Cell Wall Integrity Pathway Involved in Morphogenesis, Virulence and Antifungal Susceptibility in Cryptococcus neoformans

Due to its location, the fungal cell wall is the compartment that allows the interaction with the environment and/or the host, playing an important role during infection as well as in different biological functions such as cell morphology, cell permeability and protection against stress. All these processes involve the activation of signaling pathways within the cell. The cell wall integrity (CWI) pathway is the main route responsible for maintaining the functionality and proper structure of the cell wall. This pathway is highly conserved in the fungal kingdom and has been extensively characterized in Saccharomyces cerevisiae. However, there are still many unknown aspects of this pathway in the pathogenic fungi, such as Cryptococcus neoformans. This yeast is of particular interest because it is found in the environment, but can also behave as pathogen in multiple organisms, including vertebrates and invertebrates, so it has to adapt to multiple factors to survive in multiple niches. In this review, we summarize the components of the CWI pathway in C. neoformans as well as its involvement in different aspects such as virulence factors, morphological changes, and its role as target for antifungal therapies among others.This work was supported by Grant PID2020-114546RB-100 from the Spanish Ministry for Science and Innovation. De Oliveira H.C. was supported by Inova Fiocruz/Fundação Oswaldo Cruz. Rossi SA is funded by postdoctoral fellowship from Fundacão de Amparo á pesquisa do Estado de São Paulo (reference FAPESP-BEPE 2020/09919-0). García-Barbazán Iwas supported by a FPI fellowship (reference PRE2018-083436). Trevijano-Contador N is funded by a “Ayudas de Atracción de Talento Investigador” Contract of Community of Madrid (reference 2019-T2/BMD-14926).S

Identification of Off-Patent Compounds That Present Antifungal Activity Against the Emerging Fungal Pathogen Candida auris

Candida auris is an emerging fungal pathogen of great concern among the scientific community because it is causing an increasing number of hospital outbreaks of difficult management worldwide. In addition, isolates from this species frequently present reduced susceptibility to azole and echinocandin drugs. For this reason, it is necessary to develop new antifungal strategies to better control the disease caused by this yeast. In this work, we screened drugs from the Prestwick chemical library, which contains 1,280 off-patent compounds that are already approved by the Food and Drug Administration, with the aim of identifying molecules with antifungal activity against C. auris. In an initial screening, we looked for drugs that inhibited the growth of three different C. auris strains and found 27 of them which it did so. Ten active compounds were selected to test the susceptibility profile by using the EUCAST protocol. Antifungal activity was confirmed for seven drugs with MICs ranging from 0.5 to 64 mg/L. Some of these drugs were also tested in combination with voriconazole and anidulafungin at sub-inhibitory concentrations. Our results suggest synergistic interactions between suloctidil and voriconazole with fractional inhibitory concentration index (FICI) values of 0.11 to 0.5 and between ebselen and anidulafungin (FICI, 0.12 to 0.44). Our findings indicate that drug repurposing could be a viable alternative to managing infections by C. auris

Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals

Cryptococcus neoformans is an encapsulated pathogenic yeast that can change the size of the cells during infection. In particular, this process can occur by enlarging the size of the capsule without modifying the size of the cell body, or by increasing the diameter of the cell body, which is normally accompanied by an increase of the capsule too. This last process leads to the formation of cells of an abnormal enlarged size denominated titan cells. Previous works characterized titan cell formation during pulmonary infection but research on this topic has been hampered due to the difficulty to obtain them in vitro. In this work, we describe in vitro conditions (low nutrient, serum supplemented medium at neutral pH) that promote the transition from regular to titan-like cells. Moreover, addition of azide and static incubation of the cultures in a CO2 enriched atmosphere favored cellular enlargement. This transition occurred at low cell densities, suggesting that the process was regulated by quorum sensing molecules and it was independent of the cryptococcal serotype/species. Transition to titan-like cell was impaired by pharmacological inhibition of PKC signaling pathway. Analysis of the gene expression profile during the transition to titan-like cells showed overexpression of enzymes involved in carbohydrate metabolism, as well as proteins from the coatomer complex, and related to iron metabolism. Indeed, we observed that iron limitation also induced the formation of titan cells. Our gene expression analysis also revealed other elements involved in titan cell formation, such as calnexin, whose absence resulted in appearance of abnormal large cells even in regular rich media. In summary, our work provides a new alternative method to investigate titan cell formation devoid the bioethical problems that involve animal experimentation.OZ is funded by grant SAF2014-54336-R and SAF2017-86192-R1 from the Spanish Ministry for Economics, Industry and Competitivity. JA is funded by grants BFU2014-54591-C2-1-P and BFU2017-82574-P (Spanish Ministry for Economics, Industry and Competitivity) and an “Ajut 2014SGR-4” (Generalitat de Catalunya). NT-C was supported by a FPI fellowship (reference BES-2012-051837). SAR was supported by a fellowship from Coordenação de aperfeiçoamento de pessoal de nivel superior, CAPES, program Ciências Sem Fronteiras (202436/2015-2). HCdO is funded by postdoctoral fellowship from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP-BEPE 2016/20631-3). RG-R is funded by a "Juan de la Cierva" Contract from the Spanish Ministry for Economics, Industry and Competitivity (reference: IJCI-2015-25683). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

GAMMA RADIATION AS A METHOD FOR STERILIZATION OF ALL-IN-ONE ADMIXTURES BAGS FOR CLINICAL USE: A STUDY OF STABILITY

Objective: The aim of this work was to evaluate the stability of all-in-one (AIO) admixtures exposed to gamma irradiation sterilization.Methods: The samples were divided into four groups with 10 bags each: a) Group I: control samples (bags without sterilization or inoculation with microorganisms); b) Group II: bags sterilized by gamma irradiation; c) Group III: bags inoculated and then irradiated and, d) Group IV: bags only inoculated. The following studies were performed: macroscopic analysis of admixtures; physicochemical stability; degree of lipoperoxidation (LPO), and microbiological tests.Results: Gamma irradiation sterilization was 100% effective, since no irradiated sample showed growth of microorganisms. All groups exhibited similar particle size distribution, but a longer storage time led to a smaller percentage of large particles. In general, irradiated samples showed reduced LPO.Conclusion: Gamma irradiation sterilization of these admixtures can be extended to clinical practice, as it results in physicochemically stable admixtures

Levantamento Preliminar da Avifauna do Parque Ecológico do Basalto no Município de Araraquara/SP

O processo de urbanização vem modificando de maneira drástica a fisionomia dos ecossistemas, restando apenas pequenos fragmentos de áreas verdes, como praças, parques e terrenos baldios. Nesses ambientes ocorreu a redução dos recursos disponíveis para a manutenção da fauna e flora. O levantamento qualitativo da avifauna é uma interessante ferramenta para a avaliação de condições ambientais, pois, são suscetíveis a variações nos ecossistemas, devido ao alto grau de especificidade por espécie, no que diz respeito a território e habitat. Este levantamento teve por finalidade estabelecer uma lista preliminar da diversidade avifaunística do Parque Ecológico do Basalto, situado na região sudeste do Município de Araraquara-SP, obtendo importantes informações para o manejo e preservação da avifauna e para o seu estado de conservação. O levantamento ocorreu entre os meses de janeiro e outubro de 2005, totalizando 94 horas de observação. Foi utilizado o método de transecto onde, através de um percurso pré-determinado e com o auxílio de binóculos 7x35 e 10x50 e de fotografias e vocalizações registradas em campo e guias de campo, registramos 84 espécies de aves distribuídas em 28 famílias pertencentes a 13 ordens. Dentre estas aves registradas, 09 foram avistadas apenas sobrevoando o parque, ao contrário das outras 75 que foram vistas se alimentando e ou nidificando (16) dentro do parque. Para melhor explicitação dos dados, separamos as espécies nas seguintes guildas: fugívoras (13), insetívoras (44), nectívoras (04), carnívoras (06), granívoras (04), detritívoras (01) e onívoras (12). Esses dados preliminares revelam a importância da conservação do Parque Ecológico do Basalto para a manutenção das avifaunas que o adotaram como refúgio, por possuir os recursos como alimento, abrigo e locais para reprodução, em meio à urbanização e crescimento horizontal da cidade de Araraquara

AVALIAÇÃO DE CUSTOS DE DOIS MODELOS DE HARVESTER NO CORTE DE EUCALIPTO

http://dx.doi.org/10.5902/1980509815733The present study aimed to carry through the evaluation of costs of two models of harvester in the wood harvesting of Eucalyptus wood. The research evaluated the 6-year old tree fallen and processing, in the cut-to-length system for two models of harvester, in areas located in the cities of Conceição da Barra, Espírito Santo state and Caravelas, Bahia state. It was evaluated the models of harvester PC-228 SHO and PC-200 LC, of the Komatsu Mark. The information was collected during a period of 6 months, from March to August 2010, by the method of census. It was calculated the operational costs of the two models of harvester, for the countable method, which uses values in ‘Reais’, the Brazilian currency. It was conducted further analysis of cost sensitivity for the elements that contribute most to the final cost. We obtained the operating cost models for PC 200 and PC 228 of R$156,95 and R$ 168,84 per effective hour, respectively. In relation with the total operational costs, the most significant costs were: fuel, maintenance, and repairs/ depreciation, with 24.41%, 22.39% and 19.08%, respectively. In the sensitivity analysis, simulating a situation where the company gets a real economy of 10% in each one of these items, the same one will be able to get a reduction in the cost of production in 7%, for the two evaluated machines.http://dx.doi.org/10.5902/1980509815733O presente estudo teve o objetivo de realizar a avaliação de custos de dois modelos de harvester, na colheita de madeira de eucalipto. A pesquisa avaliou a derrubada e o processamento da árvore, com idade de 6 anos, no sistema de toras curtas, para dois modelos de harvester, em áreas localizadas nos municípios de Conceição da Barra – ES e Caravelas – BA. Avaliaram-se dois modelos de harvester, PC-228 SHO e PC-200 LC, da marca Komatsu. As informações foram coletadas durante um período de 6 meses, que compreende os meses de março a agosto de 2010, pelo método de censo. Calcularam-se os custos operacionais dos dois modelos de harvester, pelo método contábil, o qual utiliza valores estimados em reais. Realizou-se ainda a análise de sensibilidade de custos para os elementos que mais contribuem com o custo final. Obteve-se o custo operacional para os modelos PC 200 e PC 228 de R$156,95 e R$ 168,84 por hora efetiva, respectivamente. Em relação aos custos operacionais totais, os custos mais significativos foram: combustível, manutenção e reparos e depreciação, com 24,41%, 22,39% e 19,08%, respectivamente. Na análise de sensibilidade, simulando uma situação em que a empresa consiga uma economia real de 10% em cada um desses itens, a mesma poderá obter uma redução no custo de produção em 7%, para as duas máquinas avaliadas

EVALUATION OF COSTS OF TWO HARVESTER MODELS IN THE CUT OF Eucalyptus

O presente estudo teve o objetivo de realizar a avalia\ue7\ue3o de custos de dois modelos de harvester, na colheita de madeira de eucalipto. A pesquisa avaliou a derrubada e o processamento da \ue1rvore, com idade de 6 anos, no sistema de toras curtas, para dois modelos de harvester, em \ue1reas localizadas nos munic\uedpios de Concei\ue7\ue3o da Barra \u2013 ES e Caravelas \u2013 BA. Avaliaram-se dois modelos de harvester, PC-228 SHO e PC-200 LC, da marca Komatsu. As informa\ue7\uf5es foram coletadas durante um per\uedodo de 6 meses, que compreende os meses de mar\ue7o a agosto de 2010, pelo m\ue9todo de censo. Calcularam-se os custos operacionais dos dois modelos de harvester, pelo m\ue9todo cont\ue1bil, o qual utiliza valores estimados em reais. Realizou-se ainda a an\ue1lise de sensibilidade de custos para os elementos que mais contribuem com o custo final. Obteve-se o custo operacional para os modelos PC 200 e PC 228 de R$156,95 e R$ 168,84 por hora efetiva, respectivamente. Em rela\ue7\ue3o aos custos operacionais totais, os custos mais significativos foram: combust\uedvel, manuten\ue7\ue3o e reparos e deprecia\ue7\ue3o, com 24,41%, 22,39% e 19,08%, respectivamente. Na an\ue1lise de sensibilidade, simulando uma situa\ue7\ue3o em que a empresa consiga uma economia real de 10% em cada um desses itens, a mesma poder\ue1 obter uma redu\ue7\ue3o no custo de produ\ue7\ue3o em 7%, para as duas m\ue1quinas avaliadas.The present study aimed to carry through the evaluation of costs of two models of harvester in the wood harvesting of Eucalyptus wood. The research evaluated the 6-year old tree fallen and processing, in the cut-to-length system for two models of harvester, in areas located in the cities of Concei\ue7\ue3o da Barra, Esp\uedrito Santo state and Caravelas, Bahia state. It was evaluated the models of harvester PC-228 SHO and PC-200 LC, of the Komatsu Mark. The information was collected during a period of 6 months, from March to August 2010, by the method of census. It was calculated the operational costs of the two models of harvester, for the countable method, which uses values in \u2018Reais\u2019, the Brazilian currency. It was conducted further analysis of cost sensitivity for the elements that contribute most to the final cost. We obtained the operating cost models for PC 200 and PC 228 of R$156,95 and R$ 168,84 per effective hour, respectively. In relation with the total operational costs, the most significant costs were: fuel, maintenance, and repairs/ depreciation, with 24.41%, 22.39% and 19.08%, respectively. In the sensitivity analysis, simulating a situation where the company gets a real economy of 10% in each one of these items, the same one will be able to get a reduction in the cost of production in 7%, for the two evaluated machines

Dupla tarefa na doença de Parkinson: uma revisão de literatura / Dual tasks in Parkinson’s disease: a literature review

A Doença de Parkinson (DP) consiste em um transtorno neurodegenerativo crônico, causado pela degeneração de neurônios que sintetizam o neurotransmissor dopamina na região do cérebro denominada de núcleos da base, na área mais conhecida como substância negra, resultando na redução da quantidade de dopamina na região do corpo estriado, outra área cerebral.  O objetivo do presente trabalho consistiu em observar, através de uma revisão de literatura, os efeitos e os benefícios da dupla tarefa na doença de Parkinson. O formato escolhido foi o bases de dados SciELO (Scientific Electronic Library Online), Lilacs (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e PEDro (Bade de Dados em Evidências em Fisioterapia)., de uma revisão da literatura, com artigos dos últimos cinco anos provenientes das nos idiomas português, espanhol e inglês com ênfase nos seguintes descritores: Dupla Tarefa; Parkinson; Reabilitação; Fisioterapia. Os resultados destacaram melhorias em torno dos sintomas cognitivos e motores, favorecendo o equilíbrio, a marcha, desenvolvimento de habilidades de automatização, transferência de aprendizado, tempo de caminhada, diminuição do fenômeno de congelamento e atenuando significativamente o risco de quedas, de maneira que o paciente da DP tenha melhorias significativas acerca de sua qualidade de vida. Com o advento da fisioterapia no enfrentamento da Doença de Parkinson, as abordagens terapêuticas com ênfase na dupla tarefa contribuem de forma ímpar na reabilitação desses indivíduos

Antifungal Activity of Decyl Gallate against Several Species of Pathogenic Fungi

This work aims to demonstrate that the gallic acid structure modification to the decyl gallate (G14) compound contributed to increase the antifungal activity against several species of pathogenic fungi, mainly, Candida spp., Cryptococcus spp., Paracoccidioides spp., and Histoplasma capsulatum, according to standardized microdilution method described by Clinical Laboratory Standard Institute (CLSI) documents. Moreover this compound has a particularly good selectivity index value, which makes it an excellent candidate for broad-spectrum antifungal prototype and encourages the continuation of subsequent studies for the discovery of its mechanism of action

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit