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1.
J Physiol ; 601(24): 5795-5811, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37983193

RESUMEN

Inspiratory tongue dilatory movement is believed to be mediated via changes in neural drive to genioglossus. However, this has not been studied during quiet breathing in humans. Therefore, this study investigated this relationship and its potential role in obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue dilatory movement, quantified with tagged magnetic resonance imaging, and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in nine controls [apnoea-hypopnea index (AHI) ≤5 events/h] and 37 people with untreated OSA (AHI >5 events/h). Measurements were obtained for 156 neuromuscular compartments (85%). Analysis was adjusted for nadir epiglottic pressure during inspiration. Only for 106 compartments (68%) was a larger anterior (dilatory) movement associated with a higher phasic EMG [mixed linear regression, beta = 0.089, 95% CI [0.000, 0.178], t(99) = 1.995, P = 0.049, hereafter EMG↗/mvt↗]. For the remaining 50 (32%) compartments, a larger dilatory movement was associated with a lower phasic EMG [mixed linear regression, beta = -0.123, 95% CI [-0.224, -0.022], t(43) = -2.458, P = 0.018, hereafter EMG↘/mvt↗]. OSA participants had a higher odds of having at least one decoupled EMG↘/mvt↗ compartment (binary logistic regression, odds ratio [95% CI]: 7.53 [1.19, 47.47] (P = 0.032). Dilatory tongue movement was minimal (>1 mm) in nearly all participants with only EMG↗/mvt↗ compartments (86%, 18/21). These results demonstrate that upper airway dilatory mechanics cannot be predicted from genioglossus EMG, particularly in people with OSA. Tongue movement associated with minimal genioglossus activity suggests co-activation of other airway dilator muscles. KEY POINTS: Inspiratory tongue movement is thought to be mediated through changes in genioglossus activity. However, it is unknown if this relationship is altered by obstructive sleep apnoea (OSA). During awake supine quiet nasal breathing, inspiratory tongue movement, quantified with tagged magnetic resonance imaging (MRI), and inspiratory phasic genioglossus EMG normalised to maximum EMG were measured in four tongue compartments of people with and without OSA. Larger tongue anterior (dilatory) movement was associated with higher phasic genioglossus EMG for 68% of compartments. OSA participants had an ∼7-times higher odds of having at least one compartment for which a larger anterior tongue movement was not associated with a higher phasic EMG than controls. Therefore, higher genioglossus phasic EMG does not consistently translate into tongue dilatory movement, particularly in people with OSA. Large dilatory tongue movements can occur despite minimal genioglossus inspiratory activity, suggesting co-activation of other pharyngeal muscles.


Asunto(s)
Apnea Obstructiva del Sueño , Vigilia , Humanos , Vigilia/fisiología , Músculos Faríngeos , Movimiento/fisiología , Lengua , Electromiografía
2.
Nanotechnology ; 34(46)2023 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-37524056

RESUMEN

We describe the concept and roadmap of an engineered electronic nose with specificity towards analytes that differ by as little as one carbon atom, and sensitivity of being able to electrically register a single molecule of analyte. The analyte could be anything that natural noses can detect, e.g. trinitrotoluene (TNT), cocaine, aromatics, volatile organic compounds etc. The strategy envisioned is to genetically engineer a fused olfactory odorant receptor (odorant receptor (OR), a membrane-bound G-protein coupled receptor (GPCR) with high selectivity) to an ion channel protein, which opens in response to binding of the ligand to the OR. The lipid bilayer supporting the fused sensing protein would be intimately attached to a nanowire or nanotube network (either via a covalent tether or a non-covalent physisorption process), which would electrically detect the opening of the ion channel, and hence the binding of a single ligand to a single OR protein domain. Three man-made technological advances: (1) fused GPCR to ion channel protein, (2) nanowire sensing of single ion channel activity, and (3) lipid bilayer to nanotube/nanowire tethering chemistry and on natural technology (sensitivity and selectivity of OR domains to specific analytes) each have been demonstrated and/or studied independently. The combination of these three technological advances and the result of millions of years of evolution of OR proteins would enable the goal of single molecule sensing with specificity towards analytes that differ by as little as one carbon atom. This is both a review of the past and a vision of the future.


Asunto(s)
Técnicas Biosensibles , Nanocables , Receptores Odorantes , Humanos , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Membrana Dobles de Lípidos , Nariz Electrónica , Ligandos , Canales Iónicos
3.
J Physiol ; 600(24): 5311-5332, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36271640

RESUMEN

The ability to discriminate competing external stimuli and initiate contextually appropriate behaviours is a key brain function. Neurons in the deep superior colliculus (dSC) integrate multisensory inputs and activate descending projections to premotor pathways responsible for orienting, attention and defence, behaviours which involve adjustments to respiratory and cardiovascular parameters. However, the neural pathways that subserve the physiological components of orienting are poorly understood. We report that orienting responses to optogenetic dSC stimulation are accompanied by short-latency autonomic, respiratory and electroencephalographic effects in awake rats, closely mimicking those evoked by naturalistic alerting stimuli. Physiological responses were not accompanied by detectable aversion or fear, and persisted under urethane anaesthesia, indicating independence from emotional stress. Anterograde and trans-synaptic viral tracing identified a monosynaptic pathway that links the dSC to spinally projecting neurons in the medullary gigantocellular reticular nucleus (GiA), a key hub for the coordination of orienting and locomotor behaviours. In urethane-anaesthetized animals, sympathoexcitatory and cardiovascular, but not respiratory, responses to dSC stimulation were replicated by optogenetic stimulation of the dSC-GiA terminals, suggesting a likely role for this pathway in mediating the autonomic components of dSC-mediated responses. Similarly, extracellular recordings from putative GiA sympathetic premotor neurons confirmed short-latency excitatory inputs from the dSC. This pathway represents a likely substrate for autonomic components of orienting responses that are mediated by dSC neurons and suggests a mechanism through which physiological and motor components of orienting behaviours may be integrated without the involvement of higher centres that mediate affective components of defensive responses. KEY POINTS: Neurons in the deep superior colliculus (dSC) integrate multimodal sensory signals to elicit context-dependent innate behaviours that are accompanied by stereotypical cardiovascular and respiratory activities. The pathways responsible for mediating the physiological components of colliculus-mediated orienting behaviours are unknown. We show that optogenetic dSC stimulation evokes transient orienting, respiratory and autonomic effects in awake rats which persist under urethane anaesthesia. Anterograde tracing from the dSC identified projections to spinally projecting neurons in the medullary gigantocellular reticular nucleus (GiA). Stimulation of this pathway recapitulated autonomic effects evoked by stimulation of dSC neurons. Electrophysiological recordings from putative GiA sympathetic premotor neurons confirmed short latency excitatory input from dSC neurons. This disynaptic dSC-GiA-spinal sympathoexcitatory pathway may underlie autonomic adjustments to salient environmental cues independent of input from higher centres.


Asunto(s)
Formación Reticular , Colículos Superiores , Animales , Ratas , Colículos Superiores/fisiología , Formación Reticular/fisiología , Sistema Nervioso Autónomo/fisiología , Neuronas/fisiología , Vías Nerviosas/fisiología , Uretano/farmacología
4.
Anal Chem ; 94(19): 6930-6938, 2022 05 17.
Artículo en Inglés | MEDLINE | ID: mdl-35502898

RESUMEN

We demonstrate a fast and easy-to-use three-dimensional printed microfluidic platform for mitochondria isolation from cell and tissue lysates based on inertial microfluidics. We present and quantify the quality of the isolated mitochondria by measuring the respiration rate under various conditions. We demonstrate that the technology produces vital mitochondria of equal quality to traditional, but more burdensome, differential centrifugation. We anticipate that the availability of improved tools for studies of bioenergetics to the broader biological community will enable these and other links to be explored in more meaningful ways, leading to further understanding of the links between energy, health, and disease.


Asunto(s)
Microfluídica , Mitocondrias , Centrifugación , Metabolismo Energético , Tecnología
5.
Transfusion ; 62 Suppl 1: S218-S223, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35748693

RESUMEN

BACKGROUND: Hemorrhagic shock is a clinically challenging disease process with high mortality. When conventional blood products are unable to be administered, oxygen-carrying blood alternatives are sometimes utilized. The international experience with this scenario is limited. We aim to add to this body of literature. STUDY DESIGN AND METHODS: This is a case report of the administration of bovine hemoglobin-based oxygen-carrying red blood cell (RBC) substitute HBOC-201 (HemoPure®) to a patient with post-partum bleeding and hemorrhagic shock because the patient declined RBC transfusion. HBOC-201 was administered with consent under a one-time Emergency Investigational New Drug (eIND) approval from the Food and Drug Administration with appropriate notification of the Institutional Review Board. RESULTS: The patient was successfully resuscitated with HBOC-201 from hemorrhagic shock. She was weaned off of vasopressor support and extubated with the recovery of her baseline mental status within 4 h. However, approximately 36 h after this, the patient developed multi-organ system dysfunction, volume overload, right heart failure and ultimately expired early on post-partum day 4. DISCUSSION: Resuscitation from hemorrhagic shock with HBOC-201 as an RBC alternative is feasible, but significant challenges remain with the management of sequelae resulting from prolonged low-flow, ischemic states as well as the significant colloid pressure and volume overload experienced after massive transfusion with an acellular colloid oxygen carrier.


Asunto(s)
Sustitutos Sanguíneos , Obstetricia , Choque Hemorrágico , Sustitutos Sanguíneos/uso terapéutico , Femenino , Hemoglobinas/uso terapéutico , Humanos , Oxígeno , Resucitación/métodos , Choque Hemorrágico/terapia
6.
Neuroendocrinology ; 112(12): 1200-1213, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35654013

RESUMEN

INTRODUCTION: Angiotensin (Ang) II signalling in the hypothalamic paraventricular nucleus (PVN) via Ang type-1a receptors (AT1R) regulates vasopressin release and sympathetic nerve activity - two effectors of blood pressure regulation. We determined the cellular expression and function of AT1R in the PVN of a rodent model of polycystic kidney disease (PKD), the Lewis polycystic kidney (LPK) rat, to evaluate its contribution to blood pressure regulation and augmented vasopressin release in PKD. METHODS: PVN AT1R gene expression was quantified with fluorescent in situ hybridization in LPK and control rats. PVN AT1R function was assessed with pharmacology under urethane anaesthesia in LPK and control rats instrumented to record arterial pressure and sympathetic nerve activity. RESULTS: AT1R gene expression was upregulated in the PVN, particularly in corticotrophin-releasing hormone neurons, of LPK versus control rats. PVN microinjection of Ang II produced larger increases in systolic blood pressure in LPK versus control rats (36 ± 5 vs. 17 ± 2 mm Hg; p < 0.01). Unexpectedly, Ang II produced regionally heterogeneous sympathoinhibition (renal: -33%; splanchnic: -12%; lumbar: no change) in LPK and no change in controls. PVN pre-treatment with losartan, a competitive AT1R antagonist, blocked the Ang II-mediated renal sympathoinhibition and attenuated the pressor response observed in LPK rats. The Ang II pressor effect was also blocked by systemic OPC-21268, a competitive V1A receptor antagonist, but unaffected by hexamethonium, a sympathetic ganglionic blocker. DISCUSSION/CONCLUSION: Collectively, our data suggest that upregulated AT1R expression in PVN sensitizes neuroendocrine release of vasopressin in the LPK, identifying a central mechanism for the elevated vasopressin levels present in PKD.


Asunto(s)
Núcleo Hipotalámico Paraventricular , Enfermedades Renales Poliquísticas , Ratas , Animales , Núcleo Hipotalámico Paraventricular/metabolismo , Presión Sanguínea , Roedores/genética , Roedores/metabolismo , Hibridación Fluorescente in Situ , Ratas Endogámicas Lew , Vasopresinas/metabolismo , Sistema Nervioso Simpático/metabolismo , Angiotensina II , Receptor de Angiotensina Tipo 1/genética , Receptor de Angiotensina Tipo 1/metabolismo , Enfermedades Renales Poliquísticas/metabolismo , Riñón
7.
J Vasc Surg ; 74(2): 467-476.e4, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33548416

RESUMEN

OBJECTIVE: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a potentially life-saving intervention. However, recent reports of associations with limb loss and mortality have called its safety into question. We aimed to evaluate patient and hospital characteristics associated with major amputation and in-hospital mortality among patients undergoing REBOA for trauma. METHODS: The National Trauma Data Bank (2015-2017) was queried for patients presenting to trauma centers and treated with REBOA. We included REBOA performed on hospital day 1 in patients who survived 6 or more hours from presentation. Univariable and multivariable analyses evaluated associations with major amputation and in-hospital mortality. RESULTS: A total of 316 patients underwent REBOA and survived in the acute period after presentation. Overall, mean age was 45 ± 20 years and the majority were male (73%) and White (56%). Most patients presented to level I trauma centers (72%) after blunt injuries (79%) with an average Injury Severity Score (ISS) of 31 ± 15, indicating major trauma. In 15 patients (5%), there were 18 major amputations-7 above knee and 11 below knee. A subgroup of 11 amputations were either traumatic amputations (73%) or mangled limbs requiring amputation within 24 hours (27%). Of the remaining amputations, 71% were associated with ipsilateral vascular or orthopedic lower extremity injuries of serious to severe Abbreviated Injury Scale severity. Comparing patients with amputations with those without amputations, there were no significant differences in patient demographics, comorbidities, or hospital characteristics. During hospitalization, patients requiring amputation more frequently received open peripheral vascular interventions (40% vs 10%; P = .002), underwent similar numbers of endovascular interventions (6.7% vs 4.7%; P = .5), and more often developed compartment syndrome (13% vs 2%; P = .04). Overall, there were 110 deaths (35%). The major amputation prevalence was similar between patients who died vs those who survived (3.6% vs 5.3%; P = .5). In multivariable analysis, prehospital cardiac arrest (odds ratio [OR], 8.47; 95% confidence interval [CI], 1.47-48.66; P = .02), penetrating vs blunt trauma (OR, 5.5; 95% CI, 1.05-28.82; P = .04), decreased Glasgow Coma Scale score (OR, 1.18; 95% CI, 1.05-1.32; P = .01), older age (OR, 1.06; 95% CI, 1.03-1.10; P < .001), and increased Injury Severity Score (OR, 1.05; 95% CI, 1.0-1.1; P = .03) were associated with higher mortality. CONCLUSIONS: The majority of major amputations in patients undergoing REBOA were secondary to the initial traumatic mechanism. Injury type and severity, as well as initial hemodynamic derangements, are associated with mortality after REBOA. Despite concerns about prohibitive limb complications of REBOA, baseline injuries seem to be the primary cause of limb loss, but further prospective analysis is needed.


Asunto(s)
Amputación Quirúrgica , Aorta/lesiones , Oclusión con Balón/efectos adversos , Resucitación/efectos adversos , Heridas y Lesiones/terapia , Adulto , Anciano , Amputación Quirúrgica/efectos adversos , Amputación Quirúrgica/mortalidad , Aorta/diagnóstico por imagen , Aorta/fisiopatología , Oclusión con Balón/mortalidad , Bases de Datos Factuales , Femenino , Hemodinámica , Mortalidad Hospitalaria , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Resucitación/mortalidad , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/mortalidad , Heridas y Lesiones/fisiopatología
9.
Soc Sci Res ; 93: 102489, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33308687

RESUMEN

In this study, we examine the effects of the structure of a network, the dominance identity of the actors, and the actors' ability to reward or punish on the use of punishment and the development of social bonds in a network. As expected, we find that peripheral rather than central actors in a network use punishment more, as do those with a high dominance identity. We also find that persons use punishment to increase or decrease their perceived level of dominance when their dominance identity is not verified. However, the patterns of interaction that develop in the network are an interactive function of network position, actor's dominance identity, and punishment use. We discuss how the social psychological drive to control one's identity interacts with social structural factors in the network to create different cultures of dyadic interaction.


Asunto(s)
Castigo , Recompensa , Humanos , Relaciones Interpersonales , Castigo/psicología
10.
J Physiol ; 598(3): 581-597, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-31823371

RESUMEN

KEY POINTS: Coordination of the neuromuscular compartments of the tongue is critical to maintain airway patency. Currently, little is known about the extent to which regional tongue dilatory motion is coordinated in heathy people and if this coordination is altered in people with obstructive sleep apnoea (OSA). We show that regional tongue muscle coordination in people with and without OSA during wakefulness is associated with effective airway dilatation during inspiration, using dynamic tagged magnetic resonance imaging. The maximal movement of four compartments of the tongue were correlated and occurred concurrently towards the end of inspiration. If tongue movement was observed, people with more severe OSA had larger movement and moved more compartments (up to four) to maintain airway patency, while people without OSA moved only one compartment. These results suggest that airway patency is preserved during wakefulness in people with OSA via active dilatory movement of the genioglossus. ABSTRACT: Maintaining airway patency when supine requires neural drive to the genioglossus horizontal and oblique neuromuscular compartments (superior fan-like and inferior horizontal genioglossus, regions that are innervated by different branches of the hypoglossal nerve) to be coordinated during breathing, but it is unknown if this coordination is altered in obstructive sleep apnoea (OSA). This study aimed to assess coordination of airway dilatory motion across four mid-sagittal tongue compartments during inspiration (i.e. anterior and posterior of the horizontal and oblique compartments), and compare it in controls and OSA patients. Fifty-four participants (12 women, aged 20-73 years) underwent dynamic 'tagged' magnetic resonance imaging during wakefulness. Ten participants had no OSA [apnoea hypopnoea index (AHI) < 5 events h-1 ], 14 had mild OSA (5 < AHI ≤ 15 events h-1 ), 12 had moderate OSA (15 < AHI ≤ 30 events h-1 ) and 18 had severe OSA (AHI > 30 events h-1 ). A higher AHI was associated with a greater anterior movement of the anterior and posterior horizontal compartments (Spearman, r = -0.32, P = 0.02 for both), but not in the oblique compartments. If movement was observed, higher OSA severity was associated with an anterior movement of a greater number of compartments. Controls only moved the posterior horizontal compartment while the anterior horizontal compartment also moved in OSA participants. Oblique compartments moved only in people with severe OSA. The maximal anterior inspiratory movement of the four compartments was highly correlated (Spearman, P < 0.001) and occurred concurrently. The posterior horizontal compartment had the greatest anterior motion. These results suggest that airway patency is preserved during wakefulness in people with OSA via active dilatory movement of the genioglossus.


Asunto(s)
Apnea Obstructiva del Sueño , Vigilia , Adulto , Anciano , Femenino , Humanos , Nervio Hipogloso , Persona de Mediana Edad , Respiración , Lengua , Adulto Joven
11.
Am J Otolaryngol ; 41(2): 102376, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31924414

RESUMEN

PURPOSE: Develop a model for quality improvement in tracheostomy care and decrease tracheostomy-related complications. METHODS: This study was a prospective quality improvement project at an academic tertiary care hospital. A multidisciplinary team was assembled to create institutional guidelines for clinical care during the pre-operative, intra-operative, and post-operative periods. Baseline data was compiled by retrospective chart review of 160 patients, and prospective tracking of select points over 8 months in 73 patients allowed for analysis of complications and clinical parameters. RESULTS: Implementation of a quality improvement team was successful in creating guidelines, setting baseline parameters, and tracking data with run charts. Comparison of pre- and post-guideline data showed a trend toward decreased rate of major complications from 4.38% to 2.74% (p = 0.096). Variables including time to tracheotomy for prolonged intubation, surgical technique, day of first tracheostomy tube change, and specialty performing surgery did not show increased risk of complications. There were increased tracheostomy-related complications in cold months (p = 0.04). CONCLUSIONS: An interdisciplinary quality improvement team can improve tracheostomy care by identifying system factors, standardizing care among specialties, and providing continuous monitoring of select data points.


Asunto(s)
Investigación Interdisciplinaria , Complicaciones Posoperatorias/prevención & control , Mejoramiento de la Calidad , Calidad de la Atención de Salud/normas , Traqueostomía/normas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Grupo de Atención al Paciente , Estudios Prospectivos , Estudios Retrospectivos , Centros de Atención Terciaria , Traqueostomía/métodos
12.
J Surg Res ; 244: 484-491, 2019 12.
Artículo en Inglés | MEDLINE | ID: mdl-31330292

RESUMEN

BACKGROUND: Emergency general surgery (EGS) represents a diverse set of operations performed on acutely ill patients. Those undergoing EGS are at higher likelihood of complications, readmission, and death, but the effect of primary language on EGS outcomes has not been evaluated. We aimed to evaluate the association of non-English primary language on outcomes after EGS operations. METHODS: The New Jersey Statewide Inpatient Database from 2009 to 2014 was used to evaluate cases representing 80% of the national burden of EGS. Cases were restricted to ages ≥18 y, emergency department admissions, noted to be emergent or urgent, and performed between 0 and 2 d after admission. We evaluated Spanish speakers and non-English, non-Spanish (NENS) speakers compared with English. Outcomes included in-hospital mortality, 7-d readmission, and hospital length of stay (LOS). Logistic and negative binomial regression was used, and generalized linear mixed models were used to account for hierarchy in the data. RESULTS: There were 105,171 patients included. English speakers were majority white and with private insurance; Spanish speakers were younger and with fewer comorbidities. Where differences between Spanish and NENS speakers existed, NENS were more like the English-speaking group. Adjusted results indicate that Spanish speakers had reduced LOS after appendectomy (IRR: 0.92 [0.89-0.95]) and lysis of adhesion [0.93 (0.88-0.97)]. Spanish speakers had an increased LOS after higher risk operations (IRR: 1.14 [1.10-1.20]). NENS speakers had a reduced LOS after adhesiolysis (IRR: 0.94 [0.89-0.99]). There was no difference in mortality or short-term readmission CONCLUSIONS: These data from a large database suggest that the effect of primary language on LOS after EGS depends on the type of operation. Future studies should focus on long-term outcomes and determining if the lack of association we observed is generalizable to other regions of the United States.


Asunto(s)
Urgencias Médicas , Lenguaje , Procedimientos Quirúrgicos Operativos , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad
13.
Soc Sci Res ; 81: 144-156, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31130193

RESUMEN

Social exchange theories explain how differences in structural power can generate inequalities in exchange networks. We argue here that even in the absence of structural power differences, inequality can emerge out of the identity process. We posit that when structurally equivalent actors are uncertain about the resource levels available for distribution, different levels of the fairness identity and responses to identity non-verification will influence how they negotiate for resources. Results from an experiment that varies the fairness identity level and the identity verification of actors in two different equal power exchange networks confirm this. Absent structural power differences, the level of the fairness identity, identity non-verification, and structure of the network mutually influence the distribution of resources such that some dyads earn as much as two and a half times more than others. We discuss our findings as they pertain to unearthing the processes by which group inequalities arise and persist.

14.
J Neurosci ; 37(27): 6558-6574, 2017 07 05.
Artículo en Inglés | MEDLINE | ID: mdl-28576943

RESUMEN

Expression of the large extracellular glycan, polysialic acid (polySia), is restricted in the adult, to brain regions exhibiting high levels of plasticity or remodeling, including the hippocampus, prefrontal cortex, and the nucleus of the solitary tract (NTS). The NTS, located in the dorsal brainstem, receives constant viscerosensory afferent traffic as well as input from central regions controlling sympathetic nerve activity, respiration, gastrointestinal functions, hormonal release, and behavior. Our aims were to determine the ultrastructural location of polySia in the NTS and the functional effects of enzymatic removal of polySia, both in vitro and in vivo polySia immunoreactivity was found throughout the adult rat NTS. Electron microscopy demonstrated polySia at sites that influence neurotransmission: the extracellular space, fine astrocytic processes, and neuronal terminals. Removing polySia from the NTS had functional consequences. Whole-cell electrophysiological recordings revealed altered intrinsic membrane properties, enhancing voltage-gated K+ currents and increasing intracellular Ca2+ Viscerosensory afferent processing was also disrupted, dampening low-frequency excitatory input and potentiating high-frequency sustained currents at second-order neurons. Removal of polySia in the NTS of anesthetized rats increased sympathetic nerve activity, whereas functionally related enzymes that do not alter polySia expression had little effect. These data indicate that polySia is required for the normal transmission of information through the NTS and that changes in its expression alter sympathetic outflow. polySia is abundant in multiple but discrete brain regions, including sensory nuclei, in both the adult rat and human, where it may regulate neuronal function by mechanisms identified here.SIGNIFICANCE STATEMENT All cells are coated in glycans (sugars) existing predominantly as glycolipids, proteoglycans, or glycoproteins formed by the most complex form of posttranslational modification, glycosylation. How these glycans influence brain function is only now beginning to be elucidated. The adult nucleus of the solitary tract has abundant polysialic acid (polySia) and is a major site of integration, receiving viscerosensory information which controls critical homeostatic functions. Our data reveal that polySia is a determinant of neuronal behavior and excitatory transmission in the nucleus of the solitary tract, regulating sympathetic nerve activity. polySia is abundantly expressed at distinct brain sites in adult, including major sensory nuclei, suggesting that sensory transmission may also be influenced via mechanisms described here. These findings hint at the importance of elucidating how other glycans influence neural function.


Asunto(s)
Vías Aferentes/fisiología , Red Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Ácidos Siálicos/metabolismo , Núcleo Solitario/fisiología , Sistema Nervioso Simpático/fisiología , Animales , Potenciales Postsinápticos Excitadores/fisiología , Masculino , Ratas , Ratas Sprague-Dawley , Distribución Tisular
15.
Transfus Apher Sci ; 57(6): 785-789, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30455154

RESUMEN

Massive transfusion protocols (MTP) vary at different institutions. We implemented an algorithm in the transfusion service to support our Level I trauma center in 2007 and periodically monitor MTP utilization as part of ongoing quality management. At the last review in 2013, median plasma: RBC ratio was 1:1.8. We undertook a retrospective 3-year review of MTP activations stratifying by trauma versus non-trauma indications, and blood component utilization of the massive transfusion (MT) cases, adding a review of tranexamic acid (TXA) administration to the audit. The median transfused plasma: RBC ratio was 1:1.9 in trauma MT, and 1:1.6 in the non-trauma MT cases. Non-trauma MT patients at our institution were significantly older and more coagulopathic at MTP initiation compared to trauma MT patients, received fewer RBC units (15.5 versus 20.2), and had higher mortality. TXA adherence increased over the 3-year period to 60% of all trauma MTP activations in 2017.


Asunto(s)
Transfusión Sanguínea/normas , Cumplimiento de la Medicación , Ácido Tranexámico/administración & dosificación , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo
16.
Radiology ; 282(1): 84-91, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-27618453

RESUMEN

Purpose To evaluate the effect of an institutional clinical triaging algorithm on the rate of multidetector computed tomography (CT) utilization in blunt abdominopelvic trauma (BAPT) over an 8-year period at an urban level 1 trauma center. Materials and Methods Adult patients (n = 13 096; mean age, 42 years; age range, 15-95 years) admitted with BAPT from January 1, 2006, to December 31, 2013, were included. Patients with BAPT were divided into two groups: those admitted before (referred to as the prealgorithm group, from January 1, 2006, to June 30, 2010) and after (referred to as the postalgorithm group, from July 1, 2010, to December 31, 2013) the implementation of an institutional clinical triaging algorithm. The following parameters were recorded from abdominopelvic CT study reports for the pre- and postalgorithm groups: number of abdominopelvic CT examinations at admission, number of abdominopelvic CT examinations with positive BAPT-related findings, injury severity score, length of hospital stay, and number of mortalities. The unpaired t test and χ2 analysis were used to determine significant differences. Results The percentage of patients admitted for BAPT who underwent an abdominopelvic CT study was 76.7% (5900 of 7688) in the prealgorithm group and 44.6% (2413 of 5408) in the postalgorithm group, a 32.1% decrease in use of CT (P < .001). The mean injury severity score increased from 10.1 ± 9.1 (standard deviation) to 13.3 ± 11.9 after implementation of the algorithm in patients admitted for BAPT who underwent abdominopelvic CT examination (P < .001). The percentage of abdominopelvic CT examinations with BAPT-related findings increased from 17.1% (1007 of 5900) to 19.8% (479 of 2413) (P = .003). There was a significant difference in average length of stay, from 4.8 days ± 7.0 to 4.2 days ± 6.2 (P < .001). Mortality decreased from 3.1% (242 of 7688) to 2.7% (148 of 5408) after implementation of the algorithm (P = .19). Conclusion The implementation of a clinical triaging algorithm resulted in decreased use of multidetector CT in patients who presented with BAPT to the emergency department. © RSNA, 2016.


Asunto(s)
Traumatismos Abdominales/diagnóstico por imagen , Algoritmos , Tomografía Computarizada Multidetector , Triaje , Heridas no Penetrantes/diagnóstico por imagen , Traumatismos Abdominales/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Tiempo de Internación/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Centros Traumatológicos , Heridas no Penetrantes/mortalidad
17.
Proc Natl Acad Sci U S A ; 111(30): 10949-54, 2014 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-25028497

RESUMEN

In this paper, we systematically investigate three different routes of synthesizing 2% Na-doped PbTe after melting the elements: (i) quenching followed by hot-pressing (QH), (ii) annealing followed by hot-pressing, and (iii) quenching and annealing followed by hot-pressing. We found that the thermoelectric figure of merit, zT, strongly depends on the synthesis condition and that its value can be enhanced to ∼ 2.0 at 773 K by optimizing the size distribution of the nanostructures in the material. Based on our theoretical analysis on both electron and thermal transport, this zT enhancement is attributed to the reduction of both the lattice and electronic thermal conductivities; the smallest sizes (2 ∼ 6 nm) of nanostructures in the QH sample are responsible for effectively scattering the wide range of phonon wavelengths to minimize the lattice thermal conductivity to ∼ 0.5 W/m K. The reduced electronic thermal conductivity associated with the suppressed electrical conductivity by nanostructures also helped reduce the total thermal conductivity. In addition to the high zT of the QH sample, the mechanical hardness is higher than the other samples by a factor of around 2 due to the smaller grain sizes. Overall, this paper suggests a guideline on how to achieve high zT and mechanical strength of a thermoelectric material by controlling nano- and microstructures of the material.

18.
Soc Sci Res ; 64: 1-14, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28364837

RESUMEN

The initiative to increase the number of students in STEM disciplines and train them for a science-related job is a current national focus. Using longitudinal panel data from a national study that followed underrepresented college students in STEM fields, we investigate the neglected role that social psychological processes play in influencing science activity among the young. We study the impact of identity processes related to being a science student on entering a science occupation. More broadly, we examine whether an identity formulated in one institutional setting (education) has effects that persist to another institutional setting (the economy). We find that the science identity positively impacts the likelihood of entering a science occupation. It also serves as a mediator for other factors that are related to educational success. This provides insight into how an identity can guide behavior to move persons into structural positions across institutional domains.

19.
J Neurosci ; 35(2): 527-43, 2015 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-25589748

RESUMEN

In conscious mammals, hypoxia or hypercapnia stimulates breathing while theoretically exerting opposite effects on central respiratory chemoreceptors (CRCs). We tested this theory by examining how hypoxia and hypercapnia change the activity of the retrotrapezoid nucleus (RTN), a putative CRC and chemoreflex integrator. Archaerhodopsin-(Arch)-transduced RTN neurons were reversibly silenced by light in anesthetized rats. We bilaterally transduced RTN and nearby C1 neurons with Arch (PRSx8-ArchT-EYFP-LVV) and measured the cardiorespiratory consequences of Arch activation (10 s) in conscious rats during normoxia, hypoxia, or hyperoxia. RTN photoinhibition reduced breathing equally during non-REM sleep and quiet wake. Compared with normoxia, the breathing frequency reduction (Δf(R)) was larger in hyperoxia (65% FiO2), smaller in 15% FiO2, and absent in 12% FiO2. Tidal volume changes (ΔV(T)) followed the same trend. The effect of hypoxia on Δf(R) was not arousal-dependent but was reversed by reacidifying the blood (acetazolamide; 3% FiCO2). Δf(R) was highly correlated with arterial pH up to arterial pH (pHa) 7.5 with no frequency inhibition occurring above pHa 7.53. Blood pressure was minimally reduced suggesting that C1 neurons were very modestly inhibited. In conclusion, RTN neurons regulate eupneic breathing about equally during both sleep and wake. RTN neurons are the first putative CRCs demonstrably silenced by hypocapnic hypoxia in conscious mammals. RTN neurons are silent above pHa 7.5 and increasingly active below this value. During hyperoxia, RTN activation maintains breathing despite the inactivity of the carotid bodies. Finally, during hypocapnic hypoxia, carotid body stimulation increases breathing frequency via pathways that bypass RTN.


Asunto(s)
Alcalosis Respiratoria/fisiopatología , Células Quimiorreceptoras/fisiología , Hipoxia/metabolismo , Bulbo Raquídeo/fisiopatología , Alcalosis Respiratoria/metabolismo , Animales , Proteínas Arqueales/genética , Proteínas Arqueales/metabolismo , Presión Sanguínea , Dióxido de Carbono/sangre , Células Quimiorreceptoras/metabolismo , Hiperoxia/metabolismo , Hiperoxia/fisiopatología , Hipoxia/fisiopatología , Masculino , Bulbo Raquídeo/citología , Bulbo Raquídeo/metabolismo , Optogenética , Oxígeno/sangre , Ratas , Ratas Sprague-Dawley , Respiración , Fases del Sueño , Vigilia
20.
J Physiol ; 594(6): 1529-51, 2016 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-26748771

RESUMEN

We discuss recent evidence which suggests that the principal central respiratory chemoreceptors are located within the retrotrapezoid nucleus (RTN) and that RTN neurons are directly sensitive to [H(+) ]. RTN neurons are glutamatergic. In vitro, their activation by [H(+) ] requires expression of a proton-activated G protein-coupled receptor (GPR4) and a proton-modulated potassium channel (TASK-2) whose transcripts are undetectable in astrocytes and the rest of the lower brainstem respiratory network. The pH response of RTN neurons is modulated by surrounding astrocytes but genetic deletion of RTN neurons or deletion of both GPR4 and TASK-2 virtually eliminates the central respiratory chemoreflex. Thus, although this reflex is regulated by innumerable brain pathways, it seems to operate predominantly by modulating the discharge rate of RTN neurons, and the activation of RTN neurons by hypercapnia may ultimately derive from their intrinsic pH sensitivity. RTN neurons increase lung ventilation by stimulating multiple aspects of breathing simultaneously. They stimulate breathing about equally during quiet wake and non-rapid eye movement (REM) sleep, and to a lesser degree during REM sleep. The activity of RTN neurons is regulated by inhibitory feedback and by excitatory inputs, notably from the carotid bodies. The latter input operates during normo- or hypercapnia but fails to activate RTN neurons under hypocapnic conditions. RTN inhibition probably limits the degree of hyperventilation produced by hypocapnic hypoxia. RTN neurons are also activated by inputs from serotonergic neurons and hypothalamic neurons. The absence of RTN neurons probably underlies the sleep apnoea and lack of chemoreflex that characterize congenital central hypoventilation syndrome.


Asunto(s)
Células Quimiorreceptoras/metabolismo , Bulbo Raquídeo/fisiología , Protones , Respiración , Animales , Humanos , Bulbo Raquídeo/citología , Bulbo Raquídeo/metabolismo , Canales de Potasio de Dominio Poro en Tándem/genética , Canales de Potasio de Dominio Poro en Tándem/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Reflejo , Sueño REM
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