Pancreatic cancer diagnosis and management: Has the time come to prick the bubble?

Pancreatic cancer (PC) is associated with poor prognosis and very dismal survival rates. The most effective possibility of cure is tumor resection, which is only possible in about 15% of patients diagnosed at early stages of disease progression. Recent whole-genome sequencing studies pointed genetic alterations in 12 core signaling pathways in PC. These observations hint at the possibility that the initial mutation in PC might appear nearly 20 years before any symptoms occur, suggesting that a large window of opportunity may exist for early detection. Biomarkers with the potential to identify pre-neoplastic disease or very early stages of cancer are of great promise to improve patient survival. The concept of liquid biopsy refers to a minimally invasive sampling and analysis of liquid biomarkers that can be isolated from body fluids, primarily blood, urine and saliva. A myriad of circulating molecules may be useful as tumor markers, including cell-free DNA (cfDNA), cell-free RNA (cfRNA), circulating tumor cells (CTC), circulating tumor proteins, and extracellular vesicles, more specifically exosomes. In this review, we discuss with more detail the potential role of exosomes in several aspects related to PC, from initiation to tumor progression and its applicability in early detection and treatment. Exosomes are small circulating extracellular vesicles of 50-150 nm in diameter released from the plasma membrane by almost all cells and exhibit some advantages over other biomarkers. Exosomes are central players of intercellular communication and they have been implicated in a series of biological process, including tumorigenesis, migration and metastasis. Several exosomal microRNAs and proteins have been observed to distinguish PC from benign pancreatic diseases and healthy controls. Besides their possible role in diagnosis, understanding exosomes functions in cancer has clarified the importance of microenvironment in PC progression as well as its influence in proliferation, metastasis and resistance to chemotherapy. Increasing knowledge on cancer exosomes provides valuable insights on new therapeutic targets and can potentially open new strategies to treat this disease. Continuous research is needed to ascertain the reliability of using exosomes and their content as potential biomarkers, so that, hopefully, in the near future, they will provide the opportunity for early diagnosis, treatment intervention and increase survival of PC patients.The Melo team is supported by the project NORTE-01-0145-FEDER-000029, Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF) and national funds through FCT—Foundation for Science and Technology IF/00543/2013/CP1184/CT0004, PTDC/BIM-ONC/2754/2014, POCI-01-0145-FEDER-32189 and Astrazeneca Foundation, FAZ Ciencia Award

Satisfaction of quality of care in a Pediatric Emergency Room

Objective: To evaluate the satisfaction index of pediatric patients' companions in relation to the quality of care provided in an emergency service. Methods: Cross-sectional and descriptive study conducted in a Pediatric Emergency Room of a teaching hospital with participation of 300 companions of pediatric patients. A validated instrument was offered to family members for their evaluation of the emergency service quality. Results: Pediatric patients' companions demonstrated satisfaction with the quality of care provided at the Pediatric Emergency Room. There was a significant statistical difference (p<0.05) in the satisfaction index of family members of children diagnosed with dermatological diseases and who received medications administered via rectal route, and those who sought the service because they considered it a reference or because they did not have health insurance. Conclusion: The family members surveyed are satisfied with the quality of care provided to their children in the emergency room service.Objetivo: Avaliar o índice de satisfação do acompanhante do paciente pediátrico com relação à qualidade do atendimento prestado em um serviço de emergência. Métodos: Pesquisa transversal e descritiva desenvolvida em um Pronto-Socorro Infantil de um hospital universitário, com a participação de 300 acompanhantes dos pacientes pediátricos. Utilizou-se um instrumento validado oferecido aos familiares para avaliar a qualidade do serviço de emergência. Resultados: Os acompanhantes dos pacientes pediátricos demonstraram satisfação com a qualidade de atendimento prestado pelo Pronto-Socorro Infantil. Registrou-se diferença estatística significativa (p<0,05) quanto ao índice de satisfação manifestado pelos familiares das crianças diagnosticadas com doenças dermatológicas, que receberam medicações administradas pela via retal e que procuraram o serviço por considerarem-no como referência ou por não possuírem plano de saúde. Conclusão: Os familiares pesquisados encontram-se satisfeitos no que se refere à qualidade de atendimento prestado às suas crianças no serviço de pronto-socorro.Univ Fed Sao Paulo, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilUniv Fed Sao Paulo, Escola Paulista Enfermagem, Sao Paulo, SP, BrazilWeb of Scienc

Effects of high temperature on survival, symbiotic performance and genomic modifications of bean nodulating Rhizobium strains.

High temperatures can affect the survival, establishment and symbiotic properties of Rhizobium strains. Bean nodulating Rhizobium strains are considered particularly sensitive because on this strains genetic recombinations and/or deletions occur frequently, thus compromising the use of these bacteria as inoculants. Rhizobium tropici and R. leguminosarum bv. phaseoli strains isolated from cerrado soils were exposed to thermal stress and the strains' growth, survival and symbiotic relationships as well as alterations in their genotypic and phenotypic characteristics were analysed. After successive thermal shocks at 45 degrees C for four hours, survival capacity appeared to be strain-specific, independent of thermo-tolerance and was more apparent in R. tropici strains. Certain R. leguminosarum bv. phaseoli strains had significant alterations in plant dry weight and DNA patterns obtained by AP-PCR method. Rhizobium tropici strains (with the exception of FJ2.21) were more stable than R. leguminosarum bv. phaseoli strains because no significant phenotypic alterations were observed following thermal treatments and they maintained their original genotypic pattern after inoculation in plants.

Development of antimicrobial protein-based polymers for biomedical applications

Inspired in naturally occurring fibrous proteins and composed of amino acid building blocks commonly found in structural proteins, protein-based polymers (PBPs) are a group of materials with unique chemical, physical and biological properties. Coventional recombinant DNA technology allows the biological synthesis of recombinant protein-based polymers (rPBPs) with precise control over its size and composition and the incorporation of functional bioactive domains such as antimicrobial peptides (AMPs). Owing to the unique balance between their mechanical properties, biocompatibility, biodegradability and thermostability, elastin-like recombinamers (ELRs) and silk-elastin like proteins (SELPs) are two of the most remarkable families of rPBP for biotechnological applications. Here, we describe the functionalization of a SELP and an ELR with different antimicrobial peptides that showed promising results against several Gram-positive and Gram-negative bacterial strains. This will provide the basis for the development of advanced biomaterials processed into different types of structures (e.g. hydrogels, films, fibers, particles) suitable for biomedical applications

Investigating engineered ribonucleoprotein particles to improve oral RNAi delivery in crop insect pests.

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In Vitro and In Silico Evaluation of Cholinesterase Inhibition by Alkaloids Obtained from Branches of Abuta panurensis Eichler

Alkaloids are natural products known as ethnobotanicals that have attracted increasing attention due to a wide range of their pharmacological properties. In this study, cholinesterase inhibitors were obtained from branches of Abuta panurensis Eichler (Menispermaceae), an endemic species from the Amazonian rainforest. Five alkaloids were isolated, and their structure was elucidated by a combination of 1D and 2D H-1 and C-13 NMR spectroscopy, HPLC-MS, and high-resolution MS: Lindoldhamine isomer m/z 569.2674 (1), stepharine m/z 298.1461 (2), palmatine m/z 352.1616 (3), 5-N-methylmaytenine m/z 420.2669 (4) and the N-trans-feruloyltyramine m/z 314.1404 (5). The compounds 1, 3, and 5 were isolated from A. panurensis for the first time. Interaction of the above-mentioned alkaloids with acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes was investigated in silico by molecular docking and molecular dynamics. The molecules under investigation were able to bind effectively with the active sites of the AChE and BChE enzymes. The compounds 1-4 demonstrated in vitro an inhibitory effect on acetylcholinesterase with IC50 values in the range of 19.55 mu M to 61.24 mu M. The data obtained in silico corroborate the results of AChE enzyme inhibition.Peer reviewe