Secondary Endothelial Keratoplasty—A Narrative Review of the Outcomes of Secondary Corneal Endothelial Allografts

Background: We review the literature on the efficacy and safety outcomes of secondary Descemet stripping endothelial keratoplasty (DSEK) and Descemet membrane endothelial keratoplasty (DMEK). Methods: Literature search of English-written publications up to September 27, 2020 in PubMed database, using the terms "endothelial keratoplasty" in combination with keywords "secondary" or "repeat." In addition, we manually searched the references of the primary articles. Results: Twenty-seven studies (n = 651 eyes) were retained and reviewed, including 10 studies on repeat DSEK, 8 studies on repeat DMEK, 6 studies of DMEK following DSEK, and 3 studies of DSEK after failed DMEK. All studies reported significant improvement in visual acuity after secondary endothelial keratoplasty (EK). Twelve studies compared visual outcomes between primary and secondary EK, reporting conflicting findings. Sixteen studies reported endothelial cell loss rates after secondary EK, and only 1 study reported significantly increased endothelial cell loss rates compared with primary EK. Allograft rejection episodes occurred in 1.8% of eyes (range, 0%-50%). Six studies compared complication rates between primary and secondary EK eyes, and only 1 study found a higher median number of complications. However, 2 studies reported higher regraft failure rates compared with primary EK eyes. Conclusions: Secondary EK is surgically feasible and renders significant visual improvement after failed primary EK, although it is not clear whether visual outcomes and allograft survival are comparable with primary EK, raising the question of whether secondary EK eyes are "low risk" as primary EK eyes. Further larger, prospective studies are encouraged to obtain additional quality data on secondary corneal endothelial allotransplantation.info:eu-repo/semantics/publishedVersio

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

Targeted gene next-generation sequencing panel in patients with advanced lung adenocarcinoma: Paving the way for clinical implementation

Identification of targetable molecular changes is essential for selecting appropriate treatment in patients with advanced lung adenocarcinoma. Methods: In this study, a Sanger sequencing plus Fluorescence In Situ Hybridization (FISH) sequential approach was compared with a Next-Generation Sequencing (NGS)-based approach for the detection of actionable genomic mutations in an experimental cohort (EC) of 117 patients with advanced lung adenocarcinoma. Its applicability was assessed in small biopsies and cytology specimens previously tested for epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) mutational status, comparing the molecular changes identified and the impact on clinical outcomes. Subsequently, an NGS-based approach was applied and tested in an implementation cohort (IC) in clinical practice. Using Sanger and FISH, patients were classified as EGFR-mutated (n = 22, 18.8%), ALK-mutated (n = 9, 7.7%), and unclassifiable (UC) (n = 86, 73.5%). Retesting the EC with NGS led to the identification of at least one gene variant in 56 (47.9%) patients, totaling 68 variants among all samples. Still, in the EC, combining NGS plus FISH for ALK, patients were classified as 23 (19.7%) EGFR; 20 (17.1%) KRAS; five (4.3%) B-Raf proto-oncogene (BRAF); one (0.9%) Erb-B2 Receptor Tyrosine Kinase 2 (ERBB2); one (0.9%) STK11; one (0.9%) TP53, and nine (7.7%) ALK mutated. Only 57 (48.7%) remained genomically UC, reducing the UC rate by 24.8%. Fourteen (12.0%) patients presented synchronous alterations. Concordance between NGS and Sanger for EGFR status was very high (¿ = 0.972; 99.1%). In the IC, a combined DNA and RNA NGS panel was used in 123 patients. Genomic variants were found in 79 (64.2%). In addition, eight (6.3%) EML4-ALK, four (3.1%), KIF5B-RET, four (3.1%) CD74-ROS1, one (0.8%) TPM3-NTRK translocations and three (2.4%) exon 14 skipping MET Proto-Oncogene (MET) mutations were detected, and 36% were treatable alterations. Conclusions: This study supports the use of NGS as the first-line test for genomic profiling of patients with advanced lung adenocarcinoma.We acknowledge the work of the members of our department, especially doctors from the thoracic oncology unit, oncology and pulmonology nurses and, patients and their relatives. N. Martins would like to thank the Portuguese Foundation for Science and Technology (FCT-Portugal) for the Strategic project ref. UID/BIM/04293/2013 and "NORTE2020—Northern Regional Operational Program" (NORTE-01-0145-FEDER-000012)

Economic History and History of Economics: Complementary Approaches to Portuguese Economic Development

This chapter focuses on how the problems of economic development were addressed by the Portuguese historiography of the late nineteenth and twentieth centuries. The ensuing discussion benefits from the simultaneous consideration of two historiographical domains that complement each other: economic history and the history of economics. On the one hand, there are the authors and texts of economic history that seek to describe the facts and circumstances related to the functioning and dynamics of economic reality, for a given period or succession of periods, in order to establish evolutionary trends. On the other hand, there are the authors and texts of the history of economics that seek to adopt analytical forms (principles and laws) and doctrinal and programmatic frameworks (visions and ideologies) aimed at providing explanatory meaning to the observed economic changes, phenomena and regularities. A true understanding of the important issues pertaining to Portuguese economic development is to be found, however, in the intersection of these distinct but complementary historiographical perspectives.info:eu-repo/semantics/publishedVersio

PrIC3: Property Directed Reachability for MDPs

IC3 has been a leap forward in symbolic model checking. This paper proposes PrIC3 (pronounced pricy-three), a conservative extension of IC3 to symbolic model checking of MDPs. Our main focus is to develop the theory underlying PrIC3. Alongside, we present a first implementation of PrIC3 including the key ingredients from IC3 such as generalization, repushing, and propagation

AdS5AdS_{5} black hole at N=2 supergravity

In this paper, we consider the charged non-extremal black hole at five dimensional N = 2 supergravity. We study thermodynamics of AdS_{5} black hole with three equal charges (q_{1} = q_{2} = q_{3} = q). We obtain Schrodinger like equation and discuss the effective potential. Then, we consider the case of the perturbed dilaton field background and find presence of odd coefficients of the wave function. Also we find that the higher derivative corrections have no effect on the first and second even coefficients of the wave function.Comment: 17 pages, 4 figures. Published versio

Phenotypic variability among pumpkin accessions in the Brazilian semiarid

The aim of this study was to estimate the phenotypic divergence among fourteen pumpkins accessions of the cucurbits Germplasm Active Bank of Embrapa Semiárido, in order to support breeding program to these species. Nine morphoagronomic descriptors were analyzed by the principal components and by UPGMA techniques. In the analysis of principal components, the formation of three contrasting clusters was observed, each one composed of two accessions. There occurred also the formation of one core group composed of five accessions, being the accessions called 683 and 684 collected in Bahia and the other in Maranhão. The most divergent accessions were 620, 624 and 748. The variables of the greatest contribution to the genetic divergence were diameter, weight and average length of the fruit. In the UPGMA analysis, obtained from the symmetric matrices generated by the Mahalanobis distance for the nine descriptors, there was the formation of one core group, composed of ten accessions, whose similarity was 45.71%, with geographically divergent accessions presenting the greatest similarity. Three accessions were not clustered with others. The study identified phenotypic variability for the analyzed characters and the absence of relationship between place of collection and phenotypic diversity

Infrared (810-nm) low-level laser therapy on rat experimental knee inflammation

Arthritis of the knee is the most common type of joint inflammatory disorder and it is associated with pain and inflammation of the joint capsule. Few studies address the effects of the 810-nm laser in such conditions. Here we investigated the effects of low-level laser therapy (LLLT; infrared, 810-nm) in experimentally induced rat knee inflammation. Thirty male Wistar rats (230–250 g) were anesthetized and injected with carrageenan by an intra-articular route. After 6 and 12 h, all animals were killed by CO2 inhalation and the articular cavity was washed for cellular and biochemical analysis. Articular tissue was carefully removed for real-time PCR analysis in order to evaluate COX-1 and COX-2 expression. LLLT was able to significantly inhibit the total number of leukocytes, as well as the myeloperoxidase activity with 1, 3, and 6 J (Joules) of energy. This result was corroborated by cell counting showing the reduction of polymorphonuclear cells at the inflammatory site. Vascular extravasation was significantly inhibited at the higher dose of energy of 10 J. Both COX-1 and 2 gene expression were significantly enhanced by laser irradiation while PGE2 production was inhibited. Low-level laser therapy operating at 810 nm markedly reduced inflammatory signs of inflammation but increased COX-1 and 2 gene expression. Further studies are necessary to investigate the possible production of antiinflammatory mediators by COX enzymes induced by laser irradiation in knee inflammation