Aspergillus Species and Antifungals Susceptibility in Clinical Setting in the North of Portugal: Cryptic Species and Emerging Azoles Resistance in A. fumigatus

Aspergillus spp. are agents of a broad-spectrum of diseases among humans. Their growing resistance to azoles, the cornerstone in the management of human aspergillosis, is a worrisome problem around the world. Considering lack of data from Portugal on this topic, particularly from the northern region, a retrospective surveillance study was planned to assess frequency of cryptic Aspergillus species and azoles resistance. A total of 227 clinical isolates, mainly from the respiratory tract (92.1%), collected from three hospitals serving a population of about three million people, were studied for their epidemiology and antifungal susceptibility patterns determined by the E.DEF.9.3 protocol of EUCAST. Employing molecular methods, seven Aspergillus complexes were identified; Aspergillus fumigatus sensu stricto was the most frequent isolate (86.7%). A 7.5% prevalence of cryptic species was found; A. welwitschiae (A. niger complex-3.1%) and A. lentulus (A. fumigatus complex-2.2%) were the most frequent. Amongst cryptic species, it was found a percentage of resistance to voriconazole, posaconazole and isavuconazole of 47.1, 82.4, and 100%, respectively. Five A. fumigatus sensu stricto showed pan-azole resistance. Sequencing their cyp51A gene revealed the presence of one isolate with TR46/Y121F/T289A mutation and two isolates with TR34/L98H mutation. This study emphasizes the need to identify strains to the species level and to evaluate their antifungal susceptibility in all human originated Aspergillus spp. isolates, particularly those from invasive aspergillosis.This work was supported by Grant IN-PT-131-1755 from Gilead Sciences.info:eu-repo/semantics/publishedVersio

Cell therapy in pulmonary diseases: are there perspectives?

A terapia celular poderia ser conceituada de forma ampla e genérica como o emprego de células para tratamento de doenças. Apesar de um número não tão expressivo de relatos tendo o pulmão como objeto de estudo na terapia celular em pacientes humanos, há dados consistentes da literatura, tanto em humanos, quanto em modelos animais,que evidenciam a migração de células-tronco da medula óssea para o pulmão,em diferentes situações experimentais. Esses resultados forneceram o embasamento experimental para o emprego de células-tronco na regeneração do tecido pulmonar em modelos animais. Em nosso laboratório, vários projetos de pesquisa têm sido conduzidos com a finalidade de avaliar a resposta pulmonar (morfológica e funcional) ao tratamento com células-tronco adultas em camundongos com doença pulmonar obstrutiva crônica (DPOC) induzida experimentalmente. Os resultados obtidos, aliados àqueles de outros grupos de pesquisa, permitem aventar a possibilidade de aplicação, a curto prazo, da terapia celular em pacientes com DPOC. Em outra patologia pulmonar, fibrose cística (FC), cuja abordagem terapêutica com células-tronco apresenta aspectos particulares em relação às patologias pulmonares crônico-degenerativas, há avanços promissores e potencialmente interessantes; no entanto, os resultados podem ser considerados incipientes e deve-se assinalar, portanto, que a associação da terapia gênica e celular apresenta-se como uma alternativa possível, mas ainda muito distante quanto à sua consolidação e incorporação como opção terapêutica segura e eficaz em FC. Por outro lado, tendo por embasamento os resultados obtidos em modelos experimentais, é possível postular que a terapia celular com células-tronco hematopoéticas (ou de outras fontes) encerra perspectivas consistentes de aplicação em diversas outras patologias pulmonares humanas, especialmente em DPOC.Cell therapy can be briefly described as the use of cells in the treatment of diseases. Although the number of scientific reports involving lung and cell therapy in humans is not expressive, there are consistent data, both in humans and animal models. Experiments show the migration of bone marrow stem cells to the lung, in different situations. These results provide the experimental basis for the use of stem cells in the regeneration of the lung tissue in animal models. In our laboratory, several projects have been conducted aiming to evaluate the pulmonary response (morphological and functional) to treatment with adult stem cells in mice with experimentally induced chronic obstructive pulmonary disease. The results obtained, together with those from other research groups, allow us to consider the possibility of application, in the near future, of cell therapy in chronic obstructive pulmonary disease patients. For another disease, cystic fibrosis, cell therapy shows particular aspects in relation to other chronic degenerative pulmonary diseases. In this pathology, there are interesting and promising advances, however, the results are incipient and, thus, it must be said that the association between genetic and cell therapy appears to be a possibility, but still far from being consolidated and incorporated as a safe and effective therapeutic alternative in cystic fibrosis. On the other hand, based on the results obtained in experimental models, it is possible to postulate that cell therapy with hematopoietic stem cells (or from other sources) brings consistent application perspectives in several other human pulmonary diseases, especially in chronic obstructive pulmonary disease.CNPqFundunesp Fundação BiomaVal

INTERNET DAS COISAS E SEUS IMPACTOS POSITIVOS NO AMBIENTE EDUCACIONAL

A tecnologia está cada vez mais presente dentro das empresas como um ativo facilitador na busca e no compartilhamento de informações, por isso é necessário saber protegê-las, pois elas têm um grande valor no âmbito profissional. A partir dessa visão, desenvolveu-se esse trabalho com o objetivo de criar uma Política de Segurança da Informação para a instituição de ensino superior.  A necessidade da criação da política se deu a partir do resultado de uma pesquisa quantitativa em que foi possível identificar o baixo nível de maturidade por parte dos funcionários da instituição, no que diz respeito a segurança da informação. A política tem como objetivo proteger os ativos de tecnologia da instituição, determinando normas a serem seguidas para reduzir os incidentes resultantes da falta de proteção. DOI: https://doi.org/10.6084/m9.figshare.682880

Unicentric study of cell therapy in chronic obstructive pulmonary disease/pulmonary emphysema

Within the chronic obstructive pulmonary disease (COPD) spectrum, lung emphysema presents, as a primarily histopathologic feature, the destruction of pulmonary parenchyma and, accordingly, an increase in the airflow obstruction distal to the terminal bronchiole. Notwithstanding the significant advances in prevention and treatment of symptoms, no effective or curative therapy has been accomplished. In this context, cellular therapy with stem cells (SCs) arises as a new therapeutic approach, with a wide application potential. The purpose of this study is to evaluate the safety of SCs infusion procedure in patients with advanced COPD (stage IV dyspnea). After selection, patients underwent clinical examination and received granulocyte colony-stimulating factor, immediately prior to the bone marrow harvest. The bone marrow mononuclear cells (BMMC) were isolated and infused into a peripheral vein. The 12-month follow-up showed a significant improvement in the quality of life, as well as a clinical stable condition, which suggest a change in the natural process of the disease. Therefore, the proposed methodology in this study for BMMC cell therapy in sufferers of advanced COPD was demonstrated to be free of significant adverse effects. Although a larger sample and a greater follow-up period are needed, it is possible to infer that BMMC cell therapy introduces an unprecedented change in the course or in the natural history of emphysema, inhibiting or slowing the progression of disease. This clinical trial was registered with ClinicalTrials.gov (NCT01110252) and was approved by the Brazilian National Committee of Ethics in Research (registration no. 14764, CONEP report 233/2009)

Corpus Callosum Microstructural Changes Correlate with Cognitive Dysfunction in Early Stages of Relapsing-Remitting Multiple Sclerosis: Axial and Radial Diffusivities Approach

The corpus callosum is the largest fiber bundle in the central nervous system and it takes part in several cognitive pathways. It can be affected by multiple sclerosis (MS) early in the disease. DTI is capable of infering the microstructural organization of the white matter. The vectorial analysis of the DTI offers the more specific indices of axial diffusivity (AD) and radial diffusivity (RD), which have shown to be useful to discriminate myelin damage from axon loss, respectively. This study presents DTI results (mean diffusivity (MD), fractional anisotropy (FA), RD, and AD) of 23 relapsing-remitting MS patients and its correlation with cognitive performance. There were 47.8% of cognitive impaired patients (MS CI). We found signs of demyelination, reflected by increased RD, and incipient axon loss, reflected by AD increase, which was slightly higher in the MS CI. The cognitive changes correlated with the DTI parameters, suggesting that loss of complexity in CC connections can impair neural conduction. Thus, cognitive impairment can be related to callosal disconnection, and DTI can be a promising tool to evaluate those changes

Panoramic and skull imaging may aid in the identification of multiple myeloma lesions

The purpose of this study was to investigate the presence of punched-out lesions in craniofacial bones using three different radiographic protocols in a large cohort of patients. One hundred fifty-five MM patients were evaluated using panoramic and skull (frontal and lateral) radiographs, which were performed in all patients at the time of MM diagnosis. The diagnostic potential for detecting punched-out lesions was compared among the radiographic techniques. MM punched-out lesions were identified in 135 (87%) panoramic radiographs, 141 (91%) frontal and 144 (93%) lateral skull radiographs. Punched out-lesions were synchronously present in skull and jawbones in 129 (83.23 %) cases. The lesions were detected exclusively in skull in 18 (11.61%) cases and exclusively in jawbones in 6 (3.87%) cases. Punched out-lesion mainly affected the skull and the jawbones in a synchronous way (p<0.001) rather than separately. All investigated radiographic techniques (panoramic, frontal and lateral skull approaches) demonstrated high detection rates for MM punched-out lesions in craniofacial bones. Panoramic radiography may aid to the radiographic protocols to identify multiple myeloma bone lesions

New localities and lineages of the Atlas dwarf lizard Atlantolacerta andreanskyi identified using mitochondrial DNA markers

Atlantolacerta andreanskyi (Werner, 1929) is an endemic lizard from the High Atlas Mountains region of Morocco. A previous molecular assessment of this species using mitochondrial and nuclear DNA markers uncovered extensive genetic diversity with seven lineages indicative of a species complex. A morphological assessment of six of these lineages did not establish simple diagnostic features, and proposed these should be considered as a cryptic species, while highlighting the need for greater sampling across the range. In this study, we sampled 8 individuals from 5 previously unsampled localities and carried out genetic analyses to compare these populations to the known variation. Phylogenetic reconstruction based on mitochondrial DNA markers (12S rRNA and ND4) corroborates the previously described lineages and identified a new one. Interestingly, the two samples that account for this newly identified lineage have been collected from distinct localities – M’goun and Toumliline – that form a sister taxon to the population of Jbel Azourki

The effect of lesion filling on brain network analysis in multiple sclerosis using structural magnetic resonance imaging

BACKGROUND: Graph theoretical network analysis with structural magnetic resonance imaging (MRI) of multiple sclerosis (MS) patients can be used to assess subtle changes in brain networks. However, the presence of multiple focal brain lesions might impair the accuracy of automatic tissue segmentation methods, and hamper the performance of graph theoretical network analysis. Applying "lesion filling" by substituting the voxel intensities of a lesion with the voxel intensities of nearby voxels, thus creating an image devoid of lesions, might improve segmentation and graph theoretical network analysis. This study aims to determine if brain networks are different between MS subtypes and healthy controls (HC) and if the assessment of these differences is affected by lesion filling. METHODS: The study included 49 MS patients and 19 HC that underwent a T1w, and T2w-FLAIR MRI scan. Graph theoretical network analysis was performed from grey matter fractions extracted from the original T1w-images and T1w-images after lesion filling. RESULTS: Artefacts in lesion-filled T1w images correlated positively with total lesion volume (r = 0.84, p < 0.001) and had a major impact on grey matter segmentation accuracy. Differences in sensitivity for network alterations were observed between original T1w data and after application of lesion filling: graph theoretical network analysis obtained from lesion-filled T1w images produced more differences in network organization in MS patients. CONCLUSION: Lesion filling might reduce variability across subjects resulting in an increased detection rate of network alterations in MS, but also induces significant artefacts, and therefore should be applied cautiously especially in individuals with higher lesions loads