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Quantum transducers convert quantum signals through hybrid interfaces of physical platforms in quantum networks. Modeled as quantum communication channels, performance of unidirectional quantum transduction can be measured by the quantum channel capacity. However, characterizing performance of quantum transducers used for duplex quantum transduction where signals are converted bidirectionally remains an open question. Here, we propose rate regions to characterize the performance of duplex quantum transduction. Using this tool, we find that quantum transducers optimized for simultaneous duplex transduction can outperform strategies based on the standard protocol of time-shared unidirectional transduction. Integrated over the frequency domain, we demonstrate that the rate region can also characterize quantum transducers with finite bandwidth.
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AIM: Transcutaneous electrical cranial-auricular acupoint stimulation (TECAS) is a novel non-invasive therapy that stimulates acupoints innervated by the trigeminal and auricular vagus nerves. An assessor-blinded, randomized, non-inferiority trial was designed to compare the efficacy of TECAS and escitalopram in mild-to-moderate major depressive disorder. METHODS: 468 participants received two TECAS sessions per day at home (n = 233) or approximately 10-13 mg/day escitalopram (n = 235) for 8 weeks plus 4-week follow-up. The primary outcome was clinical response, defined as a baseline-to-endpoint ≥50% reduction in Montgomery-Åsberg Depression Rating Scale (MADRS) score. Secondary outcomes included remission rate, changes in the severity of depression, anxiety, sleep and life quality. RESULTS: The response rate was 66.4% on TECAS and 63.2% on escitalopram with a 3.2% difference (95% confidence interval [CI], -5.9% to 12.9%) in intention-to-treat analysis, and 68.5% versus 66.2% with a 2.3% difference (95% CI, -6.9% to 11.4%) in per-protocol analysis. The lower limit of 95% CI of the differences fell within the prespecified non-inferiority margin of -10% (P ≤ 0.004 for non-inferiority). Most secondary outcomes did not differ between the two groups. TECAS-treated participants who experienced psychological trauma displayed a markedly greater response than those without traumatic experience (81.3% vs 62.1%, P = 0.013). TECAS caused much fewer adverse events than escitalopram. CONCLUSIONS: TECAS was comparable to escitalopram in improving depression and related symptoms, with high acceptability, better safety profile, and particular efficacy in reducing trauma-associated depression. It could serve an effective portable therapy for mild-to-moderate depression.
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Trastorno Depresivo Mayor , Escitalopram , Humanos , Puntos de Acupuntura , Citalopram , Depresión/tratamiento farmacológico , Trastorno Depresivo Mayor/tratamiento farmacológico , Método Doble Ciego , Resultado del TratamientoRESUMEN
The embryo-maternal interaction occurs during the early stages of embryo development and is essential for the implantation and full-term development of the embryo. In bovines, the secretion of interferon Tau (IFNT) during elongation is the main signal for pregnancy recognition, but its expression starts around the blastocyst stage. Embryos release extracellular vesicles (EVs) as an alternative mechanism of embryo-maternal communication. The aim of the study was to determine whether EVs secreted by bovine embryos during blastulation (D5-D7) could induce transcriptomic modifications, activating IFNT signaling in endometrial cells. Additionally, it aims to assess whether the EVs secreted by embryos produced in vivo (EVs-IVV) or in vitro (EVs-IVP) have different effects on the transcriptomic profiles of the endometrial cells. In vitro- and in vivo-produced bovine morulae were selected and individually cultured for 48 h to collect embryonic EVs (E-EVs) secreted during blastulation. E-EVs stained with PKH67 were added to in vitro-cultured bovine endometrial cells to assess EV internalization. The effect of EVs on the transcriptomic profile of endometrial cells was determined by RNA sequencing. EVs from both types of embryos induced several classical and non-classical IFNT-stimulated genes (ISGs) and other pathways related to endometrial function in epithelial endometrial cells. Higher numbers of differentially expressed genes (3552) were induced by EVs released by IVP embryos compared to EVs from IVV (1838). Gene ontology analysis showed that EVs-IVP/IVV induced the upregulation of the extracellular exosome pathway, the cellular response to stimulus, and the protein modification processes. This work provides evidence regarding the effect of embryo origin (in vivo or in vitro) on the early embryo-maternal interaction mediated by extracellular vesicles.
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Embrión de Mamíferos , Vesículas Extracelulares , Animales , Bovinos , Femenino , Embarazo , Blastocisto/metabolismo , Embrión de Mamíferos/metabolismo , Desarrollo Embrionario/genética , Endometrio , Vesículas Extracelulares/metabolismo , Parto , Interferones/metabolismoRESUMEN
Solar water splitting by photoelectrochemical (PEC) reactions is promising for hydrogen production. The gold nanoparticles (AuNPs) are often applied to promote the visible response of wideband photocatalysts. However, in a typical TiO2/AuNPs structure, the opposite transfer direction of excited electrons between AuNPs and TiO2 under visible light and UV light severely limits the solar PEC performance. Here we present a unique Pt/TiO2/Cu2O/NiO/AuNPs photocathode, in which the NiO hole transport layer (HTL) is inserted between AuNPs and Cu2O to achieve unidirectional transport of charge carriers and prominent plasmon-induced resonance energy transfer (PIRET) between AuNPs and Cu2O. The measured applied bias photon-to-current efficiency and the hydrogen production rate under AM 1.5G illumination can reach 1.5% and 16.4 µmol·cm-2·h-1, respectively. This work is original in using the NiO film as the PIRET spacer and provides a promising photoelectrode for energy-efficient solar water splitting.
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We analyze the ultimate quantum limit of resolving two identical sources in a noisy environment. We prove that in the presence of noise causing false excitation, such as thermal noise, the quantum Fisher information of arbitrary quantum states for the separation of the objects, which quantifies the resolution, always converges to zero as the separation goes to zero. Noisy cases contrast with noiseless cases where the quantum Fisher information has been shown to be nonzero for a small distance in various circumstances, revealing the superresolution. In addition, we show that false excitation on an arbitrary measurement, such as dark counts, also makes the classical Fisher information of the measurement approach to zero as the separation goes to zero. Finally, a practically relevant situation resolving two identical thermal sources is quantitatively investigated by using the quantum and classical Fisher information of finite spatial mode multiplexing, showing that the amount of noise poses a limit on the resolution in a noisy system.
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BACKGROUND: There are no clear indicators for predicting return to work for patients with chronic low back pain (LBP). We aim to report the outcomes of a 14-week multidisciplinary programme targeting patients with chronic LBP who failed conventional physiotherapy to provide functional rehabilitation. Also, this study will identify factors predicting successful return to work (RTW). METHODS: A collected cohort of patients with chronic LBP was consecutively enrolled into the programme from 1996 to 2014. All recruited patients failed to RTW despite at least 3 months of conservative treatment. Patient underwent weekly multidisciplinary sessions with physiotherapists, occupational therapists and clinical psychologists. Patient perceived function was considered the primary outcome of the programme. Patients were assessed for their sitting, standing and walking tolerance. Oswestry Disability Index (ODI) and Spinal Function Sort Score (SFSS) were used to assess patient perceived disability. RESULTS: One hundred and fifty-eight patients were recruited. After the programme, statistically significant improvement was found in ODI (47.5 to 45.0, p = 0.01) and SFSS (98.0 to 109.5, p < 0.001). There was statistically significant improvement (p < 0.01) in sitting, standing, walking tolerance and straight leg raise tests. 47.4% of the patients were able to meet their work demand. Multivariate logistic regression model (R2 = 59.5%, χ2 (9) = 85.640, p < 0.001) demonstrated that lower initial job demand level and higher patient-perceived back function correlated with greater likelihood of returning to work. CONCLUSION: The results of this study may support the use of this multidisciplinary programme to improve patient function and return to work.
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Dolor de la Región Lumbar , Humanos , Dolor de la Región Lumbar/diagnóstico , Dolor de la Región Lumbar/terapia , Dimensión del Dolor , Modalidades de Fisioterapia , Reinserción al Trabajo , Resultado del TratamientoRESUMEN
OBJECTIVES: Intrathecal baclofen pump associated central nervous system (CNS) infection and meningitis is a rare but serious complication and may have dire consequences. Due to bacterial biofilm formation, the optimal treatment strategy is usually for removal of the pump, followed by systemic antibiotics for treatment of local and CNS infection. We describe this case of a patient with recurrent Staphylococcus aureus pump site empyema and meningitis leading to status dystonicus, who was successfully managed with radical debridement and intrareservoir baclofen-vancomycin co-infusion. MATERIALS AND METHODS: We retrospectively report a case of infected intrathecal baclofen pump with meningitis and provide a full review of literature. CONCLUSIONS: To the best of our knowledge, this is the first reported case of intrathecal baclofen (ITB)-associated pump site empyema and meningitis successfully treated with this technique. In selected cases where surgical explantation is deemed not feasible, this method can provide clinicians with an additional option for pump salvage and retention, while eradicating CNS infection and maintaining optimal control of spasticity and dystonia.
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Meningitis , Relajantes Musculares Centrales , Baclofeno/uso terapéutico , Desbridamiento , Humanos , Bombas de Infusión Implantables , Inyecciones Espinales , Meningitis/tratamiento farmacológico , Relajantes Musculares Centrales/uso terapéutico , Espasticidad Muscular/tratamiento farmacológico , Espasticidad Muscular/etiología , Estudios Retrospectivos , Vancomicina/uso terapéuticoRESUMEN
Ancilla systems are often indispensable to universal control of a nearly isolated quantum system. However, ancilla systems are typically more vulnerable to environmental noise, which limits the performance of such ancilla-assisted quantum control. To address this challenge of ancilla-induced decoherence, we propose a general framework that integrates quantum control and quantum error correction, so that we can achieve robust quantum gates resilient to ancilla noise. We introduce the path independence criterion for fault-tolerant quantum gates against ancilla errors. As an example, a path-independent gate is provided for superconducting circuits with a hardware-efficient design.
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During early development, embryos secrete extracellular vesicles (EVs) that participate in embryo-maternal communication. Among other molecules, EVs carry microRNAs (miRNAs) that interfere with gene expression in target cells; miRNAs participate in embryo-maternal communication. Embryo selection based on secreted miRNAs may have an impact on bovine breeding programs. This research aimed to evaluate the size, concentration, and miRNA content of EVs secreted by bovine embryos with different developmental potential, during the compaction period (days 3.5-5). Individual culture media from in vitro-produced embryos were collected at day 5, while embryos were further cultured and classified at day 7, as G1 (conditioned-culture media by embryos arrested in the 8-16-cells stage) and G2 (conditioned-culture media by embryos that reached blastocyst stages at day 7). Collected nanoparticles from embryo conditioned culture media were cataloged as EVs by their morphology and the presence of classical molecular markers. Size and concentration of EVs from G1 were higher than EVs secreted by G2. We identified 95 miRNAs; bta-miR-103, bta-miR-502a, bta-miR-100, and bta-miR-1 were upregulated in G1, whereas bta-miR-92a, bta-miR-140, bta-miR-2285a, and bta-miR-222 were downregulated. The most significant upregulated pathways were fatty acid biosynthesis and metabolism, lysine degradation, gap junction, and signaling pathways regulating pluripotency of stem cells. The characteristics of EVs secreted by bovine embryos during the compaction period vary according to embryo competence. Embryos that reach the blastocyst stage secrete fewer and smaller vesicles. Furthermore, the loading of specific miRNAs into the EVs depends on embryo developmental competence.
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Biomarcadores/metabolismo , Desarrollo Embrionario/genética , Vesículas Extracelulares/genética , MicroARNs/genética , Animales , Blastocisto/metabolismo , Bovinos , Medios de Cultivo Condicionados/farmacología , Técnicas de Cultivo de Embriones , Embrión de Mamíferos , FemeninoRESUMEN
PURPOSE: To highlight the importance of preventing visceral injury due to prominent anterior implants at the spinal column. METHODS: A 52-year-old man with cord compression was treated with a T9/10 discectomy and instrumented fusion via a right thoracotomy and trans-pleural approach. Postoperatively, he had improved lower limb numbness. However, after a bout of coughing, there was sudden increase in chest drain output, hemodynamic instability and massive fluid collection in the right chest cavity. RESULTS: Emergency re-exploration of the thoracotomy was performed and a 6 cm laceration of the right postero-medial diaphragm was identified as the bleeding source and was found to be in close proximity with the locking nut of the anterior implants. The laceration was repaired and a soft synthetic patch was used to cover the implants. Postoperatively, the hemothorax resolved and the patient recovered from the neurological deficit. CONCLUSIONS: Prevention of diaphragmatic injury can be performed using lower profile and less sharp-edged implants. Implant coverage with a soft synthetic material is necessary if unable to perform direct repair of the parietal pleura over the implants.
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Diafragma/lesiones , Discectomía/efectos adversos , Hemotórax/cirugía , Desplazamiento del Disco Intervertebral/cirugía , Laceraciones/cirugía , Complicaciones Posoperatorias/cirugía , Compresión de la Médula Espinal/cirugía , Fusión Vertebral/efectos adversos , Diafragma/cirugía , Hemotórax/etiología , Humanos , Desplazamiento del Disco Intervertebral/complicaciones , Desplazamiento del Disco Intervertebral/diagnóstico por imagen , Laceraciones/etiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Compresión de la Médula Espinal/diagnóstico por imagen , Compresión de la Médula Espinal/etiología , Toracotomía/efectos adversosRESUMEN
PURPOSE: To investigate the rate and predictive factors of post-operative neurological deterioration in ossified yellow ligament (OYL) surgery. METHODS: A retrospective review was conducted for all patients with thoracic OYL causing myelopathy requiring surgical decompression from January 1998 to December 2012. Clinical parameters under study included clinical presentation, distribution of OYL, pre-operative walking score, pre- and post-operative neurological status, status of intra-operative neurophysiological monitoring, and modified Japanese Orthopaedic Association (mJOA) score. Any complications were also recorded. All outcomes were measured at post-operative 1 week and at 2 years. RESULTS: A total of 26 patients were included in this study. Most patients (92.3%) had Frankel grade D pre-operatively. The rate of neurological deterioration was 15.4% and was correlated with the presence of dural tear, extra-dural hematoma and spinal cord injury. Pre-operative walking score was prognostic of patients' walking ability in the post-operative period. Intra-operative monitoring of Somatosensory Evoked Potentials (SSEP) was found to be useful for monitoring spinal cord injury in OYL surgery, with a positive predictive value of 100% and a negative predictive value of 92.3%. The false negative rate of a SSEP signal drop was only 7.7% CONCLUSIONS: This is the first study exploring risk factors for post-operative neurological deterioration after surgery for thoracic OYL. The rate of neurological deficit is not small and prognostic factors for poor outcome include poor pre-operative walking score, presence of intra-operative dural tear, extra-dural hematoma and spinal cord injury, and intra-operative drop of SSEP signal.
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Descompresión Quirúrgica , Ligamento Amarillo/patología , Osificación Heterotópica/complicaciones , Complicaciones Posoperatorias , Compresión de la Médula Espinal/cirugía , Vértebras Torácicas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Evaluación de la Discapacidad , Duramadre/lesiones , Femenino , Hematoma , Humanos , Masculino , Persona de Mediana Edad , Limitación de la Movilidad , Examen Neurológico , Estudios Retrospectivos , Trastornos de la Sensación/etiología , Traumatismos de la Médula EspinalRESUMEN
PURPOSE: There is much variation in the choice, timing and duration of antimicrobial prophylaxis for preventing surgical site infections (SSI) but no guideline exists for scoliosis surgery. The aim of study was to compare the efficacy of two antimicrobial prophylaxis (AMP) protocols with cephazolin in preventing SSI in adolescent idiopathic scoliosis (AIS). METHODS: A retrospective comparative analysis of two post-operative AMP protocols (two postoperative doses versus continued antibiotics till drain removal) was performed. Patient characteristics, pre-operative, intra- and post-operative risk factors for infection, drain use, generic drug name and number of doses administered were recorded from 226 patients with AIS who had undergone posterior spinal fusion. Details of superficial or deep SSI and wound healing aberrations, and serious adverse events were recorded. Analysis was performed to evaluate differences in the pre-, intra- and post-operative variables between the two groups. RESULTS: 155 patients received 2 postoperative doses of AMP and 71 patients had antibiotics till drain removal. The average follow-up was 43 months. The overall rate of SSI was 1.7 % for the spine wound and 1.3 % for the iliac crest wound. 1.9 % of patients with 2 doses of AMP and 1.4 % of patients with antibiotics till drain removal had SSI. No adverse reactions attributable to cephazolin were observed. CONCLUSIONS: This is the first study on the AMP protocol in scoliosis surgery for SSI prevention. Results suggest that two doses of AMP are as effective as continued antimicrobial use until drain removal. Cephazolin appears to be effective and safe for prophylaxis.
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Antibacterianos/administración & dosificación , Profilaxis Antibiótica , Fusión Vertebral , Infección de la Herida Quirúrgica/prevención & control , Adolescente , Adulto , Cefazolina/administración & dosificación , Niño , Remoción de Dispositivos , Drenaje , Femenino , Humanos , Masculino , Estudios Retrospectivos , Escoliosis/cirugía , Adulto JovenRESUMEN
BACKGROUND: The prevalence of pain among cancer patients vary in the cancer trajectory and nurses will encounter patients with cancers who may experience pain. Nurses routinely need to assess and manage pain to deliver quality care. AIM AND METHOD: The study aims to understand the knowledge and attitudes of nurses towards pain management using the self-administered questionnaire-the Knowledge and Attitude Survey Regarding Pain (KASRP). FINDINGS: Some 80 nurses participated in the study with an average overall KASRP score of 56%. Areas that were poorly answered are related to the knowledge about opioids, assessment of pain and management of pain in different scenarios. Factors like nurse-patient relationships and being unfamiliar with opioids may affect the knowledge and attitude of nurses towards pain management. CONCLUSION: Curriculum on pain management needs to consider strategies to help nurses translate knowledge to bedside clinical teaching. It needs to include facts of pain management, and topics regarding self-awareness and clarifying misconceptions.
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Conocimientos, Actitudes y Práctica en Salud , Manejo del Dolor , Humanos , Manejo del Dolor/métodos , Adulto , Encuestas y Cuestionarios , Femenino , Masculino , Persona de Mediana Edad , Actitud del Personal de Salud , Dimensión del Dolor , Competencia ClínicaRESUMEN
Advancements in quantum system lifetimes and control have enabled the creation of increasingly complex quantum states, such as those on multiple bosonic cavity modes. When characterizing these states, traditional tomography scales exponentially with the number of modes in both computational and experimental measurement requirement, which becomes prohibitive as the system size increases. Here, we implement a state reconstruction method whose sampling requirement instead scales polynomially with system size, and thus mode number, for states that can be represented within such a polynomial subspace. We demonstrate this improved scaling with Wigner tomography of multimode entangled W states of up to 4 modes on a 3D circuit quantum electrodynamics (cQED) system. This approach performs similarly in efficiency to existing matrix inversion methods for 2 modes, and demonstrates a noticeable improvement for 3 and 4 modes, with even greater theoretical gains at higher mode numbers.
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Mare endometrosis is a major reproductive problem associated with low fertility and is characterized by persistent inflammation, TGFß-1 signaling, and consequently, extracellular matrix deposition, which compromises endometrial glands. Mesenchymal stem cell-based products (MSCs), such as extracellular vesicles (EVs), have gained attention due to the regulatory effects exerted by their miRNA cargo. Here, we evaluated the impact of preconditioning equine adipose mesenchymal stem cells with TGFß-1 for short or long periods on the anti-fibrotic properties of secreted extracellular vesicles. MSCs were isolated from six healthy horses and exposed to TGFß-1 for 4, 24, and 0 h. The expression of anti-fibrotic and pro-fibrotic miRNAs and mRNAs in treated cells and miRNAs in the cargo of secreted extracellular vesicles was measured. The resulting EVs were added for 48 h to endometrial stromal cells previously induced to a fibrotic status. The expression of anti-fibrotic and pro-fibrotic genes and miRNAs was evaluated in said cells using qPCR and next-generation sequencing. Preconditioning MSCs with TGFß-1 for 4 h enriched the anti-fibrotic miRNAs (mir29c, mir145, and mir200) in cells and EVs. Conversely, preconditioning the cells for 24 h leads to a pro-fibrotic phenotype overexpressing mir192 and mir433. This finding might have implications for developing an EV-based protocol to treat endometrial fibrosis in mares.
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Endometrio , Vesículas Extracelulares , Fibrosis , Células Madre Mesenquimatosas , MicroARNs , Factor de Crecimiento Transformador beta1 , Animales , Caballos , Femenino , Células Madre Mesenquimatosas/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Vesículas Extracelulares/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Endometrio/metabolismo , Endometrio/citología , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Células del Estroma/metabolismo , Células del Estroma/efectos de los fármacos , Enfermedades de los Caballos , Regulación de la Expresión Génica/efectos de los fármacos , Endometriosis/veterinaria , Endometriosis/metabolismo , Endometriosis/genéticaRESUMEN
BACKGROUND: Time-resolved magnetic resonance fingerprinting (MRF), or 4D-MRF, has been demonstrated its feasibility in motion management in radiotherapy (RT). However, the prohibitive long acquisition time is one of challenges of the clinical implementation of 4D-MRF. The shortening of acquisition time causes data insufficiency in each respiratory phase, leading to poor accuracies and consistencies of the predicted tissues' properties of each phase. PURPOSE: To develop a technique for the reconstruction of multi-phase parametric maps in four-dimensional magnetic resonance fingerprinting (4D-MRF) through the optimization of local T1 and T2 sensitivities. METHODS: The proposed technique employed an iterative optimization to tailor the data arrangement of each phase by manipulation of inter-phase frames, such that the T1 and T2 sensitivities, which were quantified by the modified Minkowski distance, of the truncated signal evolution curve was maximized. The multi-phase signal evolution curves were modified by sliding window reconstruction and inter-phase frame sharing (SWIFS). Motion correction (MC) and dot product matching were sequentially performed on the modified signal evolution and dictionary to reconstruct the multi-parametric maps. The proposed technique was evaluated by numerical simulations using the extended cardiac-torso (XCAT) phantom with regular and irregular breathing patterns, and by in vivo MRF data of three health volunteers and six liver cancer patients acquired at a 3.0 T scanner. RESULTS: In simulation study, the proposed SWIFS approach achieved the overall mean absolute percentage error (MAPE) of 8.62% ± 1.59% and 16.2% ± 3.88% for the eight-phases T1 and T2 maps, respectively, in the sagittal view with irregular breathing patterns. In contrast, the overall MAPE of T1 and T2 maps generated by the conventional approach with multiple MRF repetitions were 22.1% ± 11.0% and 30.8% ± 14.9%, respectively. For in-vivo study, the predicted mean T1 and T2 of liver by the proposed SWIFS approach were 795 ms ± 38.9 ms and 58.3 ms ± 11.7 ms, respectively. CONCLUSIONS: Both simulation and in vivo results showed that the approach empowered by T1 and T2 sensitivities optimization and sliding window under the shortened acquisition of MRF had superior performance in the estimation of multi-phase T1 and T2 maps as compared to the conventional approach with oversampling of MRF data.
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Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Imagenología Tridimensional/métodos , Respiración , Fantasmas de Imagen , Procesamiento de Imagen Asistido por Computador/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , MovimientoRESUMEN
Endometrosis in mares is a disease resulting from chronic inflammation characterized by peri glandular fibrosis. There is no effective treatment so far, which opens the door for exploring the use of stem cells as a candidate. Transforming growth factor beta (TGFß) is crucial for the establishment and progression of fibrosis in mare's endometrosis. We aimed to develop regenerative approaches to treat endometrosis by using mesenchymal stem cells (MSC), for which understanding the effect of TGFß on exogenous MSC is crucial. We isolated and characterized equine adipose MSC from six donors. Cells were pooled and exposed to 10 ng/ml of TGFß for 0, 4, and 24 h, after which cells were analyzed for proliferation, migration, mesodermal differentiation, expression of fibrosis-related mRNAs, and prostaglandin E2 secretion. At 24 h of exposition to TGFß, there was a progressive increase in the contraction of the monolayer, leading to nodular structures, while cell viability did not change. Exposure to TGFß impaired adipogenic and osteogenic differentiation after 4 h of treatment, which was more marked at 24 h, represented by a decrease in Oil red and Alizarin red staining, as well as a significant drop (p < 0.05) in the expression of key gene regulators of differentiation processes (PPARG for adipose and RUNX2 for osteogenic differentiation). TGFß increased chondrogenic differentiation as shown by the upsurge in size of the resulting 3D cell pellet and intensity of Alcian Blue staining, as well as the significant up-regulation of SOX9 expression (p < 0.05) at 4 h, which reached a maximum peak at 24 h (p < 0.01), indicative of up-regulation of glycosaminoglycan synthesis. Preconditioning MSC with TGFß led to a significant increase (p < 0.05) in the expression of myofibroblast gene markers aSMA, COL1A1, and TGFß at 24 h exposition time. In contrast, the expression of COL3A1 did not change with respect to the control but registered a significant downregulation compared to 4 h (p < 0.05). TGFß also affected the expression of genes involved in PGE2 synthesis and function; COX2, PTGES, and the PGE2 receptor EP4 were all significantly upregulated early at 4 h (p < 0.05). Cells exposed to TGFß showed a significant upregulation of PGE2 secretion at 4 h compared to untreated cells (p < 0.05); conversely, at 24 h, the PGE2 values decreased significantly compared to control cells (p < 0.05). Preconditioning MSC for 4 h led to an anti-fibrotic secretory phenotype, while a longer period (24 h) led to a pro-fibrotic one. It is tempting to propose a 4-h preconditioning of exogenous MSC with TGFß to drive them towards an anti-fibrotic phenotype for cellular and cell-free therapies in fibrotic diseases such as endometrosis of mares.
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Tejido Adiposo , Enfermedades de los Caballos , Células Madre Mesenquimatosas , Factor de Crecimiento Transformador beta , Animales , Caballos , Femenino , Tejido Adiposo/citología , Tejido Adiposo/metabolismo , Enfermedades de los Caballos/terapia , Enfermedades de los Caballos/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/farmacología , Diferenciación Celular/efectos de los fármacos , Fibrosis , Células Cultivadas , Regulación de la Expresión Génica/efectos de los fármacosRESUMEN
Pre-implantation embryos release extracellular vesicles containing different molecules, including DNA. The presence of embryonic DNA in E-EVs released into the culture medium during in vitro embryo production could be useful for genetic diagnosis. However, the vesicles containing DNA might be derived from embryos suffering from apoptosis, i.e., embryos of bad quality. This work intended to confirm that embryos release DNA that is useful for genotyping by evaluating the effect of embryonic apoptosis on DNA content in E-EVs. Bovine embryos were produced by parthenogenesis and in vitro fertilization (IVF). On Day 5, morulae were transferred to individual cultures in an EV-depleted SOF medium. On Day 7, embryos were used to evaluate cellular apoptosis, and each culture medium was collected to evaluate E-EV concentration, characterization, and DNA quantification. While no effect of the origin of the embryo on the apoptotic rate was found, arrested morulae had a higher apoptotic rate. E-EVs containing DNA were identified in all samples, and the concentration of those vesicles was not affected by the origin or quality of the embryos. However, the concentration of DNA was higher in EVs released by the arrested parthenogenetic embryos. There was a correlation between the concentration of E-EVs, the concentration of DNA-positive E-EVs, and the concentration of DNA. There was no negative effect of apoptotic rate on DNA-positive E-EVs and DNA concentration; however, embryos of the best quality with a low apoptotic rate still released EVs containing DNA. This study confirms that the presence of DNA in E-EVs is independent of embryo quality. Therefore, E-EVs could be used in liquid biopsy for noninvasive genetic diagnosis.
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BACKGROUND: Scoliosis in skeletally immature children is often treated by implantation of a rod to straighten the spine. Rods can be distracted (lengthened) as the spine grows, but patients need many invasive operations under general anaesthesia. Such operations are costly and associated with negative psychosocial outcomes. We assessed the effectiveness and safety of a new magnetically controlled growing rod (MCGR) for non-invasive outpatient distractions. METHODS: We implanted the MCGR in five patients, two of whom have now reached 24 months' follow-up. Each patient underwent monthly outpatient distractions. We used radiography to measure the magnitude of the spinal curvature, rod distraction length, and spinal length. We assessed clinical outcome by measuring the degree of pain, function, mental health, satisfaction with treatment, and procedure-related complications. FINDINGS: In the two patients with 24 months' follow-up, the mean degree of scoliosis, measured by Cobb angle, was 67° (SD 10°) before implantation and 29° (4°) at 24 months. Length of the instrumented segment of the spine increased by a mean of 1·9 mm (0·4 mm) with each distraction. Mean predicted versus actual rod distraction lengths were 2·3 mm (1·2 mm) versus 1·4 mm (0·7 mm) for patient 1, and 2·0 mm (0·2 mm) and 2·1 mm (0·7 mm) versus 1·9 mm (0·6 mm) and 1·7 mm (0·8 mm) for patient 2's right and left rods, respectively. Throughout follow-up, both patients had no pain, had good functional outcome, and were satisfied with the procedure. No MCGR-related complications were noted. INTERPRETATION: The MCGR procedure can be safely and effectively used in outpatient settings, and minimises surgical scarring and psychological distress, improves quality of life, and is more cost-effective than is the traditional growing rod procedure. The technique could be used for non-invasive correction of abnormalities in other disorders. FUNDING: Ellipse Technologies.
Asunto(s)
Cifosis/cirugía , Imanes , Procedimientos Ortopédicos/instrumentación , Prótesis e Implantes , Escoliosis/cirugía , Columna Vertebral/cirugía , Adolescente , Niño , Preescolar , Femenino , Estudios de Seguimiento , Humanos , Cifosis/diagnóstico por imagen , Masculino , Satisfacción del Paciente , Estudios Prospectivos , Radiografía , Escoliosis/diagnóstico por imagen , Columna Vertebral/diagnóstico por imagen , Resultado del TratamientoRESUMEN
Pre-implantation embryos release extracellular vesicles (EVs) to extracellular environment. In this work it is hypothesized that the EVs miRNA cargo will vary during pre-implantation development due to the constant changes in gene expression that take place through this period. The concentration, size and miRNA cargo of EVs secreted by competent bovine embryos during the period from compaction to blastulation (Day 3-7) were analyzed. For this analysis tow developmental windows were defined: W2 from 8-cells (D3) to morula (D5) and W3 from morula (D5) to blastocyst (D7). For W2, in vitro produced embryos were individually cultured in EVs-depleted medium from D3 to D5; culture media were collected and assigned to Group W2. Morulae were kept in culture up to blastocyst stage to determine the developmental competence. For W3, D5 morulae were collected and cultured individually in EVs-depleted medium up to blastocyst stage; culture media were assigned to Group W3, and blastocysts were kept in culture up to day 11 to define their competence. The mean size of EVs was similar between groups, however, EVs concentration was lower in W2. A total of 140 miRNAs were identified. From them, 79 were differentially expressed between the groups, 28 upregulated and 51 downregulated. miRNAs differentially detected between both developmental windows participate in the regulation of signaling pathways which crucial for embryonic development. It was concluded that the secretion of EVs is regulated by the developmental progress of the embryo during the pre-implantation period.