The Vitamin D Metabolite Ratio (VMR) is a Biomarker of Vitamin D Status That is Not Affected by Acute Changes in Vitamin D Binding Protein.

BACKGROUND: 25-hydroxyvitamin D[25(OH)D] may be a poor marker of vitamin D status due to variability in levels of vitamin D binding protein (VDBP). The vitamin D metabolite ratio (VMR) is the ratio of 24,25-dihydroxyvitamin D[24,25(OH)2D3] to 25(OH)D3 and has been postulated to reflect vitamin D sufficiency independent of variability in VDBP. Therapeutic plasma exchange (TPE) is a procedure that removes plasma, including VDBP, and may lower bound vitamin D metabolite concentrations. Effects of TPE on the VMR are unknown. METHODS: We measured 25(OH)D, free 25(OH)D, 1,25-dihydroxyvitamin D[1,25(OH)2D], 24,25(OH)2D3, and VDBP in persons undergoing TPE, before and after treatment. We used paired t-tests to assess changes in these biomarkers during a TPE procedure. RESULTS: Study participants (n = 45) had a mean age of 55 ± 16 years; 67% were female; and 76% were white. Compared to pretreatment concentrations, TPE caused a significant decrease in total VDBP by 65% (95%CI 60,70%), as well as all the vitamin D metabolites-25(OH)D by 66% (60%,74%), free 25(OH)D by 31% (24%,39%), 24,25(OH)2D3 by 66% (55%,78%) and 1,25(OH)2D by 68% (60%,76%). In contrast, there was no significant change in the VMR before and after a single TPE treatment, with an observed mean 7% (-3%, 17%) change in VMR. CONCLUSIONS: Changes in VDBP concentration across TPE parallel changes in 25(OH)D, 1,25(OH)2D, and 24,25(OH)2D3, suggesting that concentrations of these metabolites reflect underlying VDBP concentrations. The VMR is stable across a TPE session despite a 65% reduction in VDBP. These findings suggest that the VMR is a marker of vitamin D status independent of VDBP levels.

Long Term Potentiation in Mouse Hippocampal Slices in an Undergraduate Laboratory Course.

Long-term potentiation (LTP) is thought to be a critical mechanism underlying learning and memory. Although LTP is now widely performed in neuroscience research laboratories and the theory behind it is taught in many undergraduate courses, it is rare for undergraduate students to have the opportunity to perform LTP experiments themselves. Here, we describe a series of two laboratory sessions in which upper level students learn how to perform LTP experiments in acute hippocampal slices from wild type mice. In Laboratory 1, students practice the techniques necessary to set up the experiments. These techniques include making solutions, pulling glass recording electrodes, performing brain removal, preparing hippocampal slices, and positioning electrodes in area CA1. For Laboratory 2, hippocampal slices are prepared in advance by the instructors. Students record LTP by stimulating the Schaffer collateral axons and recording postsynaptic field potential responses in the apical dendritic region of area CA1. Once the students determine appropriate stimulus strength, they collect baseline responses, deliver a tetanic stimulus, and then collect responses 10 and 30 minutes following tetanic stimulation. Students analyze the data in LabChart 7 (ADInstruments - North America, Colorado Springs, CO, 2011) and perform appropriate statistical tests to determine whether potentiation has occurred. These laboratory exercises provide a unique opportunity for students to gain an appreciation for the techniques that are fundamental to studies of neural electrophysiology and plasticity as evidenced through a learning assessment tool.

Nivolumab Immunotherapy in Malignant Mesothelioma: A Case Report Highlighting a New Opportunity for Exceptional Outcomes.

BACKGROUND Malignant pleural mesothelioma (MPM) is a highly lethal cancer with a median survival of ~12 months even with aggressive intervention. Frontline therapy relies on systemic cisplatin and pemetrexed chemotherapy and has a response rate of ~35-41%; currently, there are no US Food and Drug Administration approved second-line therapies for MPM. Herein, we present a patient with MPM who experienced rapid disease progression after standard therapy but who had an exceptional and sustained response to immune checkpoint inhibition with single agent nivolumab. CASE REPORT A 68-year-old male with a history of work-related asbestos exposure was diagnosed with MPM. He was treated with primary resection followed by systemic chemotherapy with cisplatin and pemetrexed. When chemotherapy failed, he was switched to immunotherapy with nivolumab and achieved an exceptional response. CONCLUSIONS We report the first case of a patient with MPM who experienced rapid disease progression after standard therapy but had an exceptional and sustained response to immune checkpoint inhibition with single agent nivolumab. As outcomes with traditional chemotherapy regimens remain disappointing, there is a substantial need for new approaches to MPM; our case highlights a new therapeutic opportunity even in the face of aggressive disease. Indeed, a new era of investigation utilizing immunotherapy for mesothelioma is beginning, with much anticipation.