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1.
Am J Transplant ; 21 Suppl 2: 21-137, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33595191

RESUMEN

Despite the ongoing severe shortage of available kidney grafts relative to candidates in need, data from 2019 reveal some promising trends. After remaining relatively stagnant for many years, the number of kidney transplants has increased each year since 2015, reaching the highest annual count to date of 24,273 in 2019. The number of patients waiting for a kidney transplant in the United States was relatively stable, despite an increase in the number of new candidates added in 2019 and a decrease in patients removed from the waiting list owing to death or deteriorating medical condition. However, these encouraging trends are tempered by ongoing challenges. Nationwide, only a quarter of waitlisted patients receive a deceased-donor kidney transplant within 5 years, and this proportion varies dramatically by donation service area, from 15.5% to 67.8%. The non-utilization (discard) rate of recovered organs remains at 20.1%, despite adramatic decline in the discard of organs from hepatitis C-positive donors. Non-utilization rates remain particularly high for Kidney Donor Profile Index ≥85% kidneys and kidneys from which a biopsy specimen was obtained. While the number of living-donor transplants increased again in 2019, only a small proportion of the waiting list receives living-donor transplants each year, and racial disparities in living-donor transplant access persist. As both graft and patient survival continue to improve incrementally, the total number of living kidney transplant recipients with a functioning graft is anticipated to exceed 250,000 in the next 1-2 years. Over the past decade, the total number of pediatric kidney transplants performed has remained stable. Despite numerous efforts, living donor kidney transplant remains low among pediatric recipients with continued racial disparities among recipients. Congenital anomalies of the kidney and urinary tract remain the leading cause of kidney disease. While most deceased donor recipients receive a kidney from a donor with KDPI less than 35%, the majority of pediatric recipients had four or more HLA mismatches. Graft survival continues to improve with superior outcomes for living donor recipients.


Asunto(s)
Trasplante de Riñón , Obtención de Tejidos y Órganos , Niño , Supervivencia de Injerto , Humanos , Riñón , Donadores Vivos , Sistema de Registros , Donantes de Tejidos , Estados Unidos/epidemiología , Listas de Espera
2.
BJOG ; 128(12): 2046-2053, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34013655

RESUMEN

OBJECTIVE: To determine whether all three components of the levator ani muscle (pubovisceral [= pubococcygeal], puborectal and iliococcygeal) and the external anal sphincter are equally affected by oedema associated with muscle injury after vaginal birth. DESIGN: Observational cross-sectional study. SETTING: Michigan Medicine, University of Michigan. POPULATION: Primiparous women classified as high risk for levator ani muscle injury during childbirth. METHOD: MRI scans obtained 6-8 weeks postpartum were analysed. Muscle oedema was assessed on axial and coronal fluid-sensitive magnetic resonance (MRI) scans. Presence of oedema was separately determined in each levator ani muscle component and in the external anal sphincter for all subjects. Descriptive statistics and correlation with obstetric variables were obtained. MAIN OUTCOME MEASURES: Oedema score on fluid-sensitive MRI scans. RESULTS: Of the 78 women included in this cohort, 51.3% (n = 40/78) showed muscle oedema in the pubovisceral (one bilateral avulsion excluded), 5.1% (n = 4/78) in the puborectal and 5.1% (n = 4/78) in the iliococcygeal muscle. No subject showed definite oedema on external anal sphincter. Incidence of oedema on the pubovisceral muscle was seven times higher than on any of the other analysed muscles (all paired comparisons, P < 0.001). CONCLUSIONS: Even in the absence of muscle tearing, the pubovisceral muscle shows by far the highest incidence of injury, establishing that levator components are not equally affected by childbirth. External anal sphincter did not show oedema-even in women with sphincter laceration- suggesting a different injury mechanism. Developing a databased map of injured areas helps understand injury mechanisms that can guide us in honing research on treatment and prevention. TWEETABLE ABSTRACT: Injury-associated levator ani muscle and anal sphincter oedema mapping on MRI reveals vulnerable muscle components after childbirth.


Asunto(s)
Canal Anal/lesiones , Edema/patología , Complicaciones del Trabajo de Parto/patología , Trastornos del Suelo Pélvico/patología , Diafragma Pélvico/lesiones , Adulto , Canal Anal/diagnóstico por imagen , Canal Anal/patología , Estudios Transversales , Parto Obstétrico/efectos adversos , Parto Obstétrico/métodos , Edema/diagnóstico por imagen , Edema/etiología , Femenino , Humanos , Laceraciones , Imagen por Resonancia Magnética , Parto , Diafragma Pélvico/diagnóstico por imagen , Diafragma Pélvico/patología , Trastornos del Suelo Pélvico/diagnóstico por imagen , Trastornos del Suelo Pélvico/etiología , Periodo Posparto , Embarazo
3.
Nature ; 507(7491): 207-9, 2014 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-24598545

RESUMEN

The co-evolution of a supermassive black hole with its host galaxy through cosmic time is encoded in its spin. At z > 2, supermassive black holes are thought to grow mostly by merger-driven accretion leading to high spin. It is not known, however, whether below z ≈ 1 these black holes continue to grow by coherent accretion or in a chaotic manner, though clear differences are predicted in their spin evolution. An established method of measuring the spin of black holes is through the study of relativistic reflection features from the inner accretion disk. Owing to their greater distances from Earth, there has hitherto been no significant detection of relativistic reflection features in a moderate-redshift quasar. Here we report an analysis of archival X-ray data together with a deep observation of a gravitationally lensed quasar at z = 0.658. The emission originates within three or fewer gravitational radii from the black hole, implying a spin parameter (a measure of how fast the black hole is rotating) of a = 0.87(+0.08)(-0.15) at the 3σ confidence level and a > 0.66 at the 5σ level. The high spin found here is indicative of growth by coherent accretion for this black hole, and suggests that black-hole growth at 0.5 ≤ z ≤ 1 occurs principally by coherent rather than chaotic accretion episodes.

4.
Nature ; 514(7521): 202-4, 2014 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-25297433

RESUMEN

The majority of ultraluminous X-ray sources are point sources that are spatially offset from the nuclei of nearby galaxies and whose X-ray luminosities exceed the theoretical maximum for spherical infall (the Eddington limit) onto stellar-mass black holes. Their X-ray luminosities in the 0.5-10 kiloelectronvolt energy band range from 10(39) to 10(41) ergs per second. Because higher masses imply less extreme ratios of the luminosity to the isotropic Eddington limit, theoretical models have focused on black hole rather than neutron star systems. The most challenging sources to explain are those at the luminous end of the range (more than 10(40) ergs per second), which require black hole masses of 50-100 times the solar value or significant departures from the standard thin disk accretion that powers bright Galactic X-ray binaries, or both. Here we report broadband X-ray observations of the nuclear region of the galaxy M82 that reveal pulsations with an average period of 1.37 seconds and a 2.5-day sinusoidal modulation. The pulsations result from the rotation of a magnetized neutron star, and the modulation arises from its binary orbit. The pulsed flux alone corresponds to an X-ray luminosity in the 3-30 kiloelectronvolt range of 4.9 × 10(39) ergs per second. The pulsating source is spatially coincident with a variable source that can reach an X-ray luminosity in the 0.3-10 kiloelectronvolt range of 1.8 × 10(40) ergs per second. This association implies a luminosity of about 100 times the Eddington limit for a 1.4-solar-mass object, or more than ten times brighter than any known accreting pulsar. This implies that neutron stars may not be rare in the ultraluminous X-ray population, and it challenges physical models for the accretion of matter onto magnetized compact objects.

5.
Afr Archaeol Rev ; 37(2): 271-292, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32684659

RESUMEN

The Iringa Region is famous among archaeologists for the Acheulean site of Isimila, and among historians as the stronghold where Chief Mkwawa led the Hehe resistance against German colonial forces. However, our research reveals that Iringa has a rich archaeological record that spans the period from the Stone Age into the recent past. This article summarizes the results of 14 years of research by our team, the Iringa Region Archaeological Project (IRAP). Since 2006, IRAP members have recorded 67 sites, and this only scratches the surface of the archaeological potential in the area. These sites, some of which were recorded in conjunction with local participants, have archaeological component characteristic of the Early, Middle, and Later Stone Age, the Iron Age, and the recent past. We consider the archaeological and historical value of Iringa to be high and hope that this work inspires future research, tourism, and conservation efforts in the area.


La région d'Iringa en Tanzanie est. reconnue par les archéologues pour le site acheuléen d'Isimila et parmi les historiens comme le fief où le chef Mkwawa a dirigé la résistance du Hehe contre les forces coloniales allemandes. Cependant, nos recherches révèlent qu'Iringa possède de riches archives archéologiques allant de l'âge de pierre au passé récent. Cet article résume les résultats de quatorze années de recherche de notre équipe, le projet archéologique de la région d'Iringa (PARI). Depuis 2006, les membres du PARI ont enregistré 67 sites, ce qui ne fait qu'effleurer la surface du potentiel archéologique de la région. Les sites identifiés présentent des éléments archéologiques caractéristiques de l'âge de pierre précoce, moyen et postérieur, de l'âge du fer, et du passé historique. En outre, un certain nombre de sites culturels importants ont été enregistrés en collaboration avec des participants locaux. Nous considérons que la valeur archéologique et historique d'Iringa est. élevée et espérons que ces travaux inspireront la recherche, le tourisme et la conservation dans cette région importante.

6.
Synapse ; 73(6): e22089, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30693567

RESUMEN

OBJECTIVE: We have previously reported higher brain serotonin 1A (5-HT1A ) autoreceptor binding in antidepressant-naïve patients with Major Depressive Disorder (MDD) compared with healthy volunteers, and a decrease in binding in MDD after selective serotonin reuptake inhibitor (SSRI) treatment. This SSRI effect is also present in rodents administered SSRIs chronically. We therefore sought to determine the duration of antidepressant medication effects on 5-HT1A receptor binding after medication discontinuation. METHODS: Positron emission tomography (PET) imaging with the 5-HT1A receptor radioligand [11 C]WAY-100635 was performed in 66 individuals with current DSM-IV MDD to examine relationships between 5-HT1A binding and time since most recent antidepressant treatment. All subjects were medication-free for at least 2 weeks prior to scanning. Thirty-two additional MDD comparison subjects were antidepressant naïve. RESULTS: No differences in [11 C]WAY-100635 binding were observed between antidepressant naïve and antidepressant exposed MDD groups in 13 a priori cortical and subcortical regions of interest, including raphe autoreceptors, assessed simultaneously in linear mixed effects models. Furthermore, [11 C]WAY-100635 binding did not correlate with time off antidepressants in the antidepressant exposed patients considering these ROIs. The same results were observed when effects of treatment discontinuation of any psychotropic medication used to treat their depression was examined. CONCLUSION: These results indicate that any antidepressant-associated downregulation of 5-HT1A autoreceptor binding reverses within 2 weeks of medication discontinuation. Since this effect is hypothesized to mediate the antidepressant action of SSRIs, and perhaps other antidepressants, it suggests that patients who need ongoing treatment may relapse rapidly when medication is discontinued. Moreover, 2 weeks appears to be a sufficiently long washout of antidepressant medications for a reliable measure of illness-related binding levels.


Asunto(s)
Antidepresivos/administración & dosificación , Trastorno Depresivo Mayor/metabolismo , Piperazinas/farmacocinética , Piridinas/farmacocinética , Receptor de Serotonina 5-HT1A/metabolismo , Inhibidores Selectivos de la Recaptación de Serotonina/administración & dosificación , Antagonistas del Receptor de Serotonina 5-HT1/farmacocinética , Adulto , Antidepresivos/uso terapéutico , Radioisótopos de Carbono , Trastorno Depresivo Mayor/diagnóstico por imagen , Trastorno Depresivo Mayor/tratamiento farmacológico , Esquema de Medicación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía de Emisión de Positrones , Unión Proteica , Radiofármacos/farmacocinética , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico
7.
Afr Archaeol Rev ; 34(2): 275-295, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-32025077

RESUMEN

The Mlambalasi rockshelter in the Iringa Region of southern Tanzania has rich artifactual deposits spanning the Later Stone Age (LSA), Iron Age, and historic periods. Middle Stone Age (MSA) artifacts are also present on the slope in front of the rockshelter. Extensive, systematic excavations in 2006 and 2010 by members of the Iringa Region Archaeological Project (IRAP) illustrate a complex picture of repeated occupations and reuse of the rockshelter during an important time in human history. Direct dates on Achatina shell and ostrich eggshell (OES) beads suggest that the earliest occupation levels excavated at Mlambalasi, which are associated with human burials, are terminal Pleistocene in age. This is exceptional given the rarity of archaeological sites, particularly those with human remains and other preserved organic material, from subtropical Africa between 200,000 and 10,000 years before present. This paper reports on the excavations to date and analysis of artifactual finds from the site. The emerging picture is one of varied, ephemeral use over millennia as diverse human groups were repeatedly attracted to this fixed feature on the landscape.


L'abri sous roche Mlambalasi dans la région d'Iringa au sud de la Tanzanie est riche en artéfacts du Paléolithique supérieur jusqu'à l'âge du fer et la période historique. Des artéfacts du Paléolithique moyen sont présents sur le versant en face de l'abri. Des fouilles extensives et systématiques réalisées par l'équipe d'Iringa Region Archaeological Project (IRAP) révèlent une image complexe de l'utilisation et de la réutilisation de l'abri sous roche pendant un moment important dans l'histoire de l'humanité. Des datations directes de coquilles d'Achatina et de perles en coquilles d'autruches (OES) suggèrent que l'occupation la plus ancienne excavée à Mlambalasi, associée aux sépultures humaines, parvient d'une phase terminale du Pléistocène. Ceci est exceptionnel car les sites archéologiques, en particulier contenant des corps humains et d'autres matières organiques préservées, sont rares en Afrique subtropicale entre 200,000-10,000 années avant le présent. Cet article présente les fouilles effectuées jusqu'à ce jour ainsi que l'analyse des artéfacts trouvés sur le site. L'image qui ressort est celle d'une utilisation variée et éphémère à travers les millénaires au fur et à mesure que divers groupes ont été attirés à cet endroit permanent dans le paysage.

8.
Nature ; 459(7246): 540-2, 2009 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-19478778

RESUMEN

Since the 1995 discovery of the broad iron K-line emission from the Seyfert galaxy MCG-6-30-15 (ref. 1), broad iron K lines have been found in emission from several other Seyfert galaxies, from accreting stellar-mass black holes and even from accreting neutron stars. The iron K line is prominent in the reflection spectrum created by the hard-X-ray continuum irradiating dense accreting matter. Relativistic distortion of the line makes it sensitive to the strong gravity and spin of the black hole. The accompanying iron L-line emission should be detectable when the iron abundance is high. Here we report the presence of both iron K and iron L emission in the spectrum of the narrow-line Seyfert 1 galaxy 1H 0707-495. The bright iron L emission has enabled us to detect a reverberation lag of about 30 s between the direct X-ray continuum and its reflection from matter falling into the black hole. The observed reverberation timescale is comparable to the light-crossing time of the innermost radii around a supermassive black hole. The combination of spectral and timing data on 1H 0707-495 provides strong evidence that we are witnessing emission from matter within a gravitational radius, or a fraction of a light minute, from the event horizon of a rapidly spinning, massive black hole.


Asunto(s)
Medio Ambiente Extraterrestre/química , Hierro/análisis , Hierro/química
9.
Heredity (Edinb) ; 112(3): 240-7, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24149650

RESUMEN

Heterozygosity-fitness correlations (HFCs) are often used to link individual genetic variation to differences in fitness. However, most studies examining HFCs find weak or no correlations. Here, we derive broad theoretical predictions about how many loci are needed to adequately measure genomic heterozygosity assuming different levels of identity disequilibrium (ID), a proxy for inbreeding. We then evaluate the expected ability to detect HFCs using an empirical data set of 200 microsatellites and 412 single nucleotide polymorphisms (SNPs) genotyped in two populations of bighorn sheep (Ovis canadensis), with different demographic histories. In both populations, heterozygosity was significantly correlated across marker types, although the strength of the correlation was weaker in a native population compared with one founded via translocation and later supplemented with additional individuals. Despite being bi-allelic, SNPs had similar correlations to genome-wide heterozygosity as microsatellites in both populations. For both marker types, this association became stronger and less variable as more markers were considered. Both populations had significant levels of ID; however, estimates were an order of magnitude lower in the native population. As with heterozygosity, SNPs performed similarly to microsatellites, and precision and accuracy of the estimates of ID increased as more loci were considered. Although dependent on the demographic history of the population considered, these results illustrate that genome-wide heterozygosity, and therefore HFCs, are best measured by a large number of markers, a feat now more realistically accomplished with SNPs than microsatellites.


Asunto(s)
Genoma , Heterocigoto , Modelos Genéticos , Polimorfismo de Nucleótido Simple , Borrego Cimarrón/genética , Alberta , Animales , Aptitud Genética , Genética de Población , Endogamia , Repeticiones de Microsatélite , Montana
10.
Clin Radiol ; 69(10): 1045-9, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25037148

RESUMEN

AIM: To investigate whether embolization prior to cryoablation would decrease morbidity without negative effects on tissue pathology, renal function, or recurrence. MATERIAL AND METHODS: The electronic medical records of all patients undergoing cryoablation for renal cell carcinomas were reviewed for lesion size, pre-ablative renal function, post-ablative renal function, post-ablative complications, recurrence, and quality of biopsy specimen. Comparisons were made between patients who underwent cryoablation (the Cryo-Only group) and those who underwent cryoablation after same-day coil embolization of their lesion (the Cryo-Embo group). Further comparison was made between the Cryo-Embo lesions and the subset of larger Cryo-Only lesions (≥ 3 cm), which were expected to have a higher natural complication rate. RESULTS: A total of 21 lesions in 19 patients were treated by percutaneous cryoablation (17 Cryo-Only, four Cryo-Embo). Complications were seen in 83% of the large Cryo-Only lesions (average size 3.6 cm), whereas no complication was seen amongst Cryo-Embo lesions (average size 4 cm). Embolization significantly decreased complications between size-matched lesions (p = 0.048) without impacting renal function (p = 1), biopsy quality (p = 1), or recurrence (p = 1). CONCLUSION: Performance of trans-arterial embolization prior to cryoablation of large renal cell carcinomas significantly decreases complications, such as haemorrhage, without a discernible effect on biopsy quality, renal function, or recurrence rate.


Asunto(s)
Carcinoma de Células Renales/terapia , Criocirugía/métodos , Embolización Terapéutica/métodos , Neoplasias Renales/terapia , Complicaciones Posoperatorias/prevención & control , Anciano , Carcinoma de Células Renales/cirugía , Criocirugía/efectos adversos , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Renales/cirugía , Masculino , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del Tratamiento
11.
Science ; 380(6649): 1030-1033, 2023 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-37289889

RESUMEN

Linear optical quantum computing provides a desirable approach to quantum computing, with only a short list of required computational elements. The similarity between photons and phonons points to the interesting potential for linear mechanical quantum computing using phonons in place of photons. Although single-phonon sources and detectors have been demonstrated, a phononic beam splitter element remains an outstanding requirement. Here we demonstrate such an element, using two superconducting qubits to fully characterize a beam splitter with single phonons. We further use the beam splitter to demonstrate two-phonon interference, a requirement for two-qubit gates in linear computing. This advances a new solid-state system for implementing linear quantum computing, further providing straightforward conversion between itinerant phonons and superconducting qubits.

12.
Mol Ecol ; 21(7): 1583-96, 2012 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-22257293

RESUMEN

Genetic rescue is a management intervention whereby a small population is supplemented with individuals from other populations in an attempt to reverse the effects of inbreeding and increased genetic load. One such rescue was recently documented in the population of bighorn sheep (Ovis canadensis) within the National Bison Range wildlife refuge (Montana, USA). Here, we examine the locus-specific effects of rescue in this population using a newly developed genome-wide set of 195 microsatellite loci and first-generation linkage map. We found that the rate of introgression varied among loci and that 111 loci, 57% of those examined, deviated from patterns of neutral inheritance. The most common deviation was an excess of homozygous genotypes relative to neutral expectations, indicative of directional selection. As in previous study of this rescue, individuals with more introduced alleles had higher reproductive success and longevity. In addition, we found 30 loci, distributed throughout the genome, which seem to have individual effects on these life history traits. Although the potential for outbreeding depression is a major concern when translocating individuals between populations, we found no evidence of such effects in this population.


Asunto(s)
Conservación de los Recursos Naturales/métodos , Endogamia , Borrego Cimarrón/genética , Alelos , Animales , Mapeo Cromosómico , Femenino , Aptitud Genética , Ligamiento Genético , Genotipo , Patrón de Herencia , Masculino , Repeticiones de Microsatélite , Montana , Selección Genética
13.
J Nucl Cardiol ; 19(5): 922-30, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22814771

RESUMEN

BACKGROUND: Semi-quantitative stenosis assessment by coronary CT angiography only modestly predicts stress-induced myocardial perfusion abnormalities. The performance of quantitative CT angiography (QCTA) for identifying patients with myocardial perfusion defects remains unclear. METHODS: CorE-64 is a multicenter, international study to assess the accuracy of 64-slice QCTA for detecting ≥50% coronary arterial stenoses by quantitative coronary angiography (QCA). Patients referred for cardiac catheterization with suspected or known coronary artery disease were enrolled. Area under the receiver-operating-characteristic curve (AUC) was used to evaluate the diagnostic accuracy of the most severe coronary artery stenosis in a subset of 63 patients assessed by QCTA and QCA for detecting myocardial perfusion abnormalities on exercise or pharmacologic stress SPECT. RESULTS: Diagnostic accuracy of QCTA for identifying patients with myocardial perfusion abnormalities by SPECT revealed an AUC of 0.71, compared to 0.72 by QCA (P = .75). AUC did not improve after excluding studies with fixed myocardial perfusion abnormalities and total coronary arterial occlusions. Optimal stenosis threshold for QCTA was 43% yielding a sensitivity of 0.81 and specificity of 0.50, respectively, compared to 0.75 and 0.69 by QCA at a threshold of 59%. Sensitivity and specificity of QCTA to identify patients with both obstructive lesions and myocardial perfusion defects were 0.94 and 0.77, respectively. CONCLUSIONS: Coronary artery stenosis assessment by QCTA or QCA only modestly predicts the presence and the absence of myocardial perfusion abnormalities by SPECT. Confounding variables affecting the relationship between coronary anatomy and myocardial perfusion likely account for some of the observed discrepancies between coronary angiography and SPECT results.


Asunto(s)
Angiografía Coronaria/métodos , Circulación Coronaria , Estenosis Coronaria/diagnóstico por imagen , Tomografía Computarizada Multidetector/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Tomografía Computarizada de Emisión de Fotón Único
15.
Nat Med ; 6(12): 1395-8, 2000 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-11100126

RESUMEN

Modern treatment of cardiac arrhythmias is limited to pharmacotherapy, radiofrequency ablation, or implantable devices. Antiarrhythmic medications suppress arrhythmias, but their systemic effects are often poorly tolerated and their proarrhythmic tendencies increase mortality. Radiofrequency ablation can cure only a limited number of arrhythmias. Implantable devices can be curative for bradyarrhythmias and lifesaving for tachyarrhythmias, but require a lifetime commitment to repeated procedures, are a significant expense, and may lead to severe complications. One possibility is the use of gene therapy as an antiarrhythmic strategy. As an initial attempt to explore this option, we focused on genetic modification of the atrioventricular node. First, we developed an intracoronary perfusion model for gene delivery, building on our previous work in isolated cardiac myocytes and hearts perfused ex vivo. Using this method, we infected porcine hearts with Adbetagal (recombinant adenovirus expressing Escherichia coli beta-galactosidase) or with AdGi (adenovirus encoding the Galphai2 subunit). We hypothesized that excess Galphai2 would mimic the effects of beta-adreneric antagonists, in effect creating a localized beta-blockade. Galphai2 overexpression suppressed baseline atrioventricular conduction and slowed the heart rate during atrial fibrillation without producing complete heart block. In contrast, expression of the reporter gene beta-galactosidase had no electrophysiological effects. Our results demonstrate the feasibility of using myocardial gene transfer strategies to treat common arrhythmias.


Asunto(s)
Arritmias Cardíacas/terapia , Nodo Atrioventricular/fisiología , Subunidades alfa de la Proteína de Unión al GTP Gi-Go/genética , Terapia Genética/métodos , Proteínas Proto-Oncogénicas/genética , Adenoviridae/genética , Animales , Fibrilación Atrial , Conductividad Eléctrica , Electrofisiología , Subunidad alfa de la Proteína de Unión al GTP Gi2 , Vectores Genéticos/genética , Frecuencia Cardíaca , Porcinos , Transformación Genética
16.
Noise Health ; 13(55): 432-43, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22122960

RESUMEN

Noise-induced hearing loss (NIHL) is a significant clinical, social, and economic issue. The development of novel therapeutic agents to reduce NIHL will potentially benefit multiple very large noise-exposed populations. Oxidative stress has been identified as a significant contributor to noise-induced sensory cell death and NIHL, and several antioxidant strategies have now been suggested for potential translation to human subjects. One such strategy is a combination of beta-carotene, vitamins C and E, and magnesium, which has shown promise for protection against NIHL in rodent models, and is being evaluated in a series of international human clinical trials using temporary (military gunfire, audio player use) and permanent (stamping factory, military airbase) threshold shift models (NCT00808470). The noise exposures used in the recently completed Swedish military gunfire study described in this report did not, on average, result in measurable changes in auditory function using conventional pure-tone thresholds and distortion product otoacoustic emission (DPOAE) amplitudes as metrics. However, analysis of the plasma samples confirmed significant elevations in the bloodstream 2 hours after oral consumption of active clinical supplies, indicating the dose is realistic. The plasma outcomes are encouraging, but clinical acceptance of any novel therapeutic critically depends on demonstration that the agent reduces noise-induced threshold shift in randomized, placebo-controlled, prospective human clinical trials. Although this noise insult did not induce hearing loss, the trial design and study protocol can be applied to other populations exposed to different noise insults.


Asunto(s)
Pérdida Auditiva Provocada por Ruido/prevención & control , Micronutrientes/administración & dosificación , Personal Militar , Estrés Oxidativo/efectos de los fármacos , Adulto , Ácido Ascórbico/administración & dosificación , Ácido Ascórbico/sangre , Ácido Ascórbico/fisiología , Audiometría de Tonos Puros , Estudios Cruzados , Femenino , Pérdida Auditiva Provocada por Ruido/sangre , Pérdida Auditiva Provocada por Ruido/fisiopatología , Humanos , Magnesio/administración & dosificación , Magnesio/sangre , Magnesio/fisiología , Masculino , Micronutrientes/sangre , Micronutrientes/fisiología , Emisiones Otoacústicas Espontáneas/efectos de los fármacos , Emisiones Otoacústicas Espontáneas/fisiología , Estrés Oxidativo/fisiología , Suecia , Vitamina E/administración & dosificación , Vitamina E/sangre , Vitamina E/fisiología , Adulto Joven , beta Caroteno/administración & dosificación , beta Caroteno/sangre , beta Caroteno/fisiología
17.
Neurourol Urodyn ; 29(5): 734-40, 2010 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-19816917

RESUMEN

AIMS: To explore variance in reporting continence information obtained by telephone survey with face-to-face clinician interview in a clinical setting. METHODS: As part of a cross-sectional, epidemiologic study of incontinence prevalence among Black and White women aged 35-64 years, randomly selected households were contacted from geographic areas of known racial composition. Of 2,814 women who completed a 20-min, 137-item telephone interview, 1,702 were invited for future components of the study. A subset of these women was recruited for a clinical evaluation that was conducted within a mean of 82 days (SD 38 days) following the interviews. Prior to urodynamics testing, a clinician interview was conducted inquiring about continence status. The criterion for incontinence for both the telephone interview and the clinician interview was constant: 12 or more episodes of incontinence per year. Women whose subjective reports of continence information differed between telephone and clinician interviews were designated as "switchers." RESULTS: Of the 394 women (222 Black and 172 White) who completed the clinical portion, 24.6% (n = 97) were switchers. Switchers were four times more likely to change from continent to incontinent (80.4%, N = 78) than from incontinent to continent (19.4%, N = 19; P = 0.000) and nearly three times more likely to be Black (69%, N = 67) than White (31%, N = 30; P = 0.001). Telephone qualitative interviews were completed with 72 of the switchers. The primary reason for switching was changes in women's life circumstances such as variation in seasons, activities of daily living, and health status followed by increased awareness of leakage secondary to the phone interview. CONCLUSION: One-time subjective telephone interviews assessing incontinence symptoms may underestimate the prevalence of incontinence especially among Black women.


Asunto(s)
Autoevaluación (Psicología) , Incontinencia Urinaria/diagnóstico , Adulto , Estudios Transversales , Femenino , Encuestas Epidemiológicas , Humanos , Entrevistas como Asunto , Persona de Mediana Edad , Visita a Consultorio Médico , Prevalencia , Teléfono , Incontinencia Urinaria/epidemiología
18.
J Vet Intern Med ; 24(5): 1055-62, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20666980

RESUMEN

BACKGROUND: Ectopic ureters (EUs) associated with varying combinations of urinary incontinence, hydronephrosis, and urinary tract infection have been identified in related North American Entlebucher Mountain Dogs. OBJECTIVES: To characterize the disease phenotype in affected dogs and evaluate possible modes of inheritance. ANIMALS: Twenty client-owned Entlebucher Mountain Dogs. Nine dogs had clinical signs of urinary tract disease. METHODS: Prospective case series in which 17 dogs were evaluated with excretory urography, ultrasonography, and urethrocystoscopy. Three additional dogs were evaluated by necropsy alone. Clinical and pedigree histories from 165 North American Entlebuchers were compiled for analysis. RESULTS: Eleven female and 2 male dogs were found to have EUs. Six females and 1 male were continent. Bilateral intravesicular ectopic ureters (IVEUs) were identified in 9 dogs, bilateral extravesicular ectopic ureters (EVEUs) in 3 dogs, and 1 dog had IVEU and EVEU. Hydronephrosis was identified in 5 dogs, 3 of which had bilateral IVEUs. Two necropsied dogs had bilateral hydronephrosis with presumed ureterovesical junction obstruction associated with chronic granulation tissue or lymphoplasmacytic inflammation. Twenty-six dogs with EUs were identified in the pedigree. Because of incomplete penetrance, mode of inheritance could not be determined. CONCLUSIONS AND CLINICAL IMPORTANCE: Ureteral ectopia is common in North American Entlebucher Mountain Dogs and clinical signs alone could not reliably predict disease phenotype. EVEUs were associated with urinary incontinence and occasionally hydronephrosis. IVEUs were clinically silent or associated with hydronephrosis. Further analyses are necessary to confirm and characterize the hereditary nature of the disorder.


Asunto(s)
Enfermedades de los Perros/congénito , Enfermedades Ureterales/veterinaria , Incontinencia Urinaria/veterinaria , Animales , Enfermedades de los Perros/genética , Enfermedades de los Perros/patología , Perros , Femenino , Predisposición Genética a la Enfermedad , Masculino , Linaje , Enfermedades Ureterales/congénito , Enfermedades Ureterales/patología , Incontinencia Urinaria/genética , Incontinencia Urinaria/patología
19.
AJNR Am J Neuroradiol ; 41(6): 1061-1069, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32439637

RESUMEN

BACKGROUND AND PURPOSE: Fast and accurate quantification of globe volumes in the event of an ocular trauma can provide clinicians with valuable diagnostic information. In this work, an automated workflow using a deep learning-based convolutional neural network is proposed for prediction of globe contours and their subsequent volume quantification in CT images of the orbits. MATERIALS AND METHODS: An automated workflow using a deep learning -based convolutional neural network is proposed for prediction of globe contours in CT images of the orbits. The network, 2D Modified Residual UNET (MRes-UNET2D), was trained on axial CT images from 80 subjects with no imaging or clinical findings of globe injuries. The predicted globe contours and volume estimates were compared with manual annotations by experienced observers on 2 different test cohorts. RESULTS: On the first test cohort (n = 18), the average Dice, precision, and recall scores were 0.95, 96%, and 95%, respectively. The average 95% Hausdorff distance was only 1.5 mm, with a 5.3% error in globe volume estimates. No statistically significant differences (P = .72) were observed in the median globe volume estimates from our model and the ground truth. On the second test cohort (n = 9) in which a neuroradiologist and 2 residents independently marked the globe contours, MRes-UNET2D (Dice = 0.95) approached human interobserver variability (Dice = 0.94). We also demonstrated the utility of inter-globe volume difference as a quantitative marker for trauma in 3 subjects with known globe injuries. CONCLUSIONS: We showed that with fast prediction times, we can reliably detect and quantify globe volumes in CT images of the orbits across a variety of acquisition parameters.


Asunto(s)
Aprendizaje Profundo , Interpretación de Imagen Asistida por Computador/métodos , Neuroimagen/métodos , Órbita/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Humanos , Variaciones Dependientes del Observador
20.
J Cell Biol ; 110(3): 703-14, 1990 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-2106524

RESUMEN

Structures that cap the plus ends of microtubules may be involved in the regulation of their assembly and disassembly. Growing and disassembling microtubules in the mitotic apparatus are capped by kinetochores and ciliary and flagellar microtubules are capped by the central microtubule cap and distal filaments. To compare the ciliary caps with kinetochores, isolated Tetrahymena cilia were stained with CREST (Calcinosis/phenomenon esophageal dysmotility, sclerodactyly, telangiectasia) antisera known to stain kinetochores. Immunofluorescence microscopy revealed that a CREST antiserum stained the distal tips of cilia that contained capping structures but did not stain axonemes that lacked capping structures. Both Coomassie blue-stained gels and Western blots probed with CREST antiserum revealed that a 97-kD antigen copurifies with the capping structures. Affinity-purified antibodies to the 97-kD ciliary protein stained the tips of cap-containing Tetrahymena cilia and the kinetochores in HeLa, Chinese hamster ovary, and Indian muntjak cells. These results suggest that at least one polypeptide found in the kinetochore is present in ciliary microtubule capping structures and that there may be a structural and/or functional homology between these structures that cap the plus ends of microtubules.


Asunto(s)
Antígenos/análisis , Cilios/ultraestructura , Microtúbulos/ultraestructura , Orgánulos/ultraestructura , Tetrahymena/ultraestructura , Animales , Fluoresceína-5-Isotiocianato , Fluoresceínas , Técnica del Anticuerpo Fluorescente , Colorantes Fluorescentes , Células HeLa/ultraestructura , Humanos , Sueros Inmunes , Immunoblotting , Microscopía Electrónica , Modelos Estructurales , Tiocianatos
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