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Ectopic activation of rearranged during transfection (RET) has been reported to facilitate lineage differentiation and cell proliferation in different cytogenetic subtypes of acute myeloid leukemia (AML). Herein, we demonstrate that RET is significantly (p < 0.01) upregulated in AML subtypes containing rearrangements of the lysine methyltransferase 2A gene (KMT2A), commonly referred to as KMT2A-rearranged (KMT2A-r) AML. Integrating multi-epigenomics data, we show that the KMT2A-MLLT3 fusion induces the development of CCCTC-binding (CTCF)-guided de novo extrusion enhancer loop to upregulate RET expression in KMT2A-r AML. Based on the finding that RET expression is tightly correlated with the selective chromatin remodeler and mediator (MED) proteins, we used a small-molecule inhibitor having dual inhibition against RET and MED12-associated cyclin-dependent kinase 8 (CDK8) in KMT2A-r AML cells. Dual inhibition of RET and CDK8 restricted cell proliferation by producing multimodal oxidative stress responses in treated cells. Our data suggest that epigenetically enhanced RET protects KMT2A-r AML cells from oxidative stresses, which could be exploited as a potential therapeutic strategy.
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Reordenamiento Génico , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Proto-Oncogenes , Proteína de la Leucemia Mieloide-Linfoide/genética , Proteína de la Leucemia Mieloide-Linfoide/metabolismo , Estrés Oxidativo/genética , Proteínas Proto-Oncogénicas c-ret/genéticaRESUMEN
Registered nurse retention is declining, with a national turnover rate in 2021 of 27%. After implementing a toolkit, nursing leaders in 1 organization completed 75 stay interviews with nurses in a cardiothoracic telemetry and a cardiothoracic surgical intensive care unit. Nurses reported that unit culture, team/peers, and scheduling were important in decisions to stay in their positions, but respondents considered leaving for salary, growth/development, and traveling opportunities. The stay interview process affords nurse leaders an opportunity to examine why nurses stay or leave and supports the development of targeted retention strategies.
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Enfermeras y Enfermeros , Humanos , Empleo , Reorganización del Personal , Salarios y Beneficios , Satisfacción en el TrabajoRESUMEN
INTRODUCTION: Despite increasing utilization of spinal cord stimulation (SCS), its effects on chemoefficacy, cancer progression, and chemotherapy-induced peripheral neuropathy (CIPN) pain remain unclear. Up to 30% of adults who are cancer survivors may suffer from CIPN, and there are currently no effective preventative treatments. MATERIALS AND METHODS: Through a combination of bioluminescent imaging, behavioral, biochemical, and immunohistochemical approaches, we investigated the role of SCS and paclitaxel (PTX) on tumor growth and PTX-induced peripheral neuropathy (PIPN) pain development in T-cell-deficient male rats (Crl:NIH-Foxn1rnu) with xenograft human non-small cell lung cancer. We hypothesized that SCS can prevent CIPN pain and enhance chemoefficacy partially by modulating macrophages, fractalkine (CX3CL1), and inflammatory cytokines. RESULTS: We show that preemptive SCS enhanced the antitumor efficacy of PTX and prevented PIPN pain. Without SCS, rats with and without tumors developed robust PIPN pain-related mechanical hypersensitivity, but only those with tumors developed cold hypersensitivity, suggesting T-cell dependence for different PIPN pain modalities. SCS increased soluble CX3CL1 and macrophages and decreased neuronal and nonneuronal insoluble CX3CL1 expression and inflammation in dorsal root ganglia. CONCLUSION: Collectively, our findings suggest that preemptive SCS is a promising strategy to increase chemoefficacy and prevent PIPN pain via CX3CL1-macrophage modulation.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Neuralgia , Estimulación de la Médula Espinal , Humanos , Ratas , Masculino , Animales , Paclitaxel/efectos adversos , Paclitaxel/metabolismo , Quimiocina CX3CL1/metabolismo , Quimiocina CX3CL1/farmacología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/patología , Ratas Sprague-Dawley , Neuralgia/metabolismo , Médula Espinal/patología , Ganglios Espinales/metabolismoRESUMEN
BACKGROUND: Rapid response teams (RRTs) are designed to improve patient care during deterioration in clinical condition. LOCAL PROBLEM: Patients' desired limitations of medical therapy (LOMTs) were not documented or communicated to the RRT, and patients received care not aligned with their wishes. METHODS: A multidisciplinary team developed a process for improving documentation, communication of LOMTs, and care delivery on 3 medical cardiology units. The team implemented 3 Plan-Do-Study-Act (PDSA) cycles over 6 months. INTERVENTIONS: In cycle 1, team members taught the unit nurses, RRT members, and physicians to share LOMTs during handoff communications. Cycle 2 engaged case managers in LOMT documentation. In cycle 3, unit-based RRT simulation was conducted. RESULTS: All care delivered by the RRT aligned with the documented LOMTs. Documentation of LOMTs increased from 76% to 82.5% ( P = .014). CONCLUSIONS: Education, scripting, and simulation were successful strategies to ensure that care given during RRT events aligned with patients' wishes.
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Equipo Hospitalario de Respuesta Rápida , Humanos , Mejoramiento de la CalidadRESUMEN
PURPOSE: Patients boarding in a 14-bed postanesthesia care unit (PACU) impacted throughput in a large university hospital in West Virginia. The PACU and operating room (OR) boarder rate in 2019 was 12% (n = 1241) and 5% (n = 503), respectively. The purpose of this initiative was to improve PACU throughput by developing an efficient and evidence-based handoff communication process between the PACU and the medical-surgical floors. DESIGN: The design of the project was evidence-based quality improvement. METHODS: An interprofessional team created a nursing patient dashboard in the electronic medical record to be used during handoff communication between the PACU and medical-surgical floor nurses. The dashboard displayed real-time vital signs, patient history, medications, and laboratory results. When the patient met Aldrete score requirements for transfer, PACU nurses notified the floor that the patient was ready for transfer. After allowing 20 minutes for the floor nurse to view the dashboard, the PACU nurse and floor nurse spoke on the phone to discuss any outstanding questions. PACU and OR boarder rates were obtained from the electronic medical record 12 months before and after implementing the nursing patient dashboard. User feedback was gathered via plan-do-study-act cycles, posters, and interviews. FINDINGS: The electronic dashboard was a successful strategy to improve handoff communication between the PACU and receiving units. The dashboard was accepted by the staff with 70% (n = 24) of the comments being positive. A significant decrease in the number of PACU (χ2(1, n = 20,608) =122.63, P < .00001) and OR boarding (χ2 (1, n = 20,283) =14.55, P = .000136) of patients was found in the C-year compared to 2019. For patients who were boarded in the PACU, no significant difference in PACU delay duration was found (t(11) =1.49, P = .149) with the mean in 2019 of 166.96 (SD = 68.38) and the C-Year mean 132.84 (SD = 39.74). For patients who boarded in the OR, there was a significant difference (t(11) =15.590162, P <.00001) between groups for average duration of boarding with the mean in 2019 of 19.06 minutes (SD = 3.72) compared to 1.62 (SD = 1.1) in C-year. However, in July 2020 the PACU intermittently opened 2 flexible beds when the PACU was full, suggesting that OR boarding was not a reliable measure, but PACU boarding remained an accurate measure. CONCLUSIONS: The findings of this evidence-based quality improvement project demonstrated the usefulness of an electronic dashboard tool combined with verbal report to improve patient throughput by decreasing the number of patients boarding in the PACU.
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Pase de Guardia , Mejoramiento de la Calidad , Registros Electrónicos de Salud , Electrónica , Humanos , QuirófanosRESUMEN
BACKGROUND AND PURPOSE: Cerebral white matter signal abnormalities (WMSAs) are a significant radiological marker associated with brain and vascular aging. However, understanding their clinical impact is limited because of their pathobiological heterogeneity. We determined whether use of robust reliable automated procedures can distinguish WMSA classes with different clinical consequences. METHODS: Data from generally healthy participants aged >50 years with moderate or greater WMSA were selected from the Human Connectome Project-Aging (n=130). WMSAs were segmented on T1 imaging. Features extracted from WMSA included total and regional volume, number of discontinuous clusters, size of noncontiguous lesion, contrast of lesion intensity relative to surrounding normal appearing tissue using a fully automated procedure. Hierarchical clustering was used to classify individuals into distinct classes of WMSA. Radiological and clinical variability was evaluated across the individual WMSA classes. RESULTS: Class I was characterized by multiple, small, lower-contrast lesions predominantly in the deep WM; class II by large, confluent lesions in the periventricular WM; and class III by higher-contrast lesions restricted to the juxtaventricular WM. Class II was associated with lower myelin content than the other 2 classes. Class II was more prevalent in older subjects and was associated with a higher prevalence of hypertension and lower physical activity levels. Poor sleep quality was associated with a greater risk of class I. CONCLUSIONS: We classified heterogeneous subsets of cerebral white matter lesions into distinct classes that have different clinical risk factors. This new method for identifying classes of WMSA will be important in understanding the underlying pathophysiology and in determining the impact on clinical outcomes.
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Encéfalo/diagnóstico por imagen , Sustancia Blanca/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento , Biomarcadores , Análisis por Conglomerados , Conectoma , Imagen de Difusión Tensora , Ejercicio Físico , Femenino , Voluntarios Sanos , Humanos , Hipertensión/complicaciones , Hipertensión/epidemiología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vaina de Mielina/metabolismo , Prevalencia , Trastornos del Sueño-Vigilia/complicaciones , Trastornos del Sueño-Vigilia/epidemiologíaRESUMEN
Arterial spin labeling (ASL) magnetic resonance imaging (MRI) has become a popular approach for studying cerebral hemodynamics in a range of disorders and has recently been included as part of the Human Connectome Project-Aging (HCP-A). Due to the high spatial resolution and multiple post-labeling delays, ASL data from HCP-A holds promise for localization of hemodynamic signals not only in gray matter but also in white matter. However, gleaning information about white matter hemodynamics with ASL is challenging due in part to longer blood arrival times in white matter compared to gray matter. In this work, we present an analytical approach for deriving measures of cerebral blood flow (CBF) and arterial transit times (ATT) from the ASL data from HCP-A and report on gray and white matter hemodynamics in a large cohort (n = 234) of typically aging adults (age 36-90 years). Pseudo-continuous ASL data were acquired with labeling duration = 1500 ms and five post-labeling delays = 200 ms, 700 ms, 1200, 1700 ms, and 2200 ms. ATT values were first calculated on a voxel-wise basis through normalized cross-correlation analysis of the acquired signal time course in that voxel and an expected time course based on an acquisition-specific Bloch simulation. CBF values were calculated using a two-compartment model and with age-appropriate blood water longitudinal relaxation times. Using this approach, we found that white matter CBF reduces (ρ = 0.39) and white matter ATT elongates (ρ = 0.42) with increasing age (p < 0.001). In addition, CBF is lower and ATTs are longer in white matter compared to gray matter across the adult lifespan (Wilcoxon signed-rank tests; p < 0.001). We also found sex differences with females exhibiting shorter white matter ATTs than males, independently of age (Wilcoxon rank-sum test; p < 0.001). Finally, we have shown that CBF and ATT values are spatially heterogeneous, with significant differences in cortical versus subcortical gray matter and juxtacortical versus periventricular white matter. These results serve as a characterization of normative physiology across the human lifespan against which hemodynamic impairment due to cerebrovascular or neurodegenerative diseases could be compared in future studies.
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Envejecimiento/fisiología , Arterias Cerebrales/fisiología , Circulación Cerebrovascular/fisiología , Conectoma/métodos , Longevidad/fisiología , Imagen por Resonancia Magnética/métodos , Marcadores de Spin , Adulto , Anciano , Anciano de 80 o más Años , Velocidad del Flujo Sanguíneo/fisiología , Arterias Cerebrales/diagnóstico por imagen , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Efforts to understand genetic variability involved in an individual's susceptibility to chronic pain support a role for upstream regulation by epigenetic mechanisms. METHODS: To examine the transcriptomic and epigenetic basis of chronic pain that resides in the peripheral nervous system, we used RNA-seq and ATAC-seq of the rat dorsal root ganglion (DRG) to identify novel molecular pathways associated with pain hypersensitivity in two well-studied persistent pain models induced by chronic constriction injury (CCI) of the sciatic nerve and intra-plantar injection of complete Freund's adjuvant (CFA) in rats. RESULTS: Our RNA-seq studies identify a variety of biological process related to synapse organization, membrane potential, transmembrane transport, and ion binding. Interestingly, genes that encode transcriptional regulators were disproportionately downregulated in both models. Our ATAC-seq data provide a comprehensive map of chromatin accessibility changes in the DRG. A total of 1123 regions showed changes in chromatin accessibility in one or both models when compared to the naïve and 31 shared differentially accessible regions (DAR)s. Functional annotation of the DARs identified disparate molecular functions enriched for each pain model which suggests that chromatin structure may be altered differently following sciatic nerve injury and hind paw inflammation. Motif analysis identified 17 DNA sequences known to bind transcription factors in the CCI DARs and 33 in the CFA DARs. Two motifs were significantly enriched in both models. CONCLUSIONS: Our improved understanding of the changes in chromatin accessibility that occur in chronic pain states may identify regulatory genomic elements that play essential roles in modulating gene expression in the DRG.
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Cromatina/metabolismo , Expresión Génica , Dolor/genética , Sistema Nervioso Periférico/metabolismo , Animales , Modelos Animales de Enfermedad , Epigénesis Genética , Ganglios Espinales/metabolismo , Masculino , Dolor/metabolismo , Ratas , Ratas Sprague-Dawley , TranscriptomaRESUMEN
Regions within the default mode network (DMN) are particularly vulnerable to Alzheimer's disease pathology and mechanisms of DMN disruption in mild cognitive impairment (MCI) are still unclear. White matter lesions are presumed to be mechanistically linked to vascular dysfunction whereas cortical atrophy may be related to neurodegeneration. We examined associations between DMN seed-based connectivity, white matter lesion load, and cortical atrophy in MCI and cognitively healthy controls. MCI showed decreased functional connectivity (FC) between the precuneus-seed and bilateral lateral temporal cortex (LTC), medial prefrontal cortex (mPFC), posterior cingulate cortex, and inferior parietal lobe compared to those with controls. When controlling for white matter lesion volume, DMN connectivity differences between groups were diminished within bilateral LTC, although were significantly increased in the mPFC explained by significant regional associations between white matter lesion volume and DMN connectivity only in the MCI group. When controlling for cortical thickness, DMN FC was similarly decreased across both groups. These findings suggest that white matter lesions and cortical atrophy are differentially associated with alterations in FC patterns in MCI. Associations between white matter lesions and DMN connectivity in MCI further support at least a partial but important vascular contribution to age-associated neural and cognitive impairment.
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Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Red en Modo Predeterminado/diagnóstico por imagen , Red en Modo Predeterminado/fisiopatología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/fisiopatología , Anciano , Anciano de 80 o más Años , Atrofia , Mapeo Encefálico , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/fisiopatología , Disfunción Cognitiva/psicología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Pruebas NeuropsicológicasRESUMEN
Bed flow decisions should be based on current information about capacity. The purpose of this project was to develop a real-time, enterprise-wide, capacity management dashboard. The dashboard successfully used information from the electronic medical record to create a comprehensive standardized data source, which was used to drive patient flow decisions optimizing bed space, allocating resources and maintaining safety.
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Eficiencia Organizacional , Registros Electrónicos de Salud , Hospitales Pediátricos/organización & administración , Niño , Humanos , OhioRESUMEN
BACKGROUND: Pain is a subjective experience derived from complex interactions among biological, environmental, and psychosocial pathways. Sex differences in pain sensitivity and chronic pain prevalence are well established. However, the molecular basis underlying these sex dimorphisms are poorly understood particularly with regard to the role of the peripheral nervous system. Here we sought to identify shared and distinct gene networks functioning in the peripheral nervous systems that may contribute to sex differences of pain in rats after nerve injury. RESULTS: We performed RNA-seq on dorsal root ganglia following chronic constriction injury of the sciatic nerve in male and female rats. Analysis from paired naive and injured tissues showed that 1513 genes were differentially expressed between sexes. Genes which facilitated synaptic transmission in naïve and injured females did not show increased expression in males. CONCLUSIONS: Appreciating sex-related gene expression differences and similarities in neuropathic pain models may help to improve the translational relevance to clinical populations and efficacy of clinical trials of this major health issue.
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Ganglios Espinales/metabolismo , Ganglios Espinales/patología , Regulación de la Expresión Génica , Traumatismos de los Nervios Periféricos/etiología , Animales , Femenino , Perfilación de la Expresión Génica , Masculino , Traumatismos de los Nervios Periféricos/metabolismo , Traumatismos de los Nervios Periféricos/patología , Ratas , Factores Sexuales , TranscriptomaRESUMEN
BACKGROUND: Patients at risk for clinical deterioration often show changes in vital signs up to 24 hours before a critical event. Use of modified early warning scores has demonstrated effectiveness in identifying patients at risk for clinical deterioration and improving outcomes. LOCAL PROBLEM: Documentation of vital signs, timely recognition of clinical deterioration, and compliance with the sepsis bundles remained a challenge. METHODS: An interprofessional team developed an electronic vital sign alert (VSA) system with a concurrent running sepsis screen, along with clinical protocols. INTERVENTIONS: Education was provided and the VSA system was implemented on 3 nursing units. RESULTS: After implementation, the number of unplanned transfers to the intensive care unit increased. Mortality rate and length of stay in the intensive care unit for patients transferred for respiratory failure and sepsis significantly decreased. There was a 21% increase in identification of sepsis. CONCLUSIONS: The VSA system was an effective tool to identify patients at risk for clinical deterioration and help to improve outcomes.
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Alarmas Clínicas , Protocolos Clínicos/normas , Personal de Enfermería en Hospital/educación , Sepsis/diagnóstico , Signos Vitales/fisiología , Deterioro Clínico , Femenino , Equipo Hospitalario de Respuesta Rápida/estadística & datos numéricos , Humanos , Unidades de Cuidados Intensivos/estadística & datos numéricosRESUMEN
PROBLEM: Emergency departments throughout the nation are experiencing crowding related to increased patient volumes and decreased hospital inpatient bed capacity. As a result of lengthy wait times, patients are leaving without having medical treatment, and satisfaction is poor. The purpose of this quality improvement initiative was placing a provider in triage to complement the existing split-flow process aimed to decrease wait times to see a provider, length of stay (LOS), left without being seen (LWBS) rates, and improve patient satisfaction. METHODS: A multiprofessional team was established. Nurses, advanced practice providers, and physicians collaborated on a project to place a provider in triage to assist in seeing patients as soon as possible and begin care or treatment. RESULTS: The outcomes of the initiative were positive for ED LOS metrics and patient satisfaction. Door-to-provider time decreased from a high of 56 minutes to a low of 13 minutes. The percentage of patients LWBS decreased from a high of 12% to a low of 1.62%. DISCUSSION: The project showed that the evidence-based practice of a combined split-flow and provider-in-triage model resulted in improvements in throughput for patients who were treated and released from the emergency department.
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Enfermería de Urgencia/métodos , Servicio de Urgencia en Hospital , Personal de Salud , Mejoramiento de la Calidad , Triaje/métodos , Humanos , Tiempo de Internación/estadística & datos numéricos , Satisfacción del Paciente/estadística & datos numéricos , MédicosRESUMEN
Spinal cord stimulation has become an important modality in pain treatment especially for neuropathic pain conditions refractory to pharmacotherapy. However, the molecular control of inhibitory and excitatory mechanisms observed after spinal cord stimulation are poorly understood. Here, we used RNA-seq to identify differences in the expression of genes and gene networks in spinal cord tissue from nerve-injured rats with and without repetitive conventional spinal cord stimulation treatment. Five weeks after chronic constrictive injury to the left sciatic nerve, male and female rats were randomized to receive repetitive spinal cord stimulation or no treatment. Rats receiving spinal cord stimulation underwent epidural placement of a miniature stimulating electrode and received seven sessions of spinal cord stimulation (50 Hz, 80% motor threshold, 0.2 ms, constant current bipolar stimulation, 120 min/session) over four consecutive days. Within 2 h after the last spinal cord stimulation treatment, the L4-L6 spinal segments ipsilateral to the side of nerve injury were harvested and used to generate libraries for RNA-seq. Our RNA-seq data suggest further increases of many existing upregulated immune responses in chronic constrictive injury rats after repetitive spinal cord stimulation, including transcription of cell surface receptors and activation of non-neuronal cells. We also demonstrate that repetitive spinal cord stimulation represses transcription of several key synaptic signaling genes that encode scaffold proteins in the post-synaptic density. Our transcriptional studies suggest a potential relationship between specific genes and the therapeutic effects observed in patients undergoing conventional spinal cord stimulation after nerve injury. Furthermore, our results may help identify new therapeutic targets for improving the efficacy of conventional spinal cord stimulation and other chronic pain treatments.
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Nervio Ciático/lesiones , Nervio Ciático/metabolismo , Análisis de Secuencia de ARN , Estimulación de la Médula Espinal , Médula Espinal/metabolismo , Animales , Enfermedad Crónica , Constricción Patológica , Regulación hacia Abajo/genética , Femenino , Perfilación de la Expresión Génica , Ontología de Genes , Masculino , Modelos Biológicos , Neuralgia/genética , Neuralgia/patología , Ratas Sprague-Dawley , Nervio Ciático/patología , Caracteres Sexuales , Sinapsis/metabolismo , Regulación hacia Arriba/genéticaRESUMEN
In most animals, sperm are stored in a quiescent state in the male reproductive tract and only initiate motility when released into either the female reproductive tract, or, in the case of broadcast spawners, the external environment. Male accessory gland secretions transferred into the female reproductive tract may provide factors that modulate sperm viability and storage, or aid in sperm competition, as well as activate sperm motility. In several insects, serine proteases have been implicated in activating sperm motility. Our previous studies have shown that, in Culex quinquefasciatus, either a male accessory gland extract or purified trypsin is sufficient to initiate sperm motility in vitro. The objective of this study was to identify and characterize trypsin-like enzymes produced in the Culex male accessory glands. Mass spectrometry was used to analyze accessory gland proteins and this preliminary proteomic analysis identified 4 trypsin-like proteases (trypsin, trypsin4, and two trypsin7 isoforms). When measured with the chromogenic trypsin substrate Na -benzoyl-L-arginine-ethyl-ester-hydrochloride (BAEE), trypsin-like protease activity in the accessory glands was robust, with a pH optimum of 8. The pH range for the Culex trypsin activity was substantially narrower than a mammalian homologue (porcine pancreatic trypsin). A soybean trypsin inhibitor (SBTI) -agarose affinity column was used to independently identify trypsin-like accessory gland proteins. Several proteins were enriched in the eluate, as detected by silver staining of SDS-PAGE gels. Taken together, these data demonstrate the presence of trypsin-like activity and several trypsin-like proteins in the Culex male accessory glands.
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Estructuras Animales/enzimología , Culex/metabolismo , Proteínas de Insectos/metabolismo , Serina Endopeptidasas/metabolismo , Motilidad Espermática/fisiología , Espermatozoides/metabolismo , Animales , Culex/citología , MasculinoRESUMEN
BACKGROUND: Ongoing neuropathic pain is difficult to treat. The authors examined whether dermorphin [D-Arg2, Lys4] (1-4) amide, a peripherally acting µ-opioid receptor agonist, attenuates ongoing pain-associated manifestations after nerve injury in rats and mice. METHODS: Using conditioned place preference assay, the authors tested whether animals show a preference to the environment associated with drug treatment. Wide-dynamic range and dorsal root ganglion neuronal activities were measured by electrophysiology recording and calcium imaging. RESULTS: Nerve-injured animals stayed longer in dermorphin [D-Arg2, Lys4] (1-4) amide-paired chamber after conditioning than during preconditioning (rats: 402.4 ± 61.3 vs. 322.1 ± 45.0 s, 10 mg/kg, n = 9, P = 0.009; mice: 437.8 ± 59.4 vs. 351.3 ± 95.9 s, 2 mg/kg, n = 8, P = 0.047). Topical ganglionic application of dermorphin [D-Arg2, Lys4] (1-4) amide (5 µM, 1 µl, n = 5) reduced the numbers of small-diameter dorsal root ganglion neurons that showed spontaneous activity (1.1 ± 0.4 vs. 1.5 ± 0.3, P = 0.044) and that were activated by test stimulation (15.5 ± 5.5 vs. 28.2 ± 8.2, P = 0.009) after injury. In neuropathic rats, dermorphin [D-Arg2, Lys4] (1-4) amide (10 mg/kg, n = 8) decreased spontaneous firing rates in wide-dynamic range neurons to 53.2 ± 46.6% of predrug level, and methylnaltrexone (5 mg/kg, n = 9) blocked dermorphin [D-Arg2, Lys4] (1-4) amide-induced place preference and inhibition of wide-dynamic range neurons. Dermorphin [D-Arg2, Lys4] (1-4) amide increased paw withdrawal threshold (17.5 ± 2.2 g) from baseline (3.5 ± 0.7 g, 10 mg/kg, n = 8, P = 0.002) in nerve-injured rats, but the effect diminished after repeated administrations. CONCLUSIONS: Peripherally acting µ-opioids may attenuate ongoing pain-related behavior and its neurophysiologic correlates. Yet, repeated administrations cause antiallodynic tolerance.
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Analgésicos Opioides/uso terapéutico , Neuralgia/tratamiento farmacológico , Neuralgia/fisiopatología , Receptores Opioides mu/agonistas , Receptores Opioides mu/fisiología , Nervios Espinales/fisiología , Analgésicos Opioides/farmacología , Animales , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Neuralgia/psicología , Ratas , Ratas Sprague-Dawley , Nervios Espinales/efectos de los fármacosRESUMEN
Persistent pain following breast cancer surgery is a significant problem. Both inherited and acquired mechanisms of inflammation appear to play a role in the development and maintenance of persistent pain. In this longitudinal study, growth mixture modeling was used to identify persistent breast pain phenotypes based on pain assessments obtained prior to and monthly for 6months following breast cancer surgery. Associations between the "no pain" and "mild pain" phenotypes and single nucleotide polymorphisms (SNPs) spanning 15 cytokine genes were evaluated. The methylation status of the CpG sites found in the promoters of genes associated with pain group membership was determined using bisulfite sequencing. In the multivariate analysis, three SNPs (i.e., interleukin 6 (IL6) rs2069840, C-X-C motif chemokine ligand 8 (CXCL8) rs4073, tumor necrosis factor (TNF) rs1800610) and two TNF CpG sites (i.e., c.-350C, c.-344C) were associated with pain group membership. These findings suggest that variations in IL6, CXCL8, and TNF are associated with the development and maintenance of mild persistent breast pain. CpG methylation within the TNF promoter may provide an additional mechanism through which TNF alters the risk for mild persistent breast pain after breast cancer surgery. These genetic and epigenetic variations may help to identify individuals who are predisposed to the development of mild levels of persistent breast pain following breast cancer surgery.
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Neoplasias de la Mama/cirugía , Epigénesis Genética , Estudios de Asociación Genética , Interleucina-6/genética , Interleucina-8/genética , Mastodinia/etiología , Mastodinia/genética , Factor de Necrosis Tumoral alfa/genética , Metilación de ADN/genética , Demografía , Femenino , Humanos , Modelos Logísticos , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras GenéticasRESUMEN
This project describes a multifaceted noise reduction program on 2 hospital units designed to ensure a quiet hospital environment, with the goal of improving the patient experience. The noise committee in an urban city hospital developed a plan to control noise including scripted leadership rounding, staff education, a nighttime sleep promotion cart, and visual aids to remind staff to be quiet. Postintervention improvement in patient satisfaction scores was noted.
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Ambiente de Instituciones de Salud/normas , Cuidados Nocturnos/métodos , Ruido/prevención & control , Satisfacción del Paciente , Mejoramiento de la Calidad , Disomnias/etiología , Disomnias/enfermería , Ambiente de Instituciones de Salud/estadística & datos numéricos , Hospitalización/estadística & datos numéricos , Humanos , Cuidados Nocturnos/normas , Cuidados Nocturnos/estadística & datos numéricos , Ruido/efectos adversosRESUMEN
PROBLEM: Sepsis is a leading cause of death in the United States; however, health care providers struggle with timely recognition, diagnosis, and treatment of patients. Both the Centers for Medicare and Medicaid Services and the National Quality Forum have identified this diagnosis as a priority. Presently, many patients with sepsis are identified late, resulting in significant morbidity and death. METHODS: In this project, a collaborative, interprofessional approach was created for screening and early identification of ED patients with possible sepsis. The department has 38 beds with annual patient volumes of more than 40,000 visits. Education was provided about the symptoms and treatment of patients with sepsis. A screening and management algorithm tool was instituted that consisted of early identification triggers and how to intervene according to Surviving Sepsis Campaign recommendations. The tool allowed for assessment of the patient by the ED team; the team worked to determine if sepsis was present and the extent of the illness. RESULTS: During the first 4 months after implementation, more than 240 patients were screened, assessed, and treated according to the algorithm. Project outcomes resulted in an increase in staff knowledge of sepsis, a decrease in length of stay by 3 hours, and a significant decrease in mortality when compared with the previous year's coded data. IMPLICATIONS FOR PRACTICE: This project demonstrates that sepsis education and team collaboration are an integral part of identifying and treating patients with sepsis. An interprofessional collaborative approach could be implemented in other institutions to combat the life-threatening complications of sepsis.
Asunto(s)
Algoritmos , Conducta Cooperativa , Servicio de Urgencia en Hospital/organización & administración , Grupo de Atención al Paciente/organización & administración , Sepsis/diagnóstico , Sepsis/enfermería , Humanos , Capacitación en Servicio , Sepsis/mortalidad , Análisis de Supervivencia , Atención Terciaria de Salud , Estados UnidosRESUMEN
PROBLEM: Health care professionals have not been successful in recognizing or rescuing victims of human trafficking. The purpose of this project was to implement a screening system and treatment algorithm in the emergency department to improve the identification and rescue of victims of human trafficking. The lack of recognition by health care professionals is related to inadequate education and training tools and confusion with other forms of violence such as trauma and sexual assault. METHODS: A multidisciplinary team was formed to assess the evidence related to human trafficking and make recommendations for practice. After receiving education, staff completed a survey about knowledge gained from the training. An algorithm for identification and treatment of sex trafficking victims was implemented and included a 2-pronged identification approach: (1) medical red flags created by a risk-assessment tool embedded in the electronic health record and (2) a silent notification process. Outcome measures were the number of victims who were identified either by the medical red flags or by silent notification and were offered and accepted intervention. RESULTS: Survey results indicated that 75% of participants reported that the education improved their competence level. The results demonstrated that an education and treatment algorithm may be an effective strategy to improve recognition. One patient was identified as an actual victim of human trafficking; the remaining patients reported other forms of abuse. IMPLICATIONS FOR PRACTICE: Education and a treatment algorithm were effective strategies to improve recognition and rescue of human trafficking victims and increase identification of other forms of abuse.