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1.
Animals (Basel) ; 14(6)2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38539988

RESUMEN

Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. This narrative review aims to provide relevant detailed information on (1) the canine estrus cycle and its impact on canine diabetes mellitus (CDM) etiology and management, (2) the role of pyometra as a further cause of insulin resistance, and (3) useful individual therapeutic and preventive strategies. PRDM is recognized due to diestrus, exogenous progestogen exposure, pregnancy, and P4-production ovarian dysfunction. Pyometra represents additional inflammatory and septic negative influence on insulin sensitivity, and its diagnosis associated with CDM is therapeutically challenging. The estrus cycle's hormone fluctuations seem to modulate peripheric insulin sensibility by influencing insulin receptor (IR) affinity and its binding capacity, as well as modulating tyrosine kinase activity. Pyometra was shown to negatively influence IR compensatory mechanisms to insulin resistance causing glucose intolerance. Spaying and pregnancy termination may cause diabetes remission in PRDM cases in a median time of 10 days (1-51). Pharmacological annulment of progesterone effects may benefit patients unable to undergo surgery; however, remission chances are virtually null. The ALIVE (Agreeing Language in Veterinary Endocrinology) project proposed new criteria for CDM diagnoses and subclinical diabetes recognition. These new concepts may increase the frequency of a PRDM diagnosis and, even more, its relevance. Spaying represents a preventive measure against pyometra and PRDM that should be individually assessed in light of its recognized benefits and harms.

2.
Lancet Microbe ; 5(3): e282-e290, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38432234

RESUMEN

BACKGROUND: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology. METHODS: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates. FINDINGS: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade. INTERPRETATION: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil.


Asunto(s)
Sporothrix , Esporotricosis , Animales , Humanos , Esporotricosis/epidemiología , Esporotricosis/veterinaria , Esporotricosis/microbiología , Brasil/epidemiología , Filogenia , Brotes de Enfermedades , Genómica , Sporothrix/genética
3.
Antimicrob Agents Chemother ; 68(4): e0162023, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38385701

RESUMEN

Sporothrix brasiliensis is an emerging zoonotic fungal pathogen that can be difficult to treat. Antifungal susceptibility testing was performed on the mold phase of a convenience sample of 61 Sporothrix spp. isolates from human and cat sporotrichosis cases in Brazil using the Clinical and Laboratory Standards Institute standard M38. A bimodal distribution of azole susceptibility was observed with 50% (28/56) of S. brasiliensis isolates showing elevated itraconazole minimum inhibitory concentrations ≥16 µg/mL. Phylogenetic analysis found the in vitro resistant isolates were not clonal and were distributed across three different S. brasiliensis clades. Single nucleotide polymorphism (SNP) analysis was performed to identify potential mechanisms of in vitro resistance. Two of the 28 resistant isolates (MIC ≥16 mg/L) had a polymorphism in the cytochrome P450 gene, cyp51, corresponding to the well-known G448S substitution inducing azole resistance in Aspergillus fumigatus. SNPs corresponding to other known mechanisms of azole resistance were not identified in the remaining 26 in vitro resistant isolates.


Asunto(s)
Sporothrix , Esporotricosis , Humanos , Antifúngicos/farmacología , Azoles/farmacología , Brasil , Filogenia , Itraconazol/farmacología , Esporotricosis/tratamiento farmacológico , Pruebas de Sensibilidad Microbiana , Farmacorresistencia Fúngica/genética
4.
Nat Struct Mol Biol ; 30(12): 1936-1946, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37903907

RESUMEN

α5 subunit-containing γ-aminobutyric acid type A (GABAA) receptors represent a promising drug target for neurological and neuropsychiatric disorders. Altered expression and function contributes to neurodevelopmental disorders such as Dup15q and Angelman syndromes, developmental epilepsy and autism. Effective drug action without side effects is dependent on both α5-subtype selectivity and the strength of the positive or negative allosteric modulation (PAM or NAM). Here we solve structures of drugs bound to the α5 subunit. These define the molecular basis of binding and α5 selectivity of the ß-carboline, methyl 6,7-dimethoxy-4-ethyl-ß-carboline-3-carboxylate (DMCM), type II benzodiazepine NAMs, and a series of isoxazole NAMs and PAMs. For the isoxazole series, each molecule appears as an 'upper' and 'lower' moiety in the pocket. Structural data and radioligand binding data reveal a positional displacement of the upper moiety containing the isoxazole between the NAMs and PAMs. Using a hybrid molecule we directly measure the functional contribution of the upper moiety to NAM versus PAM activity. Overall, these structures provide a framework by which to understand distinct modulator binding modes and their basis of α5-subtype selectivity, appreciate structure-activity relationships, and empower future structure-based drug design campaigns.


Asunto(s)
Receptores de GABA-A , Ácido gamma-Aminobutírico , Receptores de GABA-A/metabolismo , Isoxazoles/farmacología
5.
Med Mycol ; 61(4)2023 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-36931889

RESUMEN

Candida haemulonii complex species can be multidrug-resistant and cause infections such as candidemia. This study determined the genetic relationship between isolates from Brazil and the United States through whole-genome sequencing and performed antifungal susceptibility testing to investigate drug resistance. Contrary to what is widely described, most isolates were susceptible to azoles. However, an atypical susceptibility profile was found in 50% of Candida pseudohaemulonii strains, including resistance to the three echinocandins. Isolates from both countries formed distinct clusters with wide genetic diversity. Isolates from three hospitals in Brazil were clonal and involved in candidemia cases, pointing to the importance of improving hospital infection control measures and molecular identification.


Candida haemulonii complex species is worldwide distributed, and this study aimed to evaluate the resistance to antifungal drugs in cases from Brazil and the United States, and also compare their genetic relationships. A total of 50 strains were studied; most of them from Brazil were from cases of bloodstream infections, while the strains from the United States came from cases of wounds and may be associated with diabetic patients. The vast majority of strains were resistant to amphotericin B, one of the most effective drugs, and susceptible to fluconazole. In addition, 50% of C. pseudohaemulonii strains were resistant to echinocandins. The strains from Brazil and the United States had no genetic relationship and formed two distinct groups. In three Brazilian hospitals, strains were clonal, indicating an intra-hospital transmission. Our findings contribute to guiding therapy in bloodstream fungal infections caused by C. haemulonii species and alerting for nosocomial transmission of this yeast complex species.


Asunto(s)
Antifúngicos , Candidemia , Estados Unidos , Animales , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candidemia/microbiología , Candidemia/veterinaria , Candida , Brasil/epidemiología , Variación Genética , Pruebas de Sensibilidad Microbiana/veterinaria , Farmacorresistencia Fúngica/genética
6.
Med Mycol ; 61(3)2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36893795

RESUMEN

Military women on active duty are exposed to constant physical and mental demands, which may predispose them to some infection risks, including vulvovaginal candidiasis (VVC), a pathology considered a global public health problem. To monitor the prevalent and emerging pathogens in VVC, this study aimed to evaluate the distribution of yeast species and their in vitro antifungal susceptibility profile. We studied 104 vaginal yeast specimens obtained during routine clinical examinations. The population was attended at the Medical Center of the Military Police, São Paulo, Brazil, and was divided into two groups: infected patients (VVC) and colonised patients. Species were identified by phenotypic and proteomic methods (MALDI-TOF MS) and susceptibility to eight antifungal drugs, including azoles, polyenes, and echinocandins, was determined using microdilution broth. Candida albicans stricto sensu was found to be the most frequently isolated species (55%), but we observed a considerable rate of other Candida species isolates (30%), including Candida orthopsilosis stricto sensu only in the infected group. There were also other rare genera such as Rhodotorula, Yarrowia, and Trichosporon (15%), of which Rhodotorula mucilaginosa was the most prevalent in both groups. Fluconazole and voriconazole had the highest activity against all species in both groups. Candida parapsilosis was the most susceptible species, except for amphotericin-B in the infected group. Of note, we observed unusual resistance in C. albicans. Our results have allowed us to compile an epidemiological database on the etiology of VVC to support the empirical treatment and improve the health care of military women.


Vulvovaginal candidiasis (VVC) is an infection caused by fungi, mainly Candida albicans. Our results show that fungi other than C. albicans can cause VVC. So, our findings may help to choose the most appropriate treatment, as some may be resistant, to improve the quality of life of military women.


Asunto(s)
Antifúngicos , Candidiasis Vulvovaginal , Femenino , Animales , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candidiasis Vulvovaginal/microbiología , Candidiasis Vulvovaginal/veterinaria , Estudios Transversales , Proteómica , Brasil/epidemiología , Candida albicans , Candida parapsilosis , Pruebas de Sensibilidad Microbiana/veterinaria , Farmacorresistencia Fúngica
7.
Med Mycol ; 61(3)2023 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-36807459

RESUMEN

Trichosporonosis corresponds to a systemic fungal disease that leads to high mortality rates and is frequently associated with medical devices. It affects immunosuppressed patients in particular and is strongly linked to acquired human immunodeficiency, organ and tissue transplants, and malignant hematologic diseases such as leukemia and lymphomas. Trichosporon infections have been increasingly reported worldwide; however, little information is available either about their characteristics or the causative microorganism. Thus, the aims of the present study were: to investigate 59 yeasts of the genus Trichosporon by verifying the biofilm formation capacity of isolates; to analyze the susceptibility patterns of planktonic cells against the antifungals fluconazole, itraconazole, amphotericin-B, voriconazole, and caspofungin by comparing European Committee for Antimicrobial Susceptibility Testing (EUCAST) broth microdilution technique with the commercial method Etest; and to assess the susceptibility patterns of biofilm cells (sessile) against the same antifungals through broth microdilution. The ability to form biofilm on the surface of polystyrene plates was noted for all isolates, and 54.3% of samples were considered strong producers. Comparison between the antifungal susceptibility techniques evidenced that Etest showed higher and discordant minimum inhibitory concentrations (MICs) from those obtained by the microdilution method, especially for fluconazole, itraconazole, and caspofungin. Considering the susceptibility of biofilms, most species had high MIC50 and MIC90 against the tested antifungals, showing 4-to-66-fold higher concentrations for amphotericin B and 2-to-33-fold greater concentrations for caspofungin. These results highlight the importance of further studies with Trichosporon spp. for comparison between laboratory findings and in vivo response, considering both the susceptibility tests and the behavior of biofilm cells against drugs.


This study investigated 59 isolates of the medically important yeast Trichosporon in relation to their ability to form biofilms and the susceptibility of biofilms to antifungal agents. All isolates were able to produce biofilms and biofilms showed lower antifungal susceptibility.


Asunto(s)
Trichosporon , Tricosporonosis , Humanos , Animales , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Fluconazol/farmacología , Caspofungina , Itraconazol , Anfotericina B/farmacología , Tricosporonosis/microbiología , Tricosporonosis/veterinaria , Biopelículas , Pruebas de Sensibilidad Microbiana/veterinaria
8.
J Plant Physiol ; 280: 153900, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36525838

RESUMEN

Although several aspects of lignin metabolism have been extensively characterized, the mechanism(s) by which lignin monomers are transported across the plasma membrane remains largely unknown. Biochemical, proteomic, expression and co-expression analyses from several plant species support the involvement of active transporters, mainly those belonging to the ABC superfamily. Here, we report on the genome-wide characterization of the ABCG gene subfamily in the model C4 grass Setaria viridis and further identification of the members potentially involved in monolignol transport. A total of 48 genes encoding SvABCGs were found in the S. viridis genome, from which 21 SvABCGs were classified as full-size transporters and 27 as half-size transporters. Comprehensive analysis of the ABCG subfamily in S. viridis based on expression and co-expression analyses support a role for SvABCG17 in monolignol transport: (i) SvABCG17 is orthologous to AtABCG29, a monolignol transporter in Arabidopsis thaliana; (ii) SvABCG17 displays a similar expression profile to that of lignin biosynthetic genes in a set of different S. viridis tissues and along the elongating internode; (iii) SvABCG17 is highly co-expressed with lignin-related genes in a public transcriptomic database; (iv) SvABCG17displays particularly high expression in the top of the S. viridis elongating internode, a tissue undergoing active lignification; (v) SvABCG17 mRNA localization coincides with the histochemical pattern of lignin deposition; and (vi) the promoter of SvABCG17 is activated by secondary cell wall-associated transcription factors, especially by lignin-specific activators of the MYB family. Further studies might reveal further aspects of this potential monolignol transporter, including its real substrate specificity and whether it works redundantly with other ABC members during S. viridis lignification.


Asunto(s)
Arabidopsis , Setaria (Planta) , Lignina/metabolismo , Setaria (Planta)/genética , Proteómica , Proteínas de Transporte de Membrana/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo
9.
J Chem Inf Model ; 62(23): 6094-6104, 2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36433835

RESUMEN

Force fields form the basis for classical molecular simulations, and their accuracy is crucial for the quality of, for instance, protein-ligand binding simulations in drug discovery. The huge diversity of small-molecule chemistry makes it a challenge to build and parameterize a suitable force field. The Open Force Field Initiative is a combined industry and academic consortium developing a state-of-the-art small-molecule force field. In this report, industry members of the consortium worked together to objectively evaluate the performance of the force fields (referred to here as OpenFF) produced by the initiative on a combined public and proprietary dataset of 19,653 relevant molecules selected from their internal research and compound collections. This evaluation was important because it was completely blind; at most partners, none of the molecules or data were used in force field development or testing prior to this work. We compare the Open Force Field "Sage" version 2.0.0 and "Parsley" version 1.3.0 with GAFF-2.11-AM1BCC, OPLS4, and SMIRNOFF99Frosst. We analyzed force-field-optimized geometries and conformer energies compared to reference quantum mechanical data. We show that OPLS4 performs best, and the latest Open Force Field release shows a clear improvement compared to its predecessors. The performance of established force fields such as GAFF-2.11 was generally worse. While OpenFF researchers were involved in building the benchmarking infrastructure used in this work, benchmarking was done entirely in-house within industrial organizations and the resulting assessment is reported here. This work assesses the force field performance using separate benchmarking steps, external datasets, and involving external research groups. This effort may also be unique in terms of the number of different industrial partners involved, with 10 different companies participating in the benchmark efforts.


Asunto(s)
Proteínas , Termodinámica , Ligandos , Proteínas/química , Fenómenos Físicos
10.
Artículo en Inglés | MEDLINE | ID: mdl-36118844

RESUMEN

Background: Cryptoccocal meningitis continues to present high incidence among AIDS patients. The treatment of choice is the synergistic combination of flucytosine (5-FC) with amphotericin B deoxycholate (AmBd) or its lipid formulations. However, 5-FC is unavailable in many countries and AmB demands hospitalization. The combination of AmB with the fungistatic fluconazole (FLC) or the use of high FLC daily doses alone became the choice. Nonetheless, sterilization of cerebrospinal fluid is delayed with FLC monotherapy, mainly with high fungal burden. These findings suggest the search for new antifungal compounds, such as liriodenine. Methods: Liriodenine antifungal activity was evaluated by three procedures: determining the minimum inhibitory concentration (MIC) on 30 strains of the Cryptococcus neoformans (C. neoformans) complex and 30 of the Cryptococcus gattii (C. gattii) complex, using EUCAST methodology and amphotericin B deoxycholate as control; performing the time-kill methodology in two strains of the C. neoformans complex and one of the C. gattii complex; and injury to cryptococcal cells, evaluated by transmission electron microscopy (TEM). Liriodenine absorption and safety at 0.75 and 1.50 mg.kg-1 doses were evaluated in BALB/c mice. Results: Liriodenine MICs ranged from 3.9 to 62.5 µg.mL-1 for both species complexes, with no differences between them. Time-kill methodology confirmed its concentration-dependent fungicidal effect, killing all the strains below the limit of detection (33 CFU.mL-1) at the highest liriodenine concentration (32-fold MIC), with predominant activity during the first 48 hours. Liriodenine induced severe Cryptococcus alterations - cytoplasm with intense rarefaction and/or degradation, injury of organelles, and presence of vacuoles. Liriodenine was better absorbed at lower doses, with no histopathological alterations on the digestive tract. Conclusion: The fungicidal activity confirmed by time-kill methodology, the intense Cryptococcus injury observed by TEM, the absorption after gavage administration, and the safety at the tested doses indicate that the liriodenine molecule is a promising drug lead for development of anticryptococcal agents.

12.
Rev. bras. enferm ; 75(supl.1): e20210069, 2022.
Artículo en Inglés | LILACS-Express | LILACS, BDENF - Enfermería | ID: biblio-1341100

RESUMEN

ABSTRACT Objective: to narrate the experience of facing a long economic and political crisis and the experience of the arrival process of the coronavirus pandemic in a Spanish healthcare center. Methods: this is a descriptive qualitative study with ethnographic analysis, with data collection through interviews, participant observation and field diary records. Results: the immersion in the context allowed us to identify two axes of domain: "The crisis, work in the community and the territory in Primary Care"; "The inevitability of being a nurse in facing a health crisis". Final considerations: the narrative portrays the ethics in field research, tensions and values of nursing work in crisis situations. Nurses' experiences are presented in narratives of dissatisfaction and difficulties, but with the support of values related to guaranteeing assistance to users and cooperation and solidarity in the collective organization of workers to face the COVID-19 crisis.


RESUMEN Objetivo: narrar la experiencia de afrontar una larga crisis económico-política y la experiencia del proceso de llegada de la pandemia de coronavirus en un centro sanitario español. Métodos: se trata de un estudio cualitativo descriptivo con análisis etnográfico, con recolección de datos a través de entrevistas, observación participante y registros de diario de campo. Resultados: la inmersión en el contexto permitió identificar dos ejes de dominio: "La crisis, el trabajo en la comunidad y el territorio en Atención Primaria"; "De la inevitabilidad de ser enfermero ante la crisis sanitaria". Consideraciones finales: la narrativa retrata la ética en la investigación de campo, las tensiones y los valores del trabajo de enfermería en situaciones de crisis. La experiencia de las enfermeras se presenta en narrativas de insatisfacción y dificultades, pero con el respaldo de valores relacionados con garantizar la asistencia a los usuarios y la cooperación y solidaridad en la organización colectiva de los trabajadores para enfrentar la crisis del COVID-19.


RESUMO Objetivo: narrar a experiência do enfrentamento de uma longa crise econômico-política e a vivência do processo da chegada da pandemia do coronavírus em um centro de saúde espanhol. Métodos: trata-se de estudo descritivo qualitativo com análise etnográfica, com coleta de dados por entrevistas, observação participante e registros em diário de campo. Resultados: a imersão no contexto permitiu identificar dois eixos de domínio: "a crise, o trabalho na comunidade e o território na Atenção Primária"; "da inevitabilidade do ser enfermeiro no enfrentamento da crise sanitária". Considerações finais: a narrativa retrata a ético na pesquisa de campo, tensões e valores do trabalho da enfermagem em conjuntura de crise. A experiência dos enfermeiros é trazida em narrativas de insatisfação e dificuldades, porém com a sustentação de valores relacionados à garantia da assistência aos usuários e de cooperação e solidariedade na organização coletiva dos trabalhadores para enfrentamento da crise da COVID-19.

13.
Rev Bras Enferm ; 75(suppl 1): e20210069, 2021.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-34669788

RESUMEN

OBJECTIVE: to narrate the experience of facing a long economic and political crisis and the experience of the arrival process of the coronavirus pandemic in a Spanish healthcare center. METHODS: this is a descriptive qualitative study with ethnographic analysis, with data collection through interviews, participant observation and field diary records. RESULTS: the immersion in the context allowed us to identify two axes of domain: "The crisis, work in the community and the territory in Primary Care"; "The inevitability of being a nurse in facing a health crisis". FINAL CONSIDERATIONS: the narrative portrays the ethics in field research, tensions and values of nursing work in crisis situations. Nurses' experiences are presented in narratives of dissatisfaction and difficulties, but with the support of values related to guaranteeing assistance to users and cooperation and solidarity in the collective organization of workers to face the COVID-19 crisis.


Asunto(s)
COVID-19 , Pandemias , Humanos , Atención Primaria de Salud , SARS-CoV-2 , España
14.
J Water Health ; 19(5): 724-735, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34665766

RESUMEN

The aim of this study was to investigate the occurrence of fungi in dialysis water and dialysate, in addition to evaluating the susceptibility to antifungals and the biofilm production capacity of isolated microorganisms. The samples were collected in three hemodialysis units in Bauru (Brazil), every 15 days (July 2017-June 2018) at post-reverse osmosis, reuse, and dialysate points. The fungi were isolated by spread plate on Sabouraud dextrose agar. Filamentous fungi were phenotypically identified and yeasts were subjected to molecular evaluation of the ITS region. Susceptibility test to antifungals was carried out by the broth microdilution method and biofilm production capacity was evaluated in microtiter plates using crystal violet staining. Fungi were isolated in 52/216 (24.1%) samples, with an average count of 16.3 (10-40) CFU/mL. Overall, 61 microorganisms were identified, with 54 (88.5%) filamentous fungi and 7 (11.5%) yeasts. The main genera included were Penicillium, Cladosporium, Scedosporium, Rhinocladiella, Fusarium, and Emmonsia. Most isolates showed high values of minimum inhibitory concentration for 5-flucytosine and fluconazole and 35/45 (77.8%) isolates were classified as strong producers of biofilm. In order to increase the safety of the dialysis process, the adoption of control measures and monitoring of fungi in hemodialysis fluids is suggested.


Asunto(s)
Antifúngicos , Soluciones para Diálisis , Antifúngicos/farmacología , Biopelículas , Diálisis , Hongos , Pruebas de Sensibilidad Microbiana , Diálisis Renal , Agua
15.
J Chem Theory Comput ; 17(10): 6262-6280, 2021 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-34551262

RESUMEN

We present a methodology for defining and optimizing a general force field for classical molecular simulations, and we describe its use to derive the Open Force Field 1.0.0 small-molecule force field, codenamed Parsley. Rather than using traditional atom typing, our approach is built on the SMIRKS-native Open Force Field (SMIRNOFF) parameter assignment formalism, which handles increases in the diversity and specificity of the force field definition without needlessly increasing the complexity of the specification. Parameters are optimized with the ForceBalance tool, based on reference quantum chemical data that include torsion potential energy profiles, optimized gas-phase structures, and vibrational frequencies. These quantum reference data are computed and are maintained with QCArchive, an open-source and freely available distributed computing and database software ecosystem. In this initial application of the method, we present essentially a full optimization of all valence parameters and report tests of the resulting force field against compounds and data types outside the training set. These tests show improvements in optimized geometries and conformational energetics and demonstrate that Parsley's accuracy for liquid properties is similar to that of other general force fields, as is accuracy on binding free energies. We find that this initial Parsley force field affords accuracy similar to that of other general force fields when used to calculate relative binding free energies spanning 199 protein-ligand systems. Additionally, the resulting infrastructure allows us to rapidly optimize an entirely new force field with minimal human intervention.


Asunto(s)
Benchmarking , Petroselinum , Ecosistema , Humanos , Ligandos , Conformación Molecular
16.
Rev Bras Enferm ; 74Suppl 1(Suppl 1): e20201310, 2021.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-34287572

RESUMEN

OBJECTIVE: to reflect on social control in health and the contributions that nursing can make to cope with the COVID-19 pandemic. METHODS: this is a theoretical reflection, elaborated from discussions based on literature and the experience of authors' performance in social control and in Primary Care. It is divided into two topics: the first, related to aspects of institutionalized social control; the second, related to the perspectives for nursing in this space. RESULTS: limits and relevant aspects for nurses' role in social control are presented, contributing to a perspective of praxis in health based on their ethical-political commitment and their technical competence in the coordination and management of care to face the pandemic. FINAL CONSIDERATIONS: nurses' role in social control favors the strengthening of the struggle for the right to life above profits, especially through popular participation in the community context in Primary Care.


Asunto(s)
COVID-19 , Pandemias , Humanos , Atención Primaria de Salud , SARS-CoV-2 , Control Social Formal
17.
Motrivivência (Florianópolis) ; 33(64): [1-14], Mar. 2021.
Artículo en Portugués | LILACS-Express | LILACS | ID: biblio-1248203

RESUMEN

Este estudo se propôs a analisar a produção acadêmica brasileira no campo da Educação Física acerca do futebol/futsal feminino afins de identificar quais os indícios científicos os estudos em questão apresentam. A pesquisa possui caráter qualitativo, já que opera uma Revisão Sistemática da Literatura (RSL). Como critério para a seleção dos periódicos, foram priorizados aqueles voltados para a área de Educação Física, com estratificação B e A segundo a avaliação da CAPES (Qualis) e publicados entre 2015 e 2020. No transcurso da pesquisa, doze artigos de seis revistas, na perspetiva quanti-qualitativa, foram analisados. Para proceder com a análise, foram criadas duas categorias: (i) aspectos históricos, sociais e culturais; (ii) performance e alto rendimento. O campo de pesquisa sobre futebol/futsal feminino destaca discussões sobre gênero, incentivos e preconceitos.


This study aimed to analyze the Brazilian academic production in the field of Physical Education about women's football / futsal, in order to identify what scientific evidence the studies in question present. A qualitative approach methodology was adopted, such as Systematic Literature Review (RSL), in which searches were concentrated on magazines focused on the area of Physical Education with stratification of B and A according to Qualis (CAPES) in the period from 2015 to 2020. In the course of the research, twelve articles from six journals, from a quanti-qualitative perspective, were analyzed. To proceed with the analysis, two categories were created: (i) historical, social and cultural aspects; (ii) performance and high performance. The women's football / futsal research field highlights discussions about gender, incentives and prejudices.


Este estudio tuvo como objetivo analizar la producción académica brasileña en el campo de la Educación Física sobre fútbol / fútbol sala femenino, con el fin de identificar qué evidencia científica presentan los estudios en cuestión. La investigación tiene un carácter cualitativo, ya que opera una Revisión sistemática de literatura (RSL). Como criterio para la selección de revistas, se dio prioridad a aquellos enfocados en el área de Educación Física, con estratificación B y A según la evaluación CAPES (Qualis) y publicados entre 2015 y 2020. En el curso de la investigación, doce artículos de seis revistas, desde una perspectiva cuantitativa, se analizaron. Para proceder con el análisis, se crearon dos categorías: (i) aspectos históricos, sociales y culturales; (ii) rendimiento y alto rendimiento. El campo de investigación de fútbol femenino / fútbol sala destaca las discusiones sobre género, incentivos y prejuicios.

18.
Curr Pharm Des ; 27(3): 367-382, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-32564744

RESUMEN

Mental disorders comprise diverse human pathologies, including depression, bipolar affective disorder, schizophrenia, and dementia that affect millions of people around the world. The causes of mental disorders are unclear, but growing evidence suggests that oxidative stress and the purine/adenosine system play a key role in their development and progression. Xanthine oxidase (XO) is a flavoprotein enzyme essential for the catalysis of the oxidative hydroxylation of purines -hypoxanthine and xanthine- to generate uric acid. As a consequence of the oxidative reaction of XO, reactive oxygen species (ROS) such as superoxide and hydrogen peroxide are produced and, further, contribute to the pathogenesis of mental disorders. Altered XO activity has been associated with free radical-mediated neurotoxicity inducing cell damage and inflammation. Diverse studies reported a direct association between an increased activity of XO and diverse mental diseases including depression or schizophrenia. Small-molecule inhibitors, such as the well-known allopurinol, and dietary flavonoids, can modulate the XO activity and subsequent ROS production. In the present work, we review the available literature on XO inhibition by small molecules and their potential therapeutic application in mental disorders. In addition, we discuss the chemistry and molecular mechanism of XO inhibitors, as well as the use of structure-based and computational methods to design specific inhibitors with the capability of modulating XO activity.


Asunto(s)
Productos Biológicos , Trastornos Mentales , Alopurinol , Humanos , Trastornos Mentales/tratamiento farmacológico , Ácido Úrico , Xantina Oxidasa
19.
Diabetes Res Clin Pract ; 171: 108587, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33307134

RESUMEN

COVID-19 has gravely threatened high-risk populations, such as people with diabetes and other noncommunicable diseases, leading to disproportionate hospitalizations and deaths worldwide. It is well documented from previous outbreaks that diabetes increases the risk for poor outcomes due to SARS infection. In the present review, we bring evidence that the country and global level health crisis caused by COVID-19 could have been avoided or extremely minimized if measures to protect high-risk populations were implemented timely. In addition to general lockdowns, testing, tracing, isolation and hygiene measures, other specific interventions for diabetes and comorbidities management were shown crucial to allow the continuation of care services during the pandemic. These interventions included: teleconsultation, digital remote education andmonitoring, e-prescriptions, medicine delivery options, mobile clinics, and home point-of-care tests. In conclusion, we recommend prompt actions to protect the most vulnerable groups, valuing knowledge and experiences from previous outbreaks and lessons learned during the COVID-19 pandemic, in order to shield communities, health systems and the global economy.


Asunto(s)
COVID-19/complicaciones , Salud Global , Enfermedades no Transmisibles/epidemiología , SARS-CoV-2/aislamiento & purificación , COVID-19/transmisión , COVID-19/virología , Comorbilidad , Humanos
20.
J Med Entomol ; 58(2): 900-905, 2021 03 12.
Artículo en Inglés | MEDLINE | ID: mdl-33300572

RESUMEN

Larval therapy (LT) is a therapeutic modality that uses larvae of necrophagous flies for the treatment of wounds. The use of this therapy presents several benefits, due to the action of the larvae that remove necrotic tissue selectively, exercising antimicrobial action, and promoting healing. There are situations in which LT proves to be the only or the best alternative for the patient, such as wounds infected by multidrug-resistant microorganisms or when treatment difficulties may lead to an indication for amputation. The purpose of this study was to compare the efficiency of LT, using larvae of Chrysomya megacephala, with that of antibiotic therapy in the treatment of cutaneous wounds infected with Pseudomonas aeruginosa. Twenty-four rabbits were used to perform the experiment, distributed in four groups: group 1, induced wound without bacterial infection; group 2, induced wound with bacterial infection; group 3, induced wound with bacterial infection and antibiotic therapy; group 4, induced wound with bacterial infection and LT. The macroscopic, microscopic, and statistical analyses indicated that LT was as effective as antibiotic therapy in wound healing.


Asunto(s)
Antibacterianos/uso terapéutico , Calliphoridae , Cicatrización de Heridas , Animales , Infecciones Bacterianas/tratamiento farmacológico , Larva , Pseudomonas aeruginosa , Conejos/microbiología
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