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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
CONTEXT: Gastric and oesophageal cancers are common. They are also expected to increase in incidence in the next few years and are characterized by poor prognosis. Surprisingly, whereas the incidence of severe anxiety and depression is high in patients with gastric and oesophageal cancers, the influence of symptoms of depression and anxiety on postoperative complications has barely been explored. METHODS: In a retrospective study based on a prospectively collected database, 629 cancer patients were enrolled. Symptoms of depression and anxiety (Hospital Anxiety and Depression Scale scores) and sociodemographic and medical information were collected immediately after diagnosis and before any treatment. The surgical approach (i.e. gastrectomy or oesophagectomy) and postoperative complications according to the Clavien-Dindo classification were collected after surgery. RESULTS: After controlling for known medical predictors (i.e. surgical strategy, alcohol and tobacco consumption, American Society of Anaesthesiologists classification physical status score) of postoperative complications, no effect of symptoms of depression or anxiety was detected. DISCUSSION: The observed results are surprising given the literature. However, several potential arguments can be put forwards regarding methods and measures, controlling variables, and conceptual distinctions. Despite the absence of significant results, this topic should be more deeply investigated by applying methodological and conceptual adjustments.
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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
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
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
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: 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
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
OBJECTIVE: The main objective was to test the indirect effects of emotional competence (EC) after diagnosis (T1) on the health-related quality of life (HRQoL) after surgery (T2) of esogastric cancer patients via fewer anxiety and depression symptoms (T2). METHODS: Data were collected from 30 French centers via the clinicobiological database French EsoGastric Tumors (FREGAT). Two hundred and twenty-eight participants completed a self-reported questionnaire at T1 and T2, assessing their EC (Profile of Emotional Competence (PEC)), HRQoL (EORTC Quality of Life Questionnaire-Core (QLQ-C30)), and anxiety and depression symptoms (Hospital Anxiety and Depression Scale (HADS)). Regression analyses were used to test the direct effects of intrapersonal and interpersonal EC on their anxiety/depression symptoms and HRQoL at T1 and T2. The PROCESS Macro in SPPS v.22 with bootstrap methods was used to test the indirect effects of intrapersonal and interpersonal EC at T1 on HRQoL at T2 via anxiety and depression symptoms. RESULTS: EC predicted fewer anxiety and depression symptoms of patients at T1 and T2 and better HRQoL at T1. EC at T1 also predicted a better HRQoL at T2 via fewer anxiety and depression symptoms at T2. CONCLUSIONS: Patients who tended to use their EC in daily life could be more effective in regulating the emotional impact of the cancer diagnosis and surgery. This explains why they reported fewer anxiety and depression symptoms, which in turn enabled a better perceived HRQoL after surgery. Therefore, reinforcing the use of patients' EC in daily life following their diagnosis could decrease their emotional distress and, in this way, improve their HRQoL in the preoperative and postoperative stages.
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Ansiedad/psicología , Depresión/psicología , Inteligencia Emocional , Neoplasias Esofágicas/psicología , Calidad de Vida/psicología , Neoplasias Gástricas/psicología , Adulto , Anciano , Ansiedad/etiología , Depresión/etiología , Neoplasias Esofágicas/cirugía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Autoinforme , Neoplasias Gástricas/cirugía , Encuestas y CuestionariosRESUMEN
The objective of this study was to assess the psychometric properties of the French version of the Supportive Care Needs Survey for Partners and Caregivers (SCNS-P&C-F). The SCNS-P&C-F, the Hospital Anxiety and Depression Scale (HADS) and the CareGiver Oncology Quality of Life questionnaire (CarGOQoL) were completed by 327 caregivers at the baseline. The SCNS-P&C-F was completed a second time by 121 participants within 30 days. Four factors were retained with a good explanation of variance (82.65%) and acceptable internal consistencies (α: 0.70 to 0.94): 1) Health Care Service and Information Needs, 2) Emotional and Psychological Needs, 3) Work and Social Security Needs and 4) Communication and Family Support Needs. Overall, convergent and divergent validities were confirmed. The caregiver's gender, age, professional status and level of anxiety and depression, as well as the type of relationship with the patient and cancer, showed an effect on some caregivers' unmet supportive care needs. Lastly, the test-retest reliability was acceptable (> 0.70), except for the communication and family support dimension. The scale is appropriate for clinical and research use (e.g. good reliability and validity).
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Cuidadores/psicología , Evaluación de Necesidades , Neoplasias/enfermería , Apoyo Social , Esposos/psicología , Adulto , Anciano , Anciano de 80 o más Años , Ansiedad/psicología , Depresión/psicología , Análisis Factorial , Familia/psicología , Femenino , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Calidad de Vida/psicología , Reproducibilidad de los Resultados , Traducciones , Adulto JovenRESUMEN
PURPOSE: This study aimed to compare the self-reported perceptions of the repercussions of the disease and its treatments and emotional distress in young women with breast cancer and their partners. DESIGN: Cross-sectional study using self-reported questionnaires. SAMPLE: 491 couples in which women were aged <45 years when diagnosed with non-metastatic breast cancer in four different groups of treatment: during chemotherapy with or without Trastuzumab; under Trastuzumab with or without hormone therapy; during hormone therapy; and during the follow-up period. METHODS: Patients and partners completed a questionnaire assessing their self-reported perceptions of the disease and treatments (Patient YW-BCI and Partner YW-BCI for the partners) and their emotional distress (CESD; STAI). FINDINGS: Patients reported more difficulties than partners in the management of child(ren) and everyday life, body image and sexuality, negative affectivity about the disease and apprehension about the future, career management, and finances. While the difficulties were generally more marked in the chemotherapy and Trastuzumab groups than in the hormone therapy and follow-up groups, the negative affectivity about the disease and apprehension about the future was high in all four groups, especially in patients. The partners reported more difficulties in sharing with close relatives, and even more in those groups reflecting the latest treatment phases. No difference appeared between patients and partners in couple cohesion and deterioration of relationships with relatives. Partners were less anxious than patients but as depressed as them. CONCLUSIONS: Difficulties of patients and partners seem particularly severe in the early care pathway, maybe reflecting better adjustment in women under surveillance and their partners. A longitudinal study will substantiate this finding and enable a better identification of some explanatory processes of these differences and similarities in the daily self-reported repercussions of the disease throughout the cancer care pathway. Implications for psychosocial oncology: It seems important to support young women with breast cancer and their partners, as our results evidence distress in both and differences according to the type of treatment the woman is currently receiving. Healthcare providers need consistent methods to identify and respond to couples' distress and reduce significant disparities in support.
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Actitud Frente a la Salud , Neoplasias de la Mama/psicología , Parejas Sexuales/psicología , Adulto , Neoplasias de la Mama/terapia , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , AutoinformeRESUMEN
Despite a growing number of studies on the role of the multidimensional construct of trait emotional intelligence (EI) in health, most have focused on global EI, without examining the role of the sub-dimensions. The present systematic review aimed to highlight the current knowledge about self-reported health associated with trait-EI sub-dimensions in general and clinical populations. We searched for the articles including valid self-report scales of trait-EI and health (mental or physical or general) in general and clinical samples. Based on 42 studies, the majority of studies was based on mental health with cross-sectional designs and the TMMS scale, in the general population. Few studies have been focused on physical health and clinical population. The description of studies results revealed that trait-EI sub-dimensions are associated to a greater extent with better mental health, rather than with physical and general health. Furthermore, intrapersonal dimensions, and especially emotion regulation, have stronger effects on health than interpersonal dimensions. Finally, patients with a clinical disorder present lower trait-EI sub-dimensions than the general population. This review supports the importance of focusing on the sub-dimensions of trait-EI to understand better the role of EI in health. The use of scales exclusively based on emotional competences in health contexts is recommended. Developing interventions targeting emotional competences according to the emotional profiles and contexts of individuals could be beneficial to improve health and disease adjustment.
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Inteligencia Emocional/fisiología , Emociones/fisiología , Estado de Salud , Relaciones Interpersonales , Salud Mental , Autocontrol , HumanosRESUMEN
In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK), key players in neuritogenesis, to prion diseases. We found that overactivation of ROCK signaling occurred in neuronal stem cells infected by pathogenic prions (PrPSc) and impaired the sprouting of neurites. In reconstructed networks of mature neurons, PrPSc-induced ROCK overactivation provoked synapse disconnection and dendrite/axon degeneration. This overactivation of ROCK also disturbed overall neurotransmitter-associated functions. Importantly, we demonstrated that beyond its impact on neuronal polarity ROCK overactivity favored the production of PrPSc through a ROCK-dependent control of 3-phosphoinositide-dependent kinase 1 (PDK1) activity. In non-infectious conditions, ROCK and PDK1 associated within a complex and ROCK phosphorylated PDK1, conferring basal activity to PDK1. In prion-infected neurons, exacerbated ROCK activity increased the pool of PDK1 molecules physically interacting with and phosphorylated by ROCK. ROCK-induced PDK1 overstimulation then canceled the neuroprotective α-cleavage of normal cellular prion protein PrPC by TACE α-secretase, which physiologically precludes PrPSc production. In prion-infected cells, inhibition of ROCK rescued neurite sprouting, preserved neuronal architecture, restored neuronal functions and reduced the amount of PrPSc. In mice challenged with prions, inhibition of ROCK also lowered brain PrPSc accumulation, reduced motor impairment and extended survival. We conclude that ROCK overactivation exerts a double detrimental effect in prion diseases by altering neuronal polarity and triggering PrPSc accumulation. Eventually ROCK emerges as therapeutic target to combat prion diseases.
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Proteínas PrPSc/metabolismo , Enfermedades por Prión/metabolismo , Enfermedades por Prión/patología , Quinasas Asociadas a rho/metabolismo , Animales , Western Blotting , Modelos Animales de Enfermedad , Técnica del Anticuerpo Fluorescente , Inmunoprecipitación , Dispositivos Laboratorio en un Chip , Ratones , Ratones Endogámicos C57BL , Neuritas/metabolismo , Neurogénesis , Proteínas PrPC/metabolismoRESUMEN
Characterizing stem cell intrinsic functions is an ongoing challenge for cell therapies. Here, we report that two independent A4 and H8 stem cell lines isolated from mouse molar pulp display the overall functions of bioaminergic cells. Both clones produce neurotrophins and synthesize, catabolize, store, and transport serotonin (5-hydroxytryptamine [5-HT]) and dopamine (DA). They express 5-HT1D,2B,7 and D1,3 autoreceptors, which render pulpal stem cells competent to respond to circulating 5-HT and DA. We show that injury-activated platelets are the source of systemic 5-HT and DA necessary for dental repair since natural dentin reparation is impaired in two rat models with monoamine storage-deficient blood platelets. Moreover, selective inhibition of either D1, D3, 5-HT2B, or 5-HT7 receptor within the pulp of wild-type rat molars after lesion alters the reparative process. Altogether our data argue that 5-HT and DA coreleased by pulp injury-activated platelets are critical for stem cell-mediated dental repair through 5-HT and DA receptor signalings.
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Plaquetas/metabolismo , Pulpa Dental/metabolismo , Dopamina/metabolismo , Serotonina/metabolismo , Células Madre/metabolismo , Animales , Plaquetas/citología , Línea Celular , Ratones , Ratas , Receptores de Calcitriol/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de Serotonina/metabolismo , Células Madre/citologíaRESUMEN
Rampant caries and periodontal diseases occur in patients treated with antidepressants such as serotonin reuptake inhibitors (SRIs; e.g., Prozac) which target the serotonin transporter (SERT). As the serotonin 2B receptor (5HT2BR) regulates SERT functionality and capacity to recognize SRIs, we investigated the potential role of 5HT2BR on dental tissues by exploiting 5HT2BR knockout (KO) mice. Compared to wild-type (WT) mice, several structural differences were identified in the teeth of KO mice. In the molar of KO mice, rod curvatures and twisting were altered compared to WT mice, suggesting involvement of 5HT2BR at early stages of enamel formation. The volume of the KO enamel layer was also reduced, and larger porosities were observed in the prismatic enamel, with smaller crystallite thickness. Crystallite pattern disorganization and occlusal abrasion were enhanced in female KO mice, indicating a sexual dimorphism. In the incisor, no difference was detected in the width of the enamel layer between KO and WT mice; however, enamel maturation differed in absence of 5HT2BR. Specifically, the outer aprismatic enamel border was 1.5- to 2-fold larger in KO compared to WT mice, together with a decreased etching pattern. Finally, although no noticeable difference was observed in dentin, the micro-CT three-dimensional pulp reconstruction evidenced a decrease in both length and width of dentin formation in the root canals of the KO versus WT mice. These data provide evidence that 5HT2BR-mediated signaling pathways are involved in enamel formation and dentinogenesis.
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Esmalte Dental/metabolismo , Pulpa Dental/metabolismo , Dentina/metabolismo , Receptor de Serotonina 5-HT2B/genética , Diente/metabolismo , Animales , Esmalte Dental/citología , Pulpa Dental/citología , Dentina/citología , Femenino , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Noqueados , Diente/citología , Microtomografía por Rayos X/métodosRESUMEN
Using the proliferating cell nuclear antigen (PCNA) immunostaining, we previously identified, after pulp exposure, three zones of proliferating cells in the rat molar pulp. Zones I and II were in the crown near the pulp. Zone III was near the apex revealing a recruitment of mitotic cells at distance from the lesion. To gain further insight into the spatio-temporal evolution of proliferating pulp cells of zone III, we performed a longitudinal study of PCNA staining in rat molar mesial root at 3, 8, and 15 d after pulp exposure associated to implantation of unloaded or amelogenin loaded agarose beads. At day 3 after implantation, PCNA-positive cells were located in the central part of the radicular pulp. At day 8, PCNA-labeled cells were aligned in the lateral part of the pulp beneath the odontoblast/sub-odontoblast layer. At day 15, PCNA labeling became undetectable in the root and was located in the coronal pulp. These results suggest that after pulp exposure, PCNA-positive cells may migrate from the central part of the radicular pulp to the sub-odontoblast cell layer and then from the apical root to the crown. Electron microscopy and immunostaining analysis showed that pulpal cells were linked by desmosome-like and gap-junctions. Extracellular matrix was composed of thin collagen fibrils associated with glycosaminoglycans favoring cell mobility. These data suggest that the syncytium-like structure formed by pulp radicular cells may be a pre-request for plithotaxis, a collective cell migration process. This emergent mechanism may govern pulp healing and regeneration after dental lesion.
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Movimiento Celular/fisiología , Proliferación Celular/fisiología , Pulpa Dental/citología , Odontoblastos/citología , Regeneración/fisiología , Animales , Pulpa Dental/fisiología , Diente Molar , Ratas Sprague-DawleyRESUMEN
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.
RESUMEN
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.