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Inherited retinopathies are devastating diseases that in most cases lack treatment options. Disease-modifying therapies that mitigate pathophysiology regardless of the underlying genetic lesion are desirable due to the diversity of mutations found in such diseases. We tested a systems pharmacology-based strategy that suppresses intracellular cAMP and Ca2+ activity via G protein-coupled receptor (GPCR) modulation using tamsulosin, metoprolol, and bromocriptine coadministration. The treatment improves cone photoreceptor function and slows degeneration in Pde6ßrd10 and RhoP23H/WT retinitis pigmentosa mice. Cone degeneration is modestly mitigated after a 7-month-long drug infusion in PDE6A-/- dogs. The treatment also improves rod pathway function in an Rpe65-/- mouse model of Leber congenital amaurosis but does not protect from cone degeneration. RNA-sequencing analyses indicate improved metabolic function in drug-treated Rpe65-/- and rd10 mice. Our data show that catecholaminergic GPCR drug combinations that modify second messenger levels via multiple receptor actions provide a potential disease-modifying therapy against retinal degeneration.
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Modelos Animales de Enfermedad , Reposicionamiento de Medicamentos , Retinitis Pigmentosa , Animales , Ratones , Perros , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/genética , Mutación , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/genética , Fosfodiesterasas de Nucleótidos Cíclicos Tipo 6/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Ratones Noqueados , Amaurosis Congénita de Leber/tratamiento farmacológico , Amaurosis Congénita de Leber/genética , Bromocriptina/farmacología , Bromocriptina/uso terapéutico , cis-trans-Isomerasas/genética , cis-trans-Isomerasas/metabolismo , Humanos , Quimioterapia Combinada , Ratones Endogámicos C57BL , Células Fotorreceptoras Retinianas Conos/efectos de los fármacos , Células Fotorreceptoras Retinianas Conos/metabolismo , Células Fotorreceptoras Retinianas Conos/patología , Femenino , AMP Cíclico/metabolismo , Degeneración Retiniana/tratamiento farmacológico , Degeneración Retiniana/genética , Masculino , Calcio/metabolismoRESUMEN
The HIV envelope glycoprotein (Env) is a trimeric protein that facilitates viral binding and fusion with target cells. As the sole viral protein on the HIV surface, Env is important both for immune responses to HIV and in vaccine designs. Targeting Env in clinical applications is challenging due to its heavy glycosylation, high genetic variability, conformational camouflage, and its low abundance on virions. Thus, there is a critical need to better understand this protein. Flow virometry (FV) is a useful methodology for phenotyping the virion surface in a high-throughput, single virion manner. To demonstrate the utility of FV to characterize Env, we stained HIV virions with a panel of 85 monoclonal antibodies targeting different regions of Env. A broad range of antibodies yielded robust staining of Env, with V3 antibodies showing the highest quantitative staining. A subset of antibodies tested in parallel on viruses produced in CD4+ T cell lines, HEK293T cells, and primary cells showed that the cellular model of virus production can impact Env detection. Finally, in addition to being able to highlight Env heterogeneity on virions, we show FV can sensitively detect differences in Env conformation when soluble CD4 is added to virions before staining.
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VIH-1 , Virión , Productos del Gen env del Virus de la Inmunodeficiencia Humana , Humanos , Productos del Gen env del Virus de la Inmunodeficiencia Humana/química , Productos del Gen env del Virus de la Inmunodeficiencia Humana/metabolismo , Productos del Gen env del Virus de la Inmunodeficiencia Humana/genética , Productos del Gen env del Virus de la Inmunodeficiencia Humana/inmunología , VIH-1/genética , VIH-1/fisiología , VIH-1/inmunología , Virión/metabolismo , Células HEK293 , Anticuerpos Anti-VIH/inmunología , Anticuerpos Monoclonales/inmunología , Linfocitos T CD4-Positivos/virología , Linfocitos T CD4-Positivos/inmunología , Infecciones por VIH/virologíaRESUMEN
Animals are inherently motivated to explore social novelty cues over familiar ones, resulting in a novelty preference (NP), although the behavioral and circuit bases underlying NP are unclear. Combining calcium and neurotransmitter sensors with fiber photometry and optogenetics in mice, we find that mesolimbic dopamine (DA) neurotransmission is strongly and predominantly activated by social novelty controlling bout length of interaction during NP, a response significantly reduced by familiarity. In contrast, interpeduncular nucleus (IPN) GABAergic neurons that project to the lateral dorsal tegmentum (LDTg) were inhibited by social novelty but activated during terminations with familiar social stimuli. Inhibition of this pathway during NP increased interaction and bout length with familiar social stimuli, while activation reduced interaction and bout length with novel social stimuli via decreasing DA neurotransmission. These data indicate interest towards novel social stimuli is encoded by mesolimbic DA which is dynamically regulated by an IPNâLDTg circuit to control NP.
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Dopamina , Núcleo Interpeduncular , Ratones , Animales , Dopamina/metabolismo , Tegmento Mesencefálico/metabolismo , Núcleo Interpeduncular/metabolismo , Transmisión Sináptica , Neuronas GABAérgicas/metabolismoRESUMEN
Because the selective estrogen receptor modulator tamoxifen was shown to be retina-protective in the light damage and rd10 models of retinal degeneration, the purpose of this study was to test whether tamoxifen is retina-protective in a model where retinal pigment epithelium (RPE) toxicity appears to be the primary insult: the sodium iodate (NaIO3) model. C57Bl/6J mice were given oral tamoxifen (in the diet) or the same diet lacking tamoxifen, then given an intraperitoneal injection of NaIO3 at 25 mg/kg. The mice were imaged a week later using optical coherence tomography (OCT). ImageJ with a custom macro was utilized to measure retinal thicknesses in OCT images. Electroretinography (ERG) was used to measure retinal function one week post-injection. After euthanasia, quantitative real-time PCR (qRT-PCR) was performed. Tamoxifen administration partially protected photoreceptors. There was less photoreceptor layer thinning in OCT images of tamoxifen-treated mice. qRT-PCR revealed, in the tamoxifen-treated group, less upregulation of antioxidant and complement factor 3 mRNAs, and less reduction in the rhodopsin and short-wave cone opsin mRNAs. Furthermore, ERG results demonstrated preservation of photoreceptor function for the tamoxifen-treated group. Cone function was better protected than rods. These results indicate that tamoxifen provided structural and functional protection to photoreceptors against NaIO3. RPE cells were not protected. These neuroprotective effects suggest that estrogen-receptor modulation may be retina-protective. The fact that cones are particularly protected is intriguing given their importance for human visual function and their survival until the late stages of retinitis pigmentosa. Further investigation of this protective pathway could lead to new photoreceptor-protective therapeutics.
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Modelos Animales de Enfermedad , Electrorretinografía , Yodatos , Ratones Endogámicos C57BL , Degeneración Retiniana , Tamoxifeno , Tomografía de Coherencia Óptica , Animales , Yodatos/toxicidad , Ratones , Tomografía de Coherencia Óptica/métodos , Tamoxifeno/farmacología , Degeneración Retiniana/prevención & control , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/metabolismo , Degeneración Retiniana/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Células Fotorreceptoras de Vertebrados/patología , Rodopsina/metabolismo , Rodopsina/genética , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , ARN Mensajero/genética , Epitelio Pigmentado de la Retina/efectos de los fármacos , Epitelio Pigmentado de la Retina/patología , Epitelio Pigmentado de la Retina/metabolismo , Opsinas de Bastones/metabolismoRESUMEN
PURPOSE: Accurate documentation of lesions during transurethral resection of bladder tumors (TURBT) is essential for precise diagnosis, treatment planning, and follow-up care. However, optimizing schematic documentation techniques for bladder lesions has received limited attention. MATERIALS AND METHODS: This prospective observational study used a cMDX-based documentation system that facilitates graphical representation, a lesion-specific questionnaire, and heatmap analysis with a posterization effect. We designed a graphical scheme for bladder covering bladder landmarks to visualize anatomic features and to document the lesion location. The lesion-specific questionnaire was integrated for comprehensive lesion characterization. Finally, spatial analyses were applied to investigate the anatomic distribution patterns of bladder lesions. RESULTS: A total of 97 TURBT cases conducted between 2021 and 2023 were included, identifying 176 lesions. The lesions were distributed in different bladder areas with varying frequencies. The distribution pattern, sorted by frequency, was observed in the following areas: posterior, trigone, lateral right and anterior, and lateral left and dome. Suspicious levels were assigned to the lesions, mostly categorized either as indeterminate or moderate. Lesion size analysis revealed that most lesions fell between 5 and 29 mm. CONCLUSION: The study highlights the potential of schematic documentation techniques for informed decision making, quality assessment, primary research, and secondary data utilization of intraoperative data in the context of TURBT. Integrating cMDX and heatmap analysis provides valuable insights into lesion distribution and characteristics.
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Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/cirugía , Neoplasias de la Vejiga Urinaria/patología , Procedimientos Quirúrgicos Urológicos , Documentación , Estudios Prospectivos , Sistemas de InformaciónRESUMEN
INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a life-threatening, prenatally diagnosed congenital anomaly. We aim to characterize care and outcomes of infants with CDH in Texas and the impact of treating facilities volume of care. METHODS: Retrospective cohort study using a state-wide Hospital Inpatient Discharge Public Use Data File was conducted (2013-2021). Neonates and infants <1 year of age were included using CDH ICD-9/ICD-10 codes. Neonates transferred to an outside hospital were excluded to avoid double-counting. Descriptive statistics, chi-square and logistic regression analysis were performed. RESULTS: Of 1314 CDH patient encounters identified, 728 (55%) occurred at 5 higher volume centers (HVC, >75 cases), 326 (25%) at 9 mid-volume centers (MVC, 20-75 cases) and 268 (20%) at 79 low volume centers (LVC, <20 cases). HVC had lower mortality rates (18%, MVC 22% vs LVC 27%; p = 0.011) despite treating sicker patients (extreme illness severity: HVC 71%, MVC 62% vs LVC 50%; p < 0.001) with longer length-of-stay (p < 0.001). Extracorporeal membrane oxygenation was used in 136 (10%) and provided primarily at HVC. LVC treated proportionately more non-white Hispanic patients (p < 0.001) and patients from counties along the Mexican border (p < 0.001). The predicted probability of mortality in CDH patients decreases with higher treatment facility CDH case volume, with a 0.5% decrease in the odds of mortality for every additional CDH case treated (p < 0.001). CONCLUSIONS: Patients treated in HVC have significantly lower mortality despite increased severity. Our data suggest minority populations may be disproportionately treated at LVC associated with worse outcomes. TYPE OF STUDY: Retrospective Prognosis Study. LEVEL OF EVIDENCE: Level II.
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Oxigenación por Membrana Extracorpórea , Hernias Diafragmáticas Congénitas , Recién Nacido , Lactante , Humanos , Hernias Diafragmáticas Congénitas/terapia , Estudios Retrospectivos , Pronóstico , ProbabilidadRESUMEN
OBJECTIVE: Scoliosis is a spinal deformation in which the spine takes a lateral curvature, generating an angle in the coronal plane. The conventional method for detecting scoliosis is measurement of the Cobb angle in spine images obtained by anterior X-ray scanning. Ultrasound imaging of the spine is found to be less ionising than traditional radiographic modalities. For posterior ultrasound scanning, alternate indices of the spinous process angle (SPA) and ultrasound curve angle (UCA) were developed and have proven comparable to those of the traditional Cobb angle. In SPA, the measurements are made using the spinous processes as an anatomical reference, leading to an underestimation of the traditionally used Cobb angles. Alternatively, in UCA, more lateral features of the spine are employed for measurement of the main thoracic and thoracolumbar angles; however, clear identification of bony features is required. The current practice of UCA angle measurement is manual. This research attempts to automate the process so that the errors related to human intervention can be avoided and the scalability of ultrasound scoliosis diagnosis can be improved. The key objective is to develop an automatic scoliosis diagnosis system using 3-D ultrasound imaging. METHODS: The novel diagnosis system is a three-step process: (i) finding the ultrasound spine image with the most visible lateral features using the convolutional RankNet algorithm; (ii) segmenting the bony features from the noisy ultrasound images using joint spine segmentation and noise removal; and (iii) calculating the UCA automatically using a newly developed centroid pairing and inscribed rectangle slope method. RESULTS: The proposed method was evaluated on 109 patients with scoliosis of different severity. The results obtained had a good correlation with manually measured UCAs (R2=0.9784 for the main thoracic angle andR2=0.9671 for the thoracolumbar angle) and a clinically acceptable mean absolute difference of the main thoracic angle (2.82 ± 2.67°) and thoracolumbar angle (3.34 ± 2.83°). CONCLUSION: The proposed method establishes a very promising approach for enabling the applications of economic 3-D ultrasound volume projection imaging for mass screening of scoliosis.
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Escoliosis , Humanos , Escoliosis/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagen , Ultrasonografía/métodos , Radiografía , Imagenología TridimensionalRESUMEN
The turbocharged Miller cycle strategy is studied to improve the power density of diesel engines and reduce emissions. A thermodynamic model and a 1D simulation model of turbocharged diesel engine are established. Results show that the introduction of the Miller cycle reduces the thermal efficiency under naturally aspirated conditions because of the low effective compression ratio, whereas it increases the thermal efficiency under a turbocharged condition owing to the energy recovered by the turbocharger. Under restricted combustion pressure and fixed intake mass, the thermal efficiency first increases and then decreases with increasing Miller cycle ratio, and the peaks occur at approximately 30%-50%. The gain of isochoric combustion ratio overlaps the loss of effective compression ratio due to the Miller cycle on the lower side, whereas it reverses on the higher side. With maximum and equal intake mass, the maximum power initially increases and subsequently decreases with increasing Miller cycle ratio, reaching a peak at 40%. Under a fixed isochoric combustion ratio, the thermal efficiency first increases and then decreases with increasing intake mass, and the optimum intake mass corresponding to the highest thermal efficiency decreases with increasing Miller cycle ratio. The lower the restricted combustion pressure is, the higher the gain in power and thermal efficiency by the Miller cycle strategy. Based on the calculation of the 1D model validated using a practical engine, the power can be increased from 41.6 kW/L to 100 kW/L while the brake thermal efficiency can be increased from 34.98% into 38.55% by increasing the Miller cycle ratio from 19% to 30% and the combustion pressure from 17.7 MPa to 35 MPa. With the application of the supercharged Miller cycle, when the Miller cycle ratio is 30% and the power intensity is increased from 60 kW/L to 100 kW/L, NOx decreases by 32.4%, CO decreases by 28%, showing a tendency to decrease and then stabilize, and HC increases by 5.3%. When the power is 80 kW/L and the Miller cycle ratio is increased from 10% to 30%, NOx decreases by 8.6%, CO decreases by 2%, and HC increases by 0.04%.
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Gasolina , Emisiones de Vehículos , Termodinámica , Biocombustibles , Monóxido de Carbono/análisisRESUMEN
The safety and efficacy of transitioning from parenteral to oral antibiotics in patients aged less than 60 days with urinary tract infections were assessed. Patients who transitioned to oral therapy had a lower mean length of stay with no significant difference in medically attended urinary tract infection symptoms within 30 days of treatment.
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INTRODUCTION: Congenital diaphragmatic hernia (CDH) is a complex pathology with severe pulmonary morbidity. Administration of surfactant in CDH is controversial, and the advent of fetoscopic endoluminal tracheal occlusion (FETO) has added further complexity. While FETO has been shown to improve survival outcomes, there are risks of prematurity and potential surfactant deficiency. We aim to evaluate the characteristics and outcomes of surfactant administration for CDH infants and elucidate potential benefits or risks in this unique population. METHODS: A single-center retrospective cohort review of patients with unilateral CDH from September 2015 to July 2022 was performed. Demographics, prognostic perinatal imaging features, and outcomes were collected. Patients were stratified by surfactant administration and history of FETO. Data were analyzed with descriptive statistics, two-sample t-tests, chi-squared analyses, and logistic regression. RESULTS: Of 105 included patients, 19 (18%) underwent FETO and 25 (24%) received surfactant. Overall, surfactant recipients were born at earlier gestational ages and lower birthweights regardless of FETO history. Surfactant recipients possessed significantly worse prenatal prognostic features such as observed to expected total fetal lung volume, observed to expected lung to head ratio, and percent liver herniation. In CDH patients without FETO history, surfactant recipients demonstrated worse outcomes than nonrecipients. This association is notably absent in the FETO population, where surfactant recipients have more favorable survival and comparable outcomes. When controlling for defect severity or surfactant usage, as a proxy for respiratory status, surfactant recipients that underwent FETO trended toward improved survival and decreased ECMO use. CONCLUSIONS: Surfactant administration is not associated with increased morbidity and mortality and may be beneficial in CDH patients that have undergone FETO.
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Hernias Diafragmáticas Congénitas , Embarazo , Lactante , Femenino , Humanos , Hernias Diafragmáticas Congénitas/cirugía , Hernias Diafragmáticas Congénitas/complicaciones , Estudios Retrospectivos , Tensoactivos , Tráquea/cirugía , Fetoscopía/efectos adversos , Fetoscopía/métodosRESUMEN
INTRODUCTION: Congenital lung malformations (CLMs) have a variable natural history. Larger lesions with CLM volume ratio (CVR) ≥ 1.6 are associated with hydrops and fetal mortality. The purpose of this study is to describe the management and outcomes of high-risk (CVR ≥ 1.6) CLM patients. METHODS: A retrospective cohort study was performed for all fetuses evaluated between May 2015 and May 2022. Demographics, prenatal imaging factors, prenatal and postnatal treatment, and outcomes were collected. Descriptive statistics were used to compare the cohorts. RESULTS: Of 149 fetal CLM patients referred to our fetal center, 21/149 (14%) had CVR ≥ 1.6. One CLM patient had intrauterine fetal demise, and 2 patients were lost to follow-up. Of the remaining 18 patients, 11/18 (67%) received maternal steroids. Seven out of 18 patients (39%) underwent resection at the time of delivery with 1/7 (14%) undergoing exutero intrapartum treatment (EXIT)-to-resection, 5/7 (71%) undergoing EXIT-to-exteriorization-to-resection, and 1/7 (14%) undergoing a coordinated delivery to resection; among those undergoing resection, there were 2 fatalities (28.5%). Seven out of 18 (39%) patients required urgent neonatal open lobectomies, and the remaining 4/18 (22%) patients underwent elective thoracoscopic lobectomies with no mortality. CONCLUSIONS: The natural history and outcomes of severe CLM patients remain highly variable. The EXIT-to-exteriorization-to-resection procedure may be a safe and effective approach for a subset of CLM patients with persistent symptoms of mass effect and severe mediastinal shift due to the observed decreased operative time requiring placental support observed in our study.
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Enfermedades Pulmonares , Anomalías del Sistema Respiratorio , Recién Nacido , Humanos , Femenino , Embarazo , Estudios Retrospectivos , Placenta , Anomalías del Sistema Respiratorio/cirugía , Anomalías del Sistema Respiratorio/complicaciones , Enfermedades Pulmonares/congénito , Pulmón/cirugía , Ultrasonografía Prenatal/métodosRESUMEN
OBJECTIVE: The aim of the work described here was to determine whether 3-D ultrasound can provide results comparable to those of conventional X-ray examination in assessing curve progression in patients with adolescent idiopathic scoliosis (AIS). METHODS: One hundred thirty-six participants with AIS (42 males and 94 females; age range: 10-18 y, mean age: 14.1 ± 1.9 y) with scoliosis of different severity (Cobb angle range: 10º- 85º, mean: of 24.3 ± 14.4º) were included. Each participant underwent biplanar low-dose X-ray EOS and 3-D ultrasound system scanning with the same posture on the same date. Participants underwent the second assessment at routine clinical follow-up. Manual measurements of scoliotic curvature on ultrasound coronal projection images and posterior-anterior radiographs were expressed as the ultrasound curve angle (UCA) and radiographic Cobb angle (RCA), respectively. RCA and UCA increments ≥5º represented a scoliosis progression detected by X-ray assessment and 3-D ultrasound assessment, respectively. RESULTS: The sensitivity and specificity of UCA measurement in detecting scoliosis progression were 0.93 and 0.90, respectively. The negative likelihood ratio of the diagnostic test for scoliosis progression by the 3-D ultrasound imaging system was 0.08. CONCLUSION: The 3-D ultrasound imaging method is a valid technique for detecting coronal curve progression as compared with conventional radiography in follow-up of AIS. Substituting conventional radiography with 3-D ultrasound is effective in reducing the radiation dose to which AIS patients are exposed during their follow-up examinations.
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Cifosis , Escoliosis , Masculino , Femenino , Humanos , Adolescente , Niño , Escoliosis/diagnóstico por imagen , Cifosis/diagnóstico por imagen , Radiografía , Ultrasonografía , Rayos XRESUMEN
Sodium iodate (NaIO3) is a commonly used model for age-related macular degeneration (AMD), but its rapid and severe induction of retinal pigment epithelial (RPE) and photoreceptor degeneration can lead to the premature dismissal of potentially effective therapeutics. Additionally, little is known about how sex and age affect the retinal response to NaIO3. This study aims to establish a less severe yet reproducible regimen by testing low doses of NaIO3 while considering age- and sex-related effects, enabling a broader range of therapeutic evaluations. In this study, young (3-5 months) and old (18-24 months) male and female C57Bl/6J mice were given an intraperitoneal (IP) injection of 15, 20, or 25 mg/kg NaIO3. Damage assessment one week post-injection included in vivo imaging, histological examination, and qRT-PCR analysis. The results revealed that young mice showed no damage at 15 mg/kg IP NaIO3, with varying degrees of damage observed at 20 mg/kg. At 25 mg/kg, most young mice displayed widespread retinal damage, with females exhibiting less retinal thinning than males. In contrast, older mice at 20 and 25 mg/kg displayed a more patchy degeneration pattern, outer retinal undulations, and greater variability in degeneration than the young mice. The most effective model for minimizing damage while maintaining consistency utilizes young female mice injected with 25 mg/kg NaIO3. The observed sex- and age-related differences underscore the importance of considering these variables in research, aligning with the National Institutes of Health's guidance. While the model does not fully replicate the complexity of AMD, these findings enhance its utility as a valuable tool for testing RPE/photoreceptor protective or replacement therapies.
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Degeneración Macular , Degeneración Retiniana , Femenino , Masculino , Ratones , Animales , Retina/patología , Degeneración Retiniana/inducido químicamente , Degeneración Retiniana/patología , Degeneración Macular/tratamiento farmacológico , Degeneración Macular/patología , Yodatos/toxicidad , Ratones Endogámicos C57BL , Epitelio Pigmentado de la Retina/patología , Modelos Animales de EnfermedadRESUMEN
OBJECTIVES: Although the SynCardia total artificial heart (SynCardia Systems, LLC) was approved for use as a bridge to transplantation in 2004 in the United States, most centers do not adopt the total artificial heart as a standard bridging strategy for patients with biventricular failure. This study was designed to characterize the current use and outcomes of patients placed on total artificial heart support. METHODS: The United Network of Organ Sharing Standard Transplant Research File was queried to identify total artificial heart implantation in the United States between 2005 and 2018. Multivariable Cox regression models were used for risk prediction. RESULTS: A total of 471 patients (mean age, 49 years; standard deviation, 13 years; 88% were male) underwent total artificial heart implantation. Of 161 transplant centers, 11 centers had cumulative volume of 10 or more implants. The 6-month cumulative incidence of mortality on the total artificial heart was 24.6%. The 6-month cumulative incidence of transplant was 49.0%. The 1-year mortality post-transplantation was 20.0%. Cumulative center volume less than 10 implants was predictive of both mortality on the total artificial heart (hazard ratio, 2.2, 95% confidence interval, 1.5-3.1, P < .001) and post-transplant mortality after a total artificial heart bridge (hazard ratio, 1.5, 95% confidence interval, 1.0-2.2, P = .039). CONCLUSIONS: Total artificial heart use is low, but the total artificial heart can be an option for biventricular bridge to transplant with acceptable bridge to transplant and post-transplant survival, especially in higher-volume centers. The observation of inferior outcomes in lower-volume centers raises questions as to whether targeted training, center certifications, and minimum volume requirements could improve outcomes for patients requiring the total artificial heart.
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Insuficiencia Cardíaca , Trasplante de Corazón , Corazón Artificial , Humanos , Masculino , Estados Unidos , Persona de Mediana Edad , Femenino , Trasplante de Corazón/efectos adversos , Resultado del Tratamiento , Insuficiencia Cardíaca/cirugía , Incidencia , Estudios RetrospectivosRESUMEN
INTRODUCTION: Congenital lung malformations (CLMs) are readily identified early in pregnancy with a variable natural history. Monitoring for lesion size and mediastinal shift (MS) is recommended following diagnosis. The purpose of this study is to propose a risk-stratified clinical algorithm for prenatal monitoring of CLM. METHODS: After ethical approval, all fetuses with CLMs evaluated at our fetal center from January 2015 to June 2022 were retrospectively reviewed. Patient demographics, imaging characteristics, and fetal interventions were collected. Lesions were stratified by congenital lung malformation volume ratio (CVR) and the presence of MS. Descriptive statistics and receiver operating characteristic curves were employed in the analysis. RESULTS: We analyzed 111 patients with a mean of 23.4 wk gestational age, a median CVR of 0.5 (interquartile range, 0.3-1.2), and MS in 76 of 111(68%) patients on initial evaluation. Among low-risk patients (CVR ≤1.1), 96% remained low-risk on final evaluation. No patients transitioned from low to high risk during the growth period. Patients with CVR >1.1 often had persistent MS (P < 0.001). Hydrops (5/111, 5%) and fetal intervention (4/111, 4%) only occurred in patients with CVR >1.1 (P < 0.001, P = 0.002) and MS (P = 0.144, P = 0.214). On receiver operating characteristic curve analysis, initial CVR >1.1 had 100% sensitivity and negative predictive value for hydrops and fetal intervention. CONCLUSIONS: CLMs with initial CVR ≤1.1 are low risk for hydrops and fetal intervention. We propose a risk-stratified algorithm for the monitoring of CLM during the growth period based on CVR. While our experience suggests that patients with CLM and MS are at higher risk, the current subjective assessment of MS is not adequately predictive. Incorporating an MS grading system may further refine risk stratification in the management of CLM.
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Enfermedades Pulmonares , Anomalías del Sistema Respiratorio , Embarazo , Femenino , Humanos , Estudios Retrospectivos , Ultrasonografía Prenatal/métodos , Enfermedades Pulmonares/congénito , Pulmón/diagnóstico por imagen , Pulmón/anomalías , EdemaRESUMEN
Danionella cerebrum (DC) is a promising vertebrate animal model for systems neuroscience due to its small adult brain volume and inherent optical transparency, but the scope of their cognitive abilities remains an area of active research. In this work, we established a behavioral paradigm to study visual spatial navigation in DC and investigate their navigational capabilities and strategies. We initially observed that adult DC exhibit strong negative phototaxis in groups but less so as individuals. Using their dark preference as a motivator, we designed a spatial navigation task inspired by the Morris water maze. Through a series of environmental cue manipulations, we found that DC utilize visual cues to anticipate a reward location and found evidence for landmark-based navigational strategies wherein DC could use both proximal and distal visual cues. When subsets of proximal visual cues were occluded, DC were capable of using distant contextual visual information to solve the task, providing evidence for allocentric spatial navigation. Without proximal visual cues, DC tended to seek out a direct line of sight with at least one distal visual cue while maintaining a positional bias toward the reward location. In total, our behavioral results suggest that DC can be used to study the neural mechanisms underlying spatial navigation with cellular resolution imaging across an adult vertebrate brain.
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Cerebro , Navegación Espacial , Animales , Aprendizaje por Laberinto , Encéfalo , Señales (Psicología) , Peces , Percepción EspacialRESUMEN
Urine is assayed alongside blood in medicine, yet current clinical diagnostic tests utilize only a small fraction of its total biomolecular repertoire, potentially foregoing high-resolution insights into human health and disease. In this work, we characterized the joint landscapes of transcriptomic and metabolomic signals in human urine. We also compared the urine transcriptome to plasma cell-free RNA, identifying a distinct cell type repertoire and enrichment for metabolic signal. Untargeted metabolomic measurements identified a complementary set of pathways to the transcriptomic analysis. Our findings suggest that urine is a promising biofluid yielding prognostic and detailed insights for hard-to-biopsy tissues with low representation in the blood, offering promise for a new generation of liquid biopsies.
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PURPOSE: Development of intelligence systems for bladder lesion detection is cost intensive. An efficient strategy to develop such intelligence solutions is needed. MATERIALS AND METHODS: We used four deep learning models (ConvNeXt, PlexusNet, MobileNet, and SwinTransformer) covering a variety of model complexity and efficacy. We trained these models on a previously published educational cystoscopy atlas (n = 312 images) to estimate the ratio between normal and cancer scores and externally validated on cystoscopy videos from 68 cases, with region of interest (ROI) pathologically confirmed to be benign and cancerous bladder lesions (ie, ROI). The performance measurement included specificity and sensitivity at frame level, frame sequence (block) level, and ROI level for each case. RESULTS: Specificity was comparable between four models at frame (range, 30.0%-44.8%) and block levels (56%-67%). Although sensitivity at the frame level (range, 81.4%-88.1%) differed between the models, sensitivity at the block level (100%) and ROI level (100%) was comparable between these models. MobileNet and PlexusNet were computationally more efficient for real-time ROI detection than ConvNeXt and SwinTransformer. CONCLUSION: Educational cystoscopy atlas and efficient models facilitate the development of real-time intelligence system for bladder lesion detection.
Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Vejiga Urinaria/patología , Sensibilidad y Especificidad , CistoscopíaRESUMEN
Biomechanical studies play an important role in understanding the pathophysiology of sleep disorders and providing insights to maintain sleep health. Computational methods facilitate a versatile platform to analyze various biomechanical factors in silico, which would otherwise be difficult through in vivo experiments. The objective of this review is to examine and map the applications of computational biomechanics to sleep-related research topics, including sleep medicine and sleep ergonomics. A systematic search was conducted on PubMed, Scopus, and Web of Science. Research gaps were identified through data synthesis on variants, outcomes, and highlighted features, as well as evidence maps on basic modeling considerations and modeling components of the eligible studies. Twenty-seven studies (n = 27) were categorized into sleep ergonomics (n = 2 on pillow; n = 3 on mattress), sleep-related breathing disorders (n = 19 on obstructive sleep apnea), and sleep-related movement disorders (n = 3 on sleep bruxism). The effects of pillow height and mattress stiffness on spinal curvature were explored. Stress on the temporomandibular joint, and therefore its disorder, was the primary focus of investigations on sleep bruxism. Using finite element morphometry and fluid-structure interaction, studies on obstructive sleep apnea investigated the effects of anatomical variations, muscle activation of the tongue and soft palate, and gravitational direction on the collapse and blockade of the upper airway, in addition to the airflow pressure distribution. Model validation has been one of the greatest hurdles, while single-subject design and surrogate techniques have led to concerns about external validity. Future research might endeavor to reconstruct patient-specific models with patient-specific loading profiles in a larger cohort. Studies on sleep ergonomics research may pave the way for determining ideal spine curvature, in addition to simulating side-lying sleep postures. Sleep bruxism studies may analyze the accumulated dental damage and wear. Research on OSA treatments using computational approaches warrants further investigation.
RESUMEN
This study aims to advance the theoretical understanding of the contextual antecedents underlying abusive supervision. It provides a fresh perspective on how subordinates' perceptions of an abusive supervision climate are shaped in temporary work environments. By developing a robust model, this research examines the relationships between temporary organizational characteristics (i.e., temporariness and membership flexibility), trust in ad-hoc supervisors, and perceived abusive supervision climates. We tested the hypothesized model using data from 340 aircrew engaged in temporary and constantly shifting supervisor-subordinate relationships. The results revealed that: (a) temporariness has a direct negative relationship with trust in ad-hoc supervisors, whereas membership flexibility positively affects this trust; (b) the link between temporariness/membership flexibility and a perceived abusive supervision climate is mediated by trust in ad-hoc supervisors. Furthermore, this study highlights gender interactions in a transactional context, indicating that: (c) females perceive a stronger negative association between trust and abusive supervision climates compared to males; and (d) the relationship between temporariness/membership flexibility and trust in ad-hoc supervisors is significant for women and men, respectively. In conclusion, this study underscores the importance of considering the unique organizational characteristics of temporary work settings when examining abusive supervision. It also emphasizes the role of gender in shaping subordinates' perceptions of a workplace victimization climate, particularly in situations where leader-member exchanges are ephemeral and contractual.