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BACKGROUND: Coronavirus disease (COVID-19) has introduced a new subset of patients with acute end-stage lung damage for which lung transplantation has been successfully performed. OBJECTIVE: To describe the inpatient rehabilitation course of patients who underwent bilateral lung transplant due to severe COVID-19 pulmonary disease. DESIGN: Retrospective chart review. SETTING: Free-standing, academic, urban inpatient rehabilitation hospital. PARTICIPANTS: Seventeen patients aged 28-67 years old (mean 53.9 ± 10.7) who developed COVID-19 respiratory failure and underwent bilateral lung transplant. INTERVENTIONS: Patients participated in a comprehensive inpatient rehabilitation program including physical, occupational, and speech therapy tailored to the unique functional needs of each individual. MAIN OUTCOME MEASURES: Primary outcome measures of functional improvements, include mobility and self-care scores on section GG of the Functional Abilities and Goals of the Improving Post-Acute Care Transformation Act, as defined as quality measures by the Centers for Medicare and Medicaid Services. Other functional measures included 6 minute walk test, Berg balance scale, Mann Assessment of Swallowing Ability (MASA), and Cognition and Memory Functional Independence Measure (FIM) scores. Wilcoxon signed rank sum test was used to evaluate statistical significance of change between admission and discharge scores. RESULTS: Fourteen patients completed inpatient rehabilitation. Self-care (GG0130) mean score improved from 20.9 to 36.1. Mobility (GG0170) mean score improved from 30.7 to 70.7. Mean 6-minute walk distance improved from 174.1 to 467.6 feet. Mean Berg balance scores improved from 18.6/56 to 36.3/56. MASA scores improved from 171.3 to 182.3. All functional measures demonstrated statistically significant improvements with p value ≤ .008, except for cognition and memory FIM scores, which did not show a statistically significant difference. A majority (76%) of patients discharged home. CONCLUSION: This new and unique patient population can successfully participate in a comprehensive inpatient rehabilitation program and achieve functional improvements despite medical complications.
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COVID-19 , Trasplante de Pulmón , Estados Unidos , Humanos , Anciano , Adulto , Persona de Mediana Edad , Pacientes Internos , Estudios Retrospectivos , Recuperación de la Función , Resultado del Tratamiento , Medicare , Centros de Rehabilitación , Tiempo de InternaciónRESUMEN
Neurons respond to changes in the levels of activity they experience in a variety of ways, including structural changes at pre- and postsynaptic terminals. An essential plasticity signal required for such activity-regulated structural adjustments are reactive oxygen species (ROS). To identify sources of activity-regulated ROS required for structural plasticity in vivo we used the Drosophila larval neuromuscular junction as a highly tractable experimental model system. For adjustments of presynaptic motor terminals, we found a requirement for both NADPH oxidases, Nox and dual oxidase (Duox), that are encoded in the Drosophila genome. This contrasts with the postsynaptic dendrites from which Nox is excluded. NADPH oxidases generate ROS to the extracellular space. Here, we show that two aquaporins, Bib and Drip, are necessary ROS conduits in the presynaptic motoneuron for activity regulated, NADPH oxidase dependent changes in presynaptic motoneuron terminal growth. Our data further suggest that different aspects of neuronal activity-regulated structural changes might be regulated by different ROS sources: changes in bouton number require both NADPH oxidases, while activity-regulated changes in the number of active zones might be modulated by other sources of ROS. Overall, our results show NADPH oxidases as important enzymes for mediating activity-regulated plasticity adjustments in neurons.
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Reactive oxygen species (ROS) have been extensively studied as damaging agents associated with ageing and neurodegenerative conditions. Their role in the nervous system under non-pathological conditions has remained poorly understood. Working with the Drosophila larval locomotor network, we show that in neurons ROS act as obligate signals required for neuronal activity-dependent structural plasticity, of both pre- and postsynaptic terminals. ROS signaling is also necessary for maintaining evoked synaptic transmission at the neuromuscular junction, and for activity-regulated homeostatic adjustment of motor network output, as measured by larval crawling behavior. We identified the highly conserved Parkinson's disease-linked protein DJ-1ß as a redox sensor in neurons where it regulates structural plasticity, in part via modulation of the PTEN-PI3Kinase pathway. This study provides a new conceptual framework of neuronal ROS as second messengers required for neuronal plasticity and for network tuning, whose dysregulation in the ageing brain and under neurodegenerative conditions may contribute to synaptic dysfunction.
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Drosophila melanogaster/metabolismo , Neuronas Motoras/metabolismo , Plasticidad Neuronal , Especies Reactivas de Oxígeno/metabolismo , Animales , Animales Modificados Genéticamente , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/genética , Larva/genética , Larva/metabolismo , Microscopía Electrónica de Transmisión , Proteínas del Tejido Nervioso/metabolismo , Unión Neuromuscular/metabolismo , Unión Neuromuscular/ultraestructura , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Terminales Presinápticos/metabolismo , Terminales Presinápticos/ultraestructura , Proteína Desglicasa DJ-1 , Transducción de Señal , Transmisión SinápticaRESUMEN
Reactive oxygen species (ROS) have long been studied as destructive agents in the context of nervous system ageing, disease and degeneration. Their roles as signalling molecules under normal physiological conditions is less well understood. Recent studies have provided ample evidence of ROS-regulating neuronal development and function, from the establishment of neuronal polarity to growth cone pathfinding; from the regulation of connectivity and synaptic transmission to the tuning of neuronal networks. Appreciation of the varied processes that are subject to regulation by ROS might help us understand how changes in ROS metabolism and buffering could progressively impact on neuronal networks with age and disease.
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Conos de Crecimiento/metabolismo , Red Nerviosa/metabolismo , Neurogénesis , Especies Reactivas de Oxígeno/metabolismo , Transmisión Sináptica , Envejecimiento/genética , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Conos de Crecimiento/patología , Humanos , Red Nerviosa/patología , Enfermedades Neurodegenerativas/genética , Enfermedades Neurodegenerativas/metabolismo , Enfermedades Neurodegenerativas/patologíaRESUMEN
BACKGROUND: The number of total knee arthroplasty (TKA) procedures performed in the United States is increasing each year, and the number of bilateral TKA procedures has also increased during the past 2 decades. However, few studies in the literature have investigated the rehabilitation outcomes of patients who undergo bilateral TKA. This study was performed to provide information on the benefits and role of inpatient rehabilitation for patients after bilateral TKA. OBJECTIVE: To investigate the functional outcomes, complications, and transfer rates of patients in the inpatient rehabilitation setting who undergo simultaneous bilateral TKA. DESIGN: Retrospective cohort study. SETTING: Freestanding inpatient rehabilitation hospital. PATIENTS: Ninety-four patients admitted to an inpatient rehabilitation hospital after simultaneous bilateral TKA from 2008-2013. METHODS: Retrospective chart review of demographic, clinical, and functional data for patients admitted to inpatient rehabilitation after simultaneous bilateral TKA. MAIN OUTCOME MEASURES: Length of stay, admission and discharge Functional Independence Measure (FIM), and FIM efficiency. RESULTS: The study included 27 male (28.7%) and 67 female (71.3%) patients aged 42.0-86.9 years, with a mean of 65.6 ± 10.2 years. Mean length of time between surgery and admission to inpatient rehabilitation was 4.5 ± 3.3 days. Mean length of stay in rehabilitation was 11.7 ± 4.2 days. Mean admission and discharge FIM scores were 87.3 ± 11.7 and 113.4 ± 4.8, respectively, with a mean FIM gain of 26.1 ± 10.5. The mean FIM efficiency was 2.33 ± 0.84. Eight patients required transfer to an acute care hospital. Complications leading to transfer to acute care facilities included sepsis, cardiac arrhythmias, knee dislocation, and suspected small bowel obstruction. Eighty-eight patients were discharged home, 4 patients were discharged to skilled nursing facilities, and 2 patients were transferred to an acute care hospital and did not return to the inpatient rehabilitation hospital. CONCLUSIONS: After undergoing simultaneous bilateral TKA, patients demonstrate functional gains when admitted to inpatient rehabilitation facilities based on FIM gains and FIM efficiency scores; 8.5% of patients in this cohort required transfer to an acute care facility as a result of complications during inpatient rehabilitation, and 93.6% of patients were discharged home.
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Artroplastia de Reemplazo de Rodilla , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Pacientes Internos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Recuperación de la Función , Centros de Rehabilitación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Hereditary sensory and autonomic neuropathy type 1 (HSAN1) is characterized by a loss of distal peripheral sensory and motorneuronal function, neuropathic pain and tissue necrosis. The most common cause of HSAN1 is due to dominant mutations in serine palmitoyl-transferase subunit 1 (SPT1). SPT catalyses the condensation of serine with palmitoyl-CoA, the initial step in sphingolipid biogenesis. Identified mutations in SPT1 are known to both reduce sphingolipid synthesis and generate catalytic promiscuity, incorporating alanine or glycine into the precursor sphingolipid to generate a deoxysphingoid base (DSB). Why either loss of function in SPT1, or generation of DSBs should generate deficits in distal sensory function remains unclear. To address these questions, we generated a Drosophila model of HSAN1. Expression of dSpt1 bearing a disease-related mutation induced morphological deficits in synapse growth at the larval neuromuscular junction consistent with a dominant-negative action. Expression of mutant dSpt1 globally was found to be mildly toxic, but was completely toxic when the diet was supplemented with alanine, when DSBs were observed in abundance. Expression of mutant dSpt1 in sensory neurons generated developmental deficits in dendritic arborization with concomitant sensory deficits. A membrane trafficking defect was observed in soma of sensory neurons expressing mutant dSpt1, consistent with endoplasmic reticulum (ER) to Golgi block. We found that we could rescue sensory function in neurons expressing mutant dSpt1 by co-expressing an effector of ER-Golgi function, Rab1 suggesting compromised ER function in HSAN1 affected dendritic neurons. Our Drosophila model identifies a novel strategy to explore the pathological mechanisms of HSAN1.
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Alanina/toxicidad , Neuropatías Hereditarias Sensoriales y Autónomas/fisiopatología , Proteínas de la Membrana/metabolismo , Animales , Animales Modificados Genéticamente , Dieta , Modelos Animales de Enfermedad , Drosophila , Retículo Endoplásmico/metabolismo , Genes Esenciales , Genes de Insecto , Aparato de Golgi/metabolismo , Neuropatías Hereditarias Sensoriales y Autónomas/inducido químicamente , Neuropatías Hereditarias Sensoriales y Autónomas/genética , Neuropatías Hereditarias Sensoriales y Autónomas/metabolismo , Mutación , Unión Neuromuscular/metabolismo , Células Receptoras Sensoriales/metabolismo , Esfingolípidos/metabolismoRESUMEN
The number of individuals with heart failure and the treatment modalities available to manage heart failure are increasing. Continuous inotropic support is a treatment modality used in cases of severe heart failure. Although most patients initiated on continuous inotropic support are discharged home, those with greater functional compromise, comorbid conditions that cause disability, or other significant medical complexity may be referred to acute inpatient rehabilitation. The feasibility and benefits of acute inpatient rehabilitation in this population, however, has yet to be investigated. We report the functional progress and medical complications of 3 patients on continuous inotropic support who participated in acute inpatient rehabilitation. The patients demonstrated varying levels of success, highlighting a need for evidence-based, preadmission screening criteria for this population.
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Cardiotónicos/uso terapéutico , Evaluación de la Discapacidad , Terapia por Ejercicio/métodos , Insuficiencia Cardíaca/rehabilitación , Pacientes Internos , Recuperación de la Función , Volumen Sistólico/fisiología , Anciano , Estudios de Seguimiento , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common genetic cause of Parkinson's disease. LRRK2 is a multifunctional protein affecting many cellular processes and has been described to bind microtubules. Defective microtubule-based axonal transport is hypothesized to contribute to Parkinson's disease, but whether LRRK2 mutations affect this process to mediate pathogenesis is not known. Here we find that LRRK2 containing pathogenic Roc-COR domain mutations (R1441C, Y1699C) preferentially associates with deacetylated microtubules, and inhibits axonal transport in primary neurons and in Drosophila, causing locomotor deficits in vivo. In vitro, increasing microtubule acetylation using deacetylase inhibitors or the tubulin acetylase αTAT1 prevents association of mutant LRRK2 with microtubules, and the deacetylase inhibitor trichostatin A (TSA) restores axonal transport. In vivo knockdown of the deacetylases HDAC6 and Sirt2, or administration of TSA rescues both axonal transport and locomotor behavior. Thus, this study reveals a pathogenic mechanism and a potential intervention for Parkinson's disease.
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Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Microtúbulos/metabolismo , Mutación , Enfermedad de Parkinson/enzimología , Proteínas Serina-Treonina Quinasas/química , Proteínas Serina-Treonina Quinasas/genética , Acetilación , Animales , Axones/enzimología , Transporte Biológico , Movimiento Celular , Drosophila , Proteínas de Drosophila/metabolismo , Humanos , Proteína 2 Quinasa Serina-Treonina Rica en Repeticiones de Leucina , Neuronas/enzimología , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Proteínas Serina-Treonina Quinasas/metabolismo , Estructura Terciaria de Proteína , RatasRESUMEN
BACKGROUND: Nutrition's impact on stroke rehabilitation outcomes is controversial. Existing studies utilize albumin without correcting for inflammation in nutritional assessments. Here, prealbumin was used and inflammation assessed to determine if nutrition impacts rehabilitation outcomes. OBJECTIVE: Determine the effect of dietary intake on prealbumin level, number of complications, length of stay, and Functional Independence Measure (FIM) efficiency in rehabilitation stroke inpatients. METHODS: Patients had admission and discharge prealbumin and C-reactive protein (CRP) levels drawn; and, weekly protein and calorie counts obtained. Patients were followed for number of complications, length of stay, and FIM efficiency. RESULTS: Mean protein and calorie intake was 57.6 ± 16.2 g/d and 1452.2 ± 435.8 kcal/d, respectively. 77.6% of patients had normal prealbumin on admission with 94.9% on discharge. Prealbumin increased significantly from admission to discharge (22.3 ± 6.2 mg/dL vs. 24.6 mg/dL ± 5.1 mg/dL, P = 0.007). Number of complications and length of stay were predicted by CRP in regression models. Total, motor, and cognitive FIM efficiencies were not universally affected by prealbumin levels, protein intake, or calorie intake. CONCLUSIONS: Nearly all hypoprealbuminemic stroke rehabilitation inpatients correct their levels eating a non-supplemented diet. Number of complications, length of stay, and functional outcomes in this patient are not affected by prealbumin levels, protein intake, or calorie intake.
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Ingestión de Energía/fisiología , Tiempo de Internación , Prealbúmina/metabolismo , Proteínas/metabolismo , Accidente Cerebrovascular , Adulto , Anciano , Proteína C-Reactiva , Evaluación de la Discapacidad , Femenino , Humanos , Pacientes Internos , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Accidente Cerebrovascular/dietoterapia , Accidente Cerebrovascular/metabolismo , Rehabilitación de Accidente Cerebrovascular , Resultado del TratamientoRESUMEN
Peripheral neuropathies result from a variety of inherited and acquired pathologies. They display an assortment of clinical signs and symptoms and present with a broad range of severity. Electrodiagnosis can play a key role in the evaluation of a suspected peripheral neuropathy. A peripheral nerve disorder is first suspected on the basis of history and physical examination findings. Electrodiagnosis is then used to confirm the diagnosis and to characterize the peripheral neuropathy, providing information about its distribution, pathophysiologic process (demyelinating vs axonal), and chronicity.
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Electrodiagnóstico/métodos , Polineuropatías/diagnóstico , Diagnóstico Diferencial , Humanos , Examen Neurológico , Polineuropatías/etiología , Polineuropatías/fisiopatologíaRESUMEN
We describe how a novel thermosensitive escape behaviour in Drosophila larvae can be used to teach neurobiology principles to both undergraduates and school children. The assays are inexpensive, robust and reliably accurate employing apparatus readily available in most science classrooms. The use of Drosophila avoids the employment of vertebrate models and the ethical and expense issues that this entails. We use this practical to effectively teach the principals of calibration and neural sensory responses to post-16-year-old students and undergraduate students.
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Nocicepción/fisiología , Sistema Nervioso Periférico/fisiología , Investigación/educación , Sensación/fisiología , Enseñanza/métodos , Adolescente , Animales , Discusiones Bioéticas , Calibración , Drosophila melanogaster/fisiología , Humanos , Laboratorios , Larva/fisiología , Modelos Animales , Estudiantes , Adulto JovenRESUMEN
We describe a novel thermosensitive escape behavior in Drosophila larvae and a simple assay to accurately define the response temperature. When a larva is placed in a droplet of water that is subsequently heated, a stereotypical escape response is robustly elicited at 29°C. Larvae defective for the painless TRP receptor, or blocked in the function of class IV multi-dendritic sensory dendrites respond to this stimulus at reproducibly higher temperature (34°C). The escape response has novel behavioral components and a lower temperature threshold in comparison with the responses to touch with a hot needle. Furthermore the assay minimizes operator bias that is present in current tests of thermosensitive nociception and generates a precise determination of temperature at the point of response. This response is highly reproducible and directly applicable to genetic and neural circuit analysis of a simple escape behavior.
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Drosophila/fisiología , Reacción de Fuga , Temperatura , Animales , Drosophila/crecimiento & desarrollo , Proteínas de Drosophila/genética , Canales Iónicos/genética , Larva/fisiología , Sensación TérmicaRESUMEN
Acetals are obtained in good yields by treatment of aldehydes and ketones with trialkyl orthoformate and the corresponding alcohol in the presence of 0.1 mol % Bi(OTf)3.4H2O. A simple procedure for the formation of acetals of diaryl ketones has also been developed. The conversion of carbonyl compounds to the corresponding 1,3-dioxolane using ethylene glycol is also catalyzed by Bi(OTf)3.4H2O (1 mol %). Two methods, both of which avoid the use of benzene, have been developed.