RESUMEN
OBJECTIVE: Based on US. Centers for Disease Control and Prevention recommendations, New York State enacted legislation in 2010 requiring healthcare providers to offer non-targeted human immunodeficiency virus (HIV) testing to all patients aged 13-64. Three New York City adult emergency departments implemented an electronic alert that required clinicians to document whether an HIV test was offered before discharging a patient. The purpose of this study was to assess the impact of the electronic alert on HIV testing rates and diagnosis of HIV positive individuals. METHODS: During the pre-intervention period (2.5-4 months), an electronic "HIV Testing" order set was available for clinicians to order a test or document a reason for not offering the test (e.g., patient is not conscious). An electronic alert was then added to enforce completion of the order set, effectively preventing ED discharge until an HIV test was offered to the patient. We analyzed data from 79,786 visits, measuring HIV testing and detection rates during the pre-intervention period and during the six months following the implementation of the alert. RESULTS: The percentage of visits where an HIV test was performed increased from 5.4% in the preintervention period to 8.7% (p<0.001) after the electronic alert. After the implementation of the electronic alert, there was a 61% increase in HIV tests performed per visit. However, the percentage of patients testing positive per total patients-tested was slightly lower in the post-intervention group than the pre-intervention group (0.48% vs. 0.55%), but this was not significant. The number of patients-testing positive per total-patient visit was higher in the post-intervention group (0.04% vs. 0.03%). CONCLUSIONS: An electronic alert which enforced non-targeted screening was effective at increasing HIV testing rates but did not significantly increase the detection of persons living with HIV. The impact of this electronic alert on healthcare costs and quality of care merits further examination.
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Serodiagnóstico del SIDA/métodos , Electrónica Médica , Servicio de Urgencia en Hospital , Infecciones por VIH/diagnóstico , Tamizaje Masivo/métodos , Adulto , Demografía , Femenino , Seropositividad para VIH/diagnóstico , Humanos , Masculino , Oportunidad RelativaRESUMEN
BACKGROUND: Mobile health (mHealth) is a growing field aimed at developing mobile information and communication technologies for healthcare. Adolescents are known for their ubiquitous use of mobile technologies in everyday life. However, the use of mHealth tools among adolescents is not well described. OBJECTIVE: We examined the usability of four commonly used mobile devices (an iPhone, an Android with touchscreen keyboard, an Android with built-in keyboard, and an iPad) for accessing healthcare information among a group of urban-dwelling adolescents. METHODS: Guided by the FITT (Fit between Individuals, Task, and Technology) framework, a thinkaloud protocol was combined with a questionnaire to describe usability on three dimensions: 1) task-technology fit; 2) individual-technology fit; and 3) individual-task fit. RESULTS: For task-technology fit, we compared the efficiency, and effectiveness of each of the devices tested and found that the iPhone was the most usable had the fewest errors and prompts and had the lowest mean overall task time For individual-task fit, we compared efficiency and learnability measures by website tasks and found no statistically significant effect on tasks steps, task time and number of errors. Following our comparison of success rates by website tasks, we compared the difference between two mobile applications which were used for diet tracking and found statistically significant effect on tasks steps, task time and number of errors. For individual-technology fit, interface quality was significantly different across devices indicating that this is an important factor to be considered in developing future mobile devices. CONCLUSIONS: All of our users were able to complete all of the tasks, however the time needed to complete the tasks was significantly different by mobile device and mHealth application. Future design of mobile technology and mHealth applications should place particular importance on interface quality.
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Computadoras de Mano/estadística & datos numéricos , Atención a la Salud/métodos , Atención a la Salud/estadística & datos numéricos , Sistemas de Información en Salud/instrumentación , Sistemas de Información en Salud/estadística & datos numéricos , Telemedicina/instrumentación , Telemedicina/estadística & datos numéricos , Adolescente , Ciudades , Femenino , Humanos , MasculinoRESUMEN
Pharyngeal obstruction in patients with obstructive sleep apnea (OSA) is thought to result from decreased upper airway muscle tone during sleep. The goal of the present study was to estimate the role of the tongue muscles in maintaining pharyngeal patency during sleep. Using non-invasive, sub-lingual surface electrical stimulation (ES), we measured tongue protrusion force during wakefulness and upper airway resistance during sleep in seven healthy subjects and six patients with OSA. During wakefulness, ES produced similar protrusion forces in healthy subjects and patients with OSA. ES of the anterior sublingual surface, causing preferential contraction of the genioglossus, resulted in smaller effects than combined ES of the anterior and lateral surface, which also stimulated tongue retractors. During sleep, trans-pharyngeal resistance decreased and peak inspiratory flow rate increased from 319+/-24 to 459+/-27 and from 58+/-16 to 270+/-35 ml/sec for healthy subjects and OSA patients, respectively (P<0.001). However, ES was usually unsuccessful in reopening the upper airway in the presence of complete apneas. We conclude that non-invasive ES of the tongue improves flow dynamics during sleep. Combined activation of tongue protrusors and retractors may have a beneficial mechanical effect. The magnitude of responses observed suggests that in addition to the stimulated muscles, other muscles and/or forces have a substantial impact on pharyngeal patency.
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Apnea Obstructiva del Sueño/fisiopatología , Sueño/fisiología , Lengua/fisiología , Vigilia/fisiología , Adulto , Estimulación Eléctrica , Humanos , Hipofaringe/fisiología , Persona de Mediana Edad , Suelo de la Boca/fisiología , Tono Muscular/fisiología , Polisomnografía , Mecánica RespiratoriaRESUMEN
The male predominance in obstructive sleep apnea (OSA) is currently poorly understood although differences in pharyngeal airway anatomy and physiology have been proposed. As the response to inspiratory resistive loading (IRL) provides important information on both airway collapsibility (mechanics) and ventilatory control, we compared this respiratory response in eight normal women and eight age and body mass index (BMI)-matched men, during stable nonrapid eye movement (NREM) sleep. Upper airway mechanics, ventilation, plus activation of two dilator muscles (genioglossus [GG] and tensor palatini [TP]) were monitored during basal breathing (BL), followed by four sequentially applied loads (5, 10, 15, 25 cm H(2)O/L/s) for three breaths each. Men developed more severe hypopnea in response to identical applied external loads than did women. At a resistance of 25 cm H(2)O/L/s, VT decreased by 26 +/- 1% in women compared with 44 +/- 1% in men (differences between sexes p < 0.05). Pharyngeal resistance (Rpha) in response to IRL increased significantly more in men than women (37.3 +/- 11.2 cm H(2)O/L/s in men at maximal load, compared with an increase of 6.6 +/- 3.9 cm H(2)O/L/s in women, p < 0.05). Men and women had near identical minute ventilation responses to total load (applied extrinsic plus measured intrinsic), implying no differences in central drive or load response. There were no significant increases in GG or TP activation in response to IRL in either sex. We conclude that normal men are more vulnerable to load-induced hypoventilation than women, due to increased upper airway collapse, which could not be explained by differences in dilator muscle activation. This implies a fundamental difference in the upper airway anatomy and/or tissue characteristics between the two sexes.
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Mecánica Respiratoria , Caracteres Sexuales , Sueño/fisiología , Adulto , Resistencia de las Vías Respiratorias , Electromiografía , Femenino , Humanos , Masculino , Músculos/fisiología , Cavidad Nasal/fisiología , Faringe/fisiología , Presión , Ventilación Pulmonar , Fases del Sueño/fisiologíaRESUMEN
We report a novel approach to the determination of sleep apnea based on measuring the peripheral circulatory responses in a primary condition of disordered breathing. The apparatus is a finger plethysmograph coupled to a constant volume, variable pressure, pneumatic system. The plethysmograph's tip (measurement site) is composed of two parallel opposing longitudinal half thimbles, which is attached to a contiguous annular cuff. Each compartment consists of an internal membrane surrounded by an outer rigid wall. These provide a uniform pressure field and impart a two-point locking action preventing axial and longitudinal motion of the finger. Subdiastolic pressure is applied to prevent venous pooling, engorgement, and stasis, to inhibit retrograde venous shock wave propagation and partially unload arterial wall tension. The annular cuff extends the effective boundary of the pressure field beyond the measuring site. In 42 patients with Obstructive Sleep Apnea Syndrome (OSAS) profound, transient vasoconstriction and tachycardia usually of a periodic nature, were clearly seen with each apneic event, possibly related to transient arousal. Good agreement was found between standard total apnea-hypopnea scoring, 129.5+/-22.4 (Mean +/- SEM), and transient vasoconstriction and tachycardia events, 121.2+/-19.4 (R = .92, p<.0001). We conclude that the finger tip exemplifies the scope of peripheral vascular responsiveness due to its high density of alpha sympathetic innervation, and its high degree of blood flow rate lability. Given that elevated peripheral resistance and tightly linked transient heart rate elevation is a consistent part of the hemodynamic response to arousal and OSAS, we believe that pulsatile finger blood flow patterns can be clearly diagnostic of OSAS and other sleep-disordered breathing conditions.
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Enfermedades Vasculares Periféricas/diagnóstico , Apnea Obstructiva del Sueño/diagnóstico , Constricción Patológica , Electroencefalografía , Electrooculografía , Frecuencia Cardíaca/fisiología , Humanos , Persona de Mediana Edad , Oximetría , Periodicidad , Enfermedades Vasculares Periféricas/complicaciones , Síndrome de las Piernas Inquietas/diagnóstico , Índice de Severidad de la Enfermedad , Apnea Obstructiva del Sueño/complicacionesRESUMEN
We identified a new, unique upstream activating sequence (5'-GGTGGCAAA-3') in the promoters of 26 out of the 32 proteasomal yeast genes characterized to date, which we propose to call proteasome-associated control element. By using the one-hybrid method, we show that the factor binding to the proteasome-associated control element is Rpn4p, a protein containing a C2H2-type finger motif and two acidic domains. Electrophoretic mobility shift assays using proteasome-associated control element sequences from two regulatory proteasomal genes confirmed specific binding of purified Rpn4p to these sequences. The role of Rpn4p to function as a transregulator in yeast is corroborated by its ability of stimulating proteasome-associated control element-driven lacZ expression and by experiments using the RPT4 and RPT6 gene promoters coupled to the bacterial cat gene as a reporter. Additionally, we found the proteasome-associated control element to occur in a number of promoters to genes which are related to the ubiquitin-proteasome pathway in yeast.
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Cisteína Endopeptidasas/genética , Proteínas de Unión al ADN/genética , Complejos Multienzimáticos/genética , Regiones Promotoras Genéticas , Proteínas de Saccharomyces cerevisiae , Factores de Transcripción/genética , Levaduras/enzimología , Secuencia de Aminoácidos , Sitios de Unión , Clonación Molecular , Proteínas de Unión al ADN/química , Regulación Fúngica de la Expresión Génica , Genes Fúngicos , Genes Reporteros , Datos de Secuencia Molecular , Oligodesoxirribonucleótidos/genética , Complejo de la Endopetidasa Proteasomal , Secuencias Reguladoras de Ácidos Nucleicos , Factores de Transcripción/química , Dedos de Zinc/genéticaRESUMEN
The c-Cbl protein is tyrosine phosphorylated and forms complexes with a wide range of signalling partners in response to various growth factors. How c-Cbl interacts with proteins, such as Grb2, phosphatidylinositol 3-kinase, and phosphorylated receptors, is well understood, but its role in these complexes is unclear. Recently, the Caenorhabditis elegans Cbl homolog, Sli-1, was shown to act as a negative regulator of epidermal growth factor receptor signalling. This finding forced a reassessment of the role of Cbl proteins and highlighted the desirability of testing genetically whether c-Cbl acts as a negative regulator of mammalian signalling. Here we investigate the role of c-Cbl in development and homeostasis in mice by targeted disruption of the c-Cbl locus. c-Cbl-deficient mice were viable, fertile, and outwardly normal in appearance. Bone development and remodelling also appeared normal in c-Cbl mutants, despite a previously reported requirement for c-Cbl in osteoclast function. However, consistent with a high level of expression of c-Cbl in the hemopoietic compartment, c-Cbl-deficient mice displayed marked changes in their hemopoietic profiles, including altered T-cell receptor expression, lymphoid hyperplasia, and primary splenic extramedullary hemopoiesis. The mammary fat pads of mutant female mice also showed increased ductal density and branching compared to those of their wild-type littermates, indicating an unanticipated role for c-Cbl in regulating mammary growth. Collectively, the hyperplastic histological changes seen in c-Cbl mutant mice are indicative of a normal role for c-Cbl in negatively regulating signalling events that control cell growth. Consistent with this view, we observed greatly increased intracellular protein tyrosine phosphorylation in thymocytes following CD3epsilon cross-linking. In particular, phosphorylation of ZAP-70 kinase in thymocytes was uncoupled from a requirement for CD4-mediated Lck activation. This study provides the first biochemical characterization of any organism that is deficient in a member of this unique protein family. Our findings demonstrate critical roles for c-Cbl in hemopoiesis and in controlling cellular proliferation and signalling by the Syk/ZAP-70 family of protein kinases.
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Linfocitos T CD4-Positivos/citología , Linfocitos T CD8-positivos/citología , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/fisiología , Transducción de Señal , Ubiquitina-Proteína Ligasas , Animales , Desarrollo Óseo , Remodelación Ósea , Complejo CD3/metabolismo , Relación CD4-CD8 , Femenino , Eliminación de Gen , Marcación de Gen , Hiperplasia , Masculino , Glándulas Mamarias Animales/citología , Ratones , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas c-cbl , Esplenomegalia , Timo/citología , Proteína Tirosina Quinasa ZAP-70RESUMEN
The upper airway dilator muscles (UADMs) represent a subgroup of muscles in the pharyngeal area which, in addition to their roles in mastication, vocalization, etc., also have an important respiratory function. Failure of these muscles to maintain upper airway patency during sleep is important in the development of the obstructive sleep apnoea syndrome. In the present study, we evaluated the histochemical properties of the UADMs and compared them to those of neighbouring muscles without respiratory functions, and to the diaphragm, to determine whether the UADMs are specifically adapted to their respiratory role. Our results, both in dogs and rats, indicate that the dilator and nondilator upper airway muscles are similar and differ from the diaphragm. In rats, there were significantly less type I fibres (<12% as compared to 42% for the diaphragm) and more type IIb fibres (39-67% as compared to 27% for the diaphragm). A similar pattern was seen in dogs: type I fibres <38% as compared to 46% for the diaphragm, and type IIb fibres, 29-35% as compared to 10% for the diaphragm. These findings suggest that the upper airway dilator muscles are not specifically designed for their respiratory role. They may fail in the presence of increased loads, often encountered in patients with obstructive sleep apnoea, unless appropriate adaptive structural changes take place.
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Histocitoquímica , Músculos Respiratorios/metabolismo , Síndromes de la Apnea del Sueño/metabolismo , Animales , Diafragma/metabolismo , Perros , Fibras Musculares de Contracción Rápida/metabolismo , Fibras Musculares de Contracción Lenta/metabolismo , Músculos/metabolismo , Músculos/fisiología , Faringe/metabolismo , Ratas , Ratas Wistar , Músculos Respiratorios/fisiología , Síndromes de la Apnea del Sueño/fisiopatología , Lengua/metabolismoRESUMEN
To evaluate the possibility that healthy offspring of patients with obstructive sleep apnea syndrome (OSAS) may have covert signs of sleep disordered breathing, we compared the respiratory response to inspiratory resistive loads (IRL) in 10 adult offspring of fathers previously diagnosed with OSAS with that of 14 offspring of healthy parents. None of the offspring in either group had any sign of OSAS, and groups were age, weight, and body mass index matched. Both ventilatory response to progressively increasing levels of IRL and the IRL required to produce severe hypopnea (tidal volume [V(T)] < 20% of unloaded magnitude) were determined, during NREM sleep. Offspring of patients with OSAS (OSAS offspring) responded to all levels of IRL with greater decreases in V(T). Their V(T) decreased in the second breath on IRL of 23 cm H2O/l/s by 39 +/- 10%, as compared with a decrease of 19 +/- 4% (mean +/- SD) in the control group (p < 0.05). Severe hypopnea occurred in the OSAS offspring in response to smaller IRL compared to controls (79 +/- 20 and 153 +/- 14 cm H2O/l/s, respectively, p < 0.005). Total upper airway occlusion in response to IRL occurred in three of the OSAS offspring, but in none of the controls. We conclude that apparently healthy offspring of patients with OSAS may inherit subtle defects that reduce their ability to compensate for increased loads and maintain upper airway patency during sleep. We speculate that offspring of OSAS patients with decreased tolerance to IRL may be prone to developing OSAS later on in life.
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Resistencia de las Vías Respiratorias , Síndromes de la Apnea del Sueño/genética , Sueño/fisiología , Adolescente , Adulto , Femenino , Humanos , Masculino , Polisomnografía , Respiración , Síndromes de la Apnea del Sueño/fisiopatologíaRESUMEN
Several surgical procedures have been developed for the treatment of sleep apnea syndrome. These include nasal, uvulopalatopharyngeal, and head and neck surgery, weight reduction surgery, and tracheostomy. Despite over 15 years of experience with some of these operations, there is still a lack of consensus regarding the indications, success rate, complications, and long-term prognosis associated with these procedures. The current status of these surgical procedures is reviewed.
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Síndromes de la Apnea del Sueño/cirugía , Adulto , Causalidad , Niño , Humanos , Obesidad/complicaciones , Procedimientos Quirúrgicos Ortognáticos , Hueso Paladar/cirugía , Faringe/cirugía , Síndromes de la Apnea del Sueño/etiología , Lengua/cirugía , TraqueostomíaRESUMEN
A new noninvasive measurement method providing rapid measurement of systemic arterial blood pressure (BP) and its validation is described. The method combines precisely timed electrocardiographic-gated rapid release of occluding counter-pressure (600 mmHg/s) with photoplethysmographic detection of radial artery filling to measure arterial opening pressure. A complete BP waveform is reconstructed from multiple repetitions of the measurement cycle at successively increasing time intervals relative to the electrocardiographic signal. Systolic and diastolic values can be measured within two to four cardiac cycles at the peak and trough of the BP wave. The new method was compared with sphygmomanometry in 26 randomly selected subjects over a sphygmomanometric pressure range of 53-110 (diastolic) and 100-190 mmHg (systolic). The mean pressure differences between the sphygmomanometric and new methods were -1.3 +/- 15.2 (SD) (systolic) and 0.7 +/- 9.9 mmHg (diastolic), and corresponding BP values measured by these methods were highly correlated [P < 0.001; R2 = 0.87 (systolic); R2 = 0.80 (diastolic)]. The new method was compared with sphygmomanometry and intra-arterial BP in six patients. These tests confirmed the method's validity compared with established methods. The new method was ostensibly immune to mechanical perturbations when tested during cycle ergometry at 60 W. The new method may facilitate the study of circulatory phenomena previously inaccessible by available noninvasive methods and minimizes patient discomfort and circulatory arrest at the measurement site.
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Determinación de la Presión Sanguínea/métodos , Fotopletismografía/métodos , Adulto , Anciano , Anciano de 80 o más Años , Algoritmos , Arterias/fisiología , Auscultación , Determinación de la Presión Sanguínea/instrumentación , Electrocardiografía , Femenino , Frecuencia Cardíaca/fisiología , Humanos , Masculino , Persona de Mediana Edad , Estimulación Luminosa , Fotopletismografía/instrumentaciónRESUMEN
The present study evaluated the mechanisms by which upper airway (UAW)-dilating muscle contraction, elicited by hypoglossus nerve (HGN) stimulation, improved UAW patency. Pressure-flow (P-V) relationships of the isolated UAW as well as the negative intraluminal pressures required to cause UAW collapse were assessed before and during electrical stimulation of the HGN in 8 anesthetized, ventilated dogs. Sectioning of the HGN shifted the P-V relationship to the left, while electrical stimulation resulted in a substantial shift of the curve to the right, indicating UAW dilatation. UAW resistance decreased from 9.0 +/- 1.5 to 0.3 +/- 0.1 cm H2O.1(-1).s during HGn stimulation (p < 0.01). The magnitude of negative intraluminal pressure at which UAW collapse occurred (the critical pressure) increased from -2.7 +/- 0.7 to -13.2 +/- 2.1 cm H2O (p < 0.002). The increase in UAW conductance and stability raised the maximal flow which could be sustained without collapse from 0.28 +/- 0.07 to 2.07 +/- 0.35 l/s during HGN stimulation (p < 0.001). These findings indicate that in the anesthetized dog, UAW muscle contraction improves UAW patency both by dilating the UAW and by stiffening its walls.
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Nervio Hipogloso/fisiología , Fenómenos Fisiológicos Respiratorios , Resistencia de las Vías Respiratorias , Animales , Perros , Estimulación Eléctrica , Técnicas In Vitro , Contracción Muscular , Presión , Ventilación PulmonarRESUMEN
There is current controversy as to whether electrical stimulation of upper airway musculature can be used us a beneficial treatment modality in patients with obstructive sleep apnoea syndrome. Increased upper airway (UAW) muscle activity decreases UAW resistance (Ruaw) in isolated UAW of dogs. In the present study, we evaluated the effect of UAW muscle contraction on UAW patency in anaesthetized dogs in vivo breathing spontaneously through partially and completely obstructed UAW. Airflow and supraglottic pressure were measured to obtain Ruaw. Ruaw could be regulated by inhalation of a rubber balloon implanted transcutaneously in the pharyngeal submucosa to produce partial or complete obstruction. Wire electrodes were implanted bilaterally into the genioglossus (GG), geniohyoid (GH), sternothyroid (ST), and sternohyoid (SH) muscles for electrical stimulation (ES), and into the alae nasi for electromyographic (EMG) recording. Three levels of electrical stimulation were delivered to each muscle before and during partial or complete UAW obstruction. Genioglossus and geniohyoid stimulation both resulted in a significant reduction in Ruaw, which was most pronounced during partial obstruction, reducing Ruaw from 54 +/- 11 to 14 +/- 3 and from 74 +/- 12 to 31 +/- 5 cmH2O.L-1.s, respectively. At low voltage, stimulation of the genioglossus was more effective than stimulation of the geniohyoid in reducing Ruaw. Furthermore, electrical stimulation of the genioglossus but not of the geniohyoid released total obstruction. In contrast, electrical stimulation of the sternohyoid and sternothyroid produced no significant change in Ruaw. These findings demonstrate that selective UAW dilatory muscle contraction in spontaneously breathing anaesthetized dogs reduces Ruaw in the presence of UAW obstruction and releases UAW occlusion, with the genioglossus being the most effective muscle. This favours further attempts to investigate the benefits of electrical stimulation of selected upper airway muscles in the treatment of obstructive sleep apnoea syndrome.
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Obstrucción de las Vías Aéreas , Resistencia de las Vías Respiratorias , Músculos Faríngeos/fisiología , Obstrucción de las Vías Aéreas/fisiopatología , Resistencia de las Vías Respiratorias/fisiología , Animales , Perros , Estimulación Eléctrica , Contracción Muscular , Músculos Faríngeos/inervación , Síndromes de la Apnea del Sueño/fisiopatología , Síndromes de la Apnea del Sueño/terapia , Volumen de Ventilación PulmonarRESUMEN
In the present study we examined the effect of flexion and extension of the head on upper airway (UAW) patency in anesthetized dogs, and compared the dilatory and stabilizing effects of electrically stimulated UAW muscles at the different head positions. Flexion of the head increased UAW resistance (Ruaw) and reduced maximal flow (Vmax), but had little effect on the negative pressure at which UAW collapse occurred (Pcrit). Extension of the head, on the other hand, resulted in more negative Pcrit values and increased Vmax without significantly affecting Ruaw. Electrically induced UAW muscle contraction affected the pressure-flow curve and Ruaw, as well as Pcrit. Changing head position had a substantial effect on the dilatory and stabilizing effect of the various UAW muscles. However, independent of head position, genioglossus stimulation was most effective in reducing Ruaw and increasing Pcrit. We conclude that in the anesthetized, supine dog, head position affects the mechanical properties of the UAW and the effects of UAW muscle contraction.
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Cabeza , Contracción Muscular/fisiología , Postura , Mecánica Respiratoria , Resistencia de las Vías Respiratorias , Animales , Perros , Estimulación Eléctrica , Ventilación Pulmonar , Músculos Respiratorios/fisiología , Posición SupinaRESUMEN
During sleep, diminished activity of upper airway dilator muscles (UADMs) is believed to increase upper airway (UAW) resistance and ultimately cause collapse of the UAW. In anesthetized dogs, electrically induced UADM contraction reduces UAW resistance and collapsibility. In this study, we measured the effects of electrically induced contraction of UADMs on pharyngeal resistance (Rph) in seven awake healthy subjects. UAW partial occlusion was achieved by applying external pressure to the submental hyoid region, leading to increased Rph. Transmucosal electrical stimulation (ES) of the base of the tongue was used to preferentially stimulate the genioglossus muscle. Transcutaneous ES using submental and paralaryngeal electrodes were used to preferentially stimulate the geniohyoid and the sternohyoid and sternothyroid muscles, respectively. During the unobstructed state, Rph averaged 6.11 +/- 0.48 cmH2O.l-1.s, and ES produced minimal resistance changes for all stimulation sites tested. In contrast, during the application of external pressure, when Rph was raised to an average of 190 +/- 14% of the baseline value, sublingual ES reduced resistance from 11.67 +/- 1.90 to 6.77 +/- 1.30 cmH2O.l-1.s (P < 0.01). ES at the other sites during the raised Rph state produced only minor statistically insignificant changes in Rph, even when combined submental and paralaryngeal ES was applied. Likewise, only sublingual ES produced measurable anterior movement of the tongue. We conclude that when Rph is raised by exogenous means, sublingual transmucosal ES effectively reduces Rph in awake humans.
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Resistencia de las Vías Respiratorias/fisiología , Músculos Respiratorios/fisiología , Adulto , Obstrucción de las Vías Aéreas/fisiopatología , Estimulación Eléctrica , Femenino , Humanos , Hueso Hioides/fisiología , Laringe/fisiología , Masculino , Contracción Muscular/fisiología , Faringe/fisiología , Lengua/fisiología , Vigilia/fisiologíaRESUMEN
The yeast gene, YTA10, encodes a member of a novel family of putative ATPases. Yta10p, as deduced from the nucleotide sequence, is 761 amino acids in length (predicted molecular mass 84.5 kDa). The amino acid sequence of Yta10p exhibits high similarity to two other yeast proteins, Yta11 and Yta12, and to E. coli FtsH. Several features of Yta10p are compatible with its localization in mitochondria. We report here that Yta10p is a yeast mitochondrial protein and that import is dependent on a membrane potential and accompanied by processing to a protein of approximately 73 kDa. Disruption of YTA10 leads to a nuclear petite phenotype and to a loss of respiratory competence, as shown by spectrophotometric measurement of the activities of respiratory complexes I-III and IV, respectively. These findings together with the high similarity of Yta10p to several ATP-dependent proteases suggest that Yta10p is a mitochondrial component involved, directly or indirectly, in the correct assembly and/or maintenance of active respiratory complexes.
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Adenosina Trifosfatasas , Proteínas Fúngicas/química , Mitocondrias/enzimología , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/enzimología , Secuencia de Aminoácidos , Secuencia de Bases , Proteínas Fúngicas/genética , Potenciales de la Membrana , Datos de Secuencia Molecular , Mutación , Fenotipo , Saccharomyces cerevisiae/genética , Homología de SecuenciaRESUMEN
There is accumulating evidence for a large, highly conserved gene family of putative ATPases. We have identified 12 different members of this novel gene family (the YTA family) in yeast and determined the nucleotide sequences of nine of these genes. All of the putative gene products are characterized by the presence of a highly conserved domain of 300 amino acids containing specialized forms of the A and B boxes of ATPases. YTA1, YTA2, YTA3 and YTA5 exhibit significant similarity to proteins involved in human immunodeficiency virus Tat-mediated gene expression but more significantly to subunits of the human 26S proteasome. YTA1 and YTA2 are essential genes in yeast. Remarkably, the cDNA of human TBP-1 can compensate for the loss of YTA1. Preliminary experiments indicate that YTA1 is a component of the 26S protease complex from yeast. Our findings lead us to propose that YTA1, YTA2, YTA3 and YTA5 function as regulatory subunits of the yeast 26S proteasome. YTA10, YTA11 and YTA12 share significant homology with the Escherichia coli FtsH protein, and together with YTA4 and YTA6 may constitute a separate subclass within this family of putative ATPases.
Asunto(s)
Adenosina Trifosfatasas/genética , Genes Fúngicos , Metaloendopeptidasas , Proteínas de Saccharomyces cerevisiae , Levaduras/enzimología , Levaduras/genética , Alelos , Secuencia de Aminoácidos , Proteínas Bacterianas/genética , Secuencia de Bases , Muerte Celular/genética , Secuencia de Consenso , Cósmidos/genética , ADN Complementario , Proteínas de Unión al ADN/genética , Endopeptidasas/genética , Escherichia coli/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Regulación Fúngica de la Expresión Génica , Biblioteca de Genes , Productos del Gen tat/química , Productos del Gen tat/genética , Humanos , Proteínas Mitocondriales , Datos de Secuencia Molecular , Fenotipo , Reacción en Cadena de la Polimerasa , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
The activation of upper airway (UAW) muscles is believed to increase UAW patency to air flow. To evaluate the mechanisms by which UAW muscles act to prevent UAW collapse, pressure-flow relationships of the isolated UAW as well as the negative pressure required to cause UAW collapse (Pcrit) were assessed before and during electrical stimulation of four UAW muscle pairs in anesthetized dogs. Stimulation of each of the muscles shifted the pressure-flow curve toward lower pressures for any given flow rate, indicating UAW dilatation. UAW resistance decreased from 7.9 +/- 0.6 to 0.4 +/- 0.1, 2.7 +/- 0.6, 2.3 +/- 0.8 and to 4.8 +/- 1.5 cmH2O.L-1.sec during genioglossus, geniohyoid, sternothyroid and sternohyoid stimulation respectively (P < 0.01 in all cases). However, only genioglossus stimulation significantly increased Pcrit (from -3.4 +/- 0.6 to -12.0 +/- 1.8 cmH2O, P < 0.001). Relaxation of the genioglossus thus appears to produce the main impediment to air flow through the UAW, and contraction of this muscle improves UAW patency both by dilating the supraglottic airway and by stiffening its walls.