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1.
J Am Heart Assoc ; : e031981, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-39087582

RESUMEN

The past several decades have seen rapid advances in diagnosis and treatment of cardiovascular diseases and stroke, enabled by technological breakthroughs in imaging, genomics, and physiological monitoring, coupled with therapeutic interventions. We now face the challenge of how to (1) rapidly process large, complex multimodal and multiscale medical measurements; (2) map all available data streams to the trajectories of disease states over the patient's lifetime; and (3) apply this information for optimal clinical interventions and outcomes. Here we review new advances that may address these challenges using digital twin technology to fulfill the promise of personalized cardiovascular medical practice. Rooted in engineering mechanics and manufacturing, the digital twin is a virtual representation engineered to model and simulate its physical counterpart. Recent breakthroughs in scientific computation, artificial intelligence, and sensor technology have enabled rapid bidirectional interactions between the virtual-physical counterparts with measurements of the physical twin that inform and improve its virtual twin, which in turn provide updated virtual projections of disease trajectories and anticipated clinical outcomes. Verification, validation, and uncertainty quantification builds confidence and trust by clinicians and patients in the digital twin and establishes boundaries for the use of simulations in cardiovascular medicine. Mechanistic physiological models form the fundamental building blocks of the personalized digital twin that continuously forecast optimal management of cardiovascular health using individualized data streams. We present exemplars from the existing body of literature pertaining to mechanistic model development for cardiovascular dynamics and summarize existing technical challenges and opportunities pertaining to the foundation of a digital twin.

2.
IEEE Open J Eng Med Biol ; 5: 621-626, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39184968

RESUMEN

Goal: This paper introduces an automated post-traumatic stress disorder (PTSD) screening tool that could potentially be used as a self-assessment or inserted into routine medical visits to aid in PTSD diagnosis and treatment. Methods: With an emotion estimation algorithm providing arousal (excited to calm) and valence (pleasure to displeasure) levels through discourse, we select regions of the acoustic signal that are most salient for PTSD detection. Our algorithm was tested on a subset of data from the DVBIC-TBICoE TBI Study, which contains PTSD Check List Civilian (PCL-C) assessment scores. Results: Speech from low-arousal and positive-valence regions provide the highest discrimination for PTSD. Our model achieved an AUC (area under the curve) of 0.80 in detecting PCL-C ratings, outperforming models with no emotion filtering (AUC = 0.68). Conclusions: This result suggests that emotion drives the selection of the most salient temporal regions of an audio recording for PTSD detection.

3.
NPJ Digit Med ; 7(1): 136, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38783001

RESUMEN

Data from commercial off-the-shelf (COTS) wearables leveraged with machine learning algorithms provide an unprecedented potential for the early detection of adverse physiological events. However, several challenges inhibit this potential, including (1) heterogeneity among and within participants that make scaling detection algorithms to a general population less precise, (2) confounders that lead to incorrect assumptions regarding a participant's healthy state, (3) noise in the data at the sensor level that limits the sensitivity of detection algorithms, and (4) imprecision in self-reported labels that misrepresent the true data values associated with a given physiological event. The goal of this study was two-fold: (1) to characterize the performance of such algorithms in the presence of these challenges and provide insights to researchers on limitations and opportunities, and (2) to subsequently devise algorithms to address each challenge and offer insights on future opportunities for advancement. Our proposed algorithms include techniques that build on determining suitable baselines for each participant to capture important physiological changes and label correction techniques as it pertains to participant-reported identifiers. Our work is validated on potentially one of the largest datasets available, obtained with 8000+ participants and 1.3+ million hours of wearable data captured from Oura smart rings. Leveraging this extensive dataset, we achieve pre-symptomatic detection of COVID-19 with a performance receiver operator characteristic (ROC) area under the curve (AUC) of 0.725 without correction techniques, 0.739 with baseline correction, 0.740 with baseline correction and label correction on the training set, and 0.777 with baseline correction and label correction on both the training and the test set. Using the same respective paradigms, we achieve ROC AUCs of 0.919, 0.938, 0.943 and 0.994 for the detection of self-reported fever, and 0.574, 0.611, 0.601, and 0.635 for detection of self-reported shortness of breath. These techniques offer improvements across almost all metrics and events, including PR AUC, sensitivity at 75% specificity, and precision at 75% recall. The ring allows continuous monitoring for detection of event onset, and we further demonstrate an improvement in the early detection of COVID-19 from an average of 3.5 days to an average of 4.1 days before a reported positive test result.

4.
Physiol Behav ; 270: 114315, 2023 10 15.
Artículo en Inglés | MEDLINE | ID: mdl-37536619

RESUMEN

OBJECTIVE: During the mastication of solid food, the tongue pushes the bolus laterally to place it onto occlusal surfaces as the jaw is opened. This movement is referred to as tongue-pushing (TP). TP has an important role in efficient chewing, but its kinematic mechanisms remain unclear. The present study quantified the kinematics of TP and its coordination with masticatory jaw movements. METHODS: Videofluorography (VFG) in anteroposterior projection was recorded while 14 healthy young adults ate 6 g each of cookies and meat. Small lead markers were glued to the tongue surface (left, right, and anterior) and buccal tooth surfaces (upper molars and lower canines). The position of the tongue and lower canine markers relative to the upper occlusal plane was quantified with Cartesian coordinates, using the right upper molar as the origin. Jaw motion during chewing was divided into TP and Non-TP cycles, based on the lateral movement of the food and tongue markers. The side of the jaw that compressed food particles was defined as the working side, while the other side was termed the balancing side. Horizontal and vertical displacements of tongue and jaw markers were compared between TP and Non-TP cycles, as well as between food types. RESULTS: The mediolateral displacement of all tongue markers was significantly larger in TP than in Non-TP cycles. Vertical displacement was also significantly greater in TP than in Non-TP cycles for the anterior and working side tongue markers. TP cycles occurred more frequently with meat-chewing than with cookie-chewing. CONCLUSION: TP is accomplished by rotation and lateral movements of the tongue surface on the working side and the anterior tongue blade, along with medial movement on the balancing side. These movements produce lateral shift and rotation of the tongue surface toward the working side in concert with jaw opening. Designing exercises to improve the strength of the lateral motion and rotation of the tongue body may be useful for individuals with impaired tongue function for eating and swallowing.


Asunto(s)
Deglución , Masticación , Fenómenos Biomecánicos , Lengua/diagnóstico por imagen , Alimentos , Movimiento , Maxilares/diagnóstico por imagen
5.
Sci Rep ; 12(1): 18762, 2022 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-36335191

RESUMEN

We evaluated whether whole-body dual-energy X-ray absorptiometry (DXA) measures of lean body mass can be used as biomarkers for disease progression and treatment effects in patients with Duchenne muscular dystrophy. This post hoc analysis utilized data from a randomized, 2-period study of domagrozumab versus placebo in 120 ambulatory boys with DMD. DXA measures of lean body mass were obtained from the whole body (excluding head), arms, legs and appendicular skeleton at baseline and every 16 weeks. Treatment effects on DXA measures for domagrozumab versus placebo were assessed at Week 49. At Week 49, domagrozumab statistically significantly increased lean body mass versus placebo in the appendicular skeleton (p = 0.050) and arms (p < 0.001). The relationship between lean body mass at Week 49 and functional endpoints at Week 97 was evaluated. Changes in lean body mass at Week 49 in all regions except arms were significantly correlated with percent change from baseline in 4-stair climb (4SC) at Week 97. DXA-derived percent lean mass at Week 49 also correlated with 4SC and North Star Ambulatory Assessment at Week 97. These data indicate that whole-body DXA measures can be used as biomarkers for treatment effects and disease progression in patients with DMD, and warrant further investigation.Trial registration: ClinicalTrials.gov, NCT02310763; registered 8 December 2014.


Asunto(s)
Distrofia Muscular de Duchenne , Masculino , Humanos , Absorciometría de Fotón , Distrofia Muscular de Duchenne/diagnóstico por imagen , Distrofia Muscular de Duchenne/tratamiento farmacológico , Composición Corporal , Biomarcadores , Progresión de la Enfermedad
6.
PLoS One ; 17(8): e0272858, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35998119

RESUMEN

INTRODUCTION: The North Star Ambulatory Assessment (NSAA) tool is a key instrument for measuring clinical outcomes in patients with Duchenne muscular dystrophy (DMD). To gain a better understanding of the longitudinal utility of the NSAA, we evaluated NSAA data from a phase II trial of 120 patients with DMD treated with domagrozumab or placebo. METHODS: The NSAA exploratory analyses included assessment of individual skills gained/lost, total skills gained/lost, cumulative loss of function, and the impact of transient loss of function due to a temporary disability on NSAA total score (temporary zero score). RESULTS: There was no significant difference in the total number of NSAA skills gained (mean 1.41 and 1.04, respectively; p = 0.3314) or lost (3.90 vs. 5.0; p = 0.0998) between domagrozumab- vs. placebo-treated patients at week 49. However, domagrozumab-treated patients were less likely to lose the ability to perform a NSAA item (hazard ratio 0.80, 95% confidence interval [CI]: 0.65-0.98, p = 0.029) over 48-weeks vs. placebo-treated patients. When temporary zero scores were changed to "not obtainable" (8 values from 7 patients), domagrozumab-treated patients scored higher on the NSAA total score versus placebo-treated patients (difference at week 49: 2.0, 95% CI: 0.1-3.9, p = 0.0359). CONCLUSIONS: These exploratory analyses reveal additional approaches to interpreting the NSAA data beyond just change in NSAA total score. These observations also highlight the importance of reporting items as "not obtainable" for a patient with a temporary/transient physical disability that impacts their ability to perform the NSAA test. CLINICALTRIALS.GOV IDENTIFIER: NCT02310763.


Asunto(s)
Distrofia Muscular de Duchenne , Humanos , Evaluación de Resultado en la Atención de Salud , Modalidades de Fisioterapia
7.
Iowa Orthop J ; 42(1): 89-96, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35821918

RESUMEN

Background: High energy, lower extremity trauma is associated with longstanding pain and functional limitations. The clinical decision to proceed with early amputation or limb salvage is often controversial. This study was designed to compare differences in complications, costs, and clinical outcomes of below knee amputation (BKA) performed early after injury or after attempted limb salvage in a hospital with standardized prosthetic care following amputation. Methods: This is a retrospective comparative study of subjects who underwent BKA for a traumatic injury at a single level 1 trauma center and received standardized prosthetic care from a single manufacturer from 1999-2016 with minimum 2-year post-amputation follow up. Outcomes collected included demographics, surgical management, unplanned re-operations, and hospital and prosthetic cost data 2 years from time of injury. Results: Overall, 79 subjects met criteria. Early amputation (EA) was defined by median duration between injury and amputation (6 weeks) with 41 subjects in the EA group and 38 subjects in the late amputation (LA) group. Subjects in the EA group were more likely to have open fractures, high energy mechanism, and less likely to have medical comorbidities. Post-amputation infection was common in both groups (17/41 (42%) vs 17/38 (45%), p=0.77). Subjects undergoing EA were more likely to require unplanned post-amputation revision, 22/41 (54%) versus 10/38 (27%), p=0.017. Hospital costs and prosthetics/orthotics costs from the time of injury to two years following amputation were comparable, with mean hospital EA costs $136,044 versus LA costs $125,065, p=0.38. Mean prosthetics/orthotics costs of EA subjects were $33,252 versus LA costs $37,684, p=0.59. Conclusion: Unplanned post-amputation revision surgeries were more common when BKA was performed early after trauma. Otherwise, outcomes and cost were comparable when amputation was performed early versus late. Level of Evidence: IV.


Asunto(s)
Amputación Quirúrgica , Traumatismos de la Pierna , Humanos , Puntaje de Gravedad del Traumatismo , Traumatismos de la Pierna/complicaciones , Traumatismos de la Pierna/cirugía , Recuperación del Miembro , Estudios Retrospectivos
8.
J Deaf Stud Deaf Educ ; 27(3): 245-261, 2022 08 06.
Artículo en Inglés | MEDLINE | ID: mdl-35791669

RESUMEN

Research literature and community narratives both emphasize the importance of self-determination in the lives of deaf youth. This paper describes the development, initial validation, and potential applications of a translated measure of self-determination for deaf youth, the SDI:SR ASL Translation (SDI:SR ASL). A sample of 3,309 young people who completed the SDI:SR, of whom 392 were deaf, was used in this validation study. Results provide preliminary support for the use of SDI:SR ASL with deaf youth. Findings also indicate that deaf youth who take the SDI:SR ASL score more similarly to youth without disabilities taking the SDI:SR than youth with disabilities. The SDI:SR ASL can be an important tool for researchers and practitioners to better understand self-determination among deaf youth and facilitate continued development of self-determination skills.


Asunto(s)
Personas con Deficiencia Auditiva , Lengua de Signos , Adolescente , Humanos , Estudiantes , Traducción , Estados Unidos
9.
J Neurol ; 269(8): 4421-4435, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35396602

RESUMEN

Duchenne muscular dystrophy (DMD) is a progressive, neuromuscular disorder caused by mutations in the DMD gene that results in a lack of functional dystrophin protein. Herein, we report the use of quantitative magnetic resonance imaging (MRI) measures as biomarkers in the context of a multicenter phase 2, randomized, placebo-controlled clinical trial evaluating the myostatin inhibitor domagrozumab in ambulatory boys with DMD (n = 120 aged 6 to < 16 years). MRI scans of the thigh to measure muscle volume, muscle volume index (MVI), fat fraction, and T2 relaxation time were obtained at baseline and at weeks 17, 33, 49, and 97 as per protocol. These quantitative MRI measurements appeared to be sensitive and objective biomarkers for evaluating disease progression, with significant changes observed in muscle volume, MVI, and T2 mapping measures over time. To further explore the utility of quantitative MRI measures as biomarkers to inform longer term functional changes in this cohort, a regression analysis was performed and demonstrated that muscle volume, MVI, T2 mapping measures, and fat fraction assessment were significantly correlated with longer term changes in four-stair climb times and North Star Ambulatory Assessment functional scores. Finally, less favorable baseline measures of MVI, fat fraction of the muscle bundle, and fat fraction of lean muscle were significant risk factors for loss of ambulation over a 2-year monitoring period. These analyses suggest that MRI can be a valuable tool for use in clinical trials and may help inform future functional changes in DMD.Trial registration: ClinicalTrials.gov identifier, NCT02310763; registered December 2014.


Asunto(s)
Distrofia Muscular de Duchenne , Anticuerpos Monoclonales Humanizados , Biomarcadores/metabolismo , Progresión de la Enfermedad , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Músculo Esquelético/patología , Distrofia Muscular de Duchenne/diagnóstico por imagen , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/metabolismo
10.
Biomark Med ; 15(15): 1389-1396, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34533053

RESUMEN

Aim: Evaluate the utility of glutamate dehydrogenase (GLDH) and cardiac troponin I as safety biomarkers, and creatine kinase and muscle injury panel as muscle health biomarkers in Duchenne muscular dystrophy. Patients & methods: Data were collected during a Phase II trial of domagrozumab. Results: GLDH was a more specific biomarker for liver injury than alanine aminotransferase. Cardiac troponin I elevations were variable and not sustained, limiting its applicability as a biomarker. Muscle injury panel biomarkers were no more informative than creatine kinase as a muscle health biomarker. Conclusion: Results support the use of GLDH as a specific biomarker for liver injury in patients with Duchenne muscular dystrophy. Clinical trial registration: ClinicalTrials.gov, NCT02310763.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Biomarcadores/sangre , Monitoreo de Drogas/métodos , Distrofia Muscular de Duchenne/tratamiento farmacológico , Adolescente , Alanina Transaminasa/sangre , Anticuerpos Monoclonales Humanizados/administración & dosificación , Aspartato Aminotransferasas/sangre , Niño , Creatina Quinasa/sangre , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Glutamato Deshidrogenasa/sangre , Humanos , Masculino , Distrofia Muscular de Duchenne/sangre , Distrofia Muscular de Duchenne/diagnóstico , Sensibilidad y Especificidad , Resultado del Tratamiento , Troponina I/sangre
11.
Dysphagia ; 36(6): 1088-1094, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33507395

RESUMEN

Understanding bolus flow patterns in swallowing (rheology, the study of flow) is fundamental to assessment and treatment of dysphagia. These patterns are complex and poorly understood. A liquid swallow is typically biphasic, including air, so the actual bolus has both liquid and gas phases. We report a novel observation of annular two-phase flow (a ring of liquid around a core of air) as thin liquids passed through the upper esophageal sphincter (UES). Dynamic CT was performed on 27 healthy asymptomatic volunteers swallowing liquid barium in a semi-reclining position. Each subject swallowed 3, 10, and 20 ml of either thin (14 subjects) or thick liquid (13 subjects). Sagittal and axial images were analyzed. Flow patterns in the UES were assessed on cross-sectional images. Annular flow was seen in the majority of subjects with thin liquid but few with thick liquid swallows. The percentage of Annular flow during UES opening was 3 ml 58%, 10 ml 58%, 20 ml 56% in thin and 3 ml 0%, 10 ml 4%, 20 ml 1% in thick. Annular flow was usually observed from the second or third frames after onset of UES opening. The other pattern, Plug flow was seldom seen with thin but was typical with thick liquid swallows. Annular flow was the most common pattern for thin liquids (but not thick liquids) passing through the UES. Annular flow has been defined as a liquid continuum adjacent to the channel wall with a gas continuum (core) in the center of the channel. The two regions are demarcated by a gas-liquid interface. Annular flow is typical for two-phase gas-liquid flow in a vertical or inclined channel. It results from the interaction of viscosity with cohesive and adhesive forces in the two phases. We infer that the difference in flow pattern between thin liquid-air and thick liquid-air boluses resulted from the differing magnitudes of viscous forces.


Asunto(s)
Trastornos de Deglución , Esfínter Esofágico Superior , Bario , Deglución , Trastornos de Deglución/diagnóstico por imagen , Esfínter Esofágico Superior/diagnóstico por imagen , Humanos , Manometría , Tomografía Computarizada por Rayos X
13.
New Phytol ; 229(3): 1701-1714, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32929737

RESUMEN

Although horizontal gene transfer (HGT) is common in angiosperm mitochondrial DNAs (mtDNAs), few cases of functional foreign genes have been identified. The one outstanding candidate for large-scale functional HGT is the holoparasite Lophophytum mirabile, whose mtDNA has lost most native genes but contains intact foreign homologs acquired from legume host plants. To investigate the extent to which this situation results from functional replacement of native by foreign genes, functional mitochondrial gene transfer to the nucleus, and/or loss of mitochondrial biochemical function in the context of extreme parasitism, we examined the Lophophytum mitochondrial and nuclear transcriptomes by deep paired-end RNA sequencing. Most foreign mitochondrial genes in Lophophytum are highly transcribed, accurately spliced, and efficiently RNA edited. By contrast, we found no evidence for functional gene transfer to the nucleus or loss of mitochondrial functions in Lophophytum. Many functional replacements occurred via the physical replacement of native genes by foreign genes. Some of these events probably occurred as the final act of HGT itself. Lophophytum mtDNA has experienced an unprecedented level of functional replacement of native genes by foreign copies. This raises important questions concerning population-genetic and molecular regimes that underlie such a high level of foreign gene takeover.


Asunto(s)
Genes Mitocondriales , Genoma Mitocondrial , ADN Mitocondrial , Evolución Molecular , Transferencia de Gen Horizontal/genética , Filogenia
14.
Sci Rep ; 10(1): 14773, 2020 09 08.
Artículo en Inglés | MEDLINE | ID: mdl-32901067

RESUMEN

Current clinical tests lack the sensitivity needed for detecting subtle balance impairments associated with mild traumatic brain injury (mTBI). Patient-reported symptoms can be significant and have a huge impact on daily life, but impairments may remain undetected or poorly quantified using clinical measures. Our central hypothesis was that provocative sensorimotor perturbations, delivered in a highly instrumented, immersive virtual environment, would challenge sensory subsystems recruited for balance through conflicting multi-sensory evidence, and therefore reveal that not all subsystems are performing optimally. The results show that, as compared to standard clinical tests, the provocative perturbations illuminate balance impairments in subjects who have had mild traumatic brain injuries. Perturbations delivered while subjects were walking provided greater discriminability (average accuracy ≈ 0.90) than those delivered during standing (average accuracy ≈ 0.65) between mTBI subjects and healthy controls. Of the categories of features extracted to characterize balance, the lower limb accelerometry-based metrics proved to be most informative. Further, in response to perturbations, subjects with an mTBI utilized hip strategies more than ankle strategies to prevent loss of balance and also showed less variability in gait patterns. We have shown that sensorimotor conflicts illuminate otherwise-hidden balance impairments, which can be used to increase the sensitivity of current clinical procedures. This augmentation is vital in order to robustly detect the presence of balance impairments after mTBI and potentially define a phenotype of balance dysfunction that enhances risk of injury.


Asunto(s)
Conmoción Encefálica/complicaciones , Ambiente , Trastornos Neurológicos de la Marcha/patología , Equilibrio Postural , Caminata , Acelerometría , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Trastornos Neurológicos de la Marcha/etiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Adulto Joven
15.
J Oral Rehabil ; 47(10): 1287-1296, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32738063

RESUMEN

OBJECTIVE: This study investigated the effects of bolus consistency on pharyngeal volume during swallowing using three-dimensional kinematic analysis. METHODS: Eight subjects (2 males and 6 females, mean ± SD 44 ± 10 years old) underwent a 320-row area detector scan during swallows of 10 mL of honey-thick liquid and thin liquid. Critical event timing (hyoid, soft palate, UES) and volume of pharyngeal cavity and bolus were measured and compared between two swallows. RESULTS: The pharynx is almost completely obliterated by pharyngeal constriction against the tongue base for both consistencies. There were no significant differences in maximum volume, minimum volume and pharyngeal volume constriction ratio values between thick and thin liquids. However, the pattern of pharyngeal volume change (decrease) was different. For thick liquids, the air volume started to decrease before the onset of hyoid anterosuperior movement and decreased rapidly after onset of hyoid anterosuperior movement. During thin liquid swallowing, air volume remained relatively large throughout the swallow and started to decrease later when compared to swallowing thick liquids. At onset of UES opening, the bolus volume was not significantly different between thin and thick liquids; however, air volume was significantly larger when swallowing thin liquids, which made the total volume of the pharyngeal cavity larger. CONCLUSION: This difference between the two consistencies is associated with differences in tongue motion to propel the bolus and clear the pharynx from possible residue.


Asunto(s)
Deglución , Faringe , Adulto , Fenómenos Biomecánicos , Femenino , Humanos , Hueso Hioides/diagnóstico por imagen , Masculino , Manometría , Persona de Mediana Edad , Faringe/diagnóstico por imagen , Tomografía Computarizada por Rayos X
16.
J Pediatr Urol ; 16(4): 446.e1-446.e5, 2020 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-32622738

RESUMEN

INTRODUCTION: Correction of chordee remains a prerequisite prior to urethroplasty in children with severe hypospadias. The use of an interposition graft is indicated when significant chordee (>300) persists after division of the urethral plate. The use of free dermis or tunica vaginalis are most often used, but the use of a pre-packaged graft material is attractive with regards to efficiency. The success with small intestine submucosa (SIS) has been variable and experience with Alloderm® has not been published. OBJECTIVE: To determine if Alloderm®, an acellular dermal matrix with regenerative properties, can effectively, safely, and efficiently be used for corporal grafting in cases of severe chordee in children associated with hypospadias or intersex STUDY DESIGN: All boys underwent planned staged repair of severe hypospadias (penoscrotal or more proximal). If artificial erection (AE) demonstrated chordee >450 after penile degloving and removal of fibrotic tissue, and again after urethral plate division, the ventral tunica albuginea was incised 1800 transversely and the oval defect measured in both axes. Alloderm® was trimmed to size and sewn into the defect. AE confirmed chordee correction. At the second stage repair (>6 months later), AE was performed to confirm continued absence of chordee. CONCLUSION: Alloderm®is safe, effective and simple to use graft material for correcting severe chordee. The benefits include performance efficiency without need for separate harvesting and donor site closure, and redundancy of material, if needed. Additional series and longer follow up must confirm these results and better assess durability.


Asunto(s)
Hipospadias , Procedimientos Quirúrgicos Urológicos Masculinos , Niño , Colágeno , Humanos , Hipospadias/cirugía , Lactante , Masculino , Pene/cirugía , Uretra/cirugía
17.
Neuromuscul Disord ; 30(6): 492-502, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32522498

RESUMEN

We report results from a phase 2, randomized, double-blind, 2-period trial (48 weeks each) of domagrozumab and its open-label extension in patients with Duchenne muscular dystrophy (DMD). Of 120 ambulatory boys (aged 6 to <16 years) with DMD, 80 were treated with multiple ascending doses (5, 20, and 40 mg/kg) of domagrozumab and 40 treated with placebo. The primary endpoints were safety and mean change in 4-stair climb (4SC) time at week 49. Secondary endpoints included other functional tests, pharmacokinetics, and pharmacodynamics. Mean (SD) age was 8.4 (1.7) and 9.3 (2.3) years in domagrozumab- and placebo-treated patients, respectively. Difference in mean (95% CI) change from baseline in 4SC at week 49 for domagrozumab vs placebo was 0.27 (-7.4 to 7.9) seconds (p = 0.94). There were no significant between-group differences in any secondary clinical endpoints. Most patients had ≥1 adverse event in the first 48 weeks; most were mild and not treatment-related. Median serum concentrations of domagrozumab increased with administered dose within each dose level. Non-significant increases in muscle volume were observed in domagrozumab- vs placebo-treated patients. Domagrozumab was generally safe and well tolerated in patients with DMD. Efficacy measures did not support a significant treatment effect. Clinicaltrials.gov identifiers: NCT02310763 and NCT02907619.


Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Distrofia Muscular de Duchenne/tratamiento farmacológico , Miostatina/antagonistas & inhibidores , Evaluación de Resultado en la Atención de Salud , Adolescente , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/sangre , Niño , Prueba de Esfuerzo , Humanos , Masculino , Insuficiencia del Tratamiento
18.
Am J Bot ; 107(1): 91-115, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31814117

RESUMEN

PREMISE: Phylogenetic trees of bryophytes provide important evolutionary context for land plants. However, published inferences of overall embryophyte relationships vary considerably. We performed phylogenomic analyses of bryophytes and relatives using both mitochondrial and plastid gene sets, and investigated bryophyte plastome evolution. METHODS: We employed diverse likelihood-based analyses to infer large-scale bryophyte phylogeny for mitochondrial and plastid data sets. We tested for changes in purifying selection in plastid genes of a mycoheterotrophic liverwort (Aneura mirabilis) and a putatively mycoheterotrophic moss (Buxbaumia), and compared 15 bryophyte plastomes for major structural rearrangements. RESULTS: Overall land-plant relationships conflict across analyses, generally weakly. However, an underlying (unrooted) four-taxon tree is consistent across most analyses and published studies. Despite gene coverage patchiness, relationships within mosses, liverworts, and hornworts are largely congruent with previous studies, with plastid results generally better supported. Exclusion of RNA edit sites restores cases of unexpected non-monophyly to monophyly for Takakia and two hornwort genera. Relaxed purifying selection affects multiple plastid genes in mycoheterotrophic Aneura but not Buxbaumia. Plastid genome structure is nearly invariant across bryophytes, but the tufA locus, presumed lost in embryophytes, is unexpectedly retained in several mosses. CONCLUSIONS: A common unrooted tree underlies embryophyte phylogeny, [(liverworts, mosses), (hornworts, vascular plants)]; rooting inconsistency across studies likely reflects substantial distance to algal outgroups. Analyses combining genomic and transcriptomic data may be misled locally for heavily RNA-edited taxa. The Buxbaumia plastome lacks hallmarks of relaxed selection found in mycoheterotrophic Aneura. Autotrophic bryophyte plastomes, including Buxbaumia, hardly vary in overall structure.


Asunto(s)
Briófitas , Evolución Molecular , Consenso , Funciones de Verosimilitud , Filogenia
19.
Am J Phys Med Rehabil ; 99(5): 404-408, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31764229

RESUMEN

OBJECTIVES: Dysphagia in patients with myositis is associated with an increased risk of aspiration pneumonia. However, the pathophysiology of dysphagia is poorly understood. The aim of this study was to understand how myositis affects swallowing physiology on videofluoroscopic swallow study. DESIGN: This is a retrospective review of video fluoroscopic swallowing studies on 23 myositis patients with dysphagia from 2011 to 2016. Swallow studies were analyzed by timing of swallowing events and duration of swallowing events, diameter of upper esophageal sphincter opening, Modified Barium Swallow Impairment Profile, and Penetration-Aspiration Scale. The outcome measures for patients were compared with an archived videofluoroscopic swallow study from healthy, age-matched participants by Wilcoxon rank-sum tests. RESULTS: Patients with myositis had a shorter duration of upper esophageal sphincter opening (P < 0.0001) and laryngeal vestibule closure (P < 0.0001) than healthy subjects. The diameter of upper esophageal sphincter opening did not differ between groups. Patients with myositis presented with higher scores on the MBSIMP than healthy subjects, indicating great impairment particularly during the pharyngeal phase of swallowing, and a higher frequency of penetration and aspiration. CONCLUSIONS: Dysphagia in patients with myositis may be attributed to reduced endurance of swallowing musculature rather than mechanical obstruction of the upper esophageal sphincter.


Asunto(s)
Trastornos de Deglución/fisiopatología , Miositis/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Sulfato de Bario/administración & dosificación , Medios de Contraste/administración & dosificación , Esfínter Esofágico Superior/fisiopatología , Femenino , Fluoroscopía , Humanos , Laringe/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Estudios Retrospectivos , Grabación en Video
20.
Am Ann Deaf ; 165(4): 401-417, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33416518

RESUMEN

While most research on transition outcomes focuses on education and employment, the transition to adulthood also includes social outcomes, such as group involvement and community service. The present study examined a broader set of outcomes for young deaf adults after postsecondary education. A secondary analysis of a large-scale data set, the National Longitudinal Transition Study (NLTS2), was conducted to compare the employment, income assistance, and social/community outcomes of three postsecondary education cohorts: graduates, noncompleters, and nonattendees. The findings indicate that young deaf adults with more postsecondary education have more positive outcomes, e.g., higher employment rates, higher wages, and greater civic and social participation. These findings further demonstrate the importance of postsecondary education for young deaf adults and can be used to inform transition planning for deaf students, supporting the need to consider exploration of various career pathways available through college or postsecondary career/technical education.


Asunto(s)
Selección de Profesión , Empleo/tendencias , Personas con Deficiencia Auditiva/estadística & datos numéricos , Participación Social , Estudiantes/estadística & datos numéricos , Adulto , Escolaridad , Femenino , Humanos , Renta/tendencias , Estudios Longitudinales , Masculino , Personas con Deficiencia Auditiva/psicología , Estudiantes/psicología , Adulto Joven
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