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BACKGROUND: Cerebrovascular reserve (CVR) reflects the capacity of cerebral blood flow (CBF) to change following a vasodilation challenge. Decreased CVR is associated with a higher stroke risk in patients with cerebrovascular diseases. While revascularization can improve CVR and reduce this risk in adult patients with vasculopathy such as those with Moyamoya disease, its impact on hemodynamics in pediatric patients remains to be elucidated. Arterial spin labeling (ASL) is a quantitative MRI technique that can measure CBF, CVR, and arterial transit time (ATT) non-invasively. PURPOSE: To investigate the short- and long-term changes in hemodynamics after bypass surgeries in patients with Moyamoya disease. STUDY TYPE: Longitudinal. POPULATION: Forty-six patients (11 months-18 years, 28 females) with Moyamoya disease. FIELD STRENGTH/SEQUENCE: 3-T, single- and multi-delay ASL, T1-weighted, T2-FLAIR, 3D MRA. ASSESSMENT: Imaging was performed 2 weeks before and 1 week and 6 months after surgical intervention. Acetazolamide was employed to induce vasodilation during the imaging procedure. CBF and ATT were measured by fitting the ASL data to the general kinetic model. CVR was computed as the percentage change in CBF. The mean CBF, ATT, and CVR values were measured in the regions affected by vasculopathy. STATISTICAL TESTS: Pre- and post-revascularization CVR, CBF, and ATT were compared for different regions of the brain. P-values <0.05 were considered statistically significant. RESULTS: ASL-derived CBF in flow territories affected by vasculopathy significantly increased after bypass by 41 ± 31% within a week. At 6 months, CBF significantly increased by 51 ± 34%, CVR increased by 68 ± 33%, and ATT was significantly reduced by 6.6 ± 2.9%. DATA CONCLUSION: There may be short- and long-term improvement in the hemodynamic parameters of pediatric Moyamoya patients after bypass surgery. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.
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Enfermedad de Moyamoya , Adulto , Femenino , Humanos , Niño , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/cirugía , Imagen por Resonancia Magnética/métodos , Encéfalo , Hemodinámica , Circulación Cerebrovascular/fisiología , Marcadores de SpinRESUMEN
STUDY OBJECTIVE: Following discharge from a pediatric emergency department (ED) or urgent care, many families do not pick up their prescribed medications. The aim of this quality improvement study was to increase the percentage of patients discharged home with medications in-hand from 6% to 30% within 6 months. METHODS: Due to the planned construction of a new ED, urgent care, and dedicated pharmacy, a multidisciplinary team was formed to increase access to discharge medications. We performed a pilot study in the urgent care to improve the discharge prescription process and expanded its scope to the ED. We evaluated the effect of our interventions on the percentage of patients discharged with medications in-hand through statistical process control charts. Process measures included the percentage of prescriptions electronically prescribed and directed to an on-site pharmacy. RESULTS: Between June 21, 2021 and March 27, 2022, 7,678 patients were discharged with at least 1 medication in-hand. The percentage of patients discharged with medications in-hand increased from 6.2% to 60.6%. The percentage of prescriptions e-prescribed and directed to an on-site pharmacy increased to 94.6% and 65.6% respectively. CONCLUSIONS: In this study, the availability of a 24-hour on-site pharmacy appears to be the most impactful intervention increasing access to discharge medications for families. Other interventions, such as a pilot study in the urgent care and implementing default electronic prescribing, may have potentiated the effect of the new pharmacy.
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Servicio de Urgencia en Hospital , Alta del Paciente , Mejoramiento de la Calidad , Humanos , Proyectos Piloto , Niño , Servicio de Farmacia en Hospital/organización & administración , Servicio de Farmacia en Hospital/normas , Masculino , Accesibilidad a los Servicios de Salud , Femenino , Atención Ambulatoria , PreescolarRESUMEN
In recent years the historical subject base in psychobiography has expanded from a traditional focus on White (Caucasian) subjects to a broader more culturally inclusive population of significant personalities throughout history. A critical component of strong multicultural psychobiography is the inclusion of anchoring theories of psychology that are rooted in socio-cultural-political context. To psychologically profile culturally diverse individuals with only traditional Western theories of psychology and psychiatry (e.g. medical models, psychodynamic, existential, cognitive-behavioral) limits the ability of the research to accurately capture the erlebnis (lived experience) of extraordinary individuals in proper cultural context. This article reviews specific psychological theories that have recently set a foundation for more nuanced and culturally contextualised psychological profiles of historic personalities who represent diverse racial/ethnic/cultural backgrounds. Among the theories covered are the Integrated African Psychology Perspective (IAPP), an Indigenous (Native American) model of psychobiography, as well as theories and models on Psychological Nigrescence (Black racial identity development), Intersectionality, Politicised Collective Identity (PCI), Queered Black Racial Identity Development (QBRID), and Adultification of Black Children, among others. Examples of applications of these culture-centered theories to psychobiography, drawn from the present authors recently completed psychobiographies, as well as from other researchers internationally, are presented.
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Cultura , Personalidad , Adulto , Niño , Humanos , Indio Americano o Nativo de Alaska , Negro o Afroamericano , Población Negra , Diversidad Cultural , BlancoRESUMEN
INTRODUCTION: James Baldwin (1924-1987) was a prolific African American author and activist whose writing centered primarily on race, sexuality, and religion. Baldwin's lived experiences and breadth of knowledge provided him with a unique perspective of the Black experience in America, a theme he frequently revisited in his work and the impetus for his involvement in the Civil Rights Movement METHOD: This article presents a psychobiographical application of Queering Black Racial Identity Development to conceptualize the life story of James Baldwin. RESULTS: This study explores the life of James Baldwin, highlights his influence as a historical figure and agent of social change, and explores the "why" of his life and behavior. Specifically, his decision to return to the United States during the Civil Rights Movement and possible reasons he avoided politicizing his sexuality in the same way he did his racial identity. CONCLUSION: As an African American, nonheterosexual, male author and Civil Rights activist, Baldwin's intersectional identities played a significant role in his decision to dedicate his life to writing and activism. Limitations of the study are discussed.
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Mediator 25 (Med25) is a member of the mediator complex that relays signals from transcription factors to the RNA polymerase II machinery. Multiple transcription factors, particularly those involved in lipid metabolism, utilize the mediator complex, but how Med25 is involved in this context is unclear. We previously identified Med25 in a translatome screen of adult cardiomyocytes (CMs) in a novel cell type-specific model of LMNA cardiomyopathy. In this study, we show that Med25 upregulation is coincident with myocardial lipid accumulation. To ascertain the role of Med25 in lipid accumulation, we utilized iPSC-derived and neonatal CMs to recapitulate the in vivo phenotype by depleting lamins A and C (lamin A/C) in vitro. Although lamin A/C depletion elicits lipid accumulation, this effect appears to be mediated by divergent mechanisms dependent on the CM developmental state. To directly investigate Med25 in lipid accumulation, we induced adipogenesis in Med25-silenced 3T3-L1 preadipocytes and detected enhanced lipid accumulation. Assessment of pertinent mediators driving adipogenesis revealed that C/EBPα and PPARγ are super-induced by Med25 silencing. Our results indicate that Med25 limits adipogenic potential by suppressing the levels of master regulators that govern adipogenesis. Furthermore, we caution the use of early-developmental-stage cardiomyocytes to model adult-stage cells, particularly for dissecting metabolic perturbations emanating from LMNA mutations.
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Adipogénesis , Lamina Tipo A , Animales , Ratones , Células 3T3-L1 , Adipogénesis/genética , Diferenciación Celular , Lamina Tipo A/genética , Lamina Tipo A/metabolismo , Lípidos/farmacología , Complejo Mediador/genética , Complejo Mediador/metabolismo , PPAR gamma/metabolismo , Factores de Transcripción/metabolismoRESUMEN
Mutations in the lamin A/C gene (LMNA) encoding the nuclear intermediate filament proteins lamins A and C cause a group of tissue-selective diseases, the most common of which is dilated cardiomyopathy (herein referred to as LMNA cardiomyopathy) with variable skeletal muscle involvement. We previously showed that cardiomyocyte-specific overexpression of dual specificity protein phosphatase 4 (DUSP4) is involved in the pathogenesis of LMNA cardiomyopathy. However, how mutations in LMNA activate Dusp4 expression and whether it is necessary for the development of LMNA cardiomyopathy are currently unknown. We now show that female LmnaH222P/H222P mice, a model for LMNA cardiomyopathy, have increased Dusp4 expression and hyperactivation of extracellular signal-regulated kinase (ERK) 1/2 with delayed kinetics relative to male mice, consistent with the sex-dependent delay in the onset and progression of disease. Mechanistically, we show that the H222P amino acid substitution in lamin A enhances its binding to ERK1/2 and increases sequestration at the nuclear envelope. Finally, we show that genetic deletion of Dusp4 has beneficial effects on heart function and prolongs survival in LmnaH222P/H222P mice. These results further establish Dusp4 as a key contributor to the pathogenesis of LMNA cardiomyopathy and a potential target for drug therapy.
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Cardiomiopatías/genética , Lamina Tipo A/genética , Proteína Quinasa 3 Activada por Mitógenos/genética , Proteínas Tirosina Fosfatasas/genética , Sustitución de Aminoácidos/genética , Animales , Cardiomiopatías/fisiopatología , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Regulación de la Expresión Génica , Humanos , Lamina Tipo A/economía , Sistema de Señalización de MAP Quinasas/genética , Masculino , Ratones , MutaciónRESUMEN
OBJECTIVE: To determine the outcomes of combined stereo-electroencephalography-guided and MRI-guided stereotactic laser interstitial thermal therapy (LITT) in the treatment of patients with drug-resistant mesial temporal lobe epilepsy (mTLE). METHODS: We prospectively assessed the surgical and neuropsychological outcomes in 21 patients with medically refractory mTLE who underwent LITT at the University of Chicago Medical Center. We further compared the surgical outcomes in patients with and without mesial temporal sclerosis (MTS). RESULTS: Of the 21 patients, 19 (90%) underwent Invasive EEG study and 11 (52%) achieved freedom from disabling seizures with a mean duration of postoperative follow-up of 24±11 months after LITT. Eight (73%) of 11 patients with MTS achieved freedom from disabling seizures, whereas 3 (30 %) of 10 patients without MTS achieved freedom from disabling seizures. Patients with MTS were significantly more likely to become seizure-free, as compared with those without MTS (P=0.002). There was no significant difference in total ablation volume and the percentage of the ablated amygdalohippocampal complex between seizure-free and non-seizure-free patients. Presurgical and postsurgical neuropsychological assessments were obtained in 10 of 21 patients. While there was no group decline in any neuropsychological assessment, a significant postoperative decline in verbal memory and confrontational naming was observed in individual patients. CONCLUSIONS: MRI-guided LITT is a safe and effective alternative to selective amygdalohippocampectomy and anterior temporal lobectomy for mTLE with MTS. Nevertheless, its efficacy in those without MTS seems modest. Large multicentre and prospective studies are warranted to further determine the efficacy and safety of LITT.
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Epilepsia Refractaria/cirugía , Epilepsia del Lóbulo Temporal/cirugía , Terapia por Láser/métodos , Esclerosis/cirugía , Técnicas Estereotáxicas , Adulto , Anciano , Epilepsia Refractaria/complicaciones , Electroencefalografía , Epilepsia del Lóbulo Temporal/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Imagen Multimodal , Pruebas Neuropsicológicas , Estudios Prospectivos , Esclerosis/complicaciones , Resultado del Tratamiento , Adulto JovenRESUMEN
New therapeutics for glioblastoma multiforme and our ability to deliver them using efficient nanocarriers constitute topical areas of research. We report a comparative study of temozolomide and quercetin in the treatment of glioblastoma (GBM) in three-dimensions, and their incorporation into micelles obtained from synthetically articulated architectural copolymers, and a commercially available linear polymer poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PEG-PLGA). A versatile synthetic methodology to telodendrimers, which can be easily adapted to the needs of other therapeutic interventions, is presented. These dendritic block copolymers self-assemble into micelles and offer a platform for single or combination drug therapy. Telodendrimer micelles loaded with quercetin did not exhibit superior cell killing effect over the free drug, but acetazolamide, an inhibitor carbonic anhydrase IX, significantly reduced GBM cell viability in 3D spheroids. Results from these studies show that high loading of drugs into telodendrimer micelles requires a physical fit between the biologically active agent and telodendrimer nanocarrier, and points toward new possibilities for incorporation of chemotherapeutic and other agents to enhance their effectiveness.
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Dacarbazina/análogos & derivados , Lactatos/química , Poliésteres/química , Polietilenglicoles/química , Acetazolamida/química , Acetazolamida/farmacología , Anhidrasa Carbónica IX/antagonistas & inhibidores , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Dacarbazina/química , Dacarbazina/farmacología , Dendrímeros/química , Sistemas de Liberación de Medicamentos/métodos , Glioblastoma/metabolismo , Humanos , Micelas , Quercetina/química , Quercetina/farmacología , Esferoides Celulares/citología , Esferoides Celulares/metabolismo , TemozolomidaRESUMEN
Bipolar disorder (BD) is a common, recurring psychiatric illness with unknown pathogenesis. Recent studies suggest that microRNA (miRNA) levels in brains of BD patients are significantly altered, and these changes may offer insight into BD pathology or etiology. Previously, we observed significant alterations of miR-29c levels in extracellular vesicles (EVs) extracted from prefrontal cortex (Brodmann area 9, BA9) of BD patients. In this study, we show that EVs extracted from the anterior cingulate cortex (BA24), a crucial area for modulating emotional expression and affect, have increased levels of miR-149 in BD patients compared to controls. Because miR-149 has been shown to inhibit glial proliferation, increased miR-149 expression in BA24-derived EVs is consistent with the previously reported reduced glial cell numbers in BA24 of patients diagnosed with either familial BD or familial major depressive disorder. qPCR analysis of laser-microdissected neuronal and glial cells from BA24 cortical samples of BD patients verified that the glial, but not neuronal, population exhibits significantly increased miR-149 expression. Finally, we report altered expression of both miR-149 and miR-29c in EVs extracted from brains of Flinders Sensitive Line rats, a well-validated animal model exhibiting depressive-like behaviors and glial (astrocytic) dysfunction. These findings warrant future investigations into the potential of using EV miRNA signatures as biomarkers to further enhance the biological definition of BD. © 2017 Wiley Periodicals, Inc.
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Trastorno Bipolar/diagnóstico , Trastorno Bipolar/genética , MicroARNs/genética , Animales , Biomarcadores/sangre , Encéfalo/patología , Trastorno Depresivo Mayor/patología , Modelos Animales de Enfermedad , Vesículas Extracelulares/genética , Femenino , Giro del Cíngulo/metabolismo , Humanos , Masculino , MicroARNs/sangre , RatasRESUMEN
We previously interrogated the transcriptome in heart tissue from Lmna(H222P/H222P) mice, a mouse model of cardiomyopathy caused by lamin A/C gene (LMNA) mutation, and found that the extracellular signal-regulated kinase 1/2 and Jun N-terminal kinase branches of the mitogen-activated protein (MAP) kinase signaling pathway were abnormally hyperactivated prior to the onset of significant cardiac impairment. We have now used an alternative gene expression analysis tool to reanalyze this transcriptome and identify hyperactivation of a third branch of the MAP kinase cascade, p38α signaling. Biochemical analysis of hearts from Lmna(H222P/H222P) mice showed enhanced p38α activation prior to and after the onset of heart disease as well as in hearts from human subjects with cardiomyopathy caused by LMNA mutations. Treatment of Lmna(H222P/H222P) mice with the p38α inhibitor ARRY-371797 prevented left ventricular dilatation and deterioration of fractional shortening compared with placebo-treated mice but did not block the expression of collagen genes involved in cardiac fibrosis. These results demonstrate that three different branches of the MAP kinase signaling pathway with overlapping consequences are involved in the pathogenesis of cardiomyopathy caused by LMNA mutations. They further suggest that pharmacological inhibition of p38α may be useful in the treatment of this disease.
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Cardiomiopatía Dilatada/enzimología , Etilenodiaminas/farmacología , Indazoles/farmacología , Lamina Tipo A/genética , Proteína Quinasa 14 Activada por Mitógenos/metabolismo , Mutación Missense , Transducción de Señal , Adolescente , Animales , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/metabolismo , Células Cultivadas , Femenino , Humanos , Lamina Tipo A/metabolismo , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Proteína Quinasa 14 Activada por Mitógenos/genética , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/metabolismo , Adulto JovenRESUMEN
The final stages of dengue virus fusion are thought to occur when the membrane-proximal stem drives the transmembrane anchor of the viral envelope protein (E) toward the fusion loop, buried in the target cell membrane. Crystal structures of E have lacked this essential stem region. We expressed and crystallized soluble mutant forms of the dengue virus envelope protein (sE) that include portions of the juxtamembrane stem. Their structures represent late-stage fusion intermediates. The proximal part of the stem has both intra- and intermolecular interactions, so the chain "zips up" along the trimer seam. The penultimate interaction we detected involves the conserved residue F402, which has hydrophobic contacts with a conserved surface on domain II. These interactions do not require any larger-scale changes in trimer packing. The techniques for expression and crystallization of sE containing stem reported here may allow further characterization of the final stages of flavivirus fusion.
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Virus del Dengue/química , Proteínas del Envoltorio Viral/química , Secuencia de Aminoácidos , Cristalografía por Rayos X , Modelos Biológicos , Modelos Moleculares , Datos de Secuencia MolecularRESUMEN
BACKGROUND: Needle trauma may cause neuropathy after nerve blockade. Even without injection, nerve injury can result from forceful needle-nerve contact (NNC). High opening injection pressures (OIPs) have been associated with intrafascicular needle tip placement and nerve damage; however, the relationship between OIP and NNC is unclear. The authors conducted a prospective, observational study to define this relationship. METHODS: Sixteen patients scheduled for shoulder surgery under interscalene block were enrolled if they had clear ultrasound images of the brachial plexus roots. A 22-gauge stimulating needle was inserted within 1 mm of the root, and 1-ml D5W injected at 10 ml/min by using an automated pump. OIP was monitored using an in-line pressure manometer and injections aborted if 15 psi or greater. The needle was advanced to displace the nerve slightly (NNC), and the procedure repeated. Occurrence of evoked motor response and paresthesia were recorded. RESULTS: Fifteen patients had at least one clearly visible root. OIP at 1 mm distance from the nerve was less than 15 psi (mean peak pressure 8.2 ± 2.4 psi) and the 1-ml injection could be completed in all but two cases (3%). In contrast, OIP during NNC was 15 psi or greater (mean peak pressure 20.9 ± 3.7 psi) in 35 of 36 injections. Aborting the injection when OIP reached 15 psi prevented commencement of injection in all cases of NNC except one. CONCLUSION: High OIP (≥15 psi) consistently detected NNC, suggesting that injection pressure monitoring may be useful in preventing injection against nerve roots during interscalene block.
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Plexo Braquial/fisiología , Agujas , Bloqueo Nervioso/métodos , Presión , Ultrasonografía Intervencional/métodos , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Inyecciones/instrumentación , Inyecciones/métodos , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/instrumentación , Estudios Prospectivos , Ultrasonografía Intervencional/instrumentación , Adulto JovenRESUMEN
The ultimate purpose of signal transduction is to transmit extracellular or cytoplasmic stimuli to the nuclear interior to elicit a cellular response, mediated primarily through changes in gene expression. The evolution of the nuclear envelope and the consequent compartmentalization of the genome, which is a defining feature of eukaryotes, introduced a physical barrier to the free access of genes. Initially regarded as nothing more than this, a physical barrier with selective permeability, recent findings have transformed our view of the nuclear envelope and its diverse roles in various aspects of cell biology and human diseases, much of which is only beginning to be understood. The realization that mutations in genes encoding nuclear envelope proteins cause a diverse array of tissue-selective diseases often referred to as "laminopathies" has provided new insight into structural and regulatory functions of the nuclear envelope. Genetic mutations causing abnormalities in the nuclear envelope can lead to dysregulated signaling that underlies pathogenesis of these diseases. The emerging picture indicates that the nuclear envelope is a node that fine-tunes signaling output and as such it may play a role in the biology of cancer.
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Sistema de Señalización de MAP Quinasas , Membrana Nuclear/fisiología , Evolución Biológica , Humanos , Lamina Tipo A/genética , Mutación , Membrana Nuclear/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Mutations in the LMNA gene encoding lamins A/C cause an array of tissue-selective diseases, with the heart being the most commonly affected organ. Despite progress in understanding the perturbations emanating from LMNA mutations, an integrative understanding of the pathogenesis underlying cardiac dysfunction remains elusive. Using a novel conditional deletion model capable of translatome profiling, we observed that cardiomyocyte-specific Lmna deletion in adult mice led to rapid cardiomyopathy with pathological remodeling. Before cardiac dysfunction, Lmna-deleted cardiomyocytes displayed nuclear abnormalities, Golgi dilation/fragmentation, and CREB3-mediated stress activation. Translatome profiling identified MED25 activation, a transcriptional cofactor that regulates Golgi stress. Autophagy is disrupted in the hearts of these mice, which can be recapitulated by disrupting the Golgi. Systemic administration of modulators of autophagy or ER stress significantly delayed cardiac dysfunction and prolonged survival. These studies support a hypothesis wherein stress responses emanating from the perinuclear space contribute to the LMNA cardiomyopathy development.
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Cardiomiopatías , Lamina Tipo A , Miocitos Cardíacos , Membrana Nuclear , Animales , Lamina Tipo A/metabolismo , Lamina Tipo A/genética , Ratones , Membrana Nuclear/metabolismo , Cardiomiopatías/metabolismo , Cardiomiopatías/etiología , Cardiomiopatías/patología , Cardiomiopatías/genética , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Autofagia , Estrés Fisiológico , Modelos Animales de Enfermedad , Estrés del Retículo Endoplásmico , Aparato de Golgi/metabolismo , Ratones NoqueadosRESUMEN
BACKGROUND: Mutations in LMNA gene cause cardiomyopathy, for which mechanistic insights are lacking. RESULTS: Dusp4 expression is enhanced in hearts with LMNA cardiomyopathy, and its overexpression in mice causes it by activating AKT-mTOR signaling that impairs autophagy. CONCLUSIONS: Dusp4 causes cardiac dysfunction and may contribute to the development of LMNA cardiomyopathy. SIGNIFICANCE: Revealing pathogenic mechanisms of LMNA cardiomyopathy is essential for the development of mechanism-based therapies. Mutations in the lamin A/C gene (LMNA) cause a diverse spectrum of diseases, the most common of which is dilated cardiomyopathy often with skeletal muscular dystrophy. Lamin A and C are fundamental components of the nuclear lamina, a dynamic meshwork of intermediate filaments lining the nuclear envelope inner membrane. Prevailing evidence suggests that the nuclear envelope functions as a signaling node and that abnormality in the nuclear lamina leads to dysregulated signaling pathways that underlie disease pathogenesis. We previously showed that activated ERK1/2 in hearts of a mouse model of LMNA cardiomyopathy (Lmna(H222P/H222P) mice) contributes to disease, but the complete molecular pathogenesis remains poorly understood. Here we uncover a pathogenic role of dual specificity phosphatase 4 (Dusp4), which is transcriptionally induced by ERK1/2. Dusp4 is highly expressed in the hearts of Lmna(H222P/H222P) mice, and transgenic mice with cardiac-selective overexpression of Dusp4 display heart dysfunction similar to LMNA cardiomyopathy. In both primary tissue and cell culture models, overexpression of Dusp4 positively regulates AKT-mTOR signaling, resulting in impaired autophagy. These findings identify a pathogenic role of Dusp4 in LMNA cardiomyopathy.
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Cardiomiopatías/enzimología , Fosfatasas de Especificidad Dual/metabolismo , Lamina Tipo A/genética , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/metabolismo , Mutación Missense , Animales , Autofagia , Cardiomiopatías/genética , Cardiomiopatías/metabolismo , Cardiomiopatías/fisiopatología , Fosfatasas de Especificidad Dual/genética , Femenino , Corazón/fisiopatología , Humanos , Lamina Tipo A/metabolismo , Sistema de Señalización de MAP Quinasas , Masculino , Ratones , Ratones Endogámicos CBA , Ratones Transgénicos , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/genética , Miocardio/enzimología , Miocardio/metabolismoRESUMEN
For successful object manipulation, the central nervous system must appropriately coordinate digit placement and force distribution. It is known that digit force planning is significantly influenced by previous manipulations even when object properties cannot be predicted on a trial-to-trial basis. We sought to determine whether this effect extends beyond force control to the coordination of digit placement and force. Subjects grasped and lifted an object whose center of mass (CM) was changed unpredictably across trials. Grasp planning was quantified by measuring the torque generated on the object at lift onset. We found that both digit placement and force were systematically affected by the CM experienced on the previous trial. Additionally, the negative covariation between digit forces and positions typically found for predictable CM presentations was also found for unpredictable CM trials. A follow-up experiment revealed that these effects were not dependent on visual feedback of object roll during object lift on the previous trial. We conclude that somatosensory feedback from previous grasp experience alone can affect high-level grasp planning by constraining the relation between digit force and position even when the task behavioral consequences cannot be reliably predicted. As learning of manipulations often involves interactions with objects in novel environments, the present findings are an important step to understanding the control strategies associated with the integration of sensorimotor memories and motor planning.
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Retroalimentación Sensorial , Memoria , Destreza Motora/fisiología , Adolescente , Adulto , Femenino , Mano/inervación , Mano/fisiología , Fuerza de la Mano , Humanos , TorqueRESUMEN
BACKGROUND: We performed this randomized trial to compare the recovery profile of patients receiving single injection (SISB) and continuous interscalene brachial plexus block (CISB) or general anesthesia (GA) for arthroscopic rotator cuff repair surgery through the first postoperative week. Our primary hypothesis was that the highest pain numeric rating scale (NRS) (worst pain score) at the end of the study week would be lower for patients in the CISB group than for patients in the SISB or GA groups. METHODS: Seventy-one patients scheduled for elective outpatient arthroscopic rotator cuff repair were enrolled. CISB patients received 20 mL of 0.5% ropivacaine as a bolus through a catheter, whereas SISB patients received the same injection volume through a needle. CISB patients received an infusion of 0.2% ropivacaine at 5 mL/h with a patient-controlled bolus of 5 mL hourly for 48 hours. GA-only patients received a standardized general anesthetic. Postoperative highest NRS pain scores through the first postoperative week, time-to-first pain, analgesic consumption, fast-tracked postoperative anesthesia care unit (PACU) bypass rate, length of PACU stay, time-to-discharge home, total hours of sleep, and related adverse effects were recorded in the PACU and at home on postoperative days 1, 2, 3, and 7. RESULTS: No patient in the CISB or SISB groups reported a NRS ≥1 or required analgesics while in the PACU. While most patients in the CISB and SISB groups were fast-tracked to PACU discharge, no patient in the GA group was fast-tracked (Χ P = 0.003). Length of stay in the PACU was significantly shorter for the CISB and SISB groups than for the GA group (20 ± 31, 30 ± 42, and 165 ± 118 minutes, respectively (CISB vs GA, P < 0.001; SISB vs GA, P <0.001), and time-to-discharge home was significantly shorter when compared with the GA group. Time to first pain report was longer in the CISB group. Mean NRS scores were lower for patients in the CISB group than in the SISB and GA groups on postoperative days 1 and 2, and use of narcotics (doses ≥1) was lower until postoperative day 3. Patients who received CISB slept significantly longer than patients who received SISB or GA (P < 0.01) during the first 48 hours postoperatively. By the end of the study week, 26% of patients in the CISB group, 83% in the SISB group, and 58% of GA patients reported NRS ≥4 (both P-values ≤ 0.05). CONCLUSION: The analgesic benefits of CISB found in the PACU and immediately after discharge extend through the intermediate recovery period ending on postoperative day 7.
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Procedimientos Quirúrgicos Ambulatorios , Amidas/administración & dosificación , Anestésicos Locales/administración & dosificación , Artroscopía , Plexo Braquial , Bloqueo Nervioso/métodos , Dolor Postoperatorio/prevención & control , Manguito de los Rotadores/cirugía , Anciano , Procedimientos Quirúrgicos Ambulatorios/efectos adversos , Amidas/efectos adversos , Analgésicos/uso terapéutico , Periodo de Recuperación de la Anestesia , Anestesia General , Anestésicos Locales/efectos adversos , Artroscopía/efectos adversos , Distribución de Chi-Cuadrado , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Ciudad de Nueva York , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Alta del Paciente , Estudios Prospectivos , Sala de Recuperación , Recuperación de la Función , Ropivacaína , Lesiones del Manguito de los Rotadores , Factores de Tiempo , Resultado del TratamientoRESUMEN
Red cell distribution width (RDW), a measure of the variability in size of circulating erythrocytes, is an independent predictor of mortality in patients with cardiovascular disease. We hypothesized that RDW is a prognostic marker of death, myocardial infarction and unplanned revascularization in a broad population undergoing percutaneous coronary intervention (PCI). We investigated the prognostic value of RDW derived from a complete blood count drawn ≤24 h of PCI in 1,689 patients at four centers who underwent PCI between 2004 and 2007 in the evaluation of drug eluting stents and ischemic events registry. Patients who underwent blood transfusions were excluded. Multivariable analyses of death, MI, unplanned revascularization, and the combined occurrence of these events at 1 year were performed using methods from survival analysis. The analysis was adjusted for creatinine ≥1.5 mg/dL, hemoglobin, congestive heart failure, coronary artery bypass grafting history, male sex, BMI, atherosclerosis of ≥2 coronary vessels, and hypertension. In univariate analysis of RDW stratified by quartiles, membership in the highest quartile was a predictor of mortality as compared to the lowest quartile (HR 5.07, CI 2.07-12.40, p < 0.001). In multivariate analysis, RDW was not an independent predictor of unplanned revascularization after PCI; however, RDW remained an independent correlate of 1 year mortality (HR 1.65, CI 1.22-2.23, p = 0.001); with a continuous net reclassification improvement of 46.5% (95% CI 15.1-76.4%) and a relative integrated discrimination improvement of 57.8% (95% CI 22.1-94.9%) after PCI. RDW is a widely available independent correlate of 1-year mortality after PCI that increases the discriminative value of risk prediction in these patients.
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Eritrocitos , Insuficiencia Cardíaca , Intervención Coronaria Percutánea , Anciano , Biomarcadores/sangre , Transfusión Sanguínea , Stents Liberadores de Fármacos/efectos adversos , Recuento de Eritrocitos , Femenino , Estudios de Seguimiento , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/cirugía , Hemoglobinas/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Riesgo , Factores SexualesRESUMEN
PURPOSE OF REVIEW: There has been an increasing use of peripheral nerve blocks (PNBs) in ambulatory surgery. Several recent reports have contributed to our understanding of the optimal PNB technique for specific surgical procedures in this setting. In this review, we have summarized the available literature on indications of PNBs for outpatient surgery of the upper extremity. RECENT FINDINGS: Although many of the recent studies focus on technical aspects of PNBs, few center on evidence-based indications or their utility in the ambulatory setting. The available literature suggests that although multiple techniques have been reported for outpatient shoulder surgery, interscalene brachial plexus block (ISBPB) is currently the most preferred technique. Supraclavicular, infraclavicular, and axillary brachial plexus blocks, however, are all commonly used and effective PNBs for outpatient surgery and analgesia of the arm, forearm, and hand. SUMMARY: ISBPB is currently the most beneficial PNB for outpatient shoulder surgery. Supraclavicular block functionally can be considered an alternative to the traditional ISBPB; however, additional studies are required before routine use can be recommended. Although the review identified several reports with benefits of one PNB technique over the others, the existing literature suggests that many of these techniques may be interchangeable with regards to procedures of the distal upper extremity. Future studies are indicated to help standardize the techniques, selection, and postoperative management of PNBs for specific surgical indications.
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Procedimientos Quirúrgicos Ambulatorios , Bloqueo Nervioso/métodos , Hombro/cirugía , Codo/cirugía , Práctica Clínica Basada en la Evidencia , Mano/cirugía , Humanos , Húmero/cirugíaRESUMEN
PURPOSE OF REVIEW: Pain management in the trauma patient can be challenging, especially outside the operating room setting. Traditional analgesics such as opioids and NSAIDs are also problematic in trauma care. In this review, the use of regional anesthetic techniques outside the operating theatre is discussed. RECENT FINDINGS: Regional anesthesia is an increasing but still underutilized clinical tool for the trauma patient outside the operating room. Regional anesthesia provides well tolerated and effective analgesia and anesthesia for many indications in the trauma setting including hip fracture, reduction of joint dislocation, wound debridement, laceration repair, and multiple rib fractures. Its use can increase safety and resource allocation in emergency departments. Performance of peripheral nerve blocks, especially with ultrasound, is amenable in various medical environments with minimal training. SUMMARY: Pain is often poorly managed in the trauma patient. In addition to quality analgesia, regional anesthesia provides a variety of benefits in the trauma setting outside the traditional operating room setting. While further utilization requires increased training and structural changes, existing tools such as ultrasound are removing barriers to the widespread use of peripheral nerve block techniques across multiple disciplines.