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INTRODUCTION: Patulous Eustachian tube (PET) is a condition affecting approximately 0.3% to 6.6% of the population, with autophony being the predominant complain. The management of PET lacks a well-defined standard in the literature as no effective medical treatments have been documented but various surgical options are available. This study aims to report mid-term outcomes following surgical management of PET. MATERIALS AND METHODS: All patients who underwent surgical intervention for PET between September 2017 and June 2022 were enrolled. Data encompassing general demographics, quality of life (GBI), and procedure-specific data were collected. RESULTS: A total of 30 PET cases (in 19 patients) underwent surgical intervention including 9 injections of hyaluronic acid, 13 fat injections, 6 endoscopic shim insertions, 1 cartilage graft, and 1 injection of hydroxy apatite. After an average follow-up of 22 ± 14 months, 16 cases (53%) achieved complete symptom relief, while 8 cases (26.6%) reported partial relief. Additionally, 11(36%) cases required multiple surgeries. No specific surgical technique demonstrated superiority. Quality of life improved in 77% of cases based on 10 out of 13 GBI collected. Recurrence of PET symptoms occurred on average 10.6 ± 9.7 months after initial surgery, with an estimated global risk of 75% at 3 years. Transient serous otitis media was observed in only 4 cases (13.3%). CONCLUSION: Surgical intervention for PET was found to be effective, achieving complete symptom relief in 53% of cases and significantly improving quality of life 2 years post-surgery. However, a substantial portion of cases necessitated one or more re-interventions. The durability of effectiveness appears to diminish over time.
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Enfermedades del Oído , Trompa Auditiva , Calidad de Vida , Humanos , Trompa Auditiva/cirugía , Trompa Auditiva/fisiopatología , Femenino , Masculino , Enfermedades del Oído/cirugía , Persona de Mediana Edad , Adulto , Anciano , Resultado del Tratamiento , Ácido Hialurónico/administración & dosificación , Ácido Hialurónico/uso terapéutico , Endoscopía/métodos , Procedimientos Quirúrgicos Otológicos/métodos , Cartílago/trasplante , DurapatitaRESUMEN
INTRODUCTION: CD4/CD8 ratio is a marker of immune activation in HIV infection and has been associated with neurocognitive performance during chronic infection, but little is known about the early phases. The aim of this study was to examine the relationship between blood CD4/CD8 ratio and central nervous system endpoints in primary HIV infection (PHI) before and after antiretroviral treatment (ART). METHODS: This was a retrospective analysis of the Primary Infection Stage CNS Events Study (PISCES) cohort. We longitudinally assessed blood and cerebrospinal fluid (CSF) markers of inflammation, immune activation and neuronal injury, and neuropsychological testing performance (NPZ4, an average of three motor and one processing speed tests, and a summarized total score, NPZ11, including also executive function, learning and memory) in ART-naïve participants enrolled during PHI. Spearman correlation and linear mixed models assessed the relationships between the trajectory of CD4/CD8 ratio over time and neurocognitive performance, blood and CSF markers of immune activation and neuronal injury. RESULTS: In all, 109 PHI participants were enrolled. The mean CD4/CD8 ratio decreased with longer time from infection to starting treatment (p < 0.001). Every unit increase in NPZ4 score was independently associated with a 0.15 increase in CD4/CD8 ratio (95% CI: 0.002-0.29; p = 0.047), whereas no correlation was found between CD4/CD8 ratio and NPZ11. Among the cognitive domains, only a change in processing speed was correlated with CD4/CD8 ratio over time (p = 0.03). The trajectory of the CD4/CD8 ratio was negatively correlated with change in CSF neurofilament light chain (p = 0.04). CONCLUSIONS: The trajectory of CD4/CD8 ratio was independently associated with motor/psychomotor speed performance, suggesting that immune activation is involved in brain injury during the early stages of the infection.
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Infecciones por VIH , Humanos , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Estudios Retrospectivos , Relación CD4-CD8 , Antirretrovirales/uso terapéutico , Linfocitos T CD8-positivosRESUMEN
OBJECTIVE: Antithrombotic strategies are currently recommended for the treatment of lower extremity artery disease (LEAD) but specific scores to assess the risk of bleeding in these patients are scarce. To fill the gap, the OAC3-PAD bleeding score was recently developed and validated in German cohorts. The aim of this study was to determine whether this score performs appropriately in another real world nationwide cohort. METHODS: This 10 year retrospective, multicentre study based on French national electronic health data included patients who underwent revascularisation for LEAD between January 2013 and June 2022. The OAC3-PAD score was calculated and from this, the population was classified into four groups: low, low to moderate, moderate to high and high risk. A binary logistic regression model was applied, with major bleeding occurring at one year (defined using the International Classification of Diseases ICD-10) as the dependent variable. The performance of the OAC3-PAD bleeding score was investigated using a receiver operating characteristic curve. RESULTS: Among 161 205 patients hospitalised for LEAD treatment in French institutions, the one year incidence of major bleeding was 13 672 patients (8.5%). The distribution of the population according to the OAC3-PAD bleeding score was: 88 835 patients (55.1%), 34 369 (21.3%), 27 914 (17.3%), and 10 087 (6.3%) in the low, low to moderate, moderate to high, and high risk groups, respectively; with an incidence of one year major bleeding of 5.0%, 9.8%, 13.2%, and 21.3%. The OAC3-PAD model achieved an AUC of 0.650 to predict one year major bleeding following LEAD repair (95% CI 0.645 - 0.655), with a sensitivity of 0.67 and a specificity of 0.57. CONCLUSION: This nationwide analysis confirmed the accuracy of the OAC3-PAD model to predict one year major bleeding and served as external validation. Although further studies are required, it adds evidence and perspectives to further generalise its use to guide the management of patients with LEAD.
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Enfermedad Arterial Periférica , Humanos , Estudios Retrospectivos , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/cirugía , Enfermedad Arterial Periférica/epidemiología , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Procedimientos Quirúrgicos Vasculares/efectos adversos , Extremidad Inferior/irrigación sanguínea , Factores de RiesgoRESUMEN
Alzheimer's disease affects nearly three million people in France, and requires training for both healthcare professionals and caregivers. Our study underlines the value of supporting an adapted program based on mindfulness meditation, to reduce anxiety and stress for patients and their caregivers.
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Enfermedad de Alzheimer , Arteterapia , Meditación , Atención Plena , Humanos , Cuidadores , Enfermedad de Alzheimer/terapiaRESUMEN
BACKGROUND: The Nice terror attack of July 14, 2016 resulted in 84 deaths and 434 injured, with many hospital staff exposed to the attack, either as bystanders on site at the time of the attack ('bystander exposure') who may or may not have provided care to attack victims subsequently, or as care providers to victims only ('professional exposure only'). The objective of this study is to describe the impact on mental health among hospital staff by category of exposure with a particular focus on those with 'professional exposure only', and to assess their use of psychological support resources. METHOD: An observational, cross-sectional, multicenter study conducted from 06/20/2017 to 10/31/2017 among all staff of two healthcare institutions in Nice, using a web questionnaire. Collected data included social, demographic and professional characteristics; trauma exposure category ('bystanders to the attack'; 'professional exposure only'; 'unexposed'); indicators of psychological impact (Hospital Anxiety and Depression Scale); PTSD (PCL-5) level; support sought. Responders could enter open comments in each section of the questionnaire, which were processed by inductive analysis. RESULTS: 804 staff members' questionnaires were analysed. Among responding staff, 488 were exposed (61%): 203 were 'bystanders to the attack', 285 had 'professional exposure only'. The staff with 'professional exposure only' reported anxiety (13.2%), depression (4.6%), suicidal thoughts (5.5%); rates of full PTSD was 9.4% and of partial PTSD, 17.7%. Multivariate analysis in the 'professional exposure only' category showed that the following characteristics were associated with full or partial PTSD: female gender (OR = 2.79; 95% CI = 1.19-6.56, p = 0.019); social isolation (OR = 3.80; 95% CI = 1.30-11.16, p = 0.015); having been confronted with an unfamiliar task (OR = 3.04; 95% CI = 1.18-7.85; p = 0.022). Lastly, 70.6% of the staff with 'professional exposure only' with full PTSD did not seek psychological support. CONCLUSION: Despite a significant impact on mental health, few staff with 'professional exposure only' sought psychological support. Robust prevention and follow-up programs must be developed for hospital staff, in order to manage the health hazards they face when exposed to exceptional health-related events such as mass terror attacks. STUDY REGISTRATION: Ethical approval for the trial was obtained from the National Ethics Committee for Human Research (RCBID N° 2017-A00812-51).
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Salud Mental , Trastornos por Estrés Postraumático , Trastornos de Ansiedad , Estudios Transversales , Femenino , Humanos , Personal de Hospital , Trastornos por Estrés Postraumático/epidemiología , Trastornos por Estrés Postraumático/terapiaRESUMEN
BACKGROUND: During the COVID-19 pandemic, health professionals have been directly confronted with the suffering of patients and their families. By making them main actors in the management of this health crisis, they have been exposed to various psychosocial risks (stress, trauma, fatigue, etc). Paradoxically, stress-related symptoms are often underreported in this vulnerable population but are potentially detectable through passive monitoring of changes in speech behavior. OBJECTIVE: This study aims to investigate the use of rapid and remote measures of stress levels in health professionals working during the COVID-19 outbreak. This was done through the analysis of participants' speech behavior during a short phone call conversation and, in particular, via positive, negative, and neutral storytelling tasks. METHODS: Speech samples from 89 health care professionals were collected over the phone during positive, negative, and neutral storytelling tasks; various voice features were extracted and compared with classical stress measures via standard questionnaires. Additionally, a regression analysis was performed. RESULTS: Certain speech characteristics correlated with stress levels in both genders; mainly, spectral (ie, formant) features, such as the mel-frequency cepstral coefficient, and prosodic characteristics, such as the fundamental frequency, appeared to be sensitive to stress. Overall, for both male and female participants, using vocal features from the positive tasks for regression yielded the most accurate prediction results of stress scores (mean absolute error 5.31). CONCLUSIONS: Automatic speech analysis could help with early detection of subtle signs of stress in vulnerable populations over the phone. By combining the use of this technology with timely intervention strategies, it could contribute to the prevention of burnout and the development of comorbidities, such as depression or anxiety.
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Ansiedad/diagnóstico , Agotamiento Profesional/diagnóstico , COVID-19/psicología , Personal de Salud/psicología , Acústica del Lenguaje , Habla/fisiología , Adulto , Ansiedad/etiología , Ansiedad/psicología , Agotamiento Profesional/etiología , Agotamiento Profesional/psicología , COVID-19/epidemiología , Femenino , Humanos , Masculino , Pandemias , Proyectos Piloto , SARS-CoV-2 , Encuestas y Cuestionarios , TeléfonoRESUMEN
BACKGROUND: Cognitive and behavioral symptoms are the clinical hallmarks of neurocognitive disorders. Cognitive training may be offered to reduce the risks of cognitive decline and dementia and to reduce behavioral symptoms, such as apathy. Information and communication technology approaches, including serious games, can be useful in improving the playful aspect of computerized cognitive training and providing motivating solutions in elderly patients. OBJECTIVE: The objective of this study was to assess the effectiveness of employing the MeMo (Memory Motivation) Web app with regard to cognitive and behavioral symptoms in patients with neurocognitive disorders. METHODS: MeMo is a Web app that can be used on any Web browser (computer or tablet). The training activities proposed in MeMo are divided into the following two parts: memory and mental flexibility/attention. The study included 46 individuals (mean age 79.4 years) with a diagnosis of neurocognitive disorders at the Institut Claude Pompidou Memory Center in Nice. This randomized controlled study compared the evolution of cognition and behavior between patients not using MeMo (control group) and patients using MeMo (MeMo group) for 12 weeks (four sessions per week). Patients underwent memory and attention tests, as well as an apathy assessment at baseline, week 12 (end of the training period), and week 24 (12 weeks after the end of the training sessions). In addition, to assess the impact of high and low game uses, the MeMo group was divided into patients who used MeMo according to the instructions (about once every 2 days; active MeMo group) and those who used it less (nonactive MeMo group). RESULTS: When comparing cognitive and behavioral scores among baseline, week 12, and week 24, mixed model analysis for each cognitive and behavioral score indicated no significant interaction between testing time and group. On comparing the active MeMo group (n=9) and nonactive MeMo group (n=13), there were significant differences in two attention tests (Trial Making Test A [P=.045] and correct Digit Symbol Substitution Test items [P=.045]) and in the Apathy Inventory (AI) (P=.02). Mixed analysis (time: baseline, week 12, and week 24 × number of active days) indicated only one significant interaction for the AI score (P=.01), with a significant increase in apathy in the nonactive MeMo group. CONCLUSIONS: This study indicates that the cognitive and behavioral efficacies of MeMo, a Web-based training app, can be observed only with regular use of the app. Improvements were observed in attention and motivation. TRIAL REGISTRATION: ClinicalTrials.gov NCT04142801; https://clinicaltrials.gov/ct2/show/NCT04142801.
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Cognición/fisiología , Educación/métodos , Aplicaciones Móviles/normas , Trastornos Neurocognitivos/diagnóstico , Anciano , Femenino , Humanos , Masculino , Proyectos de InvestigaciónRESUMEN
Combining stimulated emission depletion and fluorescence correlation spectroscopy (STED-FCS) provides a powerful and sensitive tool for studying the molecular dynamics in live cells with high spatio-temporal resolution. STED-FCS gives access to molecular diffusion characteristic at the nanoscale occurring within short period of times. However due to the incomplete suppression of fluorescence in the STED process, the STED-FCS point spread function (PSF) deviates from a Gaussian shape and challenges the analysis of the auto-correlation curves obtained by FCS. Here, we model the effect of the incomplete fluorescence suppression in STED-FCS experiments and propose a new fitting model improving the accuracy of the diffusion times and average molecule numbers measurements. The implementation of a STED module with pulsed laser source on a commercial confocal/FCS microscope allowed us to apply the STED-background corrected model to fit the STED-FCS measurements. The experimental results are in good accordance with the theoretical analysis both for the number of molecules and the diffusion time which decrease accordingly with the STED power.
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Procesamiento de Imagen Asistido por Computador/métodos , Microscopía Intravital/métodos , Modelos Químicos , Espectrometría de Fluorescencia/métodos , Citoesqueleto de Actina/metabolismo , Animales , Células COS , Chlorocebus aethiops , Difusión , Fluorescencia , Microscopía Intravital/instrumentación , Citometría de Barrido por Láser/instrumentación , Citometría de Barrido por Láser/métodos , Rayos Láser , Microscopía Fluorescente/instrumentación , Microscopía Fluorescente/métodos , Programas Informáticos , Espectrometría de Fluorescencia/instrumentaciónRESUMEN
BACKGROUND: Apathy is a pervasive neuropsychiatric syndrome in people with neurocognitive and psychiatric disorders. The diagnostic criteria for apathy (DCA) have been revised in 2018. OBJECTIVES: Employing the 2018 DCA, in the present study, we investigated in groups of elderly subjects suffering from different neuropsychiatric disorders (a) the apathy prevalence; (b) the most commonly affected apathy dimensions (behavior/cognition, emotion, and social interaction); (c) the sensitivity and specificity of those dimensions for apathy diagnosis; and (d) the concurrent validity of 2018 DCA compared with the 2009 DCA. METHODS: This multicenter survey included 166 subjects. Each center checked the presence of apathy in subjects belonging to the following DSM-5 diagnoses: mild neurocognitive disorders (mild NCDs); major NCDs; affective disorders (Aff D); and subjective cognitive decline (SCD). RESULTS: The frequency of apathy varied significantly based on the diagnostic groups (0% of subjects with apathy in the SCD group; 25% in the mild NCD group; 77% in the major NCD group; and 57% in the Aff. D group). All subjects with apathy fulfilled the criteria for the behavior/cognition dimension, 73.1% fulfilled the criteria for the emotion dimension, and 97.4% fulfilled the criteria for the social interaction dimension. Behavior/cognition showed the highest sensitivity, the copresence of emotion and social interaction the highest specificity. The concordance between the 2009 and the 2018 DCA indicated an almost perfect agreement. CONCLUSIONS: These results are consistent with previous reports and confirm that the social interaction dimension added to the 2018 DCA is present in most of subjects with apathy referred to specialized memory centers.
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Apatía , Trastornos del Humor/epidemiología , Trastornos Neurocognitivos/psicología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Estudios Transversales , Femenino , Humanos , Masculino , Prevalencia , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: The terror attack of July 14, 2016, in Nice, France, resulted in 86 deaths, including children, and several hundred wounded, with a major psychological impact on the population. Hospital staff had to cope with exceptional circumstances which made them vulnerable to detrimental effects on their own health. This paper describes the method that was selected for the survey entitled "ECHOS de Nice 14 Juillet" which aimed to assess the impact of the attack on the psychological, psycho-traumatic and somatic health condition of the Nice University and Lenval hospital staff who were directly or indirectly exposed to the attack, and also to describe the support and care facilities they were offered. METHOD: ECHOS de Nice 14 juillet is an observational, cross-sectional, multicentre study focusing on all the hospital staff and students of both institutions, i.e. 10,100 persons in June 2017. A web-based questionnaire based on the model developed by Santé Publique France (IMPACTS and ESPA 13 novembre 2015) was adapted to the contexts of the healthcare professionals and students employed in these healthcare institutions in Nice and published on line from June 21 to October 30, 2017. The paper describes the tools that were used to meet the aims of the study, i.e. identification of exposure categories ('civilian' exposure for those present during the attack and/or 'professional' exposure); indicators of psychological impact (anxiety, depression, burnout, compassion fatigue, suicidal states, tobacco and alcohol use, self-medications), psycho-traumatic and somatic impact; professional and social impact. Lastly, awareness of availability and use of psychological support and care-follow-up facilities by professionals were investigated. Respondents could include extensive qualitative comments on the various themes explored in the questionnaire, with text analysis complementing that of quantitative data. DISCUSSION: The benefits and limitations of the selected methodology are discussed, in view of contributing useful information to help anticipate and manage health issues among hospital staff who have been victims of traumatic events.
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Encuestas Epidemiológicas/métodos , Personal de Hospital/psicología , Trastornos por Estrés Postraumático/epidemiología , Estudiantes del Área de la Salud/psicología , Terrorismo/psicología , Adulto , Estudios Transversales , Femenino , Francia/epidemiología , Humanos , MasculinoRESUMEN
Single-molecule localization microscopy (SMLM) enables the production of high-resolution images by imaging spatially isolated fluorescent particles. Although challenging, the result of SMLM analysis lists the position of individual molecules, leading to a valuable quantification of the stoichiometry and spatial organization of molecular actors. Both the signal/noise ratio and the density (Dframe), i.e., the number of fluorescent particles per µm2 per frame, have previously been identified as determining factors for reaching a given SMLM precision. Establishing a comprehensive theoretical study relying on these two parameters is therefore of central interest to delineate the achievable limits for accurate SMLM observations. Our study reports that in absence of prior knowledge of the signal intensity α, the density effect on particle localization is more prominent than that anticipated from theoretical studies performed at known α. A first limit appears when, under a low-density hypothesis (i.e., one-Gaussian fitting hypothesis), any fluorescent particle distant by less than â¼600 nm from the particle of interest biases its localization. In fact, all particles should be accounted for, even those dimly fluorescent, to ascertain unbiased localization of any surrounding particles. Moreover, even under a high-density hypothesis (i.e., multi-Gaussian fitting hypothesis), a second limit arises because of the impossible distinction of particles located too closely. An increase in Dframe is thus likely to deteriorate the localization precision, the image reconstruction, and more generally the quantification accuracy. Our study firstly provides a density-signal/noise ratio space diagram for use as a guide in data recording toward reaching an achievable SMLM resolution. Additionally, it leads to the identification of the essential requirements for implementing UNLOC, a parameter-free and fast computing algorithm approaching the Cramér-Rao bound for particles at high-density per frame and without any prior knowledge of their intensity. UNLOC is available as an ImageJ plugin.
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Algoritmos , Nanotecnología , Imagen Individual de Molécula , Relación Señal-RuidoRESUMEN
BACKGROUND: The benefits of supervised physical activity programs in cardiac rehabilitation have been amply demonstrated, but the quantity of physical activity often declines quickly once supervision ends. This trial assesses the effectiveness of an experimental intervention drawing on habit formation theory to maintain physical activity. METHODS: Cardiovascular patients (N = 47) were randomly assigned to one of two groups. The first group participated in two supervised physical activity (SPA) sessions per week for 20 weeks. The second group was offered a progressively autonomous physical activity (PAPA) program as follows: the same supervised program as the SPA group for 10 weeks and then a further 10 weeks with one supervised session replaced by a strategy to build and sustain the habit of autonomous physical activity. The International Physical Activity Questionnaire (IPAQ; Craig et al. Med Sci Sports Exerc 35(8):1381-1395, 2003) was used to measure the quantity of physical activity, which was the primary outcome. The number of participants was limited, and we thus took multiple IPAQ measurements (at 0, 5, 7, 9 and 12 months after the start of the intervention) and used a mixed model for analysis. Physical condition, automaticity of the physical activity behavior, motivation, and quality of life were examined for changes. RESULTS: No significant between-group differences were noted for physical activity behaviors after the program, physical condition, motivation, or behavioral automaticity. The PAPA group nevertheless completed more PA sessions during the intervention, and their quality of life was significantly higher than that of the SPA group at 12 months. CONCLUSION: Although the number of supervised sessions was lower, the progressively autonomous PA program resulted in the same or even higher positive outcomes than the fully supervised PA program. TRIAL REGISTRATION: Current Controlled Trials ISRCTN77313697 , retrospectively registered on 20 November 2015.
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Rehabilitación Cardiaca/métodos , Enfermedades Cardiovasculares/terapia , Terapia por Ejercicio/métodos , Ejercicio Físico , Conductas Relacionadas con la Salud , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Enfermedades Cardiovasculares/psicología , Femenino , Hábitos , Conocimientos, Actitudes y Práctica en Salud , Estado de Salud , Humanos , Masculino , Persona de Mediana Edad , Motivación , Autonomía Personal , Calidad de Vida , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Physical activity programs (PAP) in patients with cardiovascular disease require evidence of cost-utility. To assess improvement in health-related quality of life (QoL) and reduction of health care consumption of patients following PAP, a randomized trial was used. METHODS: Patients from a health insurance company who had experienced coronary artery disease or moderate heart failure were invited to participate (N = 1891). Positive responders (N = 50) were randomly assigned to a progressively autonomous physical activity (PAPA) program or to a standard supervised physical activity (SPA) program. The SPA group had two supervised sessions per week over 5 months. PAPA group had one session per week and support to aid habit formation (written tips, exercise program, phone call). To measure health-related quality of life EQ-5D utility score were used, before intervention, 6 months (T6) and 1 year later. Health care costs were provided from reimbursement databases. RESULTS: Mobility, usual activities and discomfort improved significantly in both group (T6). One year later, EQ-5D utility score was improved in the PAPA group only. Total health care consumption in the intervention group decreased, from a mean of 4097 euros per year before intervention to 2877 euros per year after (p = 0.05), compared to a health care consumption of 4087 euros and 4180 euros per year, in the total population of patients (N = 1891) from the health insurance company. The incremental cost effectiveness ratio was 10,928 euros per QALYs. CONCLUSION: A physical activity program is cost-effective in providing a better quality of life and reducing health care consumption in cardiovascular patients. TRIAL REGISTRATION: ISRCTN77313697 , retrospectively registered on 20 November 2015.
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Rehabilitación Cardiaca/economía , Enfermedades Cardiovasculares/economía , Enfermedades Cardiovasculares/terapia , Terapia por Ejercicio/economía , Costos de la Atención en Salud , Calidad de Vida , Anciano , Rehabilitación Cardiaca/métodos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/fisiopatología , Análisis Costo-Beneficio , Terapia por Ejercicio/métodos , Femenino , Francia , Recursos en Salud/economía , Humanos , Masculino , Persona de Mediana Edad , Años de Vida Ajustados por Calidad de Vida , Recuperación de la Función , Factores de Tiempo , Resultado del TratamientoRESUMEN
Mechanical interaction between cells and their surrounding extracellular matrix (ECM) controls key processes such as proliferation, differentiation and motility. For many years, two-dimensional (2D) models were used to better understand the interactions between cells and their surrounding ECM. More recently, variation of the mechanical properties of tissues has been reported to play a major role in physiological and pathological scenarios such as cancer progression. The 3D architecture of the ECM finely tunes cellular behavior to perform physiologically relevant tasks. Technical limitations prevented scientists from obtaining accurate assessment of the mechanical properties of physiologically realistic matrices. There is therefore a need for combining the production of high-quality cell-derived 3D matrices (CDMs) and the characterization of their topographical and mechanical properties. Here, we describe methods that allow to accurately measure the young modulus of matrices produced by various cellular types. In the first part, we will describe and review several protocols for generating CDMs matrices from endothelial, epithelial, fibroblastic, muscle and mesenchymal stem cells. We will discuss tools allowing the characterization of the topographical details as well as of the protein content of such CDMs. In a second part, we will report the methodologies that can be used, based on atomic force microscopy, to accurately evaluate the stiffness properties of the CDMs through the quantification of their young modulus. Altogether, such methodologies allow characterizing the stiffness and topography of matrices deposited by the cells, which is key for the understanding of cellular behavior in physiological conditions.
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Matriz Extracelular/fisiología , Animales , Bovinos , Módulo de Elasticidad , Matriz Extracelular/química , Células Endoteliales de la Vena Umbilical Humana/fisiología , Humanos , Células Madre Mesenquimatosas/fisiología , Ratones , Microscopía de Fuerza Atómica , Miocitos del Músculo Liso/fisiología , Células 3T3 NIHRESUMEN
Nuclear shape is different in stem cells and differentiated cells and reflects important changes in the mechanics of the nuclear envelope (NE). The current framework emphasizes the key role of the nuclear lamina in nuclear mechanics and its alterations in disease. Whether active stress controls nuclear deformations and how this stress interplays with properties of the NE to control NE dynamics is unclear. We address this in the early Drosophila embryo, in which profound changes in NE shape parallel the transcriptional activation of the zygotic genome. We show that microtubule (MT) polymerization events produce the elementary forces necessary for NE dynamics. Moreover, large-scale NE deformations associated with groove formation require concentration of MT polymerization in bundles organized by Dynein. However, MT bundles cannot produce grooves when the farnesylated inner nuclear membrane protein Kugelkern (Kuk) is absent. Although it increases stiffness of the NE, Kuk also stabilizes NE deformations emerging from the collective effect of MT polymerization forces concentrated in bundles. Finally, we report that MT-induced NE deformations control the dynamics of chromatin and its organization at steady state. Thus, the NE is a dynamic organelle, fluctuations of which increase chromatin dynamics. We propose that such mechanical regulation of chromatin dynamics by MTs might be important for gene regulation.
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Cromatina , Drosophila melanogaster/citología , Drosophila melanogaster/embriología , Microtúbulos , Membrana Nuclear , Animales , Forma de la CélulaRESUMEN
Introduction: Beta-lactamases are frequently prescribed for Gram-negative bloodstream infections (BSIs). However, chromosomally encoded AmpC-producing Enterobacterales (AE) could overproduce beta-lactamases when exposed to third-generation cephalosporins (3GCs), with a risk of clinical failure. There are few available in vivo data on the subject. Our goal was to assess the potential role of AE as a predictive factor for clinical failure in patients with BSIs. Materials and Methods: We retrospectively analyzed patients admitted to Cannes hospital between 2021 and 2022 for BSIs due to Enterobacterales. Patient demographics, comorbidities, and main clinical and laboratory parameters during hospitalization were collected. The risk factors for clinical instability after 48 h or death, as well as for ineffective initial empirical therapy, were assessed using univariate and multivariate analyses. Results: From January 2021 to December 2022, 101 subjects were included (mean age 79 years, 60% men, 97% with comorbidities, 17% with healthcare-associated infection, 13% with septic shock, 82% with qPitt severity score < 2, 58% with urinary tract infection, and 18% with AE). Septic shock [adjusted odds ratio (ORadj) = 5.30, 95% confidence interval (CI): 1.47-22.19, p = 0.014] and ineffective initial empirical therapy [ORadj 5.54, 95% CI: 1.95-17.01, p = 0.002] were independent predictive factors for clinical instability or death. Extended-spectrum beta-lactamases [ORadj 9.40, 95% CI: 1.70-62.14, p = 0.012], AE group [ORadj 5.89, 95% CI: 1.70-21.40, p = 0.006], and clinical instability or death [ORadj 4.71, 95% CI: 1.44-17.08, p = 0.012] were independently associated with ineffective empirical therapy. Conclusions: Infection with AE was associated with treatment failure. Empirical therapy may result in failure if restricted to 3GC.
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OBJECTIVE: To evaluate taste disorders after middle ear surgery, their modifying factors especially chorda tympani nerve injury or underlying otologic disease. We investigated consequences of taste disorders on quality of life. STUDY DESIGN: Prospective cohort study. SETTING: Monocentric study in tertiary care center. METHODS: A total of 214 patients who underwent middle ear surgery were included. Data regarding taste disorders were collected by questionnaires over a 1-year follow-up period. RESULTS: Taste disorders were reported in 42.7% at 10 days, in 23.3% at 4 months, and in 9.2% 1 year postoperatively. When the chorda tympani nerve was initially healthy, taste disorders were more frequent after its transection throughout the follow-up period. When it was involved in a cholesteatoma or inflammatory process, postoperative taste disorders were more frequent after nerve stretching. Postoperative discomfort in daily life was rated on the Likert scale at 3.5 out of 10. Dietary modifications were reported by 25.8% of patients, and mood alterations by 15% of patients. CONCLUSION: Taste disorders are frequent after middle ear surgery although they mostly improve in the first months. When the CTN is healthy, cutting it leads to more taste disorders than stretching it, thus advocating its preservation to prevent these symptoms. However, in cases of pathological CTN, cutting this nerve, which is sometimes necessary to control the disease, is less likely to cause taste disorders than stretching it. These taste disorders are a source of discomfort and may present risks of dietary modifications and emotional impact.