limbs. In 50,00% it was observed moderate edema and 26,67% intense edema in both limbs. Fistula occurred in 83,33% ill animals until sixth day, in 10% between seventh and eleventh days and in 6,67% of the cases it was't observed. Fistulation areas were middle point of interdigital space in 63,33%; dorsal region of interdigital space in 16,67% and in coronary corium of the abaxial region of the hoof in 10,00% and in palmar/plantar region between coronary cushion in 3,33% of cases. The septic pododermatitis showed the same clinical signs in farms considered in this study and in different periods of the year, differing in time and fistula site. The average time from diagnosis and fistulation was five days. The more commom site was the middle point of the interdigital space.Esse estudo objetivou caracterizar clinicamente a fase inicial da pododermatite séptica em bovinos. Foram utilizadas 30 fêmeas bovinas, Girolando, de propriedades rurais do Estado de Goiás, submetidas às mesmas condições de manejo. Após o diagnóstico, foram submetidas a exame clínico específico dos dígitos, diariamente, por um período de quinze dias. Considerou-se o término da fase inicial a presença de fístula no espaço interdigital ou quando se completava o período de observação. Foram identificados o tipo de solo e o período do ano (chuvoso e seco). Durante a evolução da doença, o edema e a sensibilidade intensificaram de forma progressiva. Em 73,33% dos casos, a enfermidade ocorreu no membro pélvico. Em 50,00% observou-se edema moderado e 26,67%, edema acentuado, considerando ambos os membros. A fistulação ocorreu em 83,33% animais doentes até o sexto dia, em 10% entre o sétimo e o décimo primeiro dia e em 6,67% não ocorreu. As áreas de fistulação ocorreram no ponto médio do espaço interdigital em 63,33%; na região dorsal do espaço interdigital em 16,67% e no cório-coronário da região abaxial do estojo córneo em 10,00% e na porção palmar/plantar entre os talões em 3,33% dos casos. A pododermatite séptica apresentou os mesmos sinais clínicos nas propriedades avaliadas e nos diferentes períodos do ano, variando apenas o tempo e o local de fistulação. O tempo médio transcorrido entre o diagnóstico e o a fistulação foi de cinco dias, sendo que o local de maior ocorrência foi o ponto médio do espaço interdigital

Prevalência de traumas em membros inferiores de pacientes atendidos pela fisioterapia no Hospital Regional de Ceilândia

Objetivos: verificar o perfil epidemiológico e a prevalência dos traumatismos de membros inferiores de pacientes atendidos por fisioterapeutas em um hospital público do Distrito Federal, demonstrando essa prevalência quanto à região anatômica, o tipo e o mecanismo de lesão e realizar uma análise da função muscular dos membros inferiores de dados de uma avaliação inicial. Método: Trata-se de um estudo descritivo transversal baseado na análise dos dados de fichas de avaliação realizadas durante o projeto Prevenção de Deformidades Ortopédicas em Pessoas com Deficiência Física do PET/Saúde Redes de Atenção à Saúde entre 2013 a 2015. Resultados: Foram analisadas no total 224 fichas, em que houve predomínio do sexo masculino (72,32%), idade média de 42,47±19,59 anos, etnia parda (43,30%), situação conjugal solteiro (40,63%), escolaridade de ensino fundamental completo (57,14%). A região anatômica mais acometida foi o fêmur (27,68%), a fratura (80,36%) foi o tipo de lesão mais prevalente, e o acidente de trânsito (43,75%) foi o mecanismo de lesão mais predominante. Quanto à função muscular avaliada inicialmente, no quadril e joelho houve prevalência de força muscular boa, no pé força muscular ruim e no hálux e artelhos função muscular regular

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery