Subtle heterogeneity of high-affinity choline transporter expression and localization in limbic projections of the cholinergic brainstem tegmentum

The high-affinity choline transporter (CHT) supplies the substrate, choline, for the synthesis of acetylcholine (ACh) within cholinergic neurons. Choline uptake mediated by this protein has been studied for over 30 years and many of the regulatory mechanisms governing its function are well characterized. Early studies, as well as more recent investigations, focused on specific populations of cholinergic axons in the brain, namely the cholinergic innervations of cortical, striatal, and hippocampal regions. Details of the expression and subcellular localization of the high-affinity choline transporter within the projections of the pedunculopontine (PPT) and laterodorsal (LDT) tegmental cholinergic neurons have not been examined. The studies described herein compare the cholinergic axons within two limbic regions that are innervated by the ascending projections from these brainstem nuclei. These experiments were designed to characterize: 1) the relative amount and pattern of subcellular localization of the high-affinity choline transporter protein in the axon varicosities of this projection system; 2) the co-expression of the high-affinity choline transporter and the vesicular acetylcholine transporter in these two populations of axon varicosities; and 3) the organization and possible collateralized projections of the cholinergic neurons that provide cholinergic innervation to these regions. The results of these studies indicate that the expression and localization of the high-affinity choline transporter differs only subtly across brain regions innervated by the brainstem tegmental cholinergic neurons, and suggest that these differences may be accounted for by a pattern of specific innervation arising from distinct subsets of pedunculopontine and laterodorsal tegmental cholinergic neurons

Elimination of the BKCa Channel's High-Affinity Ca2+ Sensitivity

We report here a combination of site-directed mutations that eliminate the high-affinity Ca2+ response of the large-conductance Ca2+-activated K+ channel (BKCa), leaving only a low-affinity response blocked by high concentrations of Mg2+. Mutations at two sites are required, the “Ca2+ bowl,” which has been implicated previously in Ca2+ binding, and M513, at the end of the channel's seventh hydrophobic segment. Energetic analyses of mutations at these positions, alone and in combination, argue that the BKCa channel contains three types of Ca2+ binding sites, one of low affinity that is Mg2+ sensitive (as has been suggested previously) and two of higher affinity that have similar binding characteristics and contribute approximately equally to the power of Ca2+ to influence channel opening. Estimates of the binding characteristics of the BKCa channel's high-affinity Ca2+-binding sites are provided

Digital hypertension management: clinical and cost outcomes of a pilot implementation of the OMRON hypertension management platform

ImportanceHome monitoring of blood pressure (BP) in hypertensive patients can improve outcomes, but challenges to both patient compliance and the effective transmission of home BP readings to physicians can limit the extent to which physicians can use this information to improve care. The OMRON Hypertension Management Platform (OMRON HMP) pairs a home BP cuff with a digital product that tracks data, provides reminders to improve patient compliance, and provides a streamlined source of information to physicians.ObjectiveThe primary objective of the quality improvement (QI) project was to test the hypothesis that use of the OMRON HMP could reduce the number and cost of hypertension related claims, relative to a retrospectively matched cohort of insured members. A secondary objective was to demonstrate improvement in control of BP among patients.DesignEligible members were recruited to the QI project between December 1, 2018 and December 30, 2020 and data collected for six months following recruitment. All members received the OMRON HMP intervention.SettingEnrollment and data collection were coordinated on-site at selected PCP partner providers in Western Pennsylvania. Eligible members were identified from insurance claims data as those receiving care for primary hypertension from participating primary care physicians and/or cardiologists.ParticipantsEligible members were between the ages of 35 and 85, with a diagnosis of primary hypertension. The retrospective cohort was selected from electronic medical records of Highmark-insured patients with hypertension who received care at Allegheny Health Network (AHN), a subsidiary of Highmark Health. Members were matched on baseline BP and lipid measures, age, smoking status, diabetes status, race and sex.InterventionDaily home BP readings were recorded by the OMRON HMP app. Patient data was reviewed by clinical staff on a weekly basis and treatment plans could be adjusted in response to this data.ResultsOMRON HMP users showed a significant increase in the number and cost of hypertension-related claims, contrary to the hypothesis, but did display improvements in control of BP.Conclusions and RelevanceThe use of a digital platform to facilitate at-home BP monitoring appeared to improve BP control but led to increased hypertension-related costs in the short-term

Image1_Digital hypertension management: clinical and cost outcomes of a pilot implementation of the OMRON hypertension management platform.pdf

ImportanceHome monitoring of blood pressure (BP) in hypertensive patients can improve outcomes, but challenges to both patient compliance and the effective transmission of home BP readings to physicians can limit the extent to which physicians can use this information to improve care. The OMRON Hypertension Management Platform (OMRON HMP) pairs a home BP cuff with a digital product that tracks data, provides reminders to improve patient compliance, and provides a streamlined source of information to physicians.ObjectiveThe primary objective of the quality improvement (QI) project was to test the hypothesis that use of the OMRON HMP could reduce the number and cost of hypertension related claims, relative to a retrospectively matched cohort of insured members. A secondary objective was to demonstrate improvement in control of BP among patients.DesignEligible members were recruited to the QI project between December 1, 2018 and December 30, 2020 and data collected for six months following recruitment. All members received the OMRON HMP intervention.SettingEnrollment and data collection were coordinated on-site at selected PCP partner providers in Western Pennsylvania. Eligible members were identified from insurance claims data as those receiving care for primary hypertension from participating primary care physicians and/or cardiologists.ParticipantsEligible members were between the ages of 35 and 85, with a diagnosis of primary hypertension. The retrospective cohort was selected from electronic medical records of Highmark-insured patients with hypertension who received care at Allegheny Health Network (AHN), a subsidiary of Highmark Health. Members were matched on baseline BP and lipid measures, age, smoking status, diabetes status, race and sex.InterventionDaily home BP readings were recorded by the OMRON HMP app. Patient data was reviewed by clinical staff on a weekly basis and treatment plans could be adjusted in response to this data.ResultsOMRON HMP users showed a significant increase in the number and cost of hypertension-related claims, contrary to the hypothesis, but did display improvements in control of BP.Conclusions and RelevanceThe use of a digital platform to facilitate at-home BP monitoring appeared to improve BP control but led to increased hypertension-related costs in the short-term.</p

Table1_Digital hypertension management: clinical and cost outcomes of a pilot implementation of the OMRON hypertension management platform.docx

ImportanceHome monitoring of blood pressure (BP) in hypertensive patients can improve outcomes, but challenges to both patient compliance and the effective transmission of home BP readings to physicians can limit the extent to which physicians can use this information to improve care. The OMRON Hypertension Management Platform (OMRON HMP) pairs a home BP cuff with a digital product that tracks data, provides reminders to improve patient compliance, and provides a streamlined source of information to physicians.ObjectiveThe primary objective of the quality improvement (QI) project was to test the hypothesis that use of the OMRON HMP could reduce the number and cost of hypertension related claims, relative to a retrospectively matched cohort of insured members. A secondary objective was to demonstrate improvement in control of BP among patients.DesignEligible members were recruited to the QI project between December 1, 2018 and December 30, 2020 and data collected for six months following recruitment. All members received the OMRON HMP intervention.SettingEnrollment and data collection were coordinated on-site at selected PCP partner providers in Western Pennsylvania. Eligible members were identified from insurance claims data as those receiving care for primary hypertension from participating primary care physicians and/or cardiologists.ParticipantsEligible members were between the ages of 35 and 85, with a diagnosis of primary hypertension. The retrospective cohort was selected from electronic medical records of Highmark-insured patients with hypertension who received care at Allegheny Health Network (AHN), a subsidiary of Highmark Health. Members were matched on baseline BP and lipid measures, age, smoking status, diabetes status, race and sex.InterventionDaily home BP readings were recorded by the OMRON HMP app. Patient data was reviewed by clinical staff on a weekly basis and treatment plans could be adjusted in response to this data.ResultsOMRON HMP users showed a significant increase in the number and cost of hypertension-related claims, contrary to the hypothesis, but did display improvements in control of BP.Conclusions and RelevanceThe use of a digital platform to facilitate at-home BP monitoring appeared to improve BP control but led to increased hypertension-related costs in the short-term.</p

Table2_Digital hypertension management: clinical and cost outcomes of a pilot implementation of the OMRON hypertension management platform.docx

ImportanceHome monitoring of blood pressure (BP) in hypertensive patients can improve outcomes, but challenges to both patient compliance and the effective transmission of home BP readings to physicians can limit the extent to which physicians can use this information to improve care. The OMRON Hypertension Management Platform (OMRON HMP) pairs a home BP cuff with a digital product that tracks data, provides reminders to improve patient compliance, and provides a streamlined source of information to physicians.ObjectiveThe primary objective of the quality improvement (QI) project was to test the hypothesis that use of the OMRON HMP could reduce the number and cost of hypertension related claims, relative to a retrospectively matched cohort of insured members. A secondary objective was to demonstrate improvement in control of BP among patients.DesignEligible members were recruited to the QI project between December 1, 2018 and December 30, 2020 and data collected for six months following recruitment. All members received the OMRON HMP intervention.SettingEnrollment and data collection were coordinated on-site at selected PCP partner providers in Western Pennsylvania. Eligible members were identified from insurance claims data as those receiving care for primary hypertension from participating primary care physicians and/or cardiologists.ParticipantsEligible members were between the ages of 35 and 85, with a diagnosis of primary hypertension. The retrospective cohort was selected from electronic medical records of Highmark-insured patients with hypertension who received care at Allegheny Health Network (AHN), a subsidiary of Highmark Health. Members were matched on baseline BP and lipid measures, age, smoking status, diabetes status, race and sex.InterventionDaily home BP readings were recorded by the OMRON HMP app. Patient data was reviewed by clinical staff on a weekly basis and treatment plans could be adjusted in response to this data.ResultsOMRON HMP users showed a significant increase in the number and cost of hypertension-related claims, contrary to the hypothesis, but did display improvements in control of BP.Conclusions and RelevanceThe use of a digital platform to facilitate at-home BP monitoring appeared to improve BP control but led to increased hypertension-related costs in the short-term.</p