The Moderating Role of Self-Care Behaviors in Personal Care Aides of Older Adults during the COVID-19 Pandemic.

The COVID-19 pandemic has brought new challenges and work changes for formal caregivers such as personal care aides with an impact on their quality of life (QoL). This cross-sectional study aims to analyze the relationships and contribution of sociodemographic and psychological variables towards QoL including the moderating role of self-care. This study included 127 formal caregivers from Portugal who were assessed on depression, anxiety and stress (DASS-21); professional self-care (SCAP); quality of life (SF-12); COVID-19 traumatic stress (COVID-19TSC) and preventive COVID-19 infection behaviors (PCOVID-19 IBS). Professional self-care was positively associated with QoL and also moderated the relationship between distress and QoL (p < 0.001). According to results, nursing homes should provide formal caregivers, such as personal care aides, with the professional support they need in order to promote their QoL and prevent burnout.

Cancer in Santiago Island, Cape Verde: data from the Hospital Agostinho Neto Cancer Registry (2017-2018).

This report describes the cancer cases that occurred between 2017 and 2018 in Santiago Island, Cape Verde, according to the Hospital Agostinho Neto Cancer Registry. The five most common cancers were prostate, breast, stomach, cervix and oesophageal in order of frequency. There are no national data. Therefore, it is essential to create the conditions for the establishment of Cape Verde's population-based cancer registry as quickly as possible.

Variation in treatment and survival of older patients with non-metastatic breast cancer in five European countries: a population-based cohort study from the EURECCA Breast Cancer Group.

BACKGROUND: Older patients are poorly represented in breast cancer research and guidelines do not provide evidence based recommendations for this specific group. We compared treatment strategies and survival outcomes between European countries and assessed whether variance in treatment patterns may be associated with variation in survival. METHODS: Population-based study including patients aged ≥ 70 with non-metastatic BC from cancer registries from the Netherlands, Belgium, Ireland, England and Greater Poland. Proportions of local and systemic treatments, five-year relative survival and relative excess risks (RER) between countries were calculated. RESULTS: In total, 236,015 patients were included. The proportion of stage I BC receiving endocrine therapy ranged from 19.6% (Netherlands) to 84.6% (Belgium). The proportion of stage III BC receiving no breast surgery varied between 22.0% (Belgium) and 50.8% (Ireland). For stage I BC, relative survival was lower in England compared with Belgium (RER 2.96, 95%CI 1.30-6.72, P < .001). For stage III BC, England, Ireland and Greater Poland showed significantly worse relative survival compared with Belgium. CONCLUSIONS: There is substantial variation in treatment strategies and survival outcomes in elderly with BC in Europe. For early-stage BC, we observed large variation in endocrine therapy but no variation in relative survival, suggesting potential overtreatment. For advanced BC, we observed higher survival in countries with lower proportions of omission of surgery, suggesting potential undertreatment.

Mouse genetic background influences whether HrasG12V expression plus Cdkn2a knockdown causes angiosarcoma or undifferentiated pleomorphic sarcoma.

Soft tissue sarcomas are rare mesenchymal tumours accounting for 1% of adult malignancies and are fatal in approximately one third of patients. Two of the most aggressive and lethal forms of soft tissue sarcomas are angiosarcomas and undifferentiated pleomorphic sarcomas (UPS). To examine sarcoma-relevant molecular pathways, we employed a lentiviral gene regulatory system to attempt to generate in vivo models that reflect common molecular alterations of human angiosarcoma and UPS. Mice were intraveneously injected with MuLE lentiviruses expressing combinations of shRNA against Cdkn2a, Trp53, Tsc2 and Pten with or without expression of HrasG12V , PIK3CAH1047R or Myc. The systemic injection of an ecotropic lentivirus expressing oncogenic HrasG12V together with the knockdown of Cdkn2a or Trp53 was sufficient to initiate angiosarcoma and/or UPS development, providing a flexible system to generate autochthonous mouse models of these diseases. Unexpectedly, different mouse strains developed different types of sarcoma in response to identical genetic drivers, implicating genetic background as a contributor to the genesis and spectrum of sarcomas.

Neoadjuvant Therapy in Rectal Cancer Patients With Clinical Stage II to III Across European Countries: Variations and Outcomes.

BACKGROUND: Neoadjuvant therapy improves survival of patients with clinical stage II and III rectal cancer in clinical trials. In this study, we investigated the administration of neoadjuvant radiotherapy (neo-RT) and neoadjuvant chemoradiotherapy (neo-CRT) and its association with survival in resected patients in 2 European countries (The Netherlands and Sweden) and at 3 specialist centers. MATERIALS AND METHODS: Administration of neoadjuvant treatment (all registries) and overall survival after surgery in The Netherlands and Sweden were assessed. Hazard ratios (HRs) were obtained using Cox regression adjusted for potential confounders. RESULTS: A total of 16,095 rectal cancer patients with clinical stage II and III were eligible for analyses. Large variations in administration of neo-RT and neo-CRT were observed. Elderly patients less often received neo-RT and neo-CRT. Patients with stage III disease received neo-CRT more frequently than neo-RT. Administration of neo-RT versus surgery without neoadjuvant treatment was significantly associated with improved survival in The Netherlands (HR, 0.62; 95% confidence interval [CI], 0.53-0.73) as well as in Sweden (HR, 0.79; 95% CI, 0.69-0.90). Administration of neo-CRT was associated with enhanced survival in The Netherlands (HR, 0.62; 95% CI, 0.50-0.78) but not in Sweden (HR, 0.97; 95% CI, 0.80-1.18). The mortality of patients treated with neo-CRT compared with neo-RT showed inconsistent results in population-based centers. CONCLUSIONS: Our results support an association of neo-RT with enhanced survival among stage II and III rectal cancer patients. Comparing neo-CRT with neo-RT, larger variations and inconsistent results with respect to survival were observed across centers.

Evidence of renal angiomyolipoma neoplastic stem cells arising from renal epithelial cells.

Renal angiomyolipomas (AML) contain an admixture of clonal tumour cells with features of several different mesenchymal lineages, implying the existence of an unidentified AML neoplastic stem cell. Biallelic inactivation of TSC2 or TSC1 is believed to represent the driving event in these tumours. Here we show that TSC2 knockdown transforms senescence-resistant cultured mouse and human renal epithelial cells into neoplastic stem cells that serially propagate renal AML-like tumours in mice. mTOR inhibitory therapy of mouse AML allografts mimics the clinical responses of human renal AMLs. Deletion of Tsc1 in mouse renal epithelia causes differentiation in vivo into cells expressing characteristic AML markers. Human renal AML and a renal AML cell line express proximal tubule markers. We describe the first mouse models of renal AML and provide evidence that these mesenchymal tumours originate from renal proximal tubule epithelial cells, uncovering an unexpected pathological differentiation plasticity of the proximal tubule.

O Cuidar dos enfermeiros na equipa de suporte em cuidados paliativos / The Care of Nurses in the Palliative Care Support Team

Acompanhar o processo de fim de vida implica ter uma visão holística como garantia de uma assistência integral à pessoa. Várias vezes nos confrontamos com pessoas em grande sofrimento nas unidades hospitalares, onde ainda imperam valores médicos que se direcionam para a dimensão biológica da pessoa, procurando-se a cura e negando-se a morte. Efetivamente quando a pessoa se vê na fronteira entre a vida e a morte, necessita que a ajudem a encontrar um sentido para a vida, adaptando-se a esta nova situação. Assim, o desafio consiste em que os profissionais de saúde, nomeadamente os enfermeiros, implementem modelos de cuidados centrados na pessoa e família, que consigam entrar no seu mundo interior, de forma a responder às suas necessidades. Neste sentido, tivemos como objetivo desenvolver habilidades e competências especializadas na área dos Cuidados Paliativos, pelo que optamos pela realização de um Estágio de Natureza Profissional, com 350 horas presenciais, na Equipa Intra-Hospitalar de Suporte em Cuidados Paliativos da Unidade Local de Saúde do Alto Minho. Com este estágio temos como intencionalidade a obtenção de habilidades e competências na área dos cuidados paliativos através do treino e da análise crítica e reflexiva, de forma a que possamos contribuir no nosso contexto de trabalho para a mudança/inovação de modelos de cuidados que viabilizem a construção de um fim de vida condigno. Durante a realização do estágio de natureza profissional procuramos adotar metodologias ativas, dinâmicas e participativas, integrando, mobilizando e consolidando os conhecimentos teóricos adquiridos no 1º ano do curso de mestrado. Atendemos aos princípios ético-deontológicos, visando a pessoa doente e família como uma unidade de cuidados e por conseguinte a garantia da qualidade do cuidado. A nossa participação passou pelas várias dimensões dos cuidados paliativos, nomeadamente a nível do controlo sintomático, verificamos que é primordial para o bem-estar destes doentes e uma das preocupações maiores dos cuidados de enfermagem. Assim procuramos desenvolver competências sobretudo a nível da avaliação e monitorização. A nível da comunicação enfatizamos o treino a nível de um estilo comunicacional empático, procurando sempre uma comunicação eficaz e clara. Assim estas competências foram desenvolvidas através de uma adaptação da comunicação, às situações, contextualizar as reações, perceber os pensamentos e comportamentos, de forma a desenvolver habilidades para um cuidar mais adequado e adaptado. A nível do acompanhamento familiar e processo de luto salientamos as conferências familiares. No que se refere à nossa participação no âmbito da formação permitiu o desenvolvimento de competências e novas formas de intervir. Com a realização deste estágio, percebemos que uma resposta adequada em cuidados paliativos requer competências técnicas, científicas, relacionais e humanas, sempre acompanhadas de um pensamento crítico-reflexivo. Consideramos ter desenvolvido competências necessárias para a prestação de cuidados paliativos de excelência.

To accompany the process of nearing the end of life implies to have an holistic vision that provides global care to the person. We are quite commonly confronted with people who are suffering deeply in hospitals, where medical values centered in the biological dimension of the person still prevail, where the search for the cure imposes itself and death is denied. In fact, when a person is facing the frontier between life and death, this person will need help to find a meaning for his/her life in order to adapt to this new situation. So, the challenge consists of implementing new care models focused on the person and the family that enable the health professionals, particularly, the nurses, to enter the patients' inner world and by this responding to their needs. With this in mind, it is our aim to develop specialized skills and expertise in the field of Palliative Care. Therefore, we have chose an Internship of Professional Nature, 350 hours, in the Intra-Hospital Suppot Team for Palliative Care of the Local Unit of Healthcare of Alto Minho. The objective of this internship is to achieve the skills and expertise in the field of palliative care through practice as well as critical and reflexive thinking so that we will be able to contribute to the change/innovation of care models to ensure that the end of the patient's life will occur with dignity. Troughout the intership, we tried to embrace active dynamic participatory methologies and by this integrating mobilizing and consolidating knowlegde of what had been learned in the first year of the Masters Degree. Attending to the principals of deontology ethics, aiming to consider the person and the family as a unit of care. So, being able to ensure the quality of care. We participated in the various dimensions of the palliative care, namely in symptomatic control. We realised that it is of the outmost importance for the well-being of the patient and one of the greatets concerns of the nurse's care. Therefore, we developed expertise mainly at evaluation and monitoring level. Regarding communication, we emphasized an emphatic communication, mantaining it effective and clear. This expertise was developed by adapting communication to the situations, having in consideration the reactions, thoughts and behaviours so as to develop the skills to provide the best care possible. The family benefited from counselling for accompaniment and the grieving process. In what concerns our parttaking in the Basic Course in Palliative Care, it allowed us to develop new skills and ways to intervene. viThe intership allowed us to comprehend that technical scientific relational and human skills have always to interact with critical and reflexive thinking. We understand that we have developed the required skills for the provision of excellence in pallitative care.

Minimally Invasive Colorectal Cancer Surgery in Europe: Implementation and Outcomes.

Minimally invasive surgery (MIS) of colorectal cancer (CRC) was first introduced over 20 years ago and recently has gained increasing acceptance and usage beyond clinical trials. However, data on dissemination of the method across countries and on long-term outcomes are still sparse.In the context of a European collaborative study, a total of 112,023 CRC cases from 3 population-based (N = 109,695) and 4 institute-based clinical cancer registries (N = 2328) were studied and compared on the utilization of MIS versus open surgery. Cox regression models were applied to study associations between surgery type and survival of patients from the population-based registries. The study considered adjustment for potential confounders.The percentage of CRC patients undergoing MIS differed substantially between centers and generally increased over time. MIS was significantly less often used in stage II to IV colon cancer compared with stage I in most centers. MIS tended to be less often used in older (70+) than in younger colon cancer patients. MIS tended to be more often used in women than in men with rectal cancer. MIS was associated with significantly reduced mortality among colon cancer patients in the Netherlands (hazard ratio [HR] 0.66, 95% confidence interval [CI] (0.63-0.69), Sweden (HR 0.68, 95% CI 0.60-0.76), and Norway (HR 0.73, 95% CI 0.67-0.79). Likewise, MIS was associated with reduced mortality of rectal cancer patients in the Netherlands (HR 0.74, 95% CI 0.68-0.80) and Sweden (HR 0.77, 95% CI 0.66-0.90).Utilization of MIS in CRC resection is increasing, but large variation between European countries and clinical centers prevails. Our results support association of MIS with substantially enhanced survival among colon cancer patients. Further studies controlling for selection bias and residual confounding are needed to establish role of MIS in survival of patients.

A versatile modular vector system for rapid combinatorial mammalian genetics.

Here, we describe the multiple lentiviral expression (MuLE) system that allows multiple genetic alterations to be introduced simultaneously into mammalian cells. We created a toolbox of MuLE vectors that constitute a flexible, modular system for the rapid engineering of complex polycistronic lentiviruses, allowing combinatorial gene overexpression, gene knockdown, Cre-mediated gene deletion, or CRISPR/Cas9-mediated (where CRISPR indicates clustered regularly interspaced short palindromic repeats) gene mutation, together with expression of fluorescent or enzymatic reporters for cellular assays and animal imaging. Examples of tumor engineering were used to illustrate the speed and versatility of performing combinatorial genetics using the MuLE system. By transducing cultured primary mouse cells with single MuLE lentiviruses, we engineered tumors containing up to 5 different genetic alterations, identified genetic dependencies of molecularly defined tumors, conducted genetic interaction screens, and induced the simultaneous CRISPR/Cas9-mediated knockout of 3 tumor-suppressor genes. Intramuscular injection of MuLE viruses expressing oncogenic H-RasG12V together with combinations of knockdowns of the tumor suppressors cyclin-dependent kinase inhibitor 2A (Cdkn2a), transformation-related protein 53 (Trp53), and phosphatase and tensin homolog (Pten) allowed the generation of 3 murine sarcoma models, demonstrating that genetically defined autochthonous tumors can be rapidly generated and quantitatively monitored via direct injection of polycistronic MuLE lentiviruses into mouse tissues. Together, our results demonstrate that the MuLE system provides genetic power for the systematic investigation of the molecular mechanisms that underlie human diseases.

Induction of long noncoding RNA MALAT1 in hypoxic mice.

Long thought to be "junk DNA", in recent years it has become clear that a substantial fraction of intergenic genomic DNA is actually transcribed, forming long noncoding RNA (lncRNA). Like mRNA, lncRNA can also be spliced, capped, and polyadenylated, affecting a multitude of biological processes. While the molecular mechanisms underlying the function of lncRNAs have just begun to be elucidated, the conditional regulation of lncRNAs remains largely unexplored. In genome-wide studies our group and others recently found hypoxic transcriptional induction of a subset of lncRNAs, whereof nuclear-enriched abundant/autosomal transcript 1 (NEAT1) and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) appear to be the lncRNAs most ubiquitously and most strongly induced by hypoxia in cultured cells. Hypoxia-inducible factor (HIF)-2 rather than HIF-1 seems to be the preferred transcriptional activator of these lncRNAs. For the first time, we also found strong induction primarily of MALAT1 in organs of mice exposed to inspiratory hypoxia. Most abundant hypoxic levels of MALAT1 lncRNA were found in kidney and testis. In situ hybridization revealed that the hypoxic induction in the kidney was confined to proximal rather than distal tubular epithelial cells. Direct oxygen-dependent regulation of MALAT1 lncRNA was confirmed using isolated primary kidney epithelial cells. In summary, high expression levels and acute, profound hypoxic induction of MALAT1 suggest a hitherto unrecognized role of this lncRNA in renal proximal tubular function.

Gelsolin is required for macrophage recruitment during remyelination of the peripheral nervous system.

Reorganization of the actin cytoskeleton is necessary for Schwann cell proliferation, migration and for the morphological changes associated with sorting, ensheathing and myelination of axons. Such reorganization requires regulated severing and depolymerization of actin filaments. Gelsolin is an actin filament severing protein expressed in many cell types including Schwann cells. Using Gelsolin knockout mice, we investigated the role of this protein in the myelination and remyelination of the peripheral nervous system. Our results show that although gelsolin is not necessary for developmental myelination, it is required for timely remyelination of the sciatic nerve following crush injury. Gelsolin is necessary for macrophage motility in culture, and its absence is likely to impair the recruitment of macrophages to the injury site.

Integrin-linked kinase is required for radial sorting of axons and Schwann cell remyelination in the peripheral nervous system.

During development, Schwann cells (SCs) interpret different extracellular cues to regulate their migration, proliferation, and the remarkable morphological changes associated with the sorting, ensheathment, and myelination of axons. Although interactions between extracellular matrix proteins and integrins are critical to some of these processes, the downstream signaling pathways they control are still poorly understood. Integrin-linked kinase (ILK) is a focal adhesion protein that associates with multiple binding partners to link integrins to the actin cytoskeleton and is thought to participate in integrin and growth factor-mediated signaling. Using SC-specific gene ablation, we report essential functions for ILK in radial sorting of axon bundles and in remyelination in the peripheral nervous system. Our in vivo and in vitro experiments show that ILK negatively regulates Rho/Rho kinase signaling to promote SC process extension and to initiate radial sorting. ILK also facilitates axon remyelination, likely by promoting the activation of downstream molecules such as AKT/protein kinase B.

Is there a compromise between nutrient uptake and gas exchange in the gut of Misgurnus anguillicaudatus, an intestinal air-breathing fish?

The Asian weatherloach, Misgurnus anguillicaudatus (Cobitidae), is a facultative air-breathing teleost fish that makes use of its hindgut or intestine as an accessory air-breathing organ (ABO). The hindgut is highly modified, being well vascularized with intraepithelial capillaries, which makes it well suited for gas exchange. However, the consequences for nutrient uptake, the traditional function of the intestine are unknown. The alimentary canal was examined histologically to assess differences between the fore-, mid- and hindgut regions that have been considered as the digestive, spiral and respiratory zones, respectively. In order to characterise the potential digestive (absorptive) function of the respiratory zone we used semi-quantitative polymerase chain reaction (PCR) to detect the presence of the intestinal Na(+):glucose cotransporter (SGLT1; SLC5A1) and H(+):peptide cotransporter (PEPT1a; SLC15A1) and partially sequenced the SGLT1 and PEPT1a cDNAs. These two transporters play important roles in the absorption of carbohydrate and di-/tripeptides, respectively, in the gut of fishes and other vertebrates and were therefore used as markers for potential nutrient uptake function. We also determined their tissue distributions through semi-quantitative RT-PCR. The effects of diet composition (high protein or high carbohydrate) or fasting on gene expression were also examined. SGLT1 expression was found in kidney, liver, heart, as well as in the three zones of the gut except the most distal part of the hindgut. PEPT1a mRNA was found in heart, brain, liver, and fore- and midgut, but absent in the hindgut. Our results clearly show high expression of SGLT1 (both mRNA and protein by immunolocalization) and PEPT1a (mRNA) in the foregut and midgut correlated with the digestive region of the gut. Modulatory effects of diet on the gene expression for both SGLT1 and PEPT1a were not observed. The presence of SGLT1 transcripts in the respiratory zone of the intestine suggests an overlap in function. However, in the case of PEPT1a, the distal limit was the midgut. Thus, despite its highly modified structure, the hindgut of the loach retains some potential nutrient uptake function.