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.

"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.

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.

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.

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.

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.

Calidad de vida relacionada con la salud en pacientes con diabetes mellitus en una zona básica de salud / Health-related quality of life in diabetes mellitus patients in primary health care

Objetivo: Analizar la relación entre la calidad de vida relacionada con la salud (CVRS) y variables sociodemográficas y clínicas de pacientes diagnosticados de diabetes mellitus, comparando además con los valores de referencia para la población española. Método: Estudio descriptivo-analítico observacional trasversal por muestreo no probabilístico intencional en pacientes con diabetes mellitus del Centro de Salud San Roque (Badajoz, España), usando cuestionarios de datos sociodemográficos y de cuidado de la diabetes, los cuestionarios SF-36 y Duke-UNC, y datos de la historia clínica. Resultados: Se estudiaron 60 pacientes (55% mujeres) fundamentalmente con diabetes tipo 2 (90%) y una edad media de 68,67±11,09 años. Las mujeres mayores de 75 años presentaron valores de CVRS significativamente inferiores a los de su grupo poblacional de referencia. Las mujeres mostraron una peor CVRS que los hombres. La edad, los años de evolución de la diabetes, la presencia de complicaciones agudas y crónicas, así como de comorbilidades, el régimen farmacológico y el control glucémico afectan a la CVRS. Vivir solo, tener un nivel socioeconómico bajo, un apoyo social percibido bajo y necesitar ayuda para el cuidado de la diabetes están relacionados con una deficiente CVRS. Conclusiones: La evaluación de la CVRS permite detectar alteraciones en sus diferentes dominios e intervenir precozmente, pudiendo incorporar estos aspectos a la valoración e intervención enfermera en el plan de cuidados, lo que permite establecer estrategias individualizadas de atención y programas de educación diabetológica que contribuyan a la mejora de la calidad de vida en pacientes con diabetes.(AU)

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.(AU)

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.

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.

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.

Progression and Resolution of SARS-1 CoV-2 Infection in Golden Syrian Hamsters

To catalyze SARS-CoV-2 research including development of novel interventive and preventive strategies, we characterized progression of disease in depth in a robust 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 day 2, 4, 7, 14, and 28 days post-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 timepoints, 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 post-inoculation, corresponding with widespread necrosis and inflammation. At day 7, when 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 post-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.

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.

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.

Understanding Resilience Factors Among Caregivers of People with Alzheimer's Disease in Spain.

INTRODUCTION: Alzheimer's disease (AD) caregivers resilience involves the interaction between different risk and protective factors. Context of care, objective stressors, perceived stressors caregiver assessment, mediators factors and consequences of care were associated with resilience. We have developed a more integrated and operational conceptual model of resilience and care than previous models in our sociocultural environment. PURPOSE: To assess the resilience of caregivers of people with AD and the related factors grouped according to an established operational conceptual model of Alzheimer´s caregivers stress. PATIENTS AND METHODS: A total of 120 primary informal caregivers of AD persons in Badajoz (Spain) were included in a cross-sectional design. The following variables have been measured on AD persons and caregivers: socio-demographic data, dependency level, cognitive decline, neuropsychiatric and behavioral symptoms, anxiety, depression, severity of somatic symptoms, level of burden, self-esteem, coping, social support, health-related quality of life (HRQOL) and resilience. RESULTS: Most of the caregivers reported symptoms of anxiety (63.3%) and depression (62.5%). We found out higher levels of resilience in caregivers with lower dependence caring (p=0.004). Higher resilience levels of caregivers were related to minor depressive (p=0.006) and anxiety symptoms (p=0.000), and higher HRQOL (p=0.000). Coping dimension mostly used was problem-based strategies such as active coping, positive reinterpretation and acceptance (p= 0.000). CONCLUSION: Those caregivers reporting higher levels of resilience exhibited moderate to intense indicators of burden, fewer symptoms of depression and anxiety and fewer somatic symptoms. They also used adequate problem-focused coping strategies, showed higher levels of HRQOL and demonstrated an appropriate perception of social support. Despite the fact that the characteristics relating to the care context and to social support exert an undeniable influence on caregiver resilience, it would appear that the caregiver's own intra-psychic resources reveal stronger correlations. RELEVANCE FOR CLINICAL PRACTICE: The early and accurate identification of caregivers with lower levels of resilience could enable the implementation of vital psychological and educative support interventions to help caregivers to improve their well-being.

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.

The importance of early identification of infusion-related reactions to monoclonal antibodies.

Monoclonal antibodies constitute important and useful tools in clinical practice and biotechnology for diagnosing and treating infectious, inflammatory, immunological and neoplastic diseases. This article reviews evidence on the different acute adverse effects of monoclonal antibodies, specifically infusion-related reactions (IRRs), and on the measures that should be taken before and during crises. A literature search using key terms relating to IRRs produced by monoclonal antibodies was undertaken to generate a comprehensive narrative review of the information available. Immunomodulatory monoclonal antibodies may produce IRRs and hypersensitivity-related reactions. Strategies to avoid or minimize the appearance of IRRs depend on the monoclonal antibody and type of patient and reaction (pre-medication, slowing infusion rates, infusion interruption or desensitization, etc.). Considering the great number of available monoclonal antibodies in current practice and those which will soon be authorized, it is mandatory to have clear guidelines that can give support to practitioners and nurses to help them respond quickly and safely to the different IRRs related to the use of these therapeutic drugs.