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More than 650 reversible and irreversible post-translational modifications (PTMs) of proteins have been listed so far. Canonical PTMs of proteins consist of the covalent addition of functional or chemical groups on target backbone amino-acids or the cleavage of the protein itself, giving rise to modified proteins with specific properties in terms of stability, solubility, cell distribution, activity, or interactions with other biomolecules. PTMs of protein contribute to cell homeostatic processes, enabling basal cell functions, allowing the cell to respond and adapt to variations of its environment, and globally maintaining the constancy of the milieu interieur (the body's inner environment) to sustain human health. Abnormal protein PTMs are, however, associated with several disease states, such as cancers, metabolic disorders, or neurodegenerative diseases. Abnormal PTMs alter the functional properties of the protein or even cause a loss of protein function. One example of dramatic PTMs concerns the cellular prion protein (PrPC), a GPI-anchored signaling molecule at the plasma membrane, whose irreversible post-translational conformational conversion (PTCC) into pathogenic prions (PrPSc) provokes neurodegeneration. PrPC PTCC into PrPSc is an additional type of PTM that affects the tridimensional structure and physiological function of PrPC and generates a protein conformer with neurotoxic properties. PrPC PTCC into PrPSc in neurons is the first step of a deleterious sequence of events at the root of a group of neurodegenerative disorders affecting both humans (Creutzfeldt-Jakob diseases for the most representative diseases) and animals (scrapie in sheep, bovine spongiform encephalopathy in cow, and chronic wasting disease in elk and deer). There are currently no therapies to block PrPC PTCC into PrPSc and stop neurodegeneration in prion diseases. Here, we review known PrPC PTMs that influence PrPC conversion into PrPSc. We summarized how PrPC PTCC into PrPSc impacts the PrPC interactome at the plasma membrane and the downstream intracellular controlled protein effectors, whose abnormal activation or trafficking caused by altered PTMs promotes neurodegeneration. We discussed these effectors as candidate drug targets for prion diseases and possibly other neurodegenerative diseases.
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Introduction: Adolescent and young adult (AYA) survivors who have been treated for cancer during childhood and adolescence are at great risk of the physical, psychological, and social consequences of cancer and its associated treatments. However, compliance with long-term follow-up is low. One possible explanation is that follow-up care fails to meet the expectations of AYA survivors. This study explored the specific supportive care needs of AYA survivors of childhood and adolescent cancer five years post-diagnosis. Methods: Semi-structured interviews were conducted with 15 AYA aged 15 to 25 years old. Thematic analyses were conducted to establish categories of supportive care needs and classify them as being met or unmet. Results: Participants reported between 2 and 20 specific needs (M = 11), including needs concerning fertility issues and reassurance regarding relapse (each mentioned by 67% of AYA), followed by the need for locomotor care, follow-up coordination and multidisciplinary care (60% of AYA for each). Participants also reported needs regarding social relationships, administration and finance, and academic and professional domains. Most (69%) of these needs were reportedly unmet, including need of information about cancer repercussions and follow-up, support in managing fatigue and sleep problems, psychological assistance, and support from peers. Discussion: The supportive care needs are still considerable and varied in AYA survivors of childhood and adolescent cancer 5 years post-diagnosis and are largely unmet. As unmet supportive care needs highlight the gap between available care in follow-up and the real needs of AYA survivors, a better understanding of their supportive care needs and unmet needs, thanks to systematic needs assessment, would enable long-term follow-up care to be adapted, thereby improving compliance and quality of life.
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The main objective was to assess the link between emotional competence (EC) and adjustment outcomes such as supportive care needs (SCN) and anxious-depressive symptoms in cancer patients starting chemotherapy. The second objective was to assess the interaction effect between EC and the COVID-19 pandemic (i.e. patients included before or during the pandemic) on these outcomes. At the beginning of care, 255 patients with digestive or hematological cancer, recruited before the pandemic began (n = 156, 61.2%) or during the pandemic (n = 99, 38.8%), completed the Short Profile of Emotional Competence, the Hospital Anxiety and Depression Scale, and the Supportive Care Needs Survey Short Form. Partial correlations and multiple regressions were used. Intrapersonal EC showed negative significant correlations with psychological unmet SCN (r = -.32, p < .001), anxiety (r = -.37, p < .001), and depression (r = -.46, p < .001). Interpersonal EC showed only significant interaction effects (p < .05): it was only associated with fewer unmet physical and daily SCN (p < .002) and fewer depressive symptoms (p < .004) during pandemic. Results show significant associations between intrapersonal EC and better adjustment of cancer patients from the early stage of care. Interpersonal EC seems to be a significant resource to deal with illness only in difficult contexts such as the COVID-19 pandemic.
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PURPOSE: This cross-sectional study explored the associations between intrapersonal and interpersonal emotional competence (EC) and the unmet supportive care needs (SCN), anxiety, and depression of informal caregivers at the beginning of gastrointestinal or haematological cancer care, i.e. during chemotherapy and within 6 months after diagnosis. METHODS: The participants completed a self-reported questionnaire, comprising the Short Profile of Emotional Competence (S-PEC), the SCN survey for partners and caregivers (SCNS-P&C), and the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression models were performed to explore the influence of EC on unmet SCN and the presence of moderate/severe anxiety or depression. RESULTS: Most of the 203 caregivers were women (n = 141, 69.80%) and the partners of patients (n = 148, 73.27%) suffering from gastrointestinal (n = 112, 55.17%) and haematological (n = 91, 44.83%) cancer. Only intrapersonal EC showed a significant influence out of all the dimensions of unmet SCN related to healthcare services and information (odds ratio (OR) = 0.35 [95%CI 0.19; 0.65]), emotional and psychological needs (OR = 0.43 [95%CI 0.25; 0.74]), work and social security (OR = 0.57 [95%CI 0.37; 0.88]), and communication and family support (OR = 0.61 [95%CI 0.39; 0.95]). A one-unit increase in the intrapersonal EC score significantly reduced the probability of anxiety (OR = 0.42, [95%CI 0.26; 0.68]) and depression (OR = 0.34, [95%CI 0.21; 0.55]). CONCLUSION: Intrapersonal EC of caregivers is crucial to reduce the risk of unmet SCN, anxiety, and depression from the beginning of care. Identifying caregivers with lower intrapersonal EC may be necessary to increase vigilance from healthcare professionals and psychologists.
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Ansiedad , Cuidadores , Depresión , Emociones , Apoyo Social , Humanos , Cuidadores/psicología , Femenino , Masculino , Persona de Mediana Edad , Estudios Transversales , Ansiedad/etiología , Depresión/etiología , Depresión/epidemiología , Anciano , Encuestas y Cuestionarios , Adulto , Modelos Logísticos , Neoplasias Gastrointestinales/psicología , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/psicología , Neoplasias/psicología , Necesidades y Demandas de Servicios de Salud , Análisis MultivarianteRESUMEN
Introduction: Among immune cells, activated monocytes play a detrimental role in chronic and viral-induced inflammatory pathologies, particularly in Juvenile Idiopathic Arthritis (JIA), a childhood rheumatoid arthritis (RA) disease. The uncontrolled activation of monocytes and excessive production of inflammatory factors contribute to the damage of bone-cartilage joints. Despite the moderate beneficial effect of current therapies and clinical trials, there is still a need for alternative strategies targeting monocytes to treat RA. Methods: To explore such an alternative strategy, we investigated the effects of targeting the CXCR4 receptor using the histamine analog clobenpropit (CB). Monocytes were isolated from the blood and synovial fluids of JIA patients to assess CB's impact on their production of key inflammatory cytokines. Additionally, we administered daily intraperitoneal CB treatment to arthritic mice to evaluate its effects on circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, as indicators of disease progression. Results: Our findings demonstrated that CXCR4 targeting with CB significantly inhibited the spontaneous and induced-production of key inflammatory cytokines by monocytes isolated from JIA patients. Furthermore, CB treatment in a mouse model of collagen-induce arthritis resulted in a significant decrease in circulating inflammatory cytokine levels, immune cell infiltrates, joints erosion, and bone resorption, leading to a reduction in disease progression. Discussion: In conclusion, targeting CXCR4 with the small amino compound CB shows promise as a therapeutic option for chronic and viral-induced inflammatory diseases, including RA. CB effectively regulated inflammatory cytokine production of monocytes, presenting a potential targeted approach with potential advantages over current therapies. These results warrant further research and clinical trials to explore the full therapeutic potential of targeting CXCR4 with CB-like molecules in the management of various inflammatory diseases.
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Artritis Juvenil , Artritis Reumatoide , Resorción Ósea , Histamina , Animales , Humanos , Ratones , Artritis Juvenil/tratamiento farmacológico , Citocinas , Progresión de la Enfermedad , Histamina/análogos & derivados , Inflamación/tratamiento farmacológico , Receptores CXCR4RESUMEN
PURPOSE: Previous research conducted among caregivers of patients with cancer revealed a poor Quality of Life (QoL) and high levels of distress. In addition to the influence of patients' clinical state, caregivers' appraisals of patients' difficulties should be considered as another predictor of poor caregiver health. This study aims to test the association between caregivers' health (i.e., QoL, depression and anxiety) and their perception of patients' difficulties. METHODS: 199 caregivers of patients with cancer completed an online survey based on questionnaires measuring their QoL, depression and anxiety, as well as their perception of patients' cognitive, emotional, functional, psychiatric and interpersonal difficulties. RESULTS: It was found that the appraisal of patients' impairments in all domains was mainly correlated with poor caregivers' QoL (Pearson correlations ranged from 0.14 to 0.45; p ≤ .05). Furthermore, linear regression analyses showed that, after controlling for age, sex education level, professional activity and living with or without the patient, the appraisal of patients' interpersonal abilities (ß = 0.25, p ≤ .05), psychiatric difficulties (ß = -0.25, p ≤ .01) and living with the patient were the main predictors of caregivers' QoL. CONCLUSION: This study highlights the importance of better understanding the role of patients' social and psychiatric difficulties when examining caregivers' health. This indicates the importance of providing support and offering information to caregivers to alert them to the role of patients' social and psychiatric difficulties on their own health. Future studies should better understand how these difficulties are associated with caregivers' perception of identity/sociability alterations in patients and how caregivers cope with these changes.
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INTRODUCTION: The existing literature shows a significant impact of cancer on caregivers' quality of life (QoL) and divergent results according to associated factors. To better understand the experience of cancer patients' caregivers, the present study aimed at comparing caregivers' QoL according to cancer care pathway and type of cancer, and at identifying the factors associated with their QoL. METHODS: Caregivers were included in the study either during chemotherapy or follow-up to assess their QoL (CARGOQoL), unmet supportive care needs (SCNS-P&C), and anxiety and depression levels (HADS). CARGOQoL scores were then compared using ANOVA or Mann-Whitney non-parametric tests (objective 1). Based on univariate analyses, a multivariate analysis of covariance or linear regression model was performed for each CARGOQoL dimension (objective 2). RESULTS: Among 583 participants (57.29% included during the follow-up phase), 523 completed the questionnaires. There was no effect of treatment phase and little effect of cancer site or disease stage on caregivers' QoL. Although significant factors associated with caregivers' QoL varied according to the dimensions assessed, the main associated factors were psychological experience (p < 0.05), satisfaction with the patient's care and supportive care needs (p < 0.01), and age of the patient or caregiver (p < 0.005). CONCLUSION: This study shows the necessity to support caregivers during both active treatment and follow-up. It highlights the crucial role of emotional distress, supportive care and age in caregivers' QoL, regardless of the patients' oncological status.
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Neoplasias , Distrés Psicológico , Humanos , Calidad de Vida/psicología , Cuidadores/psicología , Estudios Transversales , Depresión/psicología , Neoplasias/psicología , Encuestas y CuestionariosRESUMEN
INTRODUCTION: Several studies have shown that emotional competence (EC) impacts cancer adjustment via anxiety and depression symptoms. The objective was to test this model for the quality of life (QoL) of partners: first, the direct effect of partners' EC on their QoL, anxiety and depression symptoms after cancer diagnosis (T1), after chemotherapy (T2) and after radiotherapy (T3); Second, the indirect effects of partners' EC at T1 on their QoL at T2 and T3 through anxiety and depression symptoms. METHODS: 192 partners of women with breast cancer completed a questionnaire at T1, T2 and T3 to assess their EC (PEC), anxiety and depression symptoms (HADS) and QoL (Partner-YW-BCI). Partial correlations and regression analyses were performed to test direct and indirect effects of EC on issues. RESULTS: EC at T1 predicted fewer anxiety and depression symptoms at each time and all dimensions of QoL, except for career management and financial difficulties. EC showed different significant indirect effects (i.e. via anxiety or depression symptoms) on all sub-dimensions of QoL, except for financial difficulties, according to the step of care pathway (T2 and T3). Anxiety and depression played a different role in the psychological processes that influence QoL. CONCLUSION: Findings confirm the importance of taking emotional processes into account in the adjustment of partners, especially regarding their QoL and the support they may provide to patients. It, thus, seems important to integrate EC in future health models and psychosocial interventions focused on partners or caregivers.
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Neoplasias de la Mama , Humanos , Femenino , Calidad de Vida/psicología , Estudios Longitudinales , Depresión/psicología , Emociones , Ansiedad/psicologíaRESUMEN
PURPOSE: The objectives of this study were to compare the unmet supportive care needs (SCN) of caregivers and describe the 10 most frequent of them according to various cancer settings: phase of cancer care pathway (i.e., treatment vs. follow-up), cancer site (i.e., breast, digestive, or lung cancer), and cancer status (i.e., metastatic vs. non-metastatic). METHODS: Participants completed a self-reported questionnaire to assess their unmet SCN (SCNS-P&C). According to their cancer settings, non-parametric ANOVA or Mann-Whitney tests were performed to compare the SCNS-P&C scores. The prevalence of caregivers with unmet SCN was described using percentages. RESULTS: Among 583 participants, 516 caregivers (88.5%) completed the SCNS-P&C questionnaire. Most patients had digestive (47.3%), non-metastatic cancer (67.6%) and were recruited during the follow-up phase (56.2%). The results revealed no significant difference in SCNS-P&C scores according to cancer settings except for caregivers of patients with metastatic cancer, who reported more unmet SCN related to health care service and information needs. The more qualitative item per item analysis seems to indicate the existence of five frequently unsatisfied SCN across situations, especially concerns about the recurrence and reduction of stress in patients, with variable ranking among the most unmet SCN. CONCLUSION: Although there was no significant difference in unmet SCN scores between medical settings, examining the prevalence of unmet SCN helps identify the issues to focus on when supporting caregivers and developing dedicated consultations or interventions for them.
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Cuidadores , Neoplasias , Humanos , Estudios Transversales , Neoplasias/terapia , Encuestas y Cuestionarios , Prevalencia , Necesidades y Demandas de Servicios de Salud , Apoyo SocialRESUMEN
BACKGROUND: Epidemiological emerging evidence shows that human exposure to some nanosized materials present in the environment would contribute to the onset and/or progression of Alzheimer's disease (AD). The cellular and molecular mechanisms whereby nanoparticles would exert some adverse effects towards neurons and take part in AD pathology are nevertheless unknown. RESULTS: Here, we provide the prime evidence that titanium dioxide (TiO2) and carbon black (CB) nanoparticles (NPs) bind the cellular form of the prion protein (PrPC), a plasma membrane protein well known for its implication in prion diseases and prion-like diseases, such as AD. The interaction between TiO2- or CB-NPs and PrPC at the surface of neuronal cells grown in culture corrupts PrPC signaling function. This triggers PrPC-dependent activation of NADPH oxidase and subsequent production of reactive oxygen species (ROS) that alters redox equilibrium. Through PrPC interaction, NPs also promote the activation of 3-phosphoinositide-dependent kinase 1 (PDK1), which in turn provokes the internalization of the neuroprotective TACE α-secretase. This diverts TACE cleavage activity away from (i) TNFα receptors (TNFR), whose accumulation at the plasma membrane augments the vulnerability of NP-exposed neuronal cells to TNFα -associated inflammation, and (ii) the amyloid precursor protein APP, leading to overproduction of neurotoxic amyloid Aß40/42 peptides. The silencing of PrPC or the pharmacological inhibition of PDK1 protects neuronal cells from TiO2- and CB-NPs effects regarding ROS production, TNFα hypersensitivity, and Aß rise. Finally, we show that dysregulation of the PrPC-PDK1-TACE pathway likely occurs in the brain of mice injected with TiO2-NPs by the intra-cerebro-ventricular route as we monitor a rise of TNFR at the cell surface of several groups of neurons located in distinct brain areas. CONCLUSION: Our in vitro and in vivo study thus posits for the first time normal cellular prion protein PrPC as being a neuronal receptor of TiO2- and CB-NPs and identifies PrPC-coupled signaling pathways by which those nanoparticles alter redox equilibrium, augment the intrinsic sensitivity of neurons to neuroinflammation, and provoke a rise of Aß peptides. By identifying signaling cascades dysregulated by TiO2- and CB-NPs in neurons, our data shed light on how human exposure to some NPs might be related to AD.
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Enfermedad de Alzheimer , Nanopartículas , Priones , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/patología , Animales , Homeostasis , Humanos , Ratones , Nanopartículas/toxicidad , Neuronas/patología , Proteínas Priónicas/metabolismo , Priones/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Hollín/toxicidad , Titanio , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
OBJECTIVE: Emotional competence (EC) is considered a substantial resource in the adjustment of cancer patients, especially via its effect on anxiety and depression symptoms. This research aimed at assessing the impact of intrapersonal EC in young women (≤45 years) with breast cancer (YWBC) on their specific quality of life (i.e. subjective experience related to daily difficulties and perceived repercussions of the disease and treatments) related to chemotherapy, via anxiety and depression symptoms. METHODS: Two hundred fifty YWBC from 24 French centers completed a self-reported questionnaire after diagnosis (T1) and after the chemotherapy phase (T2), comprising the Young Women Breast Cancer Inventory, the Profile of EC and the Hospital Anxiety and Depression Scale. The indirect effect of EC (T1) on subjective experience (T2) via anxiety and depression symptoms (T2) was tested using regressions and the Macro PROCESS. RESULTS: Emotional competence predicted fewer anxiety and depression symptoms at T1 and T2, and a better subjective experience at T2 via fewer anxiety and depression symptoms. Depression symptoms appeared to be a stronger mediator than anxiety symptoms on four dimensions (Support from close relatives, feeling of couple cohesion, body image and sexuality, management of children and everyday life), whereas anxiety symptoms appeared to be a stronger mediator on two dimensions (negative affectivity and apprehension about the future, deterioration of relationships). CONCLUSIONS: These results support the importance of developing psycho-affective interventions to reinforce the EC of YWBC during chemotherapy in order to facilitate the cognitive and emotional processes necessary for a better adjustment and subjective experience.
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Neoplasias de la Mama , Distrés Psicológico , Ansiedad/psicología , Neoplasias de la Mama/psicología , Niño , Depresión/psicología , Femenino , Humanos , Calidad de Vida/psicologíaRESUMEN
Corruption of cellular prion protein (PrPC) function(s) at the plasma membrane of neurons is at the root of prion diseases, such as Creutzfeldt-Jakob disease and its variant in humans, and Bovine Spongiform Encephalopathies, better known as mad cow disease, in cattle. The roles exerted by PrPC, however, remain poorly elucidated. With the perspective to grasp the molecular pathways of neurodegeneration occurring in prion diseases, and to identify therapeutic targets, achieving a better understanding of PrPC roles is a priority. Based on global approaches that compare the proteome and metabolome of the PrPC expressing 1C11 neuronal stem cell line to those of PrPnull-1C11 cells stably repressed for PrPC expression, we here unravel that PrPC contributes to the regulation of the energetic metabolism by orienting cells towards mitochondrial oxidative degradation of glucose. Through its coupling to cAMP/protein kinase A signaling, PrPC tones down the expression of the pyruvate dehydrogenase kinase 4 (PDK4). Such an event favors the transfer of pyruvate into mitochondria and its conversion into acetyl-CoA by the pyruvate dehydrogenase complex and, thereby, limits fatty acids ß-oxidation and subsequent onset of oxidative stress conditions. The corruption of PrPC metabolic role by pathogenic prions PrPSc causes in the mouse hippocampus an imbalance between glucose oxidative degradation and fatty acids ß-oxidation in a PDK4-dependent manner. The inhibition of PDK4 extends the survival of prion-infected mice, supporting that PrPSc-induced deregulation of PDK4 activity and subsequent metabolic derangements contribute to prion diseases. Our study posits PDK4 as a potential therapeutic target to fight against prion diseases.
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Glucosa/metabolismo , Degeneración Nerviosa/metabolismo , Proteínas PrPSc/metabolismo , Enfermedades por Prión/metabolismo , Enfermedades por Prión/patología , Animales , Modelos Animales de Enfermedad , Masculino , Ratones , Ratones Endogámicos C57BL , Degeneración Nerviosa/patología , Estrés Oxidativo/fisiología , Proteínas Quinasas/metabolismoRESUMEN
OBJECTIVE: To assess the impact of global physician empathy and its three subdimensions (establishing rapport, emotional and cognitive processes) on the severity of postoperative complications in a sample of cancer patients. METHODS: We retrospectively analyzed data on 256 patients with esogastric cancer from the French national FREGAT database. Empathy and its subdimensions were assessed using the patient-reported CARE scale and the severity of medical and surgical complications was reported with the Clavien-Dindo classification system. The usual covariates were included in multinomial logistic regression analyses. RESULTS: Physician empathy predicted the odds of reporting major complications. When patients perceived high empathy, they were less likely to report major complications compared to no complications (OR = .95, 95% CI = [.91-.99], p = .029). Among the three dimensions, only "establishing rapport" (OR = .84, 95% CI = [.73-.98], p = .019) and the "emotional process" (OR = .85, 95% CI = [.74-.98], p = .022) predicted major complications. CONCLUSIONS: Physician empathy is essential before surgery. Further research is needed to understand the mechanisms associating empathy with health outcomes in cancer. Physicians should be trained to establish good rapport with patients, especially in the preoperative period.
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Neoplasias Esofágicas , Neoplasias Gástricas , Cirujanos , Empatía , Humanos , Percepción , Relaciones Médico-Paciente , Estudios Retrospectivos , Neoplasias Gástricas/cirugíaRESUMEN
BACKGROUND: Emotional competence (EC) via anxiety and depressive symptoms impacts the postoperative health-related quality of life (HRQoL) of esophageal and gastric cancer patients after surgery. OBJECTIVE: The aim of this study was to confirm the involvement of emotional processes in postsurgery HRQoL according to the presence or absence of neoadjuvant treatments. METHODS: After diagnosis (T1) and after surgery (T2), 271 patients completed 3 questionnaires, assessing their intrapersonal and interpersonal EC, HRQoL, and anxiety and depressive symptoms. Patients were categorized into 2 groups: patients with only surgery (group 1) and patients who received neoadjuvant treatment in addition to surgery (group 2). Analyses were based on hierarchical regression analyses and the SPSS PROCESS Macro to test the indirect effect of EC on HRQoL through anxiety and depression. RESULTS: Results showed an increase in depressive symptoms and a decrease in both anxiety symptoms and HRQoL between diagnosis and surgery, regardless of neoadjuvant treatment. At T1 and T2, EC predicted fewer anxiety and depressive symptoms and a less impaired HRQoL in the surgery-only group (group 1). Emotional competence, particularly intrapersonal EC, showed a significant indirect effect on HRQoL after surgery via fewer depressive symptoms. CONCLUSION: Emotional competence promotes fewer anxiety and depressive symptoms and less impaired HRQoL after diagnosis and after surgery, especially for patients without neoadjuvant treatments. IMPLICATIONS FOR PRACTICE: It is important for oncology nurses and other clinicians to consider the role of emotional processes in postsurgical HRQoL in relation to the type of received treatments and to reinforce the use of EC by cancer patients to improve their adjustment.
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Neoplasias Esofágicas , Neoplasias Gástricas , Ansiedad , Depresión , Neoplasias Esofágicas/cirugía , Humanos , Terapia Neoadyuvante , Calidad de Vida , Neoplasias Gástricas/cirugía , Encuestas y CuestionariosRESUMEN
Amyloid-based neurodegenerative diseases such as prion, Alzheimer's, and Parkinson's diseases have distinct etiologies and clinical manifestations, but they share common pathological events. These diseases are caused by abnormally folded proteins (pathogenic prions PrPSc in prion diseases, ß-amyloids/Aß and Tau in Alzheimer's disease, α-synuclein in Parkinson's disease) that display ß-sheet-enriched structures, propagate and accumulate in the nervous central system, and trigger neuronal death. In prion diseases, PrPSc-induced corruption of the physiological functions exerted by normal cellular prion proteins (PrPC) present at the cell surface of neurons is at the root of neuronal death. For a decade, PrPC emerges as a common cell surface receptor for other amyloids such as Aß and α-synuclein, which relays, at least in part, their toxicity. In lipid-rafts of the plasma membrane, PrPC exerts a signaling function and controls a set of effectors involved in neuronal homeostasis, among which are the RhoA-associated coiled-coil containing kinases (ROCKs). Here we review (i) how PrPC controls ROCKs, (ii) how PrPC-ROCK coupling contributes to neuronal homeostasis, and (iii) how the deregulation of the PrPC-ROCK connection in amyloid-based neurodegenerative diseases triggers a loss of neuronal polarity, affects neurotransmitter-associated functions, contributes to the endoplasmic reticulum stress cascade, renders diseased neurons highly sensitive to neuroinflammation, and amplifies the production of neurotoxic amyloids.
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OBJECTIVE: The mechanisms associating physician empathy (PE) with patient outcomes remain unclear. PE can be considered as a whole (one process) or three subcomponents can be identified (an establishing rapport process; an emotional process; a cognitive process). The objective was to test two competitive models of PE in cancer care: a three-process model adapted from Neumann's model versus a one-process model, with the use of the Consultation and Relational Empathy measure (CARE). METHODS: The CARE was completed by 488 oesogastric cancer patients from the national French database FREGAT. A confirmatory factor analysis (CFA) and a bifactor model were performed to test the two competitive models. RESULTS: The CFA revealed that the one-factor structure showed a moderate fit to the data whereas the three-factor structure showed a good fit. However, the bifactor model favoured unidimensionality. CONCLUSION: We cannot provide a clear-cut conclusion about whether PE should be considered as on unique process or not. Further work is still needed. Meanwhile, one should not preclude the use of three subscores in cancer care if specific elements of the encounter need to be assessed.
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Empatía , Neoplasias , Actitud del Personal de Salud , Comunicación , Humanos , Neoplasias/terapia , Relaciones Médico-Paciente , Derivación y ConsultaRESUMEN
BACKGROUND: Intrapersonal and interpersonal Emotional Competence (EC) predicts better health and disease adjustment. This study aimed to validate a short version of the Profile of Emotional Competence (PEC) scale for cancer patients. METHODS: Five hundred and thirty-five patients with cancer completed a self-reported questionnaire assessing their intra- and interpersonal EC (PEC), their anxiety and depression symptoms (HADS), and their health-related quality of life (QLQ-C30). Confirmatory factor analyses and Item Response Theory models with the Partial Credit Model were performed to validate and reduce the scale. FINDINGS: The Short-PEC (13 items), composed of 2 sub-scores of intra- (6 items) and interpersonal (7 items) EC, showed an improved factorial structure (Root Mean Square Error of Approximation (RMSEA) = 0.075 (90% confidence interval 0.066-0.085), comparative fit index = 0.915) with good psychometric properties. DISCUSSION: Future studies should use the Short-PEC to explain and predict the adjustment of cancer patients. The short-PEC could be also used in clinical routine to assess the level of EC of patients and to adapt psychosocial intervention.
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Ajuste Emocional , Emociones , Neoplasias/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad , Depresión , Femenino , Humanos , Relaciones Interpersonales , Masculino , Persona de Mediana Edad , Neoplasias/diagnóstico , Pronóstico , Psicometría , Calidad de Vida , AutoinformeRESUMEN
PURPOSE: This study aimed to identify profiles of caregivers to cancer patients at higher risk of having at least one moderately or highly unmet supportive care need based on 1) relevant socio-demographic (e.g. age, gender) and clinical (e.g. type of cancer, phase of the cancer pathway) variables highlighted in the literature and easily identifiable in routine, and 2) caregivers' anxiety and depression symptoms. METHOD: Three hundred and sixty-four main caregivers completed a questionnaire assessing their supportive care needs (SCNS-P&C-F) and anxiety and depression symptoms (HADS) during the treatment or follow-up stage of patients with digestive, breast, or lung cancer. Decision trees were used to identify profiles of caregivers with the Conditional inference Tree (CTree) technique. RESULTS: In our study, only the combination of three main variables was important to predict the risk of unmet supportive care needs of caregivers: anxiety and/or depression symptoms, the age of caregivers or patients, and the presence/absence of metastases. Emotional distress has the greatest impact, exceeding that of the socio-demographic and clinical variables considered in this study. CONCLUSIONS: This study shows the importance of considering a set of variables and their combinations rather than evaluating their effects separately. Routinely assessing the anxiety and depression symptoms of caregivers using the HADS could improve the screening of caregivers at higher risk of unmet supportive care needs based on socio-demographic and clinical variables only. This study provides recommendations on how to identify caregivers at risk of unmet needs, in the context of an inability to support all caregivers.
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Ansiedad/epidemiología , Cuidadores , Depresión/epidemiología , Neoplasias/terapia , Apoyo Social , Adulto , Anciano , Ansiedad/psicología , Cuidadores/psicología , Estudios Transversales , Depresión/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Neoplasias/psicología , Encuestas y CuestionariosRESUMEN
The presence of amyloid beta (Aß) plaques in the brain of some individuals with Creutzfeldt-Jakob or Gertsmann-Straussler-Scheinker diseases suggests that pathogenic prions (PrPSc) would have stimulated the production and deposition of Aß peptides. We here show in prion-infected neurons and mice that deregulation of the PDK1-TACE α-secretase pathway reduces the Amyloid Precursor Protein (APP) α-cleavage in favor of APP ß-processing, leading to Aß40/42 accumulation. Aß predominates as monomers, but is also found as trimers and tetramers. Prion-induced Aß peptides do not affect prion replication and infectivity, but display seedable properties as they can deposit in the mouse brain only when seeds of Aß trimers are co-transmitted with PrPSc. Importantly, brain Aß deposition accelerates death of prion-infected mice. Our data stress that PrPSc, through deregulation of the PDK1-TACE-APP pathway, provokes the accumulation of Aß, a prerequisite for the onset of an Aß seeds-induced Aß pathology within a prion-infectious context.