Progression and Resolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Golden Syrian Hamsters.

To catalyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research, including development of novel interventive and preventive strategies, the progression of disease was characterized in a robust coronavirus disease 2019 (COVID-19) animal model. In this model, male and female golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 USA-WA1/2020. Groups of inoculated and mock-inoculated uninfected control animals were euthanized at 2, 4, 7, 14, and 28 days after inoculation to track multiple clinical, pathology, virology, and immunology outcomes. SARS-CoV-2-inoculated animals consistently lost body weight during the first week of infection, had higher lung weights at terminal time points, and developed lung consolidation per histopathology and quantitative image analysis measurements. High levels of infectious virus and viral RNA were reliably present in the respiratory tract at days 2 and 4 after inoculation, corresponding with widespread necrosis and inflammation. At day 7, when the presence of infectious virus was rare, interstitial and alveolar macrophage infiltrates and marked reparative epithelial responses (type II hyperplasia) dominated in the lung. These lesions resolved over time, with only residual epithelial repair evident by day 28 after inoculation. The use of quantitative approaches to measure cellular and morphologic alterations in the lung provides valuable outcome measures for developing therapeutic and preventive interventions for COVID-19 using the hamster COVID-19 model.

Biofortification of Kidney Bean (Phaseolus vulgaris L.) Crops Applying Zinc Sulfate and Ferric Sulfate: Pilot Crop in Colombia.

Agriculture is one of the economic activities with the most potential in Colombia, given its climatic and geographical conditions. Bean cultivation is classified as climbing, which grows in a branched way, and bushy, whose growth occurs up to 70 cm. The objective of this research was to study zinc and iron sulfates in different concentrations as fertilizers capable of increasing the nutritional value of kidney beans (Phaseolus vulgaris L.), whose strategy is known as biofortification, and thus determine the most effective sulfate. The methodology details the sulfate formulations, their preparation, the application of additives, sampling and quantification methods of total iron, total zinc, °Brix, carotenoids, chlorophylls a, b, and antioxidant capacity using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method in leaves and pods. As for the results, it was found that biofortification with iron sulfate and zinc sulfate is a strategy that favors the country's economy and human health, because it allows the increase of minerals, antioxidant capacity and total soluble solids.

Effect of Single Housing on Innate Immune Activation in Immunodeficiency Virus-Infected Pigtail Macaques ( Macaca nemestrina ) as a Model of Psychosocial Stress in Acute HIV Infection.

OBJECTIVE: Simian immunodeficiency virus (SIV) infection of macaques recapitulates many aspects of HIV pathogenesis and is similarly affected by both genetic and environmental factors. Psychosocial stress is associated with immune system dysregulation and worse clinical outcomes in people with HIV. This study assessed the impact of single housing, as a model of psychosocial stress, on innate immune responses of pigtailed macaques ( Macaca nemestrina ) during acute SIV infection. METHODS: A retrospective analysis of acute SIV infection of 2- to si6-year-old male pigtailed macaques was performed to compare the innate immune responses of socially ( n = 41) and singly ( n = 35) housed animals. Measures included absolute monocyte count and subsets, and in a subset ( n ≤ 18) platelet counts and activation data. RESULTS: SIV infection resulted in the expected innate immune parameter changes with a modulating effect from housing condition. Monocyte number increased after infection for both groups, driven by classical monocytes (CD14 + CD16 - ), with a greater increase in socially housed animals (227%, p < .001, by day 14 compared with preinoculation time points). Platelet numbers recovered more quickly in the socially housed animals. Platelet activation (P-selectin) increased by 65% ( p = .004) and major histocompatibility complex class I surface expression by 40% ( p = .009) from preinoculation only in socially housed animals, whereas no change in these measures occurred in singly housed animals. CONCLUSIONS: Chronic psychosocial stress produced by single housing may play an immunomodulatory role in the innate immune response to acute retroviral infection. Dysregulated innate immunity could be one of the pathways by which psychosocial stress contributes to immune suppression and increased disease severity in people with HIV.

Psychosocial Stress Alters the Immune Response and Results in Higher Viral Load During Acute Simian Immunodeficiency Virus Infection in a Pigtailed Macaque Model of Human Immunodeficiency Virus.

BACKGROUND: Although social distancing is a key public health response during viral pandemics, psychosocial stressors, such as social isolation, have been implicated in adverse health outcomes in general [1] and in the context of infectious disease, such as human immunodeficiency virus (HIV) [2, 3]. A comprehensive understanding of the direct pathophysiologic effects of psychosocial stress on viral pathogenesis is needed to provide strategic and comprehensive care to patients with viral infection. METHODS: To determine the effect of psychosocial stress on HIV pathogenesis during acute viral infection without sociobehavioral confounders inherent in human cohorts, we compared commonly measured parameters of HIV progression between singly (n = 35) and socially (n = 41) housed simian immunodeficiency virus (SIV)-infected pigtailed macaques (Macaca nemestrina). RESULTS: Singly housed macaques had a higher viral load in the plasma and cerebrospinal fluid and demonstrated greater CD4 T-cell declines and more CD4 and CD8 T-cell activation compared with socially housed macaques throughout acute SIV infection. CONCLUSIONS: These data demonstrate that psychosocial stress directly impacts the pathogenesis of acute SIV infection and imply that it may act as an integral variable in the progression of HIV infection and potentially of other viral infections.

The functions and regulation of heat shock proteins; key orchestrators of proteostasis and the heat shock response.

Cells respond to protein-damaging (proteotoxic) stress by activation of the Heat Shock Response (HSR). The HSR provides cells with an enhanced ability to endure proteotoxic insults and plays a crucial role in determining subsequent cell death or survival. The HSR is, therefore, a critical factor that influences the toxicity of protein stress. While named for its vital role in the cellular response to heat stress, various components of the HSR system and the molecular chaperone network execute essential physiological functions as well as responses to other diverse toxic insults. The effector molecules of the HSR, the Heat Shock Factors (HSFs) and Heat Shock Proteins (HSPs), are also important regulatory targets in the progression of neurodegenerative diseases and cancers. Modulation of the HSR and/or its extended network have, therefore, become attractive treatment strategies for these diseases. Development of effective therapies will, however, require a detailed understanding of the HSR, important features of which continue to be uncovered and are yet to be completely understood. We review recently described and hallmark mechanistic principles of the HSR, the regulation and functions of HSPs, and contexts in which the HSR is activated and influences cell fate in response to various toxic conditions.

Platelet-endothelial associations may promote cytomegalovirus replication in the salivary gland in mice.

Platelet decline is a feature of many acute viral infections, including cytomegalovirus (CMV) infection in humans and mice. Platelet sequestration in association with other cells, including endothelium and circulating leukocytes, can contribute to this decline and influence the immune response to and pathogenesis of viral infection. We sought to determine if platelet-endothelial associations (PEAs) contribute to platelet decline during acute murine CMV (mCMV) infection, and if these associations affect viral load and production. Male BALB/c mice were infected with mCMV (Smith strain), euthanized at timepoints throughout acute infection and compared to uninfected controls. An increase in PEA formation was confirmed in the salivary gland at all post-inoculation timepoints using immunohistochemistry for CD41+ platelets co-localizing with CD34+ vessels. Platelet depletion did not change amount of viral DNA or timecourse of infection, as measured by qPCR. However, platelet depletion reduced viral titer of mCMV in the salivary glands while undepleted controls demonstrated robust replication in the tissue by plaque assay. Thus, platelet associations with endothelium may enhance the ability of mCMV to replicate within the salivary gland. Further work is needed to determine the mechanisms behind this effect and if pharmacologic inhibition of PEAs may reduce CMV production in acutely infected patients.

Impact factor evolution of nursing research journals: 2009 to 2014.

BACKGROUND: The use of bibliometric indicators (impact factor [IF], impact index, h-index, etc.) is now believed to be a fundamental measure of the quality of scientific research output. In this context, the presence of scientific nursing journals in international databases and the factors influencing their impact ratings is being widely analyzed. PURPOSE: The aim of this study was to analyze the presence of scientific nursing journals in international databases and track the changes in their IF. METHODS: A secondary analysis was carried out on data for the years 2009 to 2014 held in the JCR database (subject category: nursing). Additionally, the presence of scientific nursing journals in Medline, CINAHL, Scopus, and SJR was analyzed. DISCUSSION: During the period studied, the number of journals indexed in the JCR under the nursing subject category increased from 70 in 2009 (mean IF: 0.99, standard deviation: 0.53) to 115 in 2014 (mean IF: 1.04, standard deviation: 0.42), of which only 70 were listed for the full six years. Although mean IF showed an upward trend throughout this time, no statistically significant differences were found in the variations to this figure. CONCLUSION: Although IF and other bibliometric indicators have their limitations, it is nonetheless true that bibliometry is now the most widely used tool for evaluating scientific output in all disciplines, including nursing, highlighting the importance of being familiar with how they are calculated and their significance when deciding the journal or journals in which to publish the results of our research. That said, it is also necessary to consider other possible alternative ways of assessing the quality and impact of scientific contributions.

The trans fatty acid elaidate affects the global DNA methylation profile of cultured cells and in vivo.

BACKGROUND: The deleterious effects of dietary trans fatty acids (tFAs) on human health are well documented. Although significantly reduced or banned in various countries, tFAs may trigger long-term responses that would represent a valid human health concern, particularly if tFAs alter the epigenome. METHODS: Based on these considerations, we asked whether the tFA elaidic acid (EA; tC18:1) has any effects on global DNA methylation and the transcriptome in cultured human THP-1 monocytes, and whether the progeny of EA-supplemented dams during either pregnancy or lactation in mice (n = 20 per group) show any epigenetic change after exposure. RESULTS: EA induced a biphasic effect on global DNA methylation in THP-1 cells, i.e. hypermethylation in the 1-50 µM concentration range, followed by hypomethylation up to the 200 µM dose. On the other hand, the cis isomer oleic acid (OA), a fatty acid with documented beneficial effects on human health, exerted a distinct response, i.e. its effects were weaker and only partially overlapping with EA's. The maximal differential response between EA and OA was observed at the 50 µM dose. Array expression data revealed that EA induced a pro-inflammatory and adipogenic transcriptional profile compared with OA, although with modest effects on selected (n = 9) gene promoter methylation. In mice, maternal EA supplementation in utero or via the breastmilk induced global adipose tissue DNA hypermethylation in the progeny, that was detectable postnatally at the age of 3 months. CONCLUSION: We document that global DNA hypermethylation is a specific and consistent response to EA in cell culture and in mice, and that EA may exert long-term effects on the epigenome following maternal exposure.

[Pain in the elderly]. / Dolor en al anciano.

Pain leads to unpleasant sensory or emotional experience for any individual. In the elderly, given their biopsychosocial characteristics, the pain requires a specific approach, different from other age groups: this is the objective of this article, which dealt with the different types of pain, the assessment and treatment of the same.

"It Happened to Me and It's Serious": Conditional Indirect Effects of Infection Severity Narrated in Testimonial Tweets on COVID-19 Prevention.

The health crisis caused by COVID-19 resulted in societal breakdowns around the world. Our research is based on determining which features of testimonial messages are most relevant in increasing persuasive impact. An online experiment with a 2 (severity infection narrative: low vs. high) × 2 (infection target: narrative's protagonist vs. protagonist's father) between-subject factorial design was carried out. Young people between 18 and 28 years (N = 278) were randomly assigned to one of the four experimental conditions, where they were asked to read a narrative message in the form of a Twitter thread describing a COVID-19 infection (with mild or severe symptoms) that affected either the protagonist of the message (a 23-year-old young person) or their father. After reading the narrative message, the mediating and dependent variables were evaluated. A message describing a severe COVID-19 infection affecting their protagonist to increase the perception of personal risk increased the persuasive impact through an increase in cognitive elaboration and a reduction in reactance. Our study highlights that creating persuasive messages based on social media targeted at young people that describe a careless behavior resulting in a severe COVID-19 infection can be an appropriate strategy for designing prevention campaigns.

Melanoma cells with acquired resistance to vemurafenib have decreased autophagic flux and display enhanced ability to transfer resistance.

Over the last years, the incidence of melanoma, the deadliest form of skin cancer, has risen significantly. Nearly half of the melanoma patients exhibit the BRAFV600E mutation. Although the use of BRAF and MEK inhibitors (BRAFi and MEKi) showed an impressive success rate in melanoma patients, durability of response remains an issue because tumor quickly becomes resistant. Here, we generated and characterized Lu1205 and A375 melanoma cells resistant to vemurafenib (BRAFi). Resistant cells (Lu1205R and A375R) exhibit higher IC50 (5-6 fold increase) and phospho-ERK levels and 2-3 times reduced apoptosis than their sensitive parents (Lu1205S and A375S). Moreover, resistant cells are 2-3 times bigger, display a more elongated morphology and have a modulation of migration capacity. Interestingly, pharmacological inhibition of sphingosine kinases, that prevents sphingosine-1-phosphate production, reduces migration of Lu1205R cells by 50 %. In addition, although Lu1205R cells showed increased basal levels of the autophagy markers LC3II and p62, they have decreased autophagosome degradation and autophagy flux. Remarkably, expression of Rab27A and Rab27B, which are involved in the release of extracellular vesicles are dramatically augmented in resistant cells (i.e. 5-7 fold increase). Indeed, conditioned media obtained from Lu1205R cells increased the resistance to vemurafenib of sensitive cells. Hence, these results support that resistance to vemurafenib modulates migration and the autophagic flux and may be transferred to nearby sensitive melanoma cells by factors that are released to the extracellular milieu by resistant cells.

Chemotherapy-Related Cognitive Impairment in Patients with Breast Cancer Based on Functional Assessment and NIRS Analysis.

Background: Chemotherapy-related cognitive impairment (CRCI), or "chemobrain," isdefined as a phenomenon of cognitive deficits in cancer patients after chemotherapy and is characterized by deficits in areas of cognition, including memory, attention, speed of processing, and executive function, which seriously affect quality of life. The purpose of this study is to investigate the impact of CRCI in breast cancer (BC) patients in chemotherapy treatment (CT+) or not (CT−) and to analyze their relationship with detectable objective changes in cerebral activity during the execution of a phonological and semantic verbal fluency task (PVF and SVF). Methods: An observational, cross-sectional study was carried out at Badajoz University Hospital (Spain). A total of 180 women with BC were included. We used Cognitive Scale (FACT-Cog) for neuropsychological subjective assessment, obtaining scores of perceived cognitive impairment (PCI), and near-infrared spectroscopy system (NIRS) for neuropsychological objective assessment during a verbal fluency task (PVF and SVF), determining alterations in the prefrontal cortex (PFC) assessed as changes in regional saturation index (rSO2). Results: A total of 41.7% percent of the patients in the sample had PCI. CT+ was significantly associated with a worse impact in PCI (X¯ = 50.60 ± 15.64 vs. X¯ = 55.01 ± 12.10; p = 0.005). Average rSO2 decreased significantly in CT+ (X¯ = 63.30 ± 8.02 vs. X¯ = 67.98 ± 7.80; p < 0.001), and BC patients showed a significant decrease in PVF and SVF on average (X¯ = 41.99 ± 9.52 vs. X¯ = 47.03 ± 9.31, and X¯ = 33.43 ± 11.0 vs. X¯ = 36.14 ± 10.68, respectively; p < 0.001). Conclusions: Our findings suggest that cognitive impairments in the domain of executive functioning exist among patients with BC who received CT. The results corroborate the hypothesis that CT is an important factor in cognitive impairment in patients with BC, which has been demonstrated by both subjective (PCI) and objective (PVF, SVF, and rSO2) neuropsychological measures. The combination of doxorubicin, cyclophosphamide, and docetaxel induce cognitive impairment.

Factors Related to Anxiety, Depressive Symptoms and Quality of Life in Breast Cancer.

Breast cancer (BC) is a major public health problem internationally. Although illness survival rates have improved, patients usually suffer multiple symptoms, both physical and psychological, which can affect their quality of life (QoL). The main aim of this study was to evaluate depressive symptoms, anxiety and the QoL of people with BC. An observational, cross-sectional study was carried out at Badajoz University Hospital (Spain). A total of 200 women with BC were included. EORTC QLQ-C30 and QLQ-BR23 questionnaires were used to assess QoL. Patients were screened for depressive symptoms using the Beck Depression Inventory (BDI) and for state anxiety and trait anxiety using the State Anxiety Inventory (STAI). Thirty-eight percent of the patients in the sample had moderate to severe anxiety, which was related to the time of diagnosis, advanced stage of illness and surgical treatment. We found that 28% of patients had depressive symptoms, related mainly with time of diagnosis, adjuvant therapy and number of cycles of chemotherapy (CT). Patients with the longest time since diagnosis, in stage III, and in treatment with CT, especially those with the greatest number of cycles, had the worst scores in QoL. We found a positive association between depressive symptoms and anxiety with QoL in patients with BC.

Pharmacokinetics and biodistribution of extracellular vesicles administered intravenously and intranasally to Macaca nemestrina.

Extracellular vesicles (EVs) have potential in disease treatment since they can be loaded with therapeutic molecules and engineered for retention by specific tissues. However, questions remain on optimal dosing, administration, and pharmacokinetics. Previous studies have addressed biodistribution and pharmacokinetics in rodents, but little evidence is available for larger animals. Here, we investigated the pharmacokinetics and biodistribution of Expi293F-derived EVs labelled with a highly sensitive nanoluciferase reporter (palmGRET) in a non-human primate model (Macaca nemestrina), comparing intravenous (IV) and intranasal (IN) administration over a 125-fold dose range. We report that EVs administered IV had longer circulation times in plasma than previously reported in mice and were detectable in cerebrospinal fluid (CSF) after 30-60 minutes. EV association with PBMCs, especially B-cells, was observed as early as one minute post-administration. EVs were detected in liver and spleen within one hour of IV administration. However, IN delivery was minimal, suggesting that pretreatment approaches may be needed in large animals. Furthermore, EV circulation times strongly decreased after repeated IV administration, possibly due to immune responses and with clear implications for xenogeneic EV-based therapeutics. We hope that our findings from this baseline study in macaques will help to inform future research and therapeutic development of EVs.

The Symbiotic Relationship Between Scientific Quality and Animal Research Ethics.

Researchers have worked with animals as models for decades to expand our knowledge of basic biological processes and to systematically study the physiology of disease. In general, the public has an expectation that work with animals has a purpose and will ultimately reap benefits. The likelihood of such an outcome is directly dependent on the quality of the science being conducted with those animals. However, not all frameworks for consideration of the ethics around animal research overtly consider scientific quality. In the following review, we explore the complex relationship between scientific quality and animal research ethics. We advocate for the development of a detailed "Harm-Yield Analysis" for the evaluation of biomedical animal research that emphasizes scientific quality along with societal benefit in the ethical justification of the research. We reflect on the lost opportunity to establish best practices in animal research early in the career of scientists by introducing in the curriculum and encouraging the use of a paradigm of the iterative consideration of the ethics of animal research alongside other aspects of experimental design.

Night Shift and Decreased Brain Activity of ICU Nurses: A Near-Infrared Spectroscopy Study.

BACKGROUND: Shift working is associated with a profound desynchronization of circadian rhythm and in particular, night-shift work disrupts normal circadian physiology. Sleep deprivation affects the functioning of certain brain areas and thus impairs cognitive performance. The purpose of this study was to investigate the effects of the night shift on cognitive performance and cerebral oxygenation/haemodynamics. METHODS: A prospective, observational, comparative, randomized and cross-over study was carried out. A total of 74 intensive care unit nurses in Spain were included in the study. The following variables were measured: sociodemographic, burnout, anxiety, baseline cerebral oxygenation levels on night and day shift using a near-infrared spectroscopy system and cognitive task performance during a verbal fluency task to evaluate the alterations in the prefrontal cortex, assessed as changes in regional saturation index. RESULTS: The average regional saturation index decreased significantly in the night shift (r = 0.560, p < 0.001). The ICU nurses showed a significant decrease in the verbal fluency test on average (8.53 ± 8.49, p < 0.001) and, in general, there was also a significant increase in anxiety score (3.17 ± 7.56, p = 0.001). CONCLUSIONS: Sleep deprivation during the night shift was considered to be related to decreased dorsolateral PFC reactivity. After the night shift, the nurses showed a decrease in prefrontal cortex activity and in cognitive performance.

Depressive Symptoms and Quality of Life Associated With the Use of Monoclonal Antibodies in Breast Cancer Treatment.

OBJECTIVES: To assess the relationship between (a) chemotherapy and monoclonal antibody (mAb) treatments and (b) depressive symptoms and quality of life (QOL) in patients with breast cancer. SAMPLE & SETTING: 182 women with breast cancer in Spain who were undergoing chemotherapy with or without mAbs. METHODS & VARIABLES: An observational, cross-sectional study was carried out. The European Organisation for Research and Treatment of Cancer (EORTC) QOL Questionnaire-Core 30 and the EORTC QOL Questionnaire-Breast Cancer were used to assess QOL. Patients were screened for depressive symptoms using the Beck Depression Inventory-II. RESULTS: No relationship was found between the use of mAbs with chemotherapy and QOL, except for incidence of diarrhea. However, depressive symptoms had a negative and highly significant influence on the majority of the QOL parameters. IMPLICATIONS FOR NURSING: The presence of depressive symptoms negatively affects QOL. Used concurrently, mAbs and chemotherapy do not negatively influence QOL, but some adverse effects, such as diarrhea, are common.

Health-related quality of life in diabetes mellitus patients in primary health care.

OBJECTIVE: To analyse the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical factors in patients with diabetes mellitus, also comparing with Spanish population-based reference values. METHOD: Cross-sectional descriptive-analytical observational study through nonprobability sampling on diabetic patients from San Roque Primary Health Centre (Badajoz, Spain), using a questionnaire regarding sociodemographic and diabetes care data, SF-36 and Duke-UNC questionnaires, and clinical history data. RESULTS: Sixty patients (55% women) fundamentally with type 2 diabetes and a mean age of 68.67 ± 11.09 years were studied. Women older than 75 presented poorer HRQoL than their reference group. Women showed worse HRQoL than men. Age, evolution of diabetes, presence of acute and chronic complications, and comorbidities, pharmacological treatment, and glycaemic control affect HRQoL in these patients. Living alone, having a low socioeconomic status, and needing help with diabetes-related self-care can negatively affect quality of life. CONCLUSIONS: HRQoL assessment allows us to detect alterations in the different domains and perform an early intervention. This way, we can incorporate these aspects into the nursing evaluation and interventions in the nursing care plan; allowing us to develop individualized care strategies and diabetes education programmes that contribute to improving HRQoL in patients with diabetes.

Lung megakaryocytes are immune modulatory cells.

Although platelets are the cellular mediators of thrombosis, they are also immune cells. Platelets interact both directly and indirectly with immune cells, impacting their activation and differentiation, as well as all phases of the immune response. Megakaryocytes (Mks) are the cell source of circulating platelets, and until recently Mks were typically only considered bone marrow-resident (BM-resident) cells. However, platelet-producing Mks also reside in the lung, and lung Mks express greater levels of immune molecules compared with BM Mks. We therefore sought to define the immune functions of lung Mks. Using single-cell RNA sequencing of BM and lung myeloid-enriched cells, we found that lung Mks, which we term MkL, had gene expression patterns that are similar to antigen-presenting cells. This was confirmed using imaging and conventional flow cytometry. The immune phenotype of Mks was plastic and driven by the tissue immune environment, as evidenced by BM Mks having an MkL-like phenotype under the influence of pathogen receptor challenge and lung-associated immune molecules, such as IL-33. Our in vitro and in vivo assays demonstrated that MkL internalized and processed both antigenic proteins and bacterial pathogens. Furthermore, MkL induced CD4+ T cell activation in an MHC II-dependent manner both in vitro and in vivo. These data indicated that MkL had key immune regulatory roles dictated in part by the tissue environment.