KLF15 and PPAR α

The metabolic myocardium is an omnivore and utilizes various carbon substrates to meet its energetic demand. While the adult heart preferentially consumes fatty acids (FAs) over carbohydrates, myocardial fuel plasticity is essential for organismal survival. This metabolic plasticity governing fuel utilization is under robust transcriptional control and studies over the past decade have illuminated members of the nuclear receptor family of factors (e.g., PPARα) as important regulators of myocardial lipid metabolism. However, given the complexity of myocardial metabolism in health and disease, it is likely that other molecular pathways are likely operative and elucidation of such pathways may provide the foundation for novel therapeutic approaches. We previously demonstrated that Kruppel-like factor 15 (KLF15) is an independent regulator of cardiac lipid metabolism thus raising the possibility that KLF15 and PPARα operate in a coordinated fashion to regulate myocardial gene expression requisite for lipid oxidation. In the current study, we show that KLF15 binds to, cooperates with, and is required for the induction of canonical PPARα-mediated gene expression and lipid oxidation in cardiomyocytes. As such, this study establishes a molecular module involving KLF15 and PPARα and provides fundamental insights into the molecular regulation of cardiac lipid metabolism

Glucocorticoids promote structural and functional maturation of foetal cardiomyocytes: a role for PGC-1α

Glucocorticoid levels rise dramatically in late gestation to mature foetal organs in readiness for postnatal life. Immature heart function may compromise survival. Cardiomyocyte glucocorticoid receptor (GR) is required for the structural and functional maturation of the foetal heart in vivo, yet the molecular mechanisms are largely unknown. Here we asked if GR activation in foetal cardiomyocytes in vitro elicits similar maturational changes. We show that physiologically relevant glucocorticoid levels improve contractility of primary-mouse-foetal cardiomyocytes, promote Z-disc assembly and the appearance of mature myofibrils, and increase mitochondrial activity. Genes induced in vitro mimic those induced in vivo and include PGC-1α, a critical regulator of cardiac mitochondrial capacity. SiRNA-mediated abrogation of the glucocorticoid induction of PGC-1α in vitro abolished the effect of glucocorticoid on myofibril structure and mitochondrial oxygen consumption. Using RNA sequencing we identified a number of transcriptional regulators, including PGC-1α, induced as primary targets of GR in foetal cardiomyocytes. These data demonstrate that PGC-1α is a key mediator of glucocorticoid-induced maturation of foetal cardiomyocyte structure and identify other candidate transcriptional regulators that may play critical roles in the transition of the foetal to neonatal heart

Influence of Optic and Haptic Materials on the Adherence of <i>Staphylococcus Epidermidis</i> to Intraocular Lenses: A Pilot Study

To evaluate in vitro the adherence of Staphylococcus epidermidis to intraocular lenses (IOL) of different optic and haptic materials and design, we used a quantitative cultural method. Polymethylmethacrylate (PMMA), PMMA-prolene, polyHEMA, silicone and surface-modified PMMA (wet and dry) implants were tested. Adherence differed significantly in the various groups, with the best performance by all-PMMA IOL. </jats:p

The Evolving Role of the Oncology Nurse in the United States of America&mdash;A Survey Exploring Their Perspective

Background: The role of the oncology nurse has evolved since the COVID-19 pandemic to continuously meet patient needs, resulting in an increased virtual presence. However, there is little information about whether these roles have continued since the pandemic and how it is affecting nurses. Methods: The aim of this study, conducted via an electronic survey questionnaire, was to examine the perspective of oncology nurses in the United States of America regarding how their role has changed, the adaptation to telehealth, challenges, and needs. Results: Over 5 months, 197 respondents from 17 different states completed the survey. They were all registered nurses working in oncology with different roles, such as being nurse practitioners (23%), nurse navigators (20%), infusion nurses (23%), and working in outpatient settings (93%). The findings of the survey highlight the multifaceted responsibilities of nurses in providing care across the cancer care continuum, emphasizing patient-centered care, communication, education, and empowerment, in addition to expected duties such as the administration of anticancer therapy, monitoring of side effects, and symptom management. A total of 82.6% of United States of America oncology nurses feel their workload has increased. The role of nurses in oncology is continuously evolving and the impact of the COVID-19 pandemic, in certain areas such as telehealth, is here to stay. Conclusions: The results of the study allow a better understanding of the emergent roles of oncology nursing. The importance of self-care initiatives and education are emphasized as critical to support nurses in their complex, busy, and emotionally charged work environment and to help retain existing nurses and attract new individuals into the profession. The study ultimately seeks to inform policy and drive professional development in oncology nursing in the United States of America

Thalidomide before autologous stem cell transplantation in VAD-refractory multiple myeloma patients

We used thalidomide to treat 10 patients with advanced stage multiple myeloma who had failed to obtain at least a partial response after a VAD-based induction therapy. Seven out 10 cases achieved clinical and histologic responses and proceeded to collection of peripheral blood stem cells and transplantation and ASCT

Efficacy of bortezomib therapy for extramedullary relapse of myeloma after autologous and non-myeloablative allogeneic transplantation.

We report the successful use of bortezomib to treat a patient with multiple myeloma (MM) who had extramedullary relapse (paraspinal and thoracic masses and multiple cranial nerve palsy) after autologous and non-myeloablative allogeneic hematopoietic stem cell transplantation (HSCT)

Successful treatment of hematological and extramedullary relapse of MLL-positive acute lymphoblastic leukemia after bone marrow transplantation using donor leukocyte infusion

Low response rates (range: 0-33%) were reported in acute lymphoblastic leukemia (ALL) patients who relapsed after bone marrow transplantation (BMT) and received donor leukocyte infusions (DLI). We describe an ALL patient who presented with a relapse in blood, bone marrow, breast, and axillary nodes 3 months after BMT from an unrelated donor. She achieved a second hematological complete remission (CR) after chemotherapy, with persistence of MLL-AF4 transcript in the bone marrow. DLI induced a long-lasting molecular CR that persisted on day 630 of DLI and was associated with a grade III graft-versus-host disease, which was controlled by prednisone, cyclosporine, and infliximab. This case report suggests the existence of an important graft-versus-leukemia (GVL) effect in patients with ALL and adds evidence for the activity of DLI towards extrahematological recurrences and ALL patients carrying t(4;11)

Early chemosensitivity to VAD regimen predicts a favorable outcome after autologous stem cell transplantation in multiple myeloma

We report that early chemosensitivity, defined by a greater than 50% reduction of M-component and plasma-cell marrow infiltration, after 2 cycles of VAD was correlated with a favorable outcome following autologous stem cell transplantation in 46 patients with newly diagnosed multiple myeloma submitted to high-dose therapy

Acute visual loss and chorioretinal infarctionafter photodynamic therapy combined withintravitreal triamcinolone

.Abstract PURPOSE: To report acute visual loss associated with dynamic vascular changes after photodynamic therapy (PDT) combined with intravitreal triamcinolone (IVTA) for the treatment of occult choroidal neovascularization (CNV). METHODS: An 86-year-old woman complained of visual loss in her left eye. Angiographic examination showed a serous pigment epithelium detachment complicated by CNV. She underwent combined treatment with IVTA (4 mg) followed by standard verteporfin PDT administered after a 5-day interval. RESULTS: The patient developed vision loss 1 day after PDT. Ophthalmoscopic examination disclosed an acute serous neurosensory retinal detachment. Fluorescein angiography showed a large area of early hypofluorescence in correspondence to and extending beyond the photodynamic spot. Neurosensory retinal vessels involvement with dilation of the retinal arterioles and capillary nonperfusion were also revealed. Indocyanine green angiography showed choroidal infarction within the collateral choroid included in the area of light exposure, with associated nonperfusion of medium and large choroidal vessels being revealed. Five days after PDT, spontaneous severe bleeding with breakthrough into the vitreous occurred, in addition to an RPE tear. CONCLUSIONS: Acute loss of vision associated with vascular changes in retinal and choroidal circulation represents an uncommon but serious complication following combined PDT and IVTA. These risks should be carefully considered in combination therapies