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3.
Transplantation ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38685195

RESUMEN

BACKGROUND: The current landscape of organ donation and transplantation (ODT) registries is not well established. This narrative review sought to identify and characterize the coverage, structure, and data capture of ODT registries globally. METHODS: We conducted a literature search using Ovid Medline and web searches to identify ODT registries from 2000 to 2023. A list of ODT registries was compiled based on publications of registry design, studies, and reports. Extracted data elements included operational features of registries and the types of donor and recipient data captured. RESULTS: We identified 129 registries encompassing patients from all continents except Antarctica. Most registries were active, received funding from government or professional societies, were national in scope, included both adult and pediatric patients, and reported patient-level data. Registries included kidney (n = 99), pancreas (n = 32), liver (n = 44), heart (n = 35), lung (n = 30), intestine (n = 15), and islet cell (n = 5) transplants. Most registries captured donor data (including living versus deceased) and recipient features (including demographics, cause of organ failure, and posttransplant outcomes) but there was underreporting of other domains (eg, donor comorbidities, deceased donor referral rates, waitlist statistics). CONCLUSIONS: This review highlights existing ODT registries globally and serves as a call for increased visibility and transparency in data management and reporting practices. We propose that standards for ODT registries, a common data model, and technical platforms for collaboration, will enable a high-functioning global ODT system responsive to the needs of transplant candidates, recipients, and donors.

4.
Transpl Int ; 37: 12791, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38681973

RESUMEN

Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.


Asunto(s)
Cuidados Críticos , Obtención de Tejidos y Órganos , Humanos , Estudios Prospectivos , Masculino , Femenino , Obtención de Tejidos y Órganos/métodos , Persona de Mediana Edad , Anciano , España , Adulto , Lesiones Encefálicas , Muerte Encefálica , Unidades de Cuidados Intensivos
5.
Sensors (Basel) ; 24(6)2024 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-38544063

RESUMEN

Acquired Brain Injuries are one of the leading causes of mortality and disability worldwide. One of the most frequent sequelae is motor impairment of the upper limbs, which affects people's functionality and quality of life. Following the discovery of mirror neurons, new techniques were developed based on the mechanisms of neuronal plasticity, such as motor imagery (MI) and action observation (AO). We propose a protocol using electromyographic recordings of forearm muscles in people who have suffered a stroke during an MI task and an AO task. Three different experimental conditions will be studied during the electromyographic recordings: control recording, recording during MI, and recording during AO. Understanding the muscle activation in each technique will allow us to develop future protocols and intervention plans, improving the quality of care for people who have suffered a stroke.


Asunto(s)
Neuronas Espejo , Accidente Cerebrovascular , Humanos , Calidad de Vida , Extremidad Superior , Imágenes en Psicoterapia
6.
Front Med (Lausanne) ; 11: 1344028, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38482532

RESUMEN

Background: The study of physiotherapy is challenging and can affect the students' well-being and quality of life. The aim of this study was to describe and compare factors that could affect well-being among students across Europe. Methods: In this descriptive cross-sectional study using an online questionnaire survey, students of bachelor's physiotherapy programs from 23 European faculties, from 8 countries, were interviewed on mental health and stress burden, sleep quality, dietary habits, and physical activity. Results: Although 75% of students rated their quality of life positively and 47% were satisfied with their mental health, 65% showed higher levels of stress and 51% described impaired sleep quality. The minimum physical activity of 150 min weekly was described by 79% of students, within which 67% engaged in strengthening twice a week. Students with a higher stress load/worse psychological health also showed worse sleep quality and lower amount of physical activity, women were significantly worse off. In terms of physical activity and sleep quality, students from Finland and Kosovo achieved the best results, while students from Italy, Greece, and Portugal achieved the worst. Students from Italy indicated the greatest dissatisfaction with the organisation of the study system and communication with teachers, while in Kosovo students rated the communication and study organisation the highest. All students had a problem with adhering to nutritional habits. Students from Italy and Spain, with the lowest body mass indexes and weight averages, were closest to the nutrition recommendations. Conclusion: We demonstrated that physiotherapy students are burdened with stress, suffer from sleep disorders, and do not follow the recommendations regarding nutrition nor physical activity. There are significant differences between universities and countries in some aspects.

7.
Brain Commun ; 6(1): fcae017, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38317856

RESUMEN

The immunoproteasome is a central protease complex required for optimal antigen presentation. Immunoproteasome activity is also associated with facilitating the degradation of misfolded and oxidized proteins, which prevents cellular stress. While extensively studied during diseases with increasing evidence suggesting a role for the immunoproteasome during pathological conditions including neurodegenerative diseases, this enzyme complex is believed to be mainly not expressed in the healthy brain. In this study, we show an age-dependent increase in polyubiquitination in the brains of wild-type mice, accompanied by an induction of immunoproteasomes, which was most prominent in neurons and microglia. In contrast, mice completely lacking immunoproteasomes (triple-knockout mice), displayed a strong increase in polyubiquitinated proteins already in the young brain and developed spontaneous epileptic seizures, beginning at the age of 6 months. Injections of kainic acid led to high epilepsy-related mortality of aged triple-knockout mice, confirming increased pathological hyperexcitability states. Notably, the expression of the immunoproteasome was reduced in the brains of patients suffering from epilepsy. In addition, the aged triple-knockout mice showed increased anxiety, tau hyperphosphorylation and degeneration of Purkinje cell population with the resulting ataxic symptoms and locomotion alterations. Collectively, our study suggests a critical role for the immunoproteasome in the maintenance of a healthy brain during ageing.

8.
Transplantation ; 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38383953

RESUMEN

Global conflicts and humanitarian crises have resulted in an unprecedented number of refugees and migrants. This challenges the limited resources of health care systems and jeopardizes the availability of transplant care for these deserving migrants and refugees. This was the basis for a workshop held during the Congress of the Transplantation Society (Buenos Aires, 2022). We elaborate on the proceedings of the workshop entitled "Transplantation in the Context of Migration and Refugees," organized by the Ethics Committee of The Transplantation Society and Declaration of Istanbul Custodian Group. Transplant providers from around the world shared strategies of how each region has responded to providing access to care for refugees and migrants in need of transplant services. The potential exploitation of this vulnerable group leading to illicit organ removal was addressed for each region. The Transplantation Society, Declaration of Istanbul Custodian Group, and global transplant community should continue to focus on the status of refugees and migrants and collaborate on strategies to provide access to transplant care for this deserving population. Global cooperation will be essential to provide vigilant oversight to prevent exploitation of this vulnerable population.

9.
EFSA J ; 22(1): e8521, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38250499

RESUMEN

Listeria monocytogenes (in the meat, fish and seafood, dairy and fruit and vegetable sectors), Salmonella enterica (in the feed, meat, egg and low moisture food sectors) and Cronobacter sakazakii (in the low moisture food sector) were identified as the bacterial food safety hazards most relevant to public health that are associated with persistence in the food and feed processing environment (FFPE). There is a wide range of subtypes of these hazards involved in persistence in the FFPE. While some specific subtypes are more commonly reported as persistent, it is currently not possible to identify universal markers (i.e. genetic determinants) for this trait. Common risk factors for persistence in the FFPE are inadequate zoning and hygiene barriers; lack of hygienic design of equipment and machines; and inadequate cleaning and disinfection. A well-designed environmental sampling and testing programme is the most effective strategy to identify contamination sources and detect potentially persistent hazards. The establishment of hygienic barriers and measures within the food safety management system, during implementation of hazard analysis and critical control points, is key to prevent and/or control bacterial persistence in the FFPE. Once persistence is suspected in a plant, a 'seek-and-destroy' approach is frequently recommended, including intensified monitoring, the introduction of control measures and the continuation of the intensified monitoring. Successful actions triggered by persistence of L. monocytogenes are described, as well as interventions with direct bactericidal activity. These interventions could be efficient if properly validated, correctly applied and verified under industrial conditions. Perspectives are provided for performing a risk assessment for relevant combinations of hazard and food sector to assess the relative public health risk that can be associated with persistence, based on bottom-up and top-down approaches. Knowledge gaps related to bacterial food safety hazards associated with persistence in the FFPE and priorities for future research are provided.

10.
Am J Transplant ; 24(2): 213-221, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37739346

RESUMEN

One concern about the use of normothermic regional perfusion (NRP) in controlled donation after the circulatory determination of death (cDCD) is that the brain may be perfused. We aimed to demonstrate that certain technical maneuvers preclude such brain perfusion. A nonrandomized trial was performed on cDCD donors. In abdominal normothermic regional perfusion (A-NRP), the thoracic aorta was blocked with an intra-aortic occlusion balloon. In thoracoabdominal normothermic regional perfusion (TA-NRP), the arch vessels were clamped and the cephalad ends vented to the atmosphere. The mean intracranial arterial blood pressure (ICBP) was invasively measured at the circle of Willis. Ten cDCD donors subject to A-NRP or TA-NRP were included. Mean ICBP and mean blood pressure at the thoracic and the abdominal aorta during the circulatory arrest were 17 (standard deviation [SD], 3), 17 (SD, 3), and 18 (SD, 4) mmHg, respectively. When A-NRP started, pressure at the abdominal aorta increased to 50 (SD, 13) mmHg, while the ICBP remained unchanged. When TA-NRP was initiated, thoracic aorta pressure increased to 71 (SD, 18) mmHg, but the ICBP remained unmodified. Recorded values of ICBP during NRP were 10 mmHg. In conclusion, appropriate technical measures applied during NRP preclude perfusion of the brain in cDCD. This study might help to expand NRP and increase the number of organs available for transplantation.


Asunto(s)
Preservación de Órganos , Obtención de Tejidos y Órganos , Humanos , Muerte , Supervivencia de Injerto , Preservación de Órganos/métodos , Perfusión/métodos , Estudios Prospectivos , Donantes de Tejidos
11.
Transplantation ; 108(3): 787-801, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37867239

RESUMEN

BACKGROUND: In 2015, the Spanish National Transplant Organization developed a prioritization system (Program for Access to Transplantation for Highly Sensitized Patients [PATHI]) to increase transplant options for patients with calculated panel-reactive antibodies (cPRAs) ≥98%, based on virtual crossmatch. We describe the experience with the implementation of PATHI and assess its efficacy. METHODS: PATHI registry was used to collect characteristics of donors and patients between June 15, 2015, and March 1, 2018. One-year graft and patient survival and acute rejection were also measured. A Cox model was used to identify factors related to patient death and graft loss and logistical regression for those associated with rejection. RESULTS: One thousand eighty-nine patients were included, and 272 (25%) were transplanted. Transplant rate by cPRA was 54.9%, 40.5%, and 12.8% in patients with cPRA98%, cPRA99%, and cPRA100%, respectively. One-year patient survival was 92.5%. Recipient age ≥60, time under dialysis >7 y, and delayed graft function were mortality risk factors. One-year graft survival was 88.7%. The factor related to graft loss was delayed graft function. The rejection rate was 22%. Factors related to rejection were sex, older recipients, and posttransplant donor-specific antibodies. CONCLUSIONS: A prioritization approach increases transplant options for highly sensitized patients with appropriate short-term postransplant outcomes. Along with other programs, PATHI may inspire other countries to adopt strategies to meet transplant needs of these patients.


Asunto(s)
Trasplante de Riñón , Humanos , Trasplante de Riñón/efectos adversos , Funcionamiento Retardado del Injerto/etiología , Rechazo de Injerto/prevención & control , Donantes de Tejidos , Supervivencia de Injerto , Anticuerpos , Prueba de Histocompatibilidad , Antígenos HLA
12.
Rev Esp Cardiol (Engl Ed) ; 77(1): 69-78, 2024 Jan.
Artículo en Inglés, Español | MEDLINE | ID: mdl-37926340

RESUMEN

Heart transplant (HT) remains the best therapeutic option for patients with advanced heart failure (HF). The allocation criteria aim to guarantee equitable access to HT and prioritize patients with a worse clinical status. To review the HT allocation criteria, the Heart Failure Association of the Spanish Society of Cardiology (HFA-SEC), the Spanish Society of Cardiovascular and Endovascular Surgery (SECCE) and the National Transplant Organization (ONT), organized a consensus conference involving adult and pediatric cardiologists, adult and pediatric cardiac surgeons, transplant coordinators from all over Spain, and physicians and nurses from the ONT. The aims of the consensus conference were as follows: a) to analyze the organization and management of patients with advanced HF and cardiogenic shock in Spain; b) to critically review heart allocation and priority criteria in other transplant organizations; c) to analyze the outcomes of patients listed and transplanted before and after the modification of the heart allocation criteria in 2017; and d) to propose new heart allocation criteria in Spain after an analysis of the available evidence and multidisciplinary discussion. In this article, by the HFA-SEC, SECCE and the ONT we present the results of the analysis performed in the consensus conference and the rationale for the new heart allocation criteria in Spain.


Asunto(s)
Insuficiencia Cardíaca , Trasplante de Corazón , Adulto , Humanos , Niño , España/epidemiología , Insuficiencia Cardíaca/cirugía , Consenso , Choque Cardiogénico
13.
Am J Hosp Palliat Care ; 41(1): 26-37, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36943176

RESUMEN

BACKGROUND: Communication is one of the central axes around which end-of-life care revolves in the context of palliative care. Communication of bad news is reported as one of the most difficult and stressful tasks by palliative care professionals. Therefore, the aim of this study is to identify aspects related to the communication of bad news in palliative care in Spain. METHODS: Descriptive cross-sectional study. An ad hoc questionnaire was designed and sent by e-mail to all palliative care teams in Spain. RESULTS: Overall, 206 professionals (102 nurses, 88 physicians and 16 psychologists) completed the questionnaire. A total of 60.2% considered their communication of bad news skills to be good or very good. This was related to older age, experience in both the profession and palliative care, and to having received specific postgraduate training (P < .001). Around 42.2% perform communication of bad news with the patient first, which is associated with lower skill (P = .013). About 78.15% of the professionals do not use any specific protocol. CONCLUSION: This study suggests that patients access palliative care with little information about their diagnosis and prognosis. The barriers identified in the communication of bad news are the lack of specific education and training in protocol management, the difficult balance between hope and honesty, the young age of the patient, and the family.


Asunto(s)
Cuidados Paliativos , Relaciones Médico-Paciente , Humanos , Revelación de la Verdad , Estudios Transversales , España , Comunicación
14.
Cancers (Basel) ; 15(23)2023 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-38067285

RESUMEN

Vulvar cancer is a relatively rare neoplasm. The essential treatment is surgery for the primary tumour. However, postoperative recurrence rates are high, even in early-stage disease when tumour-free surgical margins are achieved or in the absence of associated risk factors (lymph node metastases, deep stromal invasion or invasion of the lymphatic vascular space). Radiotherapy plays an important role in the treatment of vulvar cancer. Adjuvant treatment after surgery as well as primary treatment of locally advanced vulvar cancer (LAVC) is composed of two key radiotherapy treatment scenarios, external beam radiation therapy (EBRT) either combined or not combined with brachytherapy (BT). In a recurrence setting, where surgery is not an option, BT alone or in combination with EBRT can be used. Compared to EBRT, BT has the radiobiological potential to improve dose to the target volume, minimise the dose to organs at risk, and facilitate hypofractionated-accelerated treatment. This narrative review presents recent data on the role of BT in the treatment of primary and/or recurrent vulvar cancer, including radiobiological, clinical, and therapeutic aspects.

15.
Biomedicines ; 11(12)2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-38137425

RESUMEN

BACKGROUND: Vojta Therapy is a neurorehabilitation therapy that allows to activate reflex movement patterns. The scientific literature has shown its ability to generate muscle contractions. The activation of brain neural networks has also been proven. However, the relationship between these processes has not yet been demonstrated. For this reason, the aim of this study is to verify brain activation produced by recording with near-infrared spectroscopy and its relationship with muscle activation produced in the abdominal muscles recorded with surface electromyography. METHODS: A total sample of 27 healthy subjects over 18 years of age was recruited. An experimental study on a cohort was conducted. Two experimental conditions were considered: stimuli according to the Vojta protocol, and a control non-stimuli condition. Abdominal muscle activation was measured using surface electromyography, and the activation of the motor cortex was assessed with near-infrared spectroscopy. RESULTS: In relation to the oxygenated hemoglobin concentration (HbO), an interaction between the stimulation phase and group was observed. Specifically, the Vojta stimulation group exhibited an increase in concentration from the baseline phase to the first resting period in the right hemisphere, contralateral to the stimulation area. This rise coincided with an enhanced wavelet coherence between the HbO concentration and the electromyography (EMG) signal within a gamma frequency band (very low frequency) during the first resting period. CONCLUSIONS: The results underscore the neurophysiological effects on the brain following tactile stimulation via Vojta Therapy, highlighting increased activity in pivotal areas essential for sensory processing, motor planning, and control. This activation, particularly evident in the Vojta stimulation group, aligns with previous findings, suggesting that tactile stimuli can not only evoke the intention to move but can also initiate actual muscle contractions, emphasizing the therapy's potential in enhancing innate locomotion and rolling movements in patients with neurological disorders.

16.
Transpl Int ; 36: 11498, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37767527

RESUMEN

The primary aim of this study was to describe regulations and practices concerning the family approach to discuss donation, specifically after the neurological determination of death, one of the most challenging steps in the donation pathway. A secondary objective was to assess the impact of legislation on consent rates for organ donation. The Council of Europe surveyed 39 member states about national regulations, practices, and consent rates; 34 replied. Opt-out legislation is present in 19, opt-in in 9 and a mixed system in six countries. An opt-out register is kept by 24 countries and an opt-in register by 18 countries, some keeping both. The mean consent rate was 81.2% of all family approaches. Most countries regulate how death using neurological criteria is confirmed (85.3%), while regulation of other aspects of the deceased donation pathway varies: the timing of informing the family about brain death (47.1%) and organ donation (58.8%), the profile of professional who discusses both topics with the family (52.9% and 64.7%, respectively) and the withdrawal of treatment after brain death (47.1%). We also noted a mismatch between what regulations state and what is done in practice in most countries. We suggest possible reasons for this disparity.


Asunto(s)
Trasplante de Órganos , Obtención de Tejidos y Órganos , Humanos , Muerte Encefálica , Donantes de Tejidos , Europa (Continente)
17.
Biomed Pharmacother ; 167: 115518, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37717534

RESUMEN

Head and neck squamous cell carcinoma present a high mortality rate. Melatonin has been shown to have oncostatic effects in different types of cancers. However, inconsistent results have been reported for in vivo applications. Consequently, an alternative administration route is needed to improve bioavailability and establish the optimal dosage of melatonin for cancer treatment. On the other hand, the use of patient-derived tumor models has transformed the field of drug research because they reflect the heterogeneity of patient tumor tissues. In the present study, we explore mechanisms for increasing melatonin bioavailability in tumors and investigate its potential as an adjuvant to improve the therapeutic efficacy of cisplatin in the setting of both xenotransplanted cell lines and primary human HNSCC. We analyzed the effect of two different formulations of melatonin administered subcutaneously or intratumorally in Cal-27 and SCC-9 xenografts and in patient-derived xenografts. Melatonin effects on tumor mitochondrial metabolism was also evaluated as well as melatonin actions on tumor cell migration. In contrast to the results obtained with the subcutaneous melatonin, intratumoral injection of melatonin drastically inhibited tumor progression in HNSCC-derived xenografts, as well as in patient-derived xenografts. Interestingly, intratumoral injection of melatonin potentiated CDDP effects, decreasing Cal-27 tumor growth. We demonstrated that melatonin increases ROS production and apoptosis in tumors, targeting mitochondria. Melatonin also reduces migration capacities and metastasis markers. These results illustrate the great clinical potential of intratumoral melatonin treatment and encourage a future clinical trial in cancer patients to establish a proper clinical melatonin treatment.


Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Melatonina , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Melatonina/farmacología , Melatonina/uso terapéutico , Carcinoma de Células Escamosas/patología , Xenoinjertos , Inyecciones Intralesiones , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Cisplatino/farmacología , Cisplatino/uso terapéutico , Línea Celular Tumoral , Estrés Oxidativo
19.
Transpl Int ; 36: 11394, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37547749

RESUMEN

Physical examination (PE) of donors is essential to identify potential risks to the safety and efficacy of donated organs and tissues and is mandatory in the EU. However, no detailed guidance is available as to how PE should be performed. Health authorities (HA) and health professionals (HP) in member states of the European Committee on Organ Transplantation of the Council of Europe (CD-P-TO) and observer countries completed surveys relating to the regulatory requirements for PE and the professional practice of PE in their countries for organ and tissue donors. The HA survey addressed regulatory aspects, and the HP survey addressed professional practices, training, and respondents' opinions on the value of PE. These surveys revealed significant inter-country variation in the regulatory approach to PE and the performance of PE by professionals. Most respondents opined that PE was important and yielded valuable information in identifying contraindications to donation. There is no consensus at a regulatory or professional level as to how PE should be performed on organ and tissue donors. There is a requirement for agreed best practice guidelines in this area.


Asunto(s)
Trasplante de Órganos , Obtención de Tejidos y Órganos , Humanos , Donantes de Tejidos , Europa (Continente) , Examen Físico
20.
Epilepsia ; 64(10): 2827-2840, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37543852

RESUMEN

OBJECTIVE: Posttranscriptional mechanisms are increasingly recognized as important contributors to the formation of hyperexcitable networks in epilepsy. Messenger RNA (mRNA) polyadenylation is a key regulatory mechanism governing protein expression by enhancing mRNA stability and translation. Previous studies have shown large-scale changes in mRNA polyadenylation in the hippocampus of mice during epilepsy development. The cytoplasmic polyadenylation element-binding protein CPEB4 was found to drive epilepsy-induced poly(A) tail changes, and mice lacking CPEB4 develop a more severe seizure and epilepsy phenotype. The mechanisms controlling CPEB4 function and the downstream pathways that influence the recurrence of spontaneous seizures in epilepsy remain poorly understood. METHODS: Status epilepticus was induced in wild-type and CPEB4-deficient male mice via an intra-amygdala microinjection of kainic acid. CLOCK binding to the CPEB4 promoter was analyzed via chromatin immunoprecipitation assay and melatonin levels via high-performance liquid chromatography in plasma. RESULTS: Here, we show increased binding of CLOCK to recognition sites in the CPEB4 promoter region during status epilepticus in mice and increased Cpeb4 mRNA levels in N2A cells overexpressing CLOCK. Bioinformatic analysis of CPEB4-dependent genes undergoing changes in their poly(A) tail during epilepsy found that genes involved in the regulation of circadian rhythms are particularly enriched. Clock transcripts displayed a longer poly(A) tail length in the hippocampus of mice post-status epilepticus and during epilepsy. Moreover, CLOCK expression was increased in the hippocampus in mice post-status epilepticus and during epilepsy, and in resected hippocampus and cortex of patients with drug-resistant temporal lobe epilepsy. Furthermore, CPEB4 is required for CLOCK expression after status epilepticus, with lower levels in CPEB4-deficient compared to wild-type mice. Last, CPEB4-deficient mice showed altered circadian function, including altered melatonin blood levels and altered clustering of spontaneous seizures during the day. SIGNIFICANCE: Our results reveal a new positive transcriptional-translational feedback loop involving CPEB4 and CLOCK, which may contribute to the regulation of the sleep-wake cycle during epilepsy.


Asunto(s)
Proteínas CLOCK , Epilepsia Refractaria , Epilepsia del Lóbulo Temporal , Melatonina , Proteínas de Unión al ARN , Estado Epiléptico , Animales , Humanos , Masculino , Ratones , Epilepsia del Lóbulo Temporal/metabolismo , Hipocampo , Melatonina/sangre , ARN Mensajero/metabolismo , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Convulsiones , Estado Epiléptico/inducido químicamente , Estado Epiléptico/genética , Factores de Transcripción/metabolismo , Proteínas CLOCK/genética
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