Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
1.
Mol Cell Biol ; 44(9): 345-357, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39133101

RESUMEN

LSG1 is a conserved GTPase involved in ribosome assembly. It is required for the eviction of the nuclear export adapter NMD3 from the pre-60S subunit in the cytoplasm. In human cells, LSG1 has also been shown to interact with vesicle-associated membrane protein-associated proteins (VAPs) that are found primarily on the endoplasmic reticulum. VAPs interact with a large host of proteins which contain FFAT motifs (two phenylalanines (FF) in an acidic tract) and are involved in many cellular functions including membrane traffic and regulation of lipid transport. Here, we show that human LSG1 binds to VAPs via a noncanonical FFAT-like motif. Deletion of this motif specifically disrupts the localization of LSG1 to the ER, without perturbing LSG1-dependent recycling of NMD3 in cells or modulation of LSG1 GTPase activity in vitro.


Asunto(s)
Retículo Endoplásmico , GTP Fosfohidrolasas , Humanos , Secuencias de Aminoácidos , Retículo Endoplásmico/metabolismo , GTP Fosfohidrolasas/metabolismo , GTP Fosfohidrolasas/genética , Células HEK293 , Células HeLa , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Unión Proteica , Ribosomas/metabolismo , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Transporte Vesicular/genética
2.
J Phys Chem A ; 128(25): 4992-4998, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38709555

RESUMEN

The dynamics of cyclopentadiene (CP) following optical excitation at 243 nm was investigated by time-resolved pump-probe X-ray scattering using 16.2 keV X-rays at the Linac Coherent Light Source (LCLS). We present the first ultrafast structural evidence that the reaction leads directly to the formation of bicyclo[2.1.0]pentene (BP), a strained molecule with three- and four-membered rings. The bicyclic compound decays via a thermal backreaction to the vibrationally hot CP with a time constant of 21 ± 3 ps. A minor channel leads to ring-opened structures on a subpicosecond time scale.

5.
Telemed J E Health ; 30(4): 1006-1012, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37935031

RESUMEN

Introduction: Almost half of veterans (44.6%) seen in the U.S. Department of Veterans Affairs outpatient setting are diagnosed with hypertension (HTN). Because of the widespread nature of HTN, use of virtual visits has the potential to improve blood pressure (BP) management. This evaluation assessed the effectiveness of video blood pressure visits (VBPVs) in the management of HTN in veterans enrolled in Veterans Health Administration primary care. Methods: The program was implemented within the existing veteran-centered medical home. VBPVs are scheduled where the nurse observes veterans taking their BP and provides teaching or counseling. A national training curriculum was delivered to local nurse champions through Microsoft Teams. We analyzed improvement in BP over a 2-year period. We also captured actions taken by nurses during the VBPV by searching the electronic notes. Ratings of training and comments were summarized using feedback forms completed after training. Results: In total, 81,476 veterans participated in VBPVs over 2 years. Of those, 44,682 veterans had an existing ICD-10 code related to HTN. Of the 18,078 veterans who had a pre- and post-VBPV BP, the average change to systolic measurement was -10.6 mm Hg (range -82 to 78). Average change to diastolic measurement was -4.61 mm Hg (range -59 to 55). Most interventions addressed medication management (77%). Nurses' evaluations of the program were positive. Conclusions: Video visits provide reliable and convenient veteran-centered care. Such visits enable care when unanticipated interruptions occur such as the coronavirus disease 2019 pandemic. In addition to medication management, nurse-led interventions such as counseling on lifestyle changes can be effective in HTN management.


Asunto(s)
COVID-19 , Hipertensión , Veteranos , Humanos , Presión Sanguínea , Salud de los Veteranos , Hipertensión/tratamiento farmacológico , Atención Dirigida al Paciente , COVID-19/epidemiología
6.
Reprod Health ; 20(1): 167, 2023 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-37957689

RESUMEN

BACKGROUND: Many low- and-middle-income countries are disproportionately burdened by cervical cancer, resulting in high morbidity and mortality. HPV-DNA testing coupled with treatment with thermal ablation is a recommended screening and precancer treatment strategy, but not enough is known about how this can be effectively implemented in the context of integrated services. The (Scale Up Cervical Cancer Elimination by Secondary prevention Strategy, (SUCCESS) project is conducting a study to understand this approach, integrated into existing women's health services in Burkina Faso, Cote d'Ivoire, Guatemala, and the Philippines (2020-2024). METHODS: A hybrid effectiveness-implementation type III mixed-methods observational study design is used to assess feasibility, acceptability, and costs of integrated service delivery in 10 sites per country, selected considering urban/rural location, facility level, onsite/offsite laboratories, and health services type. In each country, a sample size of 2227 women aged 25-49 years will be enrolled with about 20% being women living with HIV. The primary outcome is proportion of HPV positive women completing precancer treatment, if eligible, within three months of screening. Data collection and analysis includes; facility and client exit surveys, key informant and client interviews, registries and project records extractions, and costing data analysis. Analysis includes descriptive statistics, context description, thematic analysis, and document analysis. Quantitative analyses will be stratified by participant's HIV status. DISCUSSION: Recruitment of study participants started in April 2022 (Burkina Faso and Côte d'Ivoire) and August 2022 (Guatemala and the Philippines). Enrolment targets for women screened, client exit, in-depth and key informant interviews conducted were reached in Burkina Faso and Cote d'Ivoire in November 2022. Guatemala and Philippines are expected to complete enrolment by June 2023. Follow-up of study Participants 12-months post-treatment is ongoing and is expected to be completed for all countries by August 2024. In LMICs, integrating cervical cancer secondary prevention services into other health services will likely require specific rather than incidental recruitment of women for screening. Reconfiguration of laboratory infrastructure and planning for sample management must be made well in advance to meet induced demand for screening. Trail Registration ClinicalTrials.Gov ID: NCT05133661 (24/11/2021).


Asunto(s)
Infecciones por VIH , Infecciones por Papillomavirus , Neoplasias del Cuello Uterino , Humanos , Femenino , Masculino , Côte d'Ivoire/epidemiología , Burkina Faso/epidemiología , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Guatemala/epidemiología , Filipinas/epidemiología , Infecciones por Papillomavirus/diagnóstico , Infecciones por Papillomavirus/prevención & control , Infecciones por VIH/prevención & control , Estudios Observacionales como Asunto
7.
Eur J Med Res ; 28(1): 402, 2023 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-37798729

RESUMEN

BACKGROUND: To date, there is no consensus on whether intrauterine insemination (IUI) treatment is required in young patients with diminished ovarian reserve (DOR). Pregnancy outcomes in young DOR patients undergoing IUI are controversial. The existing studies are all single-center studies, with no existing multicenter cohort studies. The purpose of this multicenter study was to investigate the pregnancy outcomes of young DOR patients undergoing IUI. METHODS: This multicenter cohort study included a total of 4600 cycles in 2204 infertile patients who underwent IUI treatment in three reproductive medical centers between September 2018 and January 2022. The research subjects were divided into two groups according to their serum anti-Müllerian hormone (AMH) levels. Propensity score matching (PSM) was used to match the research subjects at a ratio of 1:4. The pregnancy outcomes in the two groups were compared. RESULTS: There was no significant difference in the clinical pregnancy rates (CPR), biochemical rates, and ectopic pregnancy rates between the two groups (P > 0.05). There were, however, significant differences in the miscarriage rates between the groups (P < 0.05). The live birth rates (LBR) were 6.6 vs. 9.9 between the two groups. The multivariable logistic regression models reveal that body mass index, AMH were significantly correlated with CPR; AMH were significantly correlated with LBR; BMI, follicle stimulating hormone were significantly correlated with miscarriage rate. CONCLUSIONS: The clinical pregnancy rate of DOR patients was not significantly different from that of NOR patients; however, the miscarriage rates were significantly different from those of NOR patients.


Asunto(s)
Aborto Espontáneo , Reserva Ovárica , Embarazo , Femenino , Humanos , Resultado del Embarazo , Estudios de Cohortes , Índice de Embarazo , Hormona Antimülleriana , Inseminación , Estudios Retrospectivos
8.
Cell Metab ; 35(8): 1457-1473.e13, 2023 08 08.
Artículo en Inglés | MEDLINE | ID: mdl-37329887

RESUMEN

Obesity, in which the functional importance of small nucleolar RNAs (snoRNAs) remains elusive, correlates with risk for many cancer types. Here, we identify that the serum copies of adipocyte-expressed SNORD46 correlate with body mass index (BMI), and serum SNORD46 antagonizes interleukin-15 (IL-15) signaling. Mechanically, SNORD46 binds IL-15 via G11, and G11A (a mutation that significantly enhances binding affinity) knockin drives obesity in mice. Functionally, SNORD46 blocks IL-15-induced, FER kinase-dependent phosphorylation of platelet glycoprotein 4 (CD36) and monoglyceride lipase (MGLL) in adipocytes, leading to inhibited lipolysis and browning. In natural killer (NK) cells, SNORD46 suppresses the IL-15-dependent autophagy, leading to reduced viability of obese NK. SNORD46 power inhibitors exhibit anti-obesity effects, concurring with improved viability of obese NK and anti-tumor immunity of CAR-NK cell therapy. Hence, our findings demonstrate the functional importance of snoRNAs in obesity and the utility of snoRNA power inhibitors for antagonizing obesity-associated immune resistance.


Asunto(s)
Lipólisis , ARN Nucleolar Pequeño , Animales , Ratones , ARN Nucleolar Pequeño/genética , ARN Nucleolar Pequeño/metabolismo , Interleucina-15/metabolismo , Rejuvenecimiento , Adipocitos/metabolismo , Obesidad/metabolismo , Células Asesinas Naturales
9.
Mol Ther ; 31(6): 1577-1595, 2023 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-37165619

RESUMEN

Next-generation sequencing has revealed that less than 2% of transcribed genes are translated into proteins, with a large portion transcribed into noncoding RNAs (ncRNAs). Among these, long noncoding RNAs (lncRNAs) represent the largest group and are pervasively transcribed throughout the genome. Dysfunctions in lncRNAs have been found in various diseases, highlighting their potential as therapeutic, diagnostic, and prognostic targets. However, challenges, such as unknown molecular mechanisms and nonspecific immune responses, and issues of drug specificity and delivery present obstacles in translating lncRNAs into clinical applications. In this review, we summarize recent publications that have explored lncRNA functions in human diseases. We also discuss challenges and future directions for developing lncRNA treatments, aiming to bridge the gap between functional studies and clinical potential and inspire further exploration in the field.


Asunto(s)
ARN Largo no Codificante , Humanos , ARN Largo no Codificante/metabolismo , Ingeniería Sanitaria , ARN no Traducido
10.
Sci Adv ; 9(5): eadd6995, 2023 02 03.
Artículo en Inglés | MEDLINE | ID: mdl-36724291

RESUMEN

One of the major obstacles to treating pancreatic ductal adenocarcinoma (PDAC) is its immunoresistant microenvironment. The functional importance and molecular mechanisms of Schwann cells in PDAC remains largely elusive. We characterized the gene signature of tumor-associated nonmyelinating Schwann cells (TASc) in PDAC and indicated that the abundance of TASc was correlated with immune suppressive tumor microenvironment and the unfavorable outcome of patients with PDAC. Depletion of pancreatic-specific TASc promoted the tumorigenesis of PDAC tumors. TASc-expressed long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) was triggered by the tumor cell-produced interleukin-6. Mechanistically, PVT1 modulated RAF proto-oncogene serine/threonine protein kinase-mediated phosphorylation of tryptophan 2,3-dioxygenase in TASc, facilitating its enzymatic activities in catalysis of tryptophan to kynurenine. Depletion of TASc-expressed PVT1 suppressed PDAC tumor growth. Furthermore, depletion of TASc using a small-molecule inhibitor effectively sensitized PDAC to immunotherapy, signifying the important roles of TASc in PDAC immune resistance.


Asunto(s)
Carcinoma Ductal Pancreático , Quinurenina , Neoplasias Pancreáticas , ARN Largo no Codificante , Humanos , Carcinoma Ductal Pancreático/metabolismo , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Quinurenina/genética , Quinurenina/metabolismo , Neoplasias Pancreáticas/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Microambiente Tumoral/genética , Neoplasias Pancreáticas
12.
Sci Transl Med ; 14(669): eabo1981, 2022 11 02.
Artículo en Inglés | MEDLINE | ID: mdl-36322628

RESUMEN

Immune checkpoint inhibitors (ICIs) have been increasingly used in combination for cancer treatment but are associated with myocarditis. Here, we report that tumor-bearing mice exhibited response to treatment with combinatorial anti-programmed cell death 1 and anti-cytotoxic T lymphocyte antigen-4 antibodies but also presented with cardiovascular toxicities observed clinically with ICI therapy, including myocarditis and arrhythmia. Female mice were preferentially affected with myocarditis compared to male mice, consistent with a previously described genetic model of ICI myocarditis and emerging clinical data. Mechanistically, myocardial tissue from ICI-treated mice, the genetic mouse model, and human heart tissue from affected patients with ICI myocarditis all exhibited down-regulation of MANF (mesencephalic astrocyte-derived neurotrophic factor) and HSPA5 (heat shock 70-kDa protein 5) in the heart; this down-regulation was particularly notable in female mice. ICI myocarditis was amplified by heart-specific genetic deletion of mouse Manf and was attenuated by administration of recombinant MANF protein, suggesting a causal role. Ironically, both MANF and HSPA5 were transcriptionally induced by liganded estrogen receptor ß and inhibited by androgen receptor. However, ICI treatment reduced serum estradiol concentration to a greater extent in female compared to male mice. Treatment with an estrogen receptor ß-specific agonist and androgen depletion therapy attenuated ICI-associated cardiac effects. Together, our data suggest that ICI treatment inhibits estradiol-dependent expression of MANF/HSPA5 in the heart, curtailing the cardiomyocyte response to immune injury. This endocrine-cardiac-immune pathway offers new insights into the mechanisms of sex differences in cardiac disease and may offer treatment strategies for ICI myocarditis.


Asunto(s)
Miocarditis , Humanos , Femenino , Masculino , Ratones , Animales , Miocarditis/complicaciones , Miocarditis/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico , Receptor beta de Estrógeno/metabolismo , Receptor beta de Estrógeno/uso terapéutico , Miocitos Cardíacos/metabolismo , Estradiol/efectos adversos , Estradiol/metabolismo , Factores de Crecimiento Nervioso/efectos adversos , Factores de Crecimiento Nervioso/metabolismo
13.
J Cardiothorac Vasc Anesth ; 36(2): 594-598, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-34301448

RESUMEN

Procedural guidance during structural heart disease (SHD) interventions is achieved with both two-dimensional and three-dimensional transesophageal echocardiography as well as real-time fluoroscopic imaging. Although both image the cardiac anatomy, they are based on different principles of image acquisition. In the era of multimodality imaging with coregistration of anatomic landmarks and simultaneous real-time display, it is essential to have cross-disciplinary imaging knowledge. Besides improving communication, it also enhances patient care and, possibly, outcomes. In this study, the authors used a novel fluoroscopic phantom cardiac model with enhanced structural markers to display the basic fluoroscopic images used during SHD interventions. The projected images enhance the understanding of the orientation and relationship among intracardiac structures as seen on fluoroscopy. In this study, the authors present the basic fluoroscopic views for SHD interventions and the anatomic relationship for intracardiac structures using a custom-made phantom fluoroscopic heart model.


Asunto(s)
Ecocardiografía Tridimensional , Cardiopatías , Cateterismo Cardíaco , Ecocardiografía Transesofágica , Fluoroscopía , Humanos
14.
Pain Physician ; 24(7): E973-E987, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34704708

RESUMEN

BACKGROUND: Headache is a very common condition that affects 5-9% of men and 12-25% of women in North America and Europe. Globally, the prevalence of active headaches among adults is 47%. The most common type of headache is tension headaches (38% of adults), followed by migraines (10%), and chronic headaches (3%). While the majority of headaches are benign, the disorder can severely negatively influence a patients' quality of life, which is directly reflected in societal costs. OBJECTIVE: The objective of this review was to summarize available evidence behind radiofrequency ablation (RFA) for headache, including pain outcome measures, secondary outcomes, and complications. STUDY DESIGN: Systematic review. SETTING: This systematic review examined studies that applied the use of RFA for management of headache. METHODS: This systematic review was reported following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Two reviewers independently scored the methodological quality of the selected studies. Due to heterogeneity of studies, a best-evidence synthesis of the available prognostic factors was provided. RESULTS: In the present investigation, we evaluated 18 studies composed of 6 randomized controlled trials (RCTs), 6 prospective studies, and 6 retrospective studies. All the studies assessed pain improvement with RFA in patients with headache. Most studies targeted the occipital nerve for treatment. Complications were mostly mild and self-limiting, including eyelid swelling, rash, superficial infection of the procedural site, and worsening of headache. LIMITATIONS: A large variability in definitions of trigeminal neuralgia, radiofrequency technique, and patient selection bias was observed in our selected cohort of studies. In addition, there is a paucity of strong longitudinal RCTs and prospective studies. CONCLUSION: Our review discusses several studies that suggest the efficacy of RFA in the treatment of headaches. Outcomes varied based on the difference in approaches regarding continuous radiofrequency versus pulsed radiofrequency, temperature, and duration of administration. The majority of the studies discussed in this review indicate a therapeutic benefit of RFA for headaches over a short-term period. Pain outcomes beyond one year are understudied and further studies are needed to determine the long-term effects of RFA for headaches.


Asunto(s)
Ablación por Catéter , Ablación por Radiofrecuencia , Neuralgia del Trigémino , Adulto , Femenino , Cefalea , Humanos , Masculino , Estudios Prospectivos
15.
Bioorg Med Chem Lett ; 51: 128376, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34560263

RESUMEN

We describe our efforts to introduce structural diversity to a previously described triazole-containing N1-carboline series of bromodomain and extra-terminal (BET) inhibitors. N9 carbolines were designed to retain favorable binding interactions that the N1-carbolines possess. A convergent synthetic route enabled modifications to reduce clearance, enhance physicochemical properties, and improve the overall in vitro profile. This work led to the identification of a potent BET inhibitor, (S)-2-{8-fluoro-5-[(3-fluoropyridin-2-yl)(oxan-4-yl)methyl]-7-[4-(2H3)methyl-1-methyl-1H-1,2,3-triazol-5-yl]-5H-pyrido[3,2-b]indol-3-yl}propan-2-ol (10), a compound with enhanced oral exposure in mice. Subsequent evaluation in a mouse triple-negative breast cancer tumor model revealed efficacy at 4 mg/kg of N9-carboline 10.


Asunto(s)
Antineoplásicos/farmacología , Carbolinas/farmacología , Desarrollo de Medicamentos , Proteínas/antagonistas & inhibidores , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Administración Oral , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Carbolinas/administración & dosificación , Carbolinas/química , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Neoplasias Mamarias Experimentales/tratamiento farmacológico , Neoplasias Mamarias Experimentales/patología , Ratones , Estructura Molecular , Proteínas/metabolismo , Relación Estructura-Actividad , Neoplasias de la Mama Triple Negativas/patología
16.
J Cardiothorac Vasc Anesth ; 35(6): 1611-1617, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33446403

RESUMEN

Arterial line cannulations frequently are performed in various clinical settings to facilitate hemodynamic monitoring and metabolic assessments. Palpation-guided technique generally is performed due to the superficial nature of the peripheral arteries; however, this approach may be challenging in patients with obesity, edema, and hypotension. Difficult line placements are a significant contributor of reduced operating room efficiency due to time delays seen in procedural workflow. Real-time ultrasound guidance is shown to improve success rates of arterial cannulation and reduction in multiple attempts, leading to time efficiency and less likelihood of arterial spasms or hematoma formation. In this report, the authors demonstrate the workflow of ultrasound-guided arterial line cannulation, outline the features of their institutional multi-modal training project for quality improvement, and evaluate the possible effect of the initiative on surgical delays seen with difficult line placements.


Asunto(s)
Cateterismo Periférico , Humanos , Palpación , Arteria Radial/diagnóstico por imagen , Arteria Radial/cirugía , Ultrasonografía Intervencional , Flujo de Trabajo
17.
Age Ageing ; 50(4): 1402-1405, 2021 06 28.
Artículo en Inglés | MEDLINE | ID: mdl-33301574

RESUMEN

BACKGROUND: recognition of the multifactorial causes of delirium represents a clinical challenge. OBJECTIVES: to develop and show proof of principle of a diagnostic support tool (DST) for identification of causes of delirium. METHODS: stage 1-development of the aetiology in delirium-diagnostic support tool (AiD-DST); stage 2-validation of the AiD-DST against reference standard diagnosis, based on clinical assessment from two independent consultant geriatricians. RESULTS: a series of eight steps AiD-DST were formulated by an expert group to identify possible causes of delirium. Forty inpatients admitted to a general medical unit with a consultant physician/geriatrician diagnosis of delirium were recruited, consented and reviewed against the AiD-DST. Mean age was 85.1 (standard deviation 7.9) years and 26 (65%) of participants were female. Participants had multiple chronic co-morbidities [median Charlson Comorbidity Index 7; interquartile range (IQR 6-9)] and median number of medications was 8 (IQR 6-11.75). Median number of causes of delirium detected on AiD-DST was 3 (IQR 3-4) versus 5 (IQR 3-6) using the reference standard diagnosis, with sensitivity of 88.8% (95% confidence interval, 81.6-93.9%) and specificity of 71.8% (63-79.5%). CONCLUSIONS: the aetiology in delirium DST shows promise in the identification of cause(s) in delirium.


Asunto(s)
Delirio , Anciano de 80 o más Años , Delirio/diagnóstico , Delirio/etiología , Femenino , Hospitalización , Humanos , Pacientes Internos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad
18.
Pain Physician ; 23(6): E559-E580, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33185371

RESUMEN

BACKGROUND: Neuropathic facial pain occurs due to pathologic dysfunctions of a nerve responsible for mediating sensory fibers to the head. Surgical interventions, in cases of failed medical therapy, include microvascular decompression, radiofrequency (RF) ablation, percutaneous balloon decompression, and stereotactic radiosurgery. In this review, we focused on RF ablation as a treatment for chronic facial pain. OBJECTIVES: The objective of this review was to summarize available evidence behind RF ablation for facial pain, including pain outcome measures, secondary outcomes, and complications. STUDY DESIGN: Systematic review. SETTING: This systematic review examined studies that applied the use of RF ablation for management of facial pain. METHODS: This systematic review was reported following the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Two reviewers independently scored the methodological quality of the selected studies. Due to heterogeneity of studies, a best-evidence synthesis of the available prognostic factors was provided. RESULTS: We reviewed 44 studies and assessed their short- and long-term pain relief measurements, as well as secondary outcomes including patient satisfaction, quality of life improvements, decrease in oral medication use, and recurrence rates. Maximal pain relief was achieved in treatment groups using combined continuous radiofrequency (CRF) and pulsed radiofrequency (PRF) therapies, followed by CRF therapy alone and finally PRF therapy alone. All treatment regimens improved secondary outcomes. Common complications of treatment included facial numbness, masseter weakness, cheek hematomas, diminished corneal reflex, and dry eyes. LIMITATIONS: A large variability in definitions of trigeminal neuralgia, RF technique, and patient selection bias was observed in our selected cohort of studies. In addition, there was a paucity of strong longitudinal randomized controlled trials and prospective studies. CONCLUSIONS: This systematic review found evidence that RF ablation is efficient in treating patients with facial pain, as well as in improving quality of life and reducing oral medication use. Maximal pain control is achieved using combined CRF and PRF therapy. Complications are uncommon and include facial numbness, masseter weakness, cheek hematomas, diminished corneal reflex, and dry eyes.


Asunto(s)
Dolor Facial/terapia , Manejo del Dolor/métodos , Dimensión del Dolor/métodos , Ablación por Radiofrecuencia/métodos , Dolor Crónico/diagnóstico , Dolor Crónico/psicología , Dolor Crónico/terapia , Ensayos Clínicos como Asunto/métodos , Dolor Facial/diagnóstico , Dolor Facial/psicología , Humanos , Estudios Prospectivos , Tratamiento de Radiofrecuencia Pulsada/métodos , Calidad de Vida/psicología , Terapia por Radiofrecuencia , Resultado del Tratamiento , Neuralgia del Trigémino/diagnóstico , Neuralgia del Trigémino/psicología , Neuralgia del Trigémino/terapia
19.
Nat Cell Biol ; 22(11): 1332-1345, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33106653

RESUMEN

Dystrophin proteomic regulation in muscular dystrophies (MDs) remains unclear. We report that a long noncoding RNA (lncRNA), H19, associates with dystrophin and inhibits E3-ligase-dependent polyubiquitination at Lys 3584 (referred to as Ub-DMD) and its subsequent protein degradation. In-frame deletions in BMD and a DMD non-silent mutation (C3340Y) resulted in defects in the ability of the protein to interact with H19, which caused elevated Ub-DMD levels and dystrophin degradation. Dmd C3333Y mice exhibited progressive MD, elevated serum creatine kinase, heart dilation, blood vessel irregularity and respiratory failure with concurrently reduced dystrophin and increased Ub-DMD status. H19 RNA oligonucleotides conjugated with agrin (AGR-H19) and nifenazone competed with or inhibited TRIM63. Dmd C3333Y animals, induced-pluripotent-stem-cell-derived skeletal muscle cells from patients with Becker MD and mdx mice subjected to exon skipping exhibited inhibited dystrophin degradation, preserved skeletal and cardiac muscle histology, and improved strength and heart function following AGR-H19 or nifenazone treatment. Our study paves the way for meaningful targeted therapeutics for Becker MD and for certain patients with Duchenne MD.


Asunto(s)
Músculo Esquelético/metabolismo , Distrofias Musculares/prevención & control , Oligonucleótidos/administración & dosificación , ARN Largo no Codificante/metabolismo , Animales , Antipirina/administración & dosificación , Antipirina/análogos & derivados , Cardiomiopatías/genética , Cardiomiopatías/metabolismo , Cardiomiopatías/patología , Cardiomiopatías/prevención & control , Línea Celular , Modelos Animales de Enfermedad , Distrofina/genética , Distrofina/metabolismo , Inhibidores Enzimáticos/administración & dosificación , Femenino , Semivida , Humanos , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/patología , Masculino , Ratones Endogámicos C57BL , Ratones Endogámicos mdx , Ratones Mutantes , Proteínas Musculares/antagonistas & inhibidores , Proteínas Musculares/metabolismo , Fuerza Muscular , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Distrofias Musculares/genética , Distrofias Musculares/metabolismo , Distrofias Musculares/patología , Mutación , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Niacinamida/administración & dosificación , Niacinamida/análogos & derivados , Oligonucleótidos/genética , Oligonucleótidos/metabolismo , Estabilidad Proteica , Proteolisis , ARN Largo no Codificante/genética , Proteínas de Motivos Tripartitos/antagonistas & inhibidores , Proteínas de Motivos Tripartitos/metabolismo , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
20.
Cogn Emot ; 34(1): 86-104, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31213178

RESUMEN

Initial evaluations generalise to new contexts, whereas counter-attitudinal evaluations are context-specific. Counter-attitudinal information may not change evaluations in new contexts because perceivers fail to retrieve counter-attitudinal cue-evaluation associations from memory outside the counter-attitudinal learning context. The current work examines whether an additional, counter-attitudinal retrieval cue can enhance the generalizability of counter-attitudinal evaluations. In four experiments, participants learned positive information about a target person, Bob, in one context, and then learned negative information about Bob in a different context. While learning the negative information, participants wore a wristband as a retrieval cue for counter-attitudinal Bob-negative associations. Participants then made speeded as well as deliberate evaluations of Bob while wearing or not wearing the wristband. Internal meta-analysis failed to find a reliable effect of the counter-attitudinal retrieval cue on speeded or deliberate evaluations, whereas the context cues influenced speeded and deliberate evaluations. Counter to predictions, counter-attitudinal retrieval cues did not disrupt the generalisation of first-learned evaluations or the context-specificity of second-learned evaluations (Experiments 2-4), but the counter-attitudinal retrieval cue did influence evaluations in the absence of context cues (Experiment 1). The current work provides initial evidence that additional counter-attitudinal retrieval cues fail to disrupt the renewal and generalizability of first-learned evaluations.


Asunto(s)
Aprendizaje por Asociación , Actitud , Generalización Psicológica , Memoria , Señales (Psicología) , Femenino , Humanos , Masculino , Recuerdo Mental , Adulto Joven
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA