Inward rectifier (IR) currents were studied in bovine pulmonary artery endothelial cells in the whole-cell configuration of the patch-clamp technique with extracellular K + concentrations, [K+]o, ranging from 4.5 to 160 mM. Whether the concentration of free Mg ~+ in the intraceUular solution, [Mg~+]i , was 1.9 mM or nominally 0, the IR exhibited voltage-and time-dependent gating. The IR conductance was activated by hyperpolarization and deactivated by depolarization. Small steady-state outward IR currents were present up to ~40 mV more positive than the K + reversal potential, EK, regardless of [Mg~+]i. Modeled as a first-order C ~ O gating process, both the opening rate, a, and the closing rate,/3, were exponentially dependent on voltage, with/3 more steeply voltage dependent, changing e-fold for 9 mV compared with 18 mV for an e-fold change in a. Over all [K+]o studied, the voltage dependence of a and 13 shifted along with EK, as is characteristic of IR channels in other cells. The steady-state voltage dependence of the gating process was well described by a Boltzmann function. The half-activation potential was on average ~7 mV negative to the observed reversal potential in all [K+]o regardless of [Mg~+]i. The activation curve was somewhat steeper when Mg-free pipette solutions were used (slope factor, 4.3 mV) than when pipettes contained 1.9 mM Mg 2+ (5.2 mV). The simplest interpretation of these data is that IR channels in bovine pulmonary artery endothelial cells have an intrinsic gating mechanism that is not due to Mg block.
Objective
To analyze diffusion tensor imaging (DTI) data in the substantia nigra (SN) using a more consistent region of interest defined by neuromelanin-sensitive MRI in order to assess Parkinson's disease (PD) related changes in diffusion characteristics in the SN.
Methods
T1-weighted and DTI data were obtained in a cohort of 37 subjects (20 control subjects and 17 subjects with PD). The subjects in the PD group were clinically diagnosed PD patients with an average Unified Parkinsonian Disease Rating Scale (UPDRS)-III score of 23.2±9.3. DTI data were analyzed using SN ROIs defined by neuromelanin-sensitive MRI and, for comparison, with ROIs defined on T2-weighted images (b=0 images).
Results
Compared to control subjects, significantly lower fractional anisotropy was observed in PD in the neuromelanin SN ROI but not in the ROI derived from the T2-weighted image. This decrease was largest in the rostral and lateral portions of the neuromelanin volume, which were found to have more hypointensity in the T2-weighted image and, presumably, higher iron content in the PD group. In addition, a larger decrease in fractional anisotropy was seen in the SN region of interest on the side contralateral to the side exhibiting more severe symptoms. These results indicate that the use of neuromelanin sensitive MRI to define the ROI in the SN for analyzing DTI data leads to more significant results, enhancing the robustness of DTI study and DTI based biomarkers of PD.
Patients undergoing prolonged ventilation have high hospital and 6-month mortality rates, and 6-month outcomes are not significantly different for those transferred to long-term acute-care facilities. These patients generate high costs, and acute-care hospitals are significantly underreimbursed by Medicare for these costs. Acute-care hospitals can reduce the amount of uncompensated care by earlier transfer of appropriate patients to a long-term acute-care facility.
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