Liquid biopsy for disease monitoring in non-small cell lung cancer: The link between biology and the clinic

Introduction: Cell-free DNA (cfDNA) analysis offers a non-invasive method to identify sensitising and resistance mutations in advanced Non-Small Cell Lung Cancer (NSCLC) patients. Next-generation sequencing (NGS) of circulating free DNA (cfDNA) is a valuable tool for mutations detection and disease' s clonal monitoring. Material and methods: An amplicon-based targeted gene NGS panel was used to analyse 101 plasma samples of advanced non-small cell lung cancer (NSCLC) patients with known oncogenic mutations, mostly EGFR mutations, serially collected at different clinically relevant time points of the disease. Results: The variant allelic frequency (VAF) monitoring in consecutive plasma samples demonstrated different molecular response and progression patterns. The decrease in or the clearance of the mutant alleles was associated with response and the increase in or the emergence of novel alterations with progression. At the best response, the median VAF was 0% (0.0% to 3.62%), lower than that at baseline, with a median of 0.53% (0.0% to 9.9%) (p = 0.004). At progression, the VAF was significantly higher (median 4.67; range: 0.0–36.9%) than that observed at the best response (p = 0.001) and baseline (p = 0.006). These variations anticipated radiographic changes in most cases, with a median time of 0.86 months. Overall, the VAF evolution of different oncogenic mutations predicts clinical outcomes. Conclusion: The targeted NGS of circulating tumour DNA (ctDNA) has clinical utility to monitor treatment response in patients with advanced lung adenocarcinoma.This work was supported by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation (POCI), Portugal 2020; and by FCT—Fundação para a Ciência e a Tecnologia/Ministério da Ciência, Tecnologia e Inovação in the framework of the projects “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274), and “Transferencia horizontal de resistencia à terapia: mudança de paradigma na monitorização de pacientes com cancro” (PTDC/DTPPIC/2500/2014); and by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), in the framework of the project NORTE-01-0145-FEDER-000029

A large‑scale comparison of reproduction and recruitment of the stalked barnacle Pollicipes pollicipes across Europe

Understanding large-scale spatial and temporal patterns of marine populations is a central goal in ecology, which has received renewed attention under climate change. However, few studies explore the large-scale dynamics of populations using standardized protocols and during the same time frames. We studied the phenology and intensity of reproduction and recruitment for the intertidal stalked barnacle Pollicipes pollicipes over an European scale and described their potential linkages with environmental variables. This species supports profitable fisheries in the Iberian Peninsula (Spain and Portugal). In Brittany (France), we had observed a significant lower reproductive effort (long non-breeding season, short breeding period in summer) and low values of recruitment intensity. This pattern may be related to the fact that Brittany corresponds to the northern limit of the distribution of this species in continental Europe. On the Iberian Peninsula, the most different region was Galicia (Spain), with Asturias (Spain) and SW Portugal being more similar. In Galicia, we have observed a contradictory pattern characterized by the absence of a non-breeding period and by a shorter recruitment season than observed in other Iberian regions. Our results suggest that air temperature, SST and chlorophyll-a might be related to the variability in reproduction and recruitment patterns of P. pollicipes. Moreover, spring and early summer upwelling in SW Portugal and Galicia might be inhibiting recruitment in this period. At the northern limit, the expected increase in performance under climate change might facilitate the recovery of populations after exploitation, increasing the resilience of the resource to fishing pressure

DISTRIBUTION OF DERMATOPHYTES FROM SOILS OF URBAN AND RURAL AREAS OF CITIES OF PARAIBA STATE, BRAZIL

SUMMARY The dermatophytes, keratinophilic fungi, represent important microorganisms of the soil microbiota, where there are cosmopolitan species and others with restricted geographic distribution. The aim of this study was to broaden the knowledge about the presence of dermatophytes in soils of urban (empty lots, schools, slums, squares, beaches and homes) and rural areas and about the evolution of their prevalence in soils of varying pH in cities of the four mesoregions of Paraiba State, Brazil. Soil samples were collected from 31 cities of Paraiba State. Of 212 samples, 62% showed fungal growth, particularly those from the Mata Paraibana mesoregion (43.5%), which has a tropical climate, hot and humid. Soil pH varied from 4.65 to 9.06, with 71% of the growth of dermatophytes occurring at alkaline pH (7.02 - 9.06) (ρ = 0.000). Of 131 strains isolated, 57.3% were geophilic species, particularly Trichophyton terrestre (31.3%) and Mycrosporum gypseum (21.4%). M. nanum and T. ajelloi were isolated for the first time in Paraiba State. The zoophilic species identified were T. mentagrophytes var. mentagrophytes (31.3 %) and T. verrucosum (7.6 %), and T. tonsurans was isolated as an anthropophilic species. The soils of urban areas including empty lots, schools, slums and squares of cities in the mesoregions of Paraiba State were found to be the most suitable reservoirs for almost all dermatophytes; their growth may have been influenced by environmental factors, soils with residues of human and/or animal keratin and alkaline pH

Percutaneous vertebroplasty in sheep: testing a novel mesoporous bioactive glass/calcium sulphate cement

Polymethylmethacrylate (PMMA) based cements are widely used for vertebroplasty. However, PMMA has disadvantages. To develop an innovative, resorbable and injectable composite cement – SpineGhost –, type III α-calcium sulphate hemihydrate was used as the bioresorbable matrix, while spraydried mesoporous bioactive particles were added for high bioactivity, and a zirconia containing glassceramic was added to increase radiopacity. An injectable paste was obtained by adding water. The purpose of the present work was to test in vivo the suitability of the novel injectable cement for percutaneous vertebroplasty. A sheep study was conducted, following a previously developed animal model. The paste was percutaneously injected in bone defects manually drilled percutaneously in L4 vertebral bodies of eight mature Merino sheep (Group B). A control group of eight sheep was injected with a known commercial calcium sulphate-based biphasic cement (Group A). Micro-CT overall mean tissue volume, an indicator of the injected defect volume, was 1.217±0.235 mL. All sheep survived and completed the 6-month implantation period. After sacrifice the samples were assessed by micro-CT and by histological, histormophometric and immunohistological studies. Cement resorption and new bone formation were observed in all samples with no signs of infection or inflammation