Vascular endothelial growth factor transgene expression in cell-transplanted hearts

AbstractObjectiveWe evaluated the effect of transplanted cell type, time, and region of the heart on transgene expression to determine the potential of combined gene and cell delivery for myocardial repair.MethodsLewis rats underwent myocardial cryoinjury 3 weeks before transplantation with heart cells (a mixed culture of cardiomyocytes, smooth muscle cells, endothelial cells and fibroblasts, n = 13), vascular endothelial growth factor–transfected heart cells (n = 13), skeletal myoblasts (n = 13), vascular endothelial growth factor–transfected skeletal myoblasts (n = 13), or medium (control, n = 12). Vascular endothelial growth factor expression in the scar, border zone, and normal myocardium was evaluated at 3 days and at 1, 2, and 4 weeks by means of quantitative polymerase chain reaction. Transplanted cells and vascular endothelial growth factor protein were identified immunohistologically on myocardial sections.ResultsVascular endothelial growth factor levels were very low in control scars but increased transiently after medium injection. Transplantation with heart cells and skeletal myoblasts significantly increased vascular endothelial growth factor expression in the scar and border zone. Transplantation of vascular endothelial growth factor–transfected heart cells and vascular endothelial growth factor–transfected skeletal myoblasts further augmented vascular endothelial growth factor expression, resulting in 4- to 5-fold greater expression of vascular endothelial growth factor in the scar at 1 week. Peak vascular endothelial growth factor expression was greater and earlier in vascular endothelial growth factor–transfected heart cells than in vascular endothelial growth factor–transfected skeletal myoblasts. Vascular endothelial growth factor was primarily expressed by the transplanted cells. Some of the transplanted heart cells and vascular endothelial growth factor–transfected heart cells were identified in the endothelial layer of blood vessels in the scar.ConclusionsTransplantation of heart cells and skeletal myoblasts induces vascular endothelial growth factor expression in myocardial scars and is greatly augmented by prior transfection with a vascular endothelial growth factor transgene. Vascular endothelial growth factor expression is limited to the scar and border zone for 4 weeks. Both heart cells and skeletal myoblasts may be excellent delivery vehicles for cell-based myocardial gene therapy

Predictors of contemporary coronary artery bypass grafting outcomes

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Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

AbstractDevelopmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.</jats:p

Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients’ primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy

Musik als interpretative Linse: Erfahrungen von Patient/innen nach Herzoperationen

In this article, we highlight the use of music as an interpretive lens to understand patients' experiences of discharge following open-heart surgery. We adopted an arts-informed narrative methodology and interviewed participants at 1 and 4-6 weeks following discharge. Our secondary analysis followed an aesthetic approach that involved application of musical principles including rhythm, timing, and tone to frame our interpretation. We found that the tensions, harmony and relational dynamics between patients and practitioners were best elucidated when viewed through the lens of a solo concerto; this is orchestral work that features a soloist. Our findings have an impact on the discourse of patient-centered care and the need to re-orient communication measures so that practitioners can access the internalized space of patients' mind and body. Since music as an interpretive lens is embryonic in its development, its use has expansive implications for fostering aesthetic knowing in research and health care.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1301171En este artículo, destacamos el uso de la música como una lente interpretativa para comprender las experiencias de los pacientes dados de alta luego de una cirugía a corazón abierto. Adoptamos una metodología narrativa sustentada-en-artes y se entrevistó a los participantes de 1 a 4-6 semanas después de ser dados de alta. Nuestro análisis secundario fue posterior a un enfoque estético que involucró la aplicación de principios musicales como tono, ritmo y sincronización para enmarcar nuestra interpretación. Encontramos que las tensiones, la armonía y la dinámica relacional entre pacientes y profesionales se desarrollaron mejor al ser vistas a través del lente de un concierto de solista; es decir, una obra orquestal ejecutada por un solista. Nuestros hallazgos tienen un impacto en el discurso de la atención centrada en el paciente y la necesidad de reorientar las medidas de comunicación para que los profesionales puedan acceder al espacio interiorizado de la mente y el cuerpo de los pacientes. Dado que la música como una lente interpretativa es embrionaria en su desarrollo, su uso tiene amplias implicaciones para fomentar el saber estético en la investigación y el cuidado de la salud.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs1301171In diesem Beitrag zeigen wir, wie wir Musik genutzt haben, um die Erfahrungen von Patient/innen nach einer Herzoperationen zu verstehen: Im Rahmen eines kunstbasierten narrativen Forschungsansatzes haben wir Herzpatient/innen eine Woche bzw. 4-6 Wochen nach Entlassung interviewt. Mit Blick auf die Analyse haben wir uns mit ästhetischen und musischen Prinzipien wie Rhythmus, Tonfarben usw. beschäftigt. Wir fanden schließlich heraus, dass Spannungen, Harmonien und relationale Dynamiken zwischen Patient/innen und Pflegekräften am besten nachvollzogen werden konnten, wenn hierzu die Metapher eines Solokonzertes mit Orchester hinzugezogen wird.Unsere Ergebnisse sind bedeutsam für die Konzeption einer patient/innenzentrierten Pflege; sie verweisen auf das Erfordernis einer kommunikativen Reorientierung, damit Pflegekräfte Zugang zu den internalisierten mentalen und körperlichen Räumen der Patient/innen finden können.  Die Verwendung von Musik als Mittel der Datenanalyse ist zwar noch rudimentär ist, es hätte aber enorme Konsequenzen, würde das ästhetische Wissen in der Forschung und in der Gesundheitspflege verbessert.URN: http://nbn-resolving.de/urn:nbn:de:0114-fqs130117

Music as an interpretive lens: patients' experiences of discharge following open-heart surgery

"In diesem Beitrag zeigen die Autoren, wie sie Musik genutzt haben, um die Erfahrungen von Patient/ innen nach einer Herzoperationen zu verstehen: Im Rahmen eines kunstbasierten narrativen Forschungsansatzes haben sie Herzpatient/ innen eine Woche bzw. 4-6 Wochen nach Entlassung interviewt. Mit Blick auf die Analyse haben sie sich mit ästhetischen und musischen Prinzipien wie Rhythmus, Tonfarben usw. beschäftigt. Sie fanden schließlich heraus, dass Spannungen, Harmonien und relationale Dynamiken zwischen Patient/ innen und Pflegekräften am besten nachvollzogen werden konnten, wenn hierzu die Metapher eines Solokonzertes mit Orchester hinzugezogen wird. Die Ergebnisse sind bedeutsam für die Konzeption einer patient/ innenzentrierten Pflege; sie verweisen auf das Erfordernis einer kommunikativen Reorientierung, damit Pflegekräfte Zugang zu den internalisierten mentalen und körperlichen Räumen der Patient/ innen finden können. Die Verwendung von Musik als Mittel der Datenanalyse ist zwar noch rudimentär ist, es hätte aber enorme Konsequenzen, würde das ästhetische Wissen in der Forschung und in der Gesundheitspflege verbessert." (Autorenreferat)"In this article, the authors highlight the use of music as an interpretive lens to understand patients' experiences of discharge following open-heart surgery. They adopted an arts-informed narrative methodology and interviewed participants at 1 and 4-6 weeks following discharge. Their secondary analysis followed an aesthetic approach that involved application of musical principles including rhythm, timing, and tone to frame our interpretation. They found that the tensions, harmony and relational dynamics between patients and practitioners were best elucidated when viewed through the lens of a solo concerto; this is orchestral work that features a soloist. The findings have an impact on the discourse of patient-centered care and the need to re-orient communication measures so that practitioners can access the internalized space of patients' mind and body. Since music as an interpretive lens is embryonic in its development, its use has expansive implications for fostering aesthetic knowing in research and health care." (author's abstract

The feasibility of assessing swallowing physiology following prolonged intubation after cardiovascular surgery

Abstract Background Dysphagia following prolonged intubation after cardiovascular (CV) surgery is common occurring in 67% of patients; however, this population’s swallowing physiology has never been prospectively evaluated using standardized methods. Hence, prior to conducting a larger study, our primary objective was to determine the feasibility of assessing swallowing physiology using instrumentation and validated interpretation methods in cardiovascular surgical patients following prolonged intubation. Method From July to October 2011, we approached adults undergoing CV surgery at our institution who were intubated > 48 h. Those with a tracheostomy were excluded. Videofluoroscopic swallowing study (VFS) and nasendoscopy were completed within 48 h after extubation. Feasibility measurements included recruitment rate, patient participation, task completion durations, and the inter-rater reliability of VFS measures using the intraclass correlation coefficient (ICC). VFSs were interpreted using perceptual rating tools (Modified Barium Swallow Measurement Tool for Swallow Impairment™© and Penetration Aspiration Scale) and objective displacement measurements (hyoid displacement and pharyngeal constriction ratio). Results Of the 39 patients intubated > 48 h, 16 met inclusion criteria with three enrolled and completing the VFS. All refused nasendoscopy. Across all VFSs, rating completion time ranged from 14.6 to 51.7 min per patient with ICCs for VFS scales ranging from 0.25 (95% CI − 0.10 to 0.59) to 0.99 (95% CI 0.98 to 0.99). Conclusions This study design was not feasible as recruitment was slow, few patients participated, and no patient agreed to all procedures. We discuss necessary methodological changes and lessons learned that would generalize to future research