Percepción de los pacientes sobre los cuidados de enfermería en el contexto de la crisis del COVID-19

[ES] Antecedentes: La pandemia de COVID-19 ha alterado considerablemente los procedimientos habituales de los sistemas sanitarios en todo el mundo. El trabajo diario se ha vuelto física y emocionalmente agotador para los profesionales sanitarios, obligados a afrontar y adaptarse a nuevos retos y situaciones estresantes. Esta situación pesa sobre la práctica diaria de enfermería. Objetivo: El presente estudio tuvo como objetivo determinar la percepción del paciente sobre los cuidados de enfermería humanizados recibidos durante su estancia hospitalaria. Método: Se realizó un estudio descriptivo, cuantitativo, transversal, en el que se realizaron entrevistas telefónicas a 357 personas >18 años que ingresaron durante más de 24 horas en el Hospital de León con el fin de evaluar la percepción del paciente. Uno de los instrumentos utilizados fue la Escala de Percepción de Conductas del Cuidado de Enfermería Humanizado (PCHE), para evaluar en tres dimensiones (D): cualidades de la práctica de enfermería (D1), apertura a la comunicación enfermera-paciente (D2) y disposición al cuidado (D3). El otro instrumento utilizado fue una encuesta de satisfacción institucional para conocer la opinión sobre la calidad de la atención al cliente en el área de hospitalización. Resultados: El porcentaje de pacientes que puntuaron como “siempre” cada dimensión fue: D1 = 91,2%; D2 = 81,4%; y D3 = 87,8%. La satisfacción del paciente obtuvo una puntuación media de 4,6 sobre 5. Conclusión: A pesar del impacto negativo del COVID-19 en el sistema de salud, los pacientes percibieron la atención de enfermería humanizada recibida como muy satisfactoria.[EN] Background: The COVID-19 pandemic has heavily altered regular procedures of healthcare systems worldwide. Daily work has become physically and emotionally exhausting for health care professionals, forced to face and adapt to new challenges and stressful situations. This situation weighs on the daily nursing practice and might have an impact on the quality of care provided and on the level of satisfaction perceived by hospitalized patients. Thus, the present study aimed to determine the patient’s perception of humanized nursing care received during their hospital stay. Methods: A descriptive, quantitative, cross-sectional study was carried out, in which telephone interviews were conducted in 357 people >18 years of age who were admitted for more than 24 hours to the Hospital de León in order to asses patient ́s perception. One instrument used was The Perception of Behaviors of Humanized Nursing Care Scale (PCHE), to evaluate in three dimensions (D): qualities of nursing practice (D1), openness to nurse–patient communication (D2), and willingness to care (D3). In addition, an institutional satisfaction survey was performed to know the opinion on the quality of customer service in hospitalization area. Results: The percentage of patients scoring as “always” every dimension was: D1 = 91.2%; D2= 81.4%; and D3= 87.8%. Patient satisfaction obtained a mean score of 4.6 out of 5. 42.3% of population were men and 57.7% were women, most in the age range 61–75 years. The predominant marital status and educational level were married and basic–medium, respectively. Conclusion: Despite the negative impact of COVID-19 in the health care system, patients perceived humanized nursing care received as very successful.S

Nuclear Reorganization in Hippocampal Granule Cell Neurons from a Mouse Model of Down Syndrome: Changes in Chromatin Configuration, Nucleoli and Cajal Bodies

Down syndrome (DS) or trisomy of chromosome 21 (Hsa21) is characterized by impaired hippocampal-dependent learning and memory. These alterations are due to defective neurogenesis and to neuromorphological and functional anomalies of numerous neuronal populations, including hippocampal granular cells (GCs). It has been proposed that the additional gene dose in trisomic cells induces modifications in nuclear compartments and on the chromatin landscape, which could contribute to some DS phenotypes. The Ts65Dn (TS) mouse model of DS carries a triplication of 92 genes orthologous to those found in Hsa21, and shares many phenotypes with DS individuals, including cognitive and neuromorphological alterations. Considering its essential role in hippocampal memory formation, we investigated whether the triplication of this set of Hsa21 orthologous genes in TS mice modifies the nuclear architecture of their GCs. Our results show that the TS mouse presents alterations in the nuclear architecture of its GCs, affecting nuclear compartments involved in transcription and pre-rRNA and pre-mRNA processing. In particular, the GCs of the TS mouse show alterations in the nucleolar fusion pattern and the molecular assembly of Cajal bodies (CBs). Furthermore, hippocampal GCs of TS mice present an epigenetic dysregulation of chromatin that results in an increased heterochromatinization and reduced global transcriptional activity. These nuclear alterations could play an important role in the neuromorphological and/or functional alterations of the hippocampal GCs implicated in the cognitive dysfunction characteristic of TS mice

Oxidative-Stress-Associated Proteostasis Disturbances and Increased DNA Damage in the Hippocampal Granule Cells of the Ts65Dn Model of Down Syndrome

Oxidative stress (OS) is one of the neuropathological mechanisms responsible for the deficits in cognition and neuronal function in Down syndrome (DS). The Ts65Dn (TS) mouse replicates multiple DS phenotypes including hippocampal-dependent learning and memory deficits and similar brain oxidative status. To better understand the hippocampal oxidative profile in the adult TS mouse, we analyzed cellular OS-associated alterations in hippocampal granule cells (GCs), a neuronal population that plays an important role in memory formation and that is particularly affected in DS. For this purpose, we used biochemical, molecular, immunohistochemical, and electron microscopy techniques. Our results indicate that TS GCs show important OS-associated alterations in the systems essential for neuronal homeostasis: DNA damage response and proteostasis, particu larly of the proteasome and lysosomal system. Specifically, TS GCs showed: (i) increased DNA damage, (ii) reorganization of nuclear proteolytic factories accompanied by a decline in proteasome activity and cytoplasmic aggregation of ubiquitinated proteins, (iii) formation of lysosomal-related structures containing lipid droplets of cytotoxic peroxidation products, and (iv) mitochondrial ultrastructural defects. These alterations could be implicated in enhanced cellular senescence, accelerated aging and neurodegeneration, and the early development of Alzheimer?s disease neuropathology present in TS mice and the DS population.Funding: This work was supported by the following grants: “Instituto de Investigación Valdecilla” (IDIVAL; NVAL 19/23), Santander, Spain; “Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas” (CIBERNED; CB06/05/0037) Spain; and “Agencia Estatal de Investicación, MICIN” (grant number: PID2020-117601RB-I00). Acknowledgments: The authors would like to thank Raquel García-Ceballos and Eva García Iglesias for their technical assistance

Non-homogeneous dispersion of graphene in polyacrylonitrile substrates induces a migrastatic response and epithelial-like differentiation in MCF7 breast cancer cells

Background: Recent advances from studies of graphene and graphene-based derivatives have highlighted the great potential of these nanomaterials as migrastatic agents with the ability to modulate tumor microenvironments. Nevertheless, the administration of graphene nanomaterials in suspensions in vivo is controversial. As an alternative approach, herein, we report the immobilization of high concentrations of graphene nanoplatelets in polyacrylonitrile film substrates (named PAN/G10) and evaluate their potential use as migrastatic agents on cancer cells. Results: Breast cancer MCF7 cells cultured on PAN/G10 substrates presented features resembling mesenchymal-to-epithelial transition, e.g., (i) inhibition of migratory activity; (ii) activation of the expression of E-cadherin, cytokeratin 18, ZO-1 and EpCAM, four key molecular markers of epithelial differentiation; (iii) formation of adherens junctions with clustering and adhesion of cancer cells in aggregates or islets, and (iv) reorganization of the actin cytoskeleton resulting in a polygonal cell shape. Remarkably, assessment with Raman spectroscopy revealed that the above-mentioned events were produced when MCF7 cells were preferentially located on top of graphene-rich regions of the PAN/G10 substrates. Conclusions: The present data demonstrate the capacity of these composite substrates to induce an epithelial-like differentiation in MCF7 breast cancer cells, resulting in a migrastatic effect without any chemical agent-mediated signaling. Future works will aim to thoroughly evaluate the mechanisms of how PAN/G10 substrates trigger these responses in cancer cells and their potential use as antimetastatics for the treatment of solid cancers.This work was supported by Grants from the “Asociación Luchamos por la Vida” (Corrales de Buelna, Cantabria, Spain), Health Research Institute “Valdecilla” (INNVAL17/20, IDIVAL), MINECO/EIG-Concert Japan (X-MEM PCI2018-092929 project, International Joint Program 2018) and the Spanish Research Agency (PID2019-105827RB-I00 supported by MCIN/AEI/10.13039/501100011033)

Bexarotene Impairs Cognition and Produces Hypothyroidism in a Mouse Model of Down Syndrome and Alzheimer’s Disease

All individuals with Down syndrome (DS) eventually develop Alzheimer's disease (AD) neuropathology, including neurodegeneration, increases in ?-amyloid (A?) expression, and aggregation and neurofibrillary tangles, between the third and fourth decade of their lives. There is currently no effective treatment to prevent AD neuropathology and the associated cognitive degeneration in DS patients. Due to evidence that the accumulation of A? aggregates in the brain produces the neurodegenerative cascade characteristic of AD, many strategies which promote the clearance of A? peptides have been assessed as potential therapeutics for this disease. Bexarotene, a member of a subclass of retinoids that selectively activates retinoid receptors, modulates several pathways essential for cognitive performance and A? clearance. Consequently, bexarotene might be a good candidate to treat AD-associated neuropathology. However, the effects of bexarotene treatment in AD remain controversial. In the present study, we aimed to elucidate whether chronic bexarotene treatment administered to the most commonly used murine model of DS, the Ts65Dn (TS) mouse could reduce A? expression in their brains and improve their cognitive abilities. Chronic administration of bexarotene to aged TS mice and their CO littermates for 9 weeks diminished the reference, working, and spatial learning and memory of TS mice, and the spatial memory of CO mice in the Morris water maze. This treatment also produced marked hypoactivity in the plus maze, open field, and hole board tests in TS mice, and in the open field and hole board tests in CO mice. Administration of bexarotene reduced the expression of A?1-40, but not of A?1-42, in the hippocampi of TS mice. Finally, bexarotene increased Thyroid-stimulating hormone levels in TS mice and reduced Thyroid-stimulating hormone levels in CO mice, while animals of both karyotypes displayed reduced thyroxine levels after bexarotene administration. The bexarotene-induced hypothyroidism could be responsible for the hypoactivity of TS and CO mice and their diminished performance in the Morris water maze. Together, these results do not provide support for the use of bexarotene as a potential treatment of AD neuropathology in the DS population.FUNDING: This study was supported by the Institute of Research Valdecilla (IDIVAL) (NVAL 16/21 and NVAL 19/23) and the Consejería de Universidades, Igualdad, Cultura y Deporte del Gobierno de Cantabria (16. VP39.64662)

Nusinersen ameliorates motor function and prevents motoneuron Cajal body disassembly and abnormal poly(A) RNA distribution in a SMA mouse model

Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease characterized by degeneration of spinal cord alpha motor neurons (αMNs). SMA is caused by the homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene, resulting in reduced expression of SMN protein, which leads to αMN degeneration and muscle atrophy. The majority of transcripts of a second gene (SMN2) generate an alternative spliced isoform that lacks exon 7 and produces a truncated nonfunctional form of SMN. A major function of SMN is the biogenesis of spliceosomal snRNPs, which are essential components of the pre-mRNA splicing machinery, the spliceosome. In recent years, new potential therapies have been developed to increase SMN levels, including treatment with antisense oligonucleotides (ASOs). The ASO-nusinersen (Spinraza) promotes the inclusion of exon 7 in SMN2 transcripts and notably enhances the production of full-length SMN in mouse models of SMA. In this work, we used the intracerebroventricular injection of nusinersen in the SMN∆7 mouse model of SMA to evaluate the effects of this ASO on the behavior of Cajal bodies (CBs), nuclear structures involved in spliceosomal snRNP biogenesis, and the cellular distribution of polyadenylated mRNAs in αMNs. The administration of nusinersen at postnatal day (P) 1 normalized SMN expression in the spinal cord but not in skeletal muscle, rescued the growth curve and improved motor behavior at P12 (late symptomatic stage). Importantly, this ASO recovered the number of canonical CBs in MNs, significantly reduced the abnormal accumulation of polyadenylated RNAs in nuclear granules, and normalized the expression of the pre-mRNAs encoding chondrolectin and choline acetyltransferase, two key factors for αMN homeostasis. We propose that the splicing modulatory function of nusinersen in SMA αMN is mediated by the rescue of CB biogenesis, resulting in enhanced polyadenylated pre-mRNA transcription and splicing and nuclear export of mature mRNAs for translation. Our results support that the selective restoration of SMN expression in the spinal cord has a beneficial impact not only on αMNs but also on skeletal myofibers. However, the rescue of SMN expression in muscle appears to be necessary for the complete recovery of motor function.The authors wish to thank Raquel García-Ceballos for technical assistance and Alfonso Nieva for video editing. We are also grateful to Prof. A. I. Lamond (University of Dundee, UK) for anti-coilin antibody (204.10) and Prof. Larry Gerace (The Scripps Research Institute, La Jolla, USA) for anti-LaminA/C antibody. The authors are also indebted to Prof. Josep E. Esquerda for critical reading of the manuscript and helpful suggestions. This work was supported by the following grants: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0037) Spain; Instituto de Investigación Sanitaria Valdecilla (IDIVAL, Next-Val 17/22), Santander, Spain; and Spanish Ministerio de Ciencia, Innovación y Universidades cofinanced by Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-099278-B-I00)

Tough Love Lessons: Lateral Violence among Hospital Nurses

Background: Workplace violence is a growing social problem among many professions, but it particularly affects the health sector. Studies have mainly focused on evaluating user violence toward health professionals, with less attention being paid to other sources of conflict, such as co-workers themselves. There are different manifestations of this violence in what has been called a context of tolerated or normalized violence among co-workers. However, its effects are far from being tolerable, as they have an impact on general health and job satisfaction and contribute to burnout among professionals. Based on this idea, and following the line of the previous literature, nursing staff are a population at high risk of exposure to workplace violence. For this reason, the present study aims to evaluate exposure to lateral violence or violence among co-workers in nursing staff in public health services and the relationship of this exposure with some of the most studied consequences. (2) Methods: A cross-sectional associative study was carried out in which scales of workplace violence (HABS-CS), burnout (MBI-GS), job satisfaction (OJS), and general health (GHQ-28) were applied to a sample of 950 nursing staff from 13 public hospitals located in the southeast of Spain. (3) Results: The results show that nursing staff have a high exposure to violence from their co-workers, which is more common in male nurses. Greater exposure is observed in professionals with between 6 and 10 years of experience in the profession, and it is not characteristic of our sample to receive greater violence when they have less experience or are younger. A positive correlation is observed with high levels of burnout and a negative correlation with general health and job satisfaction. (4) Conclusions: The results of this work contribute to increasing the scientific evidence of the consequences of a type of workplace violence frequent among nursing staff and to which less attention has been paid in relative terms to other types of prevalent violence. Organizations should be aware of the importance of this type of workplace violence, its frequency and impact, and implement appropriate prevention policies that include the promotion of a culture that does not reward violence or minimize reporting. A change of mentality in the academic environment is also recommended in order to promote a more adequate training of nursing staff in this field

Tumor xenograft modeling identifies an association between TCF4 loss and breast cancer chemoresistance

Understanding the mechanisms of cancer therapeutic resistance is fundamental to improving cancer care. There is clear benefit from chemotherapy in different breast cancer settings; however, knowledge of the mutations and genes that mediate resistance is incomplete. In this study, by modeling chemoresistance in patientderived xenografts (PDXs), we show that adaptation to therapy is genetically complex and identify that loss of transcription factor 4 (TCF4; also known as ITF2) is associated with this process. A triple-negative BRCA1-mutaied PDX was used to study the genetics of chemoresistance. The PDX was treated in parallel with four chemotherapies for five iterative cycles. Exome sequencing identified few genes with de novo or enriched mutations in common among the different therapies, whereas many common depleted mutations/ genes were observed. Analysis of somatic mutations from The Cancer Genome Atlas (TCGA) supported the prognostic relevance of the identified genes. A mutation in TCF4 was found de novo in all treatments, and analysis of drug sensitivity profiles across cancer cell lines supported the link to chemoresistance. Loss of TCF4 conferred chemoresistance in breast cancer cell models, possibly by altering cell cycle regulation. Targeted sequencing in chemoresistant tumors identified an intronic variant of TCF4 that may represent an expression quantitative trait locus associated with relapse outcome in TCGA. Immunohistochemical studies suggest a common loss of nuclear TCF4 expression post-chemotherapy. Together, these results from tumor xenograft modeling depict a link between altered TCF4 expression and breast cancer chemoresistance

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p 0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.Depto. de MedicinaFac. de MedicinaTRUEInstituto de Salud Carlos IIIFundación CRIS Contra el CáncerInstituto de Investigación Hospital 12 de OctubreUnión Europeapu

Abdominal obesity and dsyglycemia are risk factors for liver fibrosis progression in NAFLD subjects : A population-based study

To investigate longitudinal changes in the liver stiffness measurement (LSM) in the general adult population without known liver disease and to describe its association with metabolic risk factors, with a special focus on subjects with non-alcoholic fatty liver disease (NAFLD) and dysglycemia. A longitudinal adult population-based cohort study was conducted in Catalonia. LSM was measured by transient elastography (TE) at baseline and follow-up (median: 4.2 years). Subgroup with NAFLD and dysglycemia were analyzed. Moderate-to-advanced liver fibrosis was defined as LSM ≥8.0 kPa and LSM ≥9.2 kPa respectively. Among 1.478 subjects evaluated, the cumulative incidence of LSM ≥8.0 kPa and ≥9.2 kPa at follow-up was 2.8% and 1.9%, respectively. This incidence was higher in NAFLD (7.1% for LSM ≥8.0 kPa and 5% for LSM ≥9.2 kPa) and dysglycemia (6.2% for LSM ≥8.0 kPa and 4.7% for LSM ≥9.2 kPa) subgroups. In the global cohort, the multivariate analyses showed that dysglycemia, abdominal obesity and atherogenic dyslipidemia were significantly associated with progression to moderate-to-advanced liver fibrosis. Female sex was negatively associated. In subjects with NAFLD, abdominal obesity and dysglycemia were associated with changes in LSM to ≥8.0 kPa and ≥9.2 kPa at follow-up. A decline in LSM value to <8 kPa was observed in 64% of those subjects with a baseline LSM ≥8.0 kPa. In this population study, the presence of abdominal obesity and dysglycemia were the main risk metabolic factors associated with moderate-to-advanced liver fibrosis development over time in general populations as well as in subjects with NAFLD