IFT88 maintains sensory function by localising signalling proteins along Drosophila cilia.

Ciliary defects cause several ciliopathies, some of which have late onset, suggesting cilia are actively maintained. Still, we have a poor understanding of the mechanisms underlying their maintenance. Here, we show Drosophila melanogaster IFT88 (DmIFT88/nompB) continues to move along fully formed sensory cilia. We further identify Inactive, a TRPV channel subunit involved in Drosophila hearing and negative-gravitaxis behaviour, and a yet uncharacterised Drosophila Guanylyl Cyclase 2d (DmGucy2d/CG34357) as DmIFT88 cargoes. We also show DmIFT88 binding to the cyclase´s intracellular part, which is evolutionarily conserved and mutated in several degenerative retinal diseases, is important for the ciliary localisation of DmGucy2d. Finally, acute knockdown of both DmIFT88 and DmGucy2d in ciliated neurons of adult flies caused defects in the maintenance of cilium function, impairing hearing and negative-gravitaxis behaviour, but did not significantly affect ciliary ultrastructure. We conclude that the sensory ciliary function underlying hearing in the adult fly requires an active maintenance program which involves DmIFT88 and at least two of its signalling transmembrane cargoes, DmGucy2d and Inactive.

Quality and Safety of Proximity Care Centered on the Person and Their Domiciliation: Systematic Literature Review.

The quality and safety of health care are a priority for health organizations and social institutions to progressively provide people with a higher level of health and well-being. It is in the development of this path that home care currently represents an area of gradual investment and where health care services and the scientific community have shown interest in building circuits and instruments that can respond to needs. The purpose of this article is to identify areas and criteria for quality and safety in home care. The method used was a systematic review registered in PROSPERO (CRD42022380989). The search was systematically carried out in CINAHL Plus with Full Text, MEDLINE with Full Text and Psychology and Behavioral Sciences Collection, using the following criteria: articles published in Portuguese and English, from January 2017 to November 2022. The results of the analysis of the articles showed areas of quality and safety in home care with their respective dimensions and operational criteria. We concluded that there are three areas: the intervention with the patient, with proximity and patient-centered care, which integrates the individual care plan and the proximity of professionals to the patient and family; the intervention of care and service management, with care management and clinical governance that includes the integrated model of health care, goal management, and context management; and the intervention related to training and professional development, where we have the skills and training of professionals.

Abordagem à pessoa nos Serviço de Urgência e Unidade de Cuidados Intensivos após a pandemia COVID-19: scoping review / Approach to the person in emergency and intensive care after the pandemic covid-19: scoping review

Objetivo: Perceber quais as alterações que ocorreram na abordagem à pessoa em situação crítica no Serviço de Urgência e Unidade de Cuidados Intensivos após início da pandemia COVID-19. Método: A estratégia de pesquisa para a scopingreview foi realizada nas bases de dados Medline via PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS e Scielo através da utilização de descritores MeSH e DeCS, artigos com fulltext gratuito, publicados em língua portuguesa, inglesa e espanhola, com datas de publicação entre 2019 e 2021, implementados critérios de inclusão e exclusão.Resultados: Foram identificados 4 estudos elegíveis para análise, publicados em 2020, nenhum dos estudos em Português. Conclusão: As principais alterações estão relacionadas com a utilização de equipamento de proteção individual, colocando o enfoque na segurança dos profissionais de saúde.(AU)

Aim: To understand the changes that occurred in the approach to critically ill patients in the Emergency Department and Intensive Care Unit after the beginning of the COVID-19 pandemic. Method: The search strategy for the scoping review was conducted in Medline databases via PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS and Scielo by using MeSH and DeCS descriptors, articles with free full text, published in Portuguese, English and Spanish language, with publication dates between 2019 and 2021, implemented inclusion and exclusion criteria.Results: Four eligible studies were identified for analysis, published in 2020, and none of the studies was in Portuguese. Conclusion: The main changes are related to the use of personal protective equipment, focusing on the safety of health professionals.(AU)

Objetivo: Conocer qué cambios se han producido en el abordaje a los pacientes críticos en el Servicio de Urgencia y enUnidades de Cuidados Intensivos tras el inicio de la pandemia COVID-19.Método: La estrategia de búsqueda para la revisión se realizó en las bases de datos Medline e PubMed, EBSCO Host, BioMed Central, ScienceDirect, BVS y Scielo con el uso de descriptores MeSH y DeCS, artículos con libre acceso a texto completo, publicados en portugués, inglés y español, entre el 2019 y 2021, usando criterios de inclusión y exclusión.Resultados: Identificamos 4 estudios elegibles para el análisis, todos publicados en 2020, e ninguno en portugués.Conclusión: Los principales cambios están relacionados con el uso de equipamientos de protección personal, conel enfoque en la seguridad de los profesionales de salud.(AU)

Quality and Safety of Proximity Care Centered on the Person and Their Home: A Systematic Review Protocol.

The quality and safety of health care is a priority, a requirement and a demand of health organizations and social institutions with concrete purposes of progressively providing people with a higher level of health and well-being. It is in the development of this path that home care currently represents an area of gradual investment and where health care services and the scientific community have shown interest in building circuits and instruments that can respond to needs. It is essencial that care must be centered and in close proximity to the person and their family, their context. On the other hand, in Portugal, there are already quality and safety models for the institutionalization context however it is non-existent for home care. In this sense, our objective is to identify, through a systematic review of the literature, particularly from the last 5 years, areas of quality and safety in home care.

Modulation of Fibroblast Phenotype by Colorectal Cancer Cell-Secreted Factors Is Mostly Independent of Oncogenic KRAS.

KRAS mutations have been shown to extend their oncogenic effects beyond the cancer cell, influencing the tumor microenvironment. Herein, we studied the impact of mutant KRAS on the modulation of the pro-tumorigenic properties of cancer-associated fibroblasts (CAFs), including α-SMA expression, TGFß1 and HGF production, extracellular matrix components and metalloproteinases expression as well as collagen contraction and migration capacities. To do so, CCD-18Co normal-like colon fibroblasts were challenged with conditioned media from control and KRAS silenced colorectal cancer (CRC) cells. Our results showed that the mutant KRAS CRC cell-secreted factors were capable of turning normal-like fibroblasts into CAF-like by modulating the α-SMA expression, TGFß1 and HGF production and migration capacity. Oncogenic KRAS played a secondary role as its silencing did not completely impair the capacity of CRC cells to modulate most of the fibroblast properties analyzed. In summary, our work suggests that mutant KRAS does not play a major role in controlling the CRC cell-secreted factors that modulate the behavior of fibroblasts. The fact that CRC cells retain the capacity to modulate the pro-tumorigenic features of fibroblasts independently of KRAS silencing is likely to negatively impact their response to KRAS inhibitors, thus standing as a putative mechanism of resistance to KRAS inhibition with potential therapeutical relevance.

Mutant KRAS modulates colorectal cancer cells invasive response to fibroblast-secreted factors through the HGF/C-MET axis.

Genetic alterations influence the malignant potential of cancer cells, and so does the tumor microenvironment. Herein, we combined the study of KRAS oncogenic effects in colorectal cancer cells with the influence of fibroblast-derived factors. Results revealed that mutant KRAS regulates cell fate through both autonomous and nonautonomous signaling mechanisms. Specifically, processes such as proliferation and cell-cell aggregation were autonomously controlled by mutant KRAS independently of the stimulation with fibroblasts conditioned media. However, cancer cell invasion revealed to be a KRAS-dependent nonautonomous effect, resulting from the cooperation between fibroblast-derived HGF and mutant KRAS regulation of C-MET expression. C-MET downregulation upon KRAS silencing rendered cells less responsive to HGF and thus less invasive. Yet, in one cell line, KRAS inhibition triggered invasion upon stimulation with fibroblasts conditioned media. Inhibition of PIK3CA oncogene did not promote invasion, thus showing a KRAS-specific effect. Moreover, the invasive capacity also depended on the HGF-C-MET axis. Overall, our study awards oncogenic KRAS an important role in modulating the response to fibroblast-secreted factors either by promoting or impairing invasion, and depicts the HGF-C-MET axis as a putative therapeutic target to impair the invasive properties of mutant KRAS cancer cells.

Nursing Care in Peripheral Intravenous Catheter (PIVC): Protocol of a Best Practice Implementation Project.

BACKGROUND: The use of a peripheral intravenous catheters (PIVC) is a common invasive practice in healthcare settings. It is estimated that about 70% of people with PIVCs will develop associated complications, such as infections. It is the consensus that best practices could reduce the appearance of such complications and reduce the length of stay in hospital. METHODS: A project will be applied to implement the best approach in peripheral venous catheterization, provided by clinical nurses from an inland hospital in Portugal. The Joanna Briggs Institute methodology will be used on evidence implementation projects, which will be developed in three phases. First, a baseline audit will be performed. The second phase implements corrective measures, and the third phase is a follow-up audit. CONCLUSIONS: This project will improve the practice of the nursing team on peripheral venous catheterization nursing cares, positively influencing the quality of nursing care and patient safety. The implementation and dissemination of this project could boost its replication in other centres.

Psychometric Properties of the European Portuguese Version of the Memorial Emergency Department Fall Risk Assessment Tool.

Falls are a public health problem that cause serious damage to people's health and health systems. This study aims to estimate the validity and reliability of the Memorial Emergency Department Fall Risk Assessment Tool for the European Portuguese population. The sample included 186 adults from an emergency department of a District Hospital in Portugal. Reliability and precision (inter-rater reliability) are assessed by two independent raters. The relationship between MEDFRAT and the Morse Fall Risk Scale is evaluated. All items presented a high Kappa index. The MEDFRAT showed a high and significant correlation with the Morse Fall Risk Scale. The influence of sociodemographic and clinical data was also checked. The MEDFRAT is adequate, valid and reliable for the European Portuguese population to assess the risk of falling of emergency department patients.

Differential regulation of transition zone and centriole proteins contributes to ciliary base diversity.

Cilia are evolutionarily conserved structures with many sensory and motility-related functions. The ciliary base, composed of the basal body and the transition zone, is critical for cilia assembly and function, but its contribution to cilia diversity remains unknown. Hence, we generated a high-resolution structural and biochemical atlas of the ciliary base of four functionally distinct neuronal and sperm cilia types within an organism, Drosophila melanogaster. We uncovered a common scaffold and diverse structures associated with different localization of 15 evolutionarily conserved components. Furthermore, CEP290 (also known as NPHP6) is involved in the formation of highly diverse transition zone links. In addition, the cartwheel components SAS6 and ANA2 (also known as STIL) have an underappreciated role in basal body elongation, which depends on BLD10 (also known as CEP135). The differential expression of these cartwheel components contributes to diversity in basal body length. Our results offer a plausible explanation to how mutations in conserved ciliary base components lead to tissue-specific diseases.

Over-elongation of centrioles in cancer promotes centriole amplification and chromosome missegregation.

Centrosomes are the major microtubule organising centres of animal cells. Deregulation in their number occurs in cancer and was shown to trigger tumorigenesis in mice. However, the incidence, consequence and origins of this abnormality are poorly understood. Here, we screened the NCI-60 panel of human cancer cell lines to systematically analyse centriole number and structure. Our screen shows that centriole amplification is widespread in cancer cell lines and highly prevalent in aggressive breast carcinomas. Moreover, we identify another recurrent feature of cancer cells: centriole size deregulation. Further experiments demonstrate that severe centriole over-elongation can promote amplification through both centriole fragmentation and ectopic procentriole formation. Furthermore, we show that overly long centrioles form over-active centrosomes that nucleate more microtubules, a known cause of invasiveness, and perturb chromosome segregation. Our screen establishes centriole amplification and size deregulation as recurrent features of cancer cells and identifies novel causes and consequences of those abnormalities.

KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment.

KRAS is one of the most frequently mutated oncogenes in cancer, being a potent initiator of tumorigenesis, a strong inductor of malignancy, and a predictive biomarker of response to therapy. Despite the large investment to understand the effects of KRAS activation in cancer cells, pharmacologic targeting of KRAS or its downstream effectors has not yet been successful at the clinical level. Recent studies are now describing new mechanisms of KRAS-induced tumorigenesis by analyzing its effects on the components of the tumor microenvironment. These studies revealed that the activation of KRAS on cancer cells extends to the surrounding microenvironment, affecting the properties and functions of its constituents. Herein, we discuss the most emergent perspectives on the relationship between KRAS-mutant cancer cells and their microenvironment components. Cancer Res; 78(1); 7-14. ©2017 AACR.

Methods to Study Centrosomes and Cilia in Drosophila.

Centrioles and cilia are highly conserved eukaryotic organelles. Drosophila melanogaster is a powerful genetic and cell biology model organism, extensively used to discover underlying mechanisms of centrosome and cilia biogenesis and function. Defects in centrosomes and cilia reduce fertility and affect different sensory functions, such as proprioception, olfaction, and hearing. The fly possesses a large diversity of ciliary structures and assembly modes, such as motile, immotile, and intraflagellar transport (IFT)-independent or IFT-dependent assembly. Moreover, all the diverse ciliated cells harbor centrioles at the base of the cilia, called basal bodies, making the fly an attractive model to better understand the biology of this organelle. This chapter describes protocols to visualize centrosomes and cilia by fluorescence and electron microscopy.

Rootletin organizes the ciliary rootlet to achieve neuron sensory function in Drosophila.

Cilia are essential for cell signaling and sensory perception. In many cell types, a cytoskeletal structure called the ciliary rootlet links the cilium to the cell body. Previous studies indicated that rootlets support the long-term stability of some cilia. Here we report that Drosophila melanogaster Rootletin (Root), the sole orthologue of the mammalian paralogs Rootletin and C-Nap1, assembles into rootlets of diverse lengths among sensory neuron subtypes. Root mutant neurons lack rootlets and have dramatically impaired sensory function, resulting in behavior defects associated with mechanosensation and chemosensation. Root is required for cohesion of basal bodies, but the cilium structure appears normal in Root mutant neurons. We show, however, that normal rootlet assembly requires centrioles. The N terminus of Root contains a conserved domain and is essential for Root function in vivo. Ectopically expressed Root resides at the base of mother centrioles in spermatocytes and localizes asymmetrically to mother centrosomes in neuroblasts, both requiring Bld10, a basal body protein with varied functions.

Semantic interference on a phonological task in illiterate subjects.

Previous research suggests that learning an alphabetic written language influences aspects of the auditory-verbal language system. In this study, we examined whether literacy influences the notion of words as phonological units independent of lexical semantics in literate and illiterate subjects. Subjects had to decide which item in a word- or pseudoword pair was phonologically longest. By manipulating the relationship between referent size and phonological length in three word conditions (congruent, neutral, and incongruent) we could examine to what extent subjects focused on form rather than meaning of the stimulus material. Moreover, the pseudoword condition allowed us to examine global phonological awareness independent of lexical semantics. The results showed that literate performed significantly better than illiterate subjects in the neutral and incongruent word conditions as well as in the pseudoword condition. The illiterate group performed least well in the incongruent condition and significantly better in the pseudoword condition compared to the neutral and incongruent word conditions and suggest that performance on phonological word length comparisons is dependent on literacy. In addition, the results show that the illiterate participants are able to perceive and process phonological length, albeit less well than the literate subjects, when no semantic interference is present. In conclusion, the present results confirm and extend the finding that illiterate subjects are biased towards semantic-conceptual-pragmatic types of cognitive processing.

Composition and antimicrobial activity of the essential oils from invasive species of the Azores, Hedychium gardnerianum and Pittosporum undulatum.

The compositions of the essential oils from the leaves and flowers of Hedychium gardnerianum and from the leaves of Pittosporum undulatum growing on San Miguel Island (Azores) were investigated, and the compounds were identified by GC-MS analyses. The oils in the leaves and flowers of H. gardnerianum were rich in alpha-pinene, beta-pinene and alpha-cadinol, whereas that from P. undulatum was found to contain monoterpenes, sesquiterpenes, diterpenes and alkanes, of which the sesquiterpenes, calamenene (41.4%), farnesol (10.9%), spathulenol (5.6%) and beta-selinene (5.2%) and the diterpene (8beta,13beta)-kaur-16-ene (10.7%) were the major components. Their potential antimicrobial activities were tested against Staphylococcus aureus, S. epidermis and Pseudomonas aeruginosa, and those with the highest activities against S. aureus and S. epidermis were from H. gardnerianum; none had activity against P. aeruginosa. Additionally, the essential oils from Pittosporum undulatum had good antithrombin activity whereas that from H. gardnerianum did not.