Construction and validation of an Entrepreneurship Measurement Instrument for nursing students / Construcción y validación de un Instrumento de Medición Emprendedora para estudiantes de enfermería / Construção e validação de Instrumento de Medição Empreendedora para estudantes de enfermagem

Objective. To develop a valid and reliable scale to measure entrepreneurship competences of nursing students, by assessing the level of development of diverse entrepreneurship dimensions. Methods. An Entrepreneurship Measurement Instrument, Catalonia (IME.Cat) was constructed, by adapting two existing instruments, and a psychometric study was performed to address the validity of the content and the construct, and the reliability. The internal consistency and the discrimination capacity of the instrument's items were examined. Results. The IME.Cat scale showed a high reliability (α=0.89) for the complete set of items. The Cronbach's α value of the individual dimensions were: Problem management=0.78; Creativity=0.76; Personal confidence =0.64; and Risk acceptance =0.46. The corrected homogeneity indices for each of the item in the instrument were high (>0.40). The Confirmatory Factorial Analysis validated the proposed structure of the items according to dimension. Conclusion. The IME.Cat scale showed solid psychometric values for assessing the entrepreneurship competences of nursing students within its dimensions, which are fundamental for the professional development of nursing.

Objetivo. Desarrollar una escala válida y fiable para medir competencias emprendedoras para estudiantes de enfermería, evaluando el nivel de desarrollo en diversas dimensiones del emprendimiento. Métodos. Se construyó el Instrumento de Medición Emprendedora Cataluña (IME.Cat) adaptando dos instrumentos existentes y se llevó a cabo un estudio psicométrico que abordó la validez de contenido, de constructo y la fiabilidad. Se examinaron la consistencia interna y la capacidad de discriminación de los ítems del instrumento. Resultados. La escala IME.Cat mostró una alta fiabilidad (α=0.89) para el conjunto completo de 25 ítems. Los valores del α de Cronbach de las dimensiones individuales fueron: Manejo de problemas=0.78; Creatividad=0.76; Seguridad personal=0.64; y Aceptación del riesgo=0.46. Los índices de homogeneidad corregidos para cada ítem del instrumento fueron elevados (>0.40). El Análisis Factorial Confirmatorio validó la estructura propuesta de ítems por dimensión. Conclusión. La escala IME.Cat mostró valores psicométricos sólidos para evaluar competencias emprendedoras en estudiantes de enfermería en sus dimensiones, las cuales son fundamentales en el desarrollo profesional de la enfermería.

Objetivo. Desenvolver uma escala válida e confiável para medir as competências empreendedoras dos alunos de enfermagem, avaliando o nível de desenvolvimento em várias dimensões do empreendedorismo. Métodos. O Instrumento de Medição de Empreendedorismo da Catalunha (IME.Cat) foi construído com a adaptação de dois instrumentos existentes, e um estudo psicométrico foi realizado para abordar a validade de conteúdo, a validade de construção e a confiabilidade. A consistência interna e a capacidade discriminatória dos itens do instrumento foram examinadas. Resultados. A escala IME.cat apresentou alta confiabilidade (α=0.89) para o conjunto completo de 25 itens. Os valores de α de Cronbach para as dimensões individuais foram: Tratamento de problemas=0.78; Criatividade=0.76; Segurança pessoal=0.64; e Aceitação de riscos=0.46. Os índices de homogeneidade corrigidos para cada item do instrumento foram altos (>0.40). A análise fatorial confirmatória validou a estrutura de itens proposta por dimensão. Conclusões. A escala IME.Cat apresentou bons valores psicométricos para avaliar as competências empreendedoras dos estudantes de enfermagem em suas dimensões, que são fundamentais para o desenvolvimento profissional da enfermagem.

Photoactivatable metabolic warheads enable precise and safe ablation of target cells in vivo.

Photoactivatable molecules enable ablation of malignant cells under the control of light, yet current agents can be ineffective at early stages of disease when target cells are similar to healthy surrounding tissues. In this work, we describe a chemical platform based on amino-substituted benzoselenadiazoles to build photoactivatable probes that mimic native metabolites as indicators of disease onset and progression. Through a series of synthetic derivatives, we have identified the key chemical groups in the benzoselenadiazole scaffold responsible for its photodynamic activity, and subsequently designed photosensitive metabolic warheads to target cells associated with various diseases, including bacterial infections and cancer. We demonstrate that versatile benzoselenadiazole metabolites can selectively kill pathogenic cells - but not healthy cells - with high precision after exposure to non-toxic visible light, reducing any potential side effects in vivo. This chemical platform provides powerful tools to exploit cellular metabolic signatures for safer therapeutic and surgical approaches.

JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC), the most frequent esophageal cancer (EC) subtype, entails dismal prognosis. Hypoxia, a common feature of advanced ESCC, is involved in resistance to radiotherapy (RT). RT response in hypoxia might be modulated through epigenetic mechanisms, constituting novel targets to improve patient outcome. Post-translational methylation in histone can be partially modulated by histone lysine demethylases (KDMs), which specifically removes methyl groups in certain lysine residues. KDMs deregulation was associated with tumor aggressiveness and therapy failure. Thus, we sought to unveil the role of Jumonji C domain histone lysine demethylases (JmjC-KDMs) in ESCC radioresistance acquisition. The effectiveness of RT upon ESCC cells under hypoxic conditions was assessed by colony formation assay. KDM3A/KDM6B expression, and respective H3K9me2 and H3K27me3 target marks, were evaluated by RT-qPCR, Western blot, and immunofluorescence. Effect of JmjC-KDM inhibitor IOX1, as well as KDM3A knockdown, in in vitro functional cell behavior and RT response was assessed in ESCC under hypoxic conditions. In vivo effect of combined IOX1 and ionizing radiation treatment was evaluated in ESCC cells using CAM assay. KDM3A, KDM6B, HIF-1α, and CAIX immunoexpression was assessed in primary ESCC and normal esophagus. Herein, we found that hypoxia promoted ESCC radioresistance through increased KDM3A/KDM6B expression, enhancing cell survival and migration and decreasing DNA damage and apoptosis, in vitro. Exposure to IOX1 reverted these features, increasing ESCC radiosensitivity and decreasing ESCC microtumors size, in vivo. KDM3A was upregulated in ESCC tissues compared to the normal esophagus, associating and colocalizing with hypoxic markers (HIF-1α and CAIX). Therefore, KDM3A upregulation in ESCC cell lines and primary tumors associated with hypoxia, playing a critical role in EC aggressiveness and radioresistance. KDM3A targeting, concomitant with conventional RT, constitutes a promising strategy to improve ESCC patients' survival.

Morphological and phylogenetic data do not support the split of Alexandrium into four genera.

A recently published study analyzed the phylogenetic relationship between the genera Centrodinium and Alexandrium, confirming an earlier publication showing the genus Alexandrium as paraphyletic. This most recent manuscript retained the genus Alexandrium, introduced a new genus Episemicolon, resurrected two genera, Gessnerium and Protogonyaulax, and stated that: "The polyphyly [sic] of Alexandrium is solved with the split into four genera". However, these reintroduced taxa were not based on monophyletic groups. Therefore this work, if accepted, would result in replacing a single paraphyletic taxon with several non-monophyletic ones. The morphological data presented for genus characterization also do not convincingly support taxa delimitations. The combination of weak molecular phylogenetics and the lack of diagnostic traits (i.e., autapomorphies) render the applicability of the concept of limited use. The proposal to split the genus Alexandrium on the basis of our current knowledge is rejected herein. The aim here is not to present an alternative analysis and revision, but to maintain Alexandrium. A better constructed and more phylogenetically accurate revision can and should wait until more complete evidence becomes available and there is a strong reason to revise the genus Alexandrium. The reasons are explained in detail by a review of the available molecular and morphological data for species of the genera Alexandrium and Centrodinium. In addition, cyst morphology and chemotaxonomy are discussed, and the need for integrative taxonomy is highlighted.

Alexandrium catenella cyst accumulation by passive and active dispersal agents: Implications for the potential spreading risk in Chilean Patagonian fjords.

The dinoflagellate Alexandrium catenella is responsible for paralytic shellfish poisoning and negative socioeconomic impacts on the fishing industry and aquaculture. In Chilean Patagonia, the reasons underlying the significant increase in the geographical extension (from south to north) of A. catenella blooms during the last five decades are not well understood. To assess the potential spreading risk of A. catenella during an intense austral summer bloom, we conducted an in situ experiment in a "hotspot" of this dinoflagellate in southern Chile. The objective was to assess the accumulation of A. catenella resting cysts in passive (fishing nets) and active (mussels) dispersal agents during the phase of bloom decline. Large numbers of resting cysts were detected in fishing nets (maximum of 5334 cysts net-1 per month) at 5 m depth and in mussels (maximum of 16 cysts g-1 of digestive gland) near Vergara Island. The potential of these vectors to serve as inoculum sources and the implications of our findings for A. catenella population dynamics are discussed.

Toxicity Characterisation of Gambierdiscus Species from the Canary Islands.

In the last decade, several outbreaks of ciguatera fish poisoning (CFP) have been reported in the Canary Islands (central northeast Atlantic Ocean), confirming ciguatera as an emerging alimentary risk in this region. Five Gambierdiscus species, G. australes, G. excentricus, G. silvae, G. carolinianus and G. caribaeus, have been detected in macrophytes from this area and are known to produce the ciguatoxins (CTXs) that cause CFP. A characterization of the toxicity of these species is the first step in identifying locations in the Canary Islands at risk of CFP. Therefore, in this study the toxicity of 63 strains of these five Gambierdiscus species were analysed using the erythrocyte lysis assay to evaluate their maitotoxin (MTX) content. In addition, 20 of the strains were also analysed in a neuroblastoma Neuro-2a (N2a) cytotoxicity assay to determine their CTX-like toxicity. The results allowed the different species to be grouped according to their ratios of CTX-like and MTX-like toxicity. MTX-like toxicity was especially high in G. excentricus and G. australes but much lower in the other species and lowest in G. silvae. CTX-like toxicity was highest in G. excentricus, which produced the toxin in amounts ranging between 128.2 ± 25.68 and 510.6 ± 134.2 fg CTX1B equivalents (eq) cell-1 (mean ± SD). In the other species, CTX concentrations were as follows: G. carolinianus (100.84 ± 18.05 fg CTX1B eq cell-1), G. australes (31.1 ± 0.56 to 107.16 ± 21.88 fg CTX1B eq cell-1), G. silvae (12.19 ± 0.62 to 76.79 ± 4.97 fg CTX1B eq cell-1) and G. caribaeus (

The Critical Role of Hypoxic Microenvironment and Epigenetic Deregulation in Esophageal Cancer Radioresistance.

Esophageal cancer (EC) is the seventh most common cancer worldwide and the sixth leading cause of death, according to Globocan 2018. Despite efforts made for therapeutic advances, EC remains highly lethal, portending a five-year overall survival of just 15-20%. Hence, the discovery of new molecular targets that might improve therapeutic efficacy is urgently needed. Due to high proliferative rates and also the limited oxygen and nutrient diffusion in tumors, the development of hypoxic regions and consequent activation of hypoxia-inducible factors (HIFs) are a common characteristic of solid tumors, including EC. Accordingly, HIF-1α, involved in cell cycle deregulation, apoptosis, angiogenesis induction and proliferation in cancer, constitutes a predictive marker of resistance to radiotherapy (RT). Deregulation of epigenetic mechanisms, including aberrant DNA methylation and histone modifications, have emerged as critical factors in cancer development and progression. Recently, interactions between epigenetic enzymes and HIF-1α transcription factors have been reported. Thus, further insight into hypoxia-induced epigenetic alterations in EC may allow the identification of novel therapeutic targets and predictive biomarkers, impacting on patient survival and quality of life.

Scrippsiella acuminata versus Scrippsiella ramonii: A Physiological Comparison.

Scrippsiella is a cosmopolitan dinoflagellate genus that is able to form Harmful Algal Blooms in coastal waters. The large physiological, morphological, and genetic variability that characterizes this genus suggest the existence of cryptic species. In this study, flow cytometric analyses were carried out to compare the cell cycle and life cycle of two Scrippsiella strains from two different species: Scrippsiella ramonii (VGO1053) and Scrippsiella acuminata (S3V). Both species were also investigated by internally transcribed spacer rDNA sequencing and high-performance liquid chromatography-based pigment analyses. The reddish-brown color of S. acuminata and yellowish-green hue of S. ramonii were consistent with the quantitative differences determined in their pigment profiles. Our results indicate that the cell cycle is light-controlled and that it differs in the two species. S-phase was detected during the light period in both, whereas the G2/M phase occurred during the light period in S. ramonii but under dark conditions in S. acuminata. The detection of 4C stages, mobile zygotes (planozygotes), and resting cysts in S. ramonii (nonclonal) provided convincing evidence of sexuality in this species. Sexual related processes were not found in the clonal S. acuminata strain, suggesting its heterothallic behavior (i.e., the need for outcrossing). The differences in the genome size of these species were examined as well. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.

Proteolytic and Opportunistic Breaching of the Basement Membrane Zone by Immune Cells during Tumor Initiation.

Cancer-related inflammation impacts significantly on cancer development and progression. From early stages, neutrophils and macrophages are drawn to pre-neoplastic cells in the epidermis, but before directly interacting, they must first breach the underlying extracellular matrix barrier layer that includes the basement membrane. Using several different skin cancer models and a collagen I-GFP transgenic zebrafish line, we have undertaken correlative light and electron microscopy (CLEM) to capture the moments when immune cells traverse the basement membrane. We show evidence both for active proteolytic burrowing and for the opportunistic use of pre-existing weak spots in the matrix layer. We show that these small holes, as well as much larger, cancer cell-generated or wound-triggered gaps in the matrix barrier, provide portals for immune cells to access cancer cells in the epidermis and thus are rate limiting in cancer progression.

The Hippo Pathway Regulates Caveolae Expression and Mediates Flow Response via Caveolae.

The Hippo pathway plays major roles in development, regeneration, and cancer. Its activity is tightly regulated by both diffusible chemical ligands and mechanical stimuli. The pathway consists of a series of kinases that can control the sub-cellular localization and stability of YAP or TAZ, homologous transcriptional co-factors. Caveolae, small (60-100 nm) bulb-like invaginations of the plasma membrane, are comprised predominantly of caveolin and cavin proteins and can respond to mechanical stimuli. Here, we show that YAP/TAZ, the major transcriptional mediators of the Hippo pathway, are critical for expression of caveolae components and therefore caveolae formation in both mammalian cells and zebrafish. In essence, without YAP/TAZ, the cell loses an entire organelle. CAVEOLIN1 and CAVIN1, the two essential caveolar genes, are direct target genes of YAP/TAZ, regulated via TEA domain (TEAD) transcription factors. Notably, YAP/TAZ become nuclear enriched and facilitate target gene transcription in cells with diminished levels of caveolae. Furthermore, caveolar-mediated shear stress response activates YAP/TAZ. These data link caveolae to Hippo signaling in the context of cellular responses to mechanical stimuli and suggest activity-based feedback regulation between components of caveolae and the outputs of the Hippo pathway.

TP53 Arg72Pro polymorphism is associated with increased overall survival but not response to therapy in Portuguese/Caucasian patients with advanced cervical cancer.

Identification of mechanisms that influence the therapeutic response and survival in patients with cancer is important. It is known that the genetic variability of the host, including presence of genetic polymorphisms in genes involved in DNA damage response, serves a crucial role in the prognosis of these patients. The present hospital-based retrospective cohort study aimed to evaluate the influence of TP53 Arg72Pro (rs1042522) polymorphism in the clinical outcome of 260 Caucasian patients diagnosed with cervical cancer and treated with concomitant radiotherapy and chemotherapy. The polymorphism genotyping was assessed using allelic discrimination by quantiative polymerase chain reaction. The results indicate that the TP53 Arg72Pro polymorphism did not significantly impact the response to therapy (P=0.571) nor disease-free survival (P=0.081). However, the polymorphism did influence overall survival, as increased median survival time was observed for patients carrying Arg/Pro genotype when compared with patients with Arg/Arg and Pro/Pro genotypes (126 months vs. 111 months, respectively; P=0.047). To conclude, the present findings suggest that a pharmacogenomic profile based on the genetic background of patients, including the analysis of the TP53 genotypes, may individualize treatment nad assist in the selection of therapies that may improve clinical outcome and lower toxicity for the patients.

Relationship between clinical toxicities and ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms in cervical cancer patients.

BACKGROUND: Several studies have suggested that there are single nucleotide polymorphisms (SNPs) that can be considered potential biomarkers in the prognosis and therapeutic response of cancer patients. The present study investigated the association between ERCC1 rs3212986 and XRCC3 rs861539 polymorphisms and clinical toxicities induced by chemoradiotherapy (CRT) in cervical cancer. METHODS: This hospital-based retrospective cohort study included 260 patients with cervical cancer, FIGO stages Ib2-IVa, who underwent CRT (cisplatin). Genetic polymorphisms analysis was performed by allelic discrimination with real-time polymerase chain reaction (RT-PCR). RESULTS: Our results indicated a link between ERCC1 rs3212986 and the onset of late gastrointestinal toxicity (p = 0.038). Furthermore, using a recessive model (AA vs. CC/CA), we found that patients carrying AA homozygous genotype presented a fourfold increased risk of developing late gastrointestinal toxicity when compared with patients with the C allele (odds ratio = 3.727, 95% confidence interval, 1.199-11.588; p = 0.017). No association was found regarding the XRCC3 rs861539 polymorphism and any clinical toxicity event. CONCLUSIONS: This is the first study evaluating the relationship between these polymorphisms and clinical toxicities in cervical cancer patients submitted to CRT with cisplatin. These results may contribute toward a better understanding of the influence of genetic polymorphisms in genes associated with DNA repair in the clinical response to CRT of patients with cervical cancer.

Benthic flattened cells of the phylogenetically related marine dinoflagellates Protoceratium reticulatum and Ceratocorys mariaovidiorum (Gonyaulacales): a new type of cyst?

A planktonic-benthic relationship has been described for many dinoflagellate species as part of their ecological strategy to overcome highly variable aquatic environments. Here, the phylogenetically and morphologically related marine dinoflagellates Protoceratium reticulatum and Ceratocorys mariaovidiorum were studied in relation to an unknown benthic life form. In vivo and fixed samples from cultures were analyzed in detail by light and scanning electron microscopy. In both species, a cell type with a morphology different from that of vegetative cells was observed in cultures grown until stationary phase. This cell type was always benthic, swimming sporadically only when it was disturbed. Its main feature included a strong dorsoventral compression. These cells originated from vegetative cells whose protoplasm underwent a progressive flattening, resulting in a gradual detachment of the reticulate and thick thecal plates and the formation of very thin non-reticulated new plates with pores. When returned to fresh full-strength medium, the cells recovered their spherical vegetative-like morphology, including new reticulated thick plates and subsequent cell divisions. The kinetics of flattened cell formation showed that in both species, this cell type increased exponentially until the onset of the culture stationary phase and then decreased. The results of this study are discussed in the context of the planktonic-benthic coupling in dinoflagellate life cycles, including those newly appreciated to be well adapted to the benthic environment.

The life history of the toxic marine dinoflagellate Protoceratium reticulatum (Gonyaulacales) in culture.

Asexual and sexual life cycle events were studied in cultures of the toxic marine dinoflagellate Protoceratium reticulatum. Asexual division by desmoschisis was characterized morphologically and changes in DNA content were analyzed by flow cytometry. The results indicated that haploid cells with a C DNA content occurred only during the light period whereas a shift from a C to a 2C DNA content (indicative of S phase) took place only during darkness. The sexual life cycle was documented by examining the mating type as well as the morphology of the sexual stages and nuclei. Gamete fusion resulted in a planozygote with two longitudinal flagella, but longitudinally biflagellated cells arising from planozygote division were also observed, so one of the daughter cells retained two longitudinal flagella while the other daughter cell lacked them. Presumed planozygotes (identified by their longitudinally biflagellated form) followed two life-cycle routes: division and encystment (resting cyst formation). Both the division of longitudinally biflagellated cells and resting cyst formation are morphologically described herein. Resting cyst formation through sexual reproduction was observed in 6.1% of crosses and followed a complex heterothallic pattern. Clonal strains underwent sexuality (homothallism for planozygote formation and division) but without the production of resting cysts. Ornamental processes of resting cysts formed from the cyst wall under an outer balloon-shaped membrane and were fully developed in <1h. Obligatory dormancy period was of ∼4 months. Excystment resulted in a large, rounded, pigmented, longitudinally biflagellated but motionless, thecate germling that divided by desmoschisis. Like the planozygote, the first division of the germling yielded one longitudinally biflagellated daughter cell and another without longitudinal flagella. The longitudinal biflagellation state of both sexual stages and of the first division products of these cells is discussed.

Endovascular treatment in the acute and non-acute phases of carotid dissection: a therapeutic approach.

BACKGROUND: Carotid dissection (CD) may, in certain cases, lead to significant stenosis, occlusion, or pseudoaneurysm formation, causing embolic stroke or hemodynamic failure, despite medical therapy. OBJECTIVE: To evaluate the results of endovascular treatment and clinical outcomes of patients with CD. METHODS: A four-hospital retrospective study of endovascular treatment of extracranial CD in which medical treatment had failed or patients presented with a National Institute of Health Stroke Scale (NIHSS) score ≥8. RESULTS: Thirty-eight patients (mean age 46.6±13.5 years, 78.9% male, 84.2% spontaneous CD, 44.7% left CD and 26.3% bilateral CD) were analyzed. In 24 patients (63.2%) treatment was undertaken in the acute-phase CD (APCD). IV recombinant tissue plasminogen activator was administered in 7 (29.2%) APCD cases. The patients with APCD exhibited a high rate of successful revascularization (Thrombolysis In Cerebral Infarction ≥2b; 19 patients (79.2%)), a low risk of symptomatic intracranial hemorrhage (n=2 (8.3%)), and good global functional outcomes (modified Rankin Scale (mRS) ≤2; n=17 (70.8%)). Good recanalization correlated (p=0.001) with good clinical evolution (mRS ≤2) in the patients with APCD. Of the 14 patients with non-acute phase CD (NAPCD), seven were treated for pseudoaneurysm with multiple stents (six patients) or covered prostheses, with stenosis being treated in the remaining seven patients. CONCLUSIONS: Endovascular treatment of selected cases of patients with CD associated with thromboembolic events and hemodynamic failure after unsuccessful medical therapy is a safe and effective method of restoring vessel lumen integrity, with good short-term clinical evolution.