Alveolar epithelial type II (AT2) cell dysfunction is implicated in the pathogenesis of familial and sporadic idiopathic pulmonary fibrosis (IPF). We previously described that expression of an AT2 cell exclusive disease-associated protein isoform (SP-CI73T) in murine and patient-specific induced pluripotent stem cell (iPSC)-derived AT2 cells leads to a block in late macroautophagy and promotes time-dependent mitochondrial impairments; however, how a metabolically dysfunctional AT2 cell results in fibrosis remains elusive. Here using murine and human iPSC-derived AT2 cell models expressing SP-CI73T, we characterize the molecular mechanisms governing alterations in AT2 cell metabolism that lead to increased glycolysis, decreased mitochondrial biogenesis, disrupted fatty acid oxidation, accumulation of impaired mitochondria, and diminished AT2 cell progenitor capacity manifesting as reduced AT2 self-renewal and accumulation of transitional epithelial cells. We identify deficient AMP-kinase signaling as a key upstream signaling hub driving disease in these dysfunctional AT2 cells and augment this pathway to restore alveolar epithelial metabolic function, thus successfully alleviating lung fibrosis in vivo.

Background: The use of personal continuous glucose monitors (CGMs) in patients with diabetes has increased substantially and is expected to continue to increase as CGMs become more affordable and insurance plans improve coverage. The utilization of CGMs has improved diabetes management and reduced hypoglycemic events. Objectives: To create pharmacist-led personal CGM workflow and evaluate its impact on glycemic management in patients with diabetes. Practice Description: The study took place at an Internal Medicine Clinic. The practice providers include 2 medical doctors, 5 physician assistants, 2 nurse practitioners, and 1 clinical pharmacist. Practice Innovation: To create and implement a sustainable pharmacy led CGM workflow for enhanced CGM use within an internal medicine clinic. Evaluation Methods: This was a prospective, investigator-initiated pilot study conducted at an Atrium Health Internal Medicine clinic over 28 weeks. In this pilot, 42 patients were qualifying candidates with diabetes and personal CGM use. In addition, 30 patients were followed until study completion and included into final analysis. Results: The average baseline A1c was reduced from 8.3% to 7.1% over a 3- to 6-month period. The pharmacist-led CGM workflow revealed a statistically significant reduction in A1c from baseline by an average of 1.2% (95% CI-0.6 to-1.8, P = 0.0006). On average, patients were enrolled for 19.9 weeks and had an average of 5 visits during this time. During the study duration, 100 medications changes were implemented under the existing clinical pharmacist practitioner agreement between the pharmacists and the provider. Overall, 58 Current Procedural Terminology 95251 codes were billed yielding $7052.00 in billed CGM services for the clinic. This project generated 40.6 provider relative value units. Conclusion: The utilization of a pharmacist-led personal CGM workflow can improve diabetes outcomes. (c) 2024 American Pharmacists Association (R). Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

BACKGROUND:Nearly half of adults in America have hypertension (HTN), and only approximately 1 in 4 adults has their blood pressure (BP) under control. High BP is more common in African Americans adults, and BP control is lower among minority adults. Pharmacist-led interventions for HTN have been shown to be effective in improving BP control and reducing the risk of cardiovascular events.OBJECTIVE:This study aimed to leverage electronic health record (EHR) data to improve BP control through pharmacist-led interventions.METHODS:This was a prospective, cohort study conducted at Atrium Health Concord Internal Medicine, a large suburban practice in Concord, North Carolina. Patients with uncontrolled HTN were identified using an EHR data tool. Patients were included if they were at least 18 years of age, had sustained uncontrolled HTN, and were of a minority race or ethnicity. The primary outcome was proportion of patients achieving a BP of < 140/90 mm Hg in the intervention group compared with a control group. Secondary outcomes included mean change in BP from baseline, number and type of visits, and number and type of interventions.RESULTS:A total of 110 patients were enrolled in this study, 55 patients in each cohort. The baseline characteristics were generally well balanced between the 2 groups. The mean age was 62 years, and most patients were female and African American. For the primary outcome, 70.9% of the patients in the intervention group achieved a BP of < 140/90 mm Hg compared with 32.7% of the patients in the control group (P < 0.001). The most common intervention was lifestyle modifications, followed by BP monitoring technique education and medication adherence interventions.CONCLUSION:In this study, pharmacist-led interventions resulted in clinically and statistically significant improvements in sustained uncontrolled HTN among minority populations.

Idiopathic pulmonary fibrosis (IPF) is a chronic progressive fibrotic interstitial lung disease. A barrier to developing more effective therapies for IPF is the dearth of preclinical models that recapitulate the early pathobiology of this disease. Intratracheal bleomycin, the conventional preclinical murine model of IPF, fails to reproduce the intrinsic dysfunction to the alveolar epithelial type 2 cell (AEC2) that is believed to be a proximal event in the pathogenesis of IPF. Murine fibrosis models based on SFTPC (Surfactant Protein C gene) mutations identified in patients with interstitial lung disease cause activation of the AEC2 unfolded protein response and endoplasmic reticulum stress-an AEC2 dysfunction phenotype observed in IPF. Although these models achieve spontaneous fibrosis, they do so with precedent lung injury and thus are challenged to phenocopy the general clinical course of patients with IPF-gradual progressive fibrosis and loss of lung function. Here, we report a refinement of a murine Sftpc mutation model to recapitulate the clinical course, physiological impairment, parenchymal cellular composition, and biomarkers associated with IPF. This platform provides the field with an innovative model to understand IPF pathogenesis and index preclinical therapeutic candidates.

Pulmonary Fibrosis (PF), a devastating lung disease with rising prevalence, is defined by a physiologic defect in gas exchange owing to two cardinal pathological features: intrusion of myofibroblasts into the distal lung parenchyma and an alteration of normal alveolar epithelial composition most clearly defined by a loss of the squamous alveolar epithelial type 1 cell (AEC1) and the presence of a recently identified aberrant alveolar epithelial "transitional state" enriched in profibrotic mediators. While this transitional cell state has been identified transiently in the epithelium of murine lung injury models, the mechanism by which it arises in human fibrotic lung disease is unknown. We previously reported the in vivo modeling of PF utilizing inducible, knock-in expression of a clinical Surfactant Protein C (SP-C) mutation in alveolar type 2 cells (AEC2). Expression of the SP-C mutation in the adult mouse AEC2s led to activation of Unfolded Protein Response (UPR) signaling pathways, endoplasmic reticulum (ER) stress and spontaneous fibrosis providing proof of concept for disruption to proteostasis as a proximal driver of PF. We hypothesized that disruption of AEC2 protein quality control and specifically UPR signaling causes cell autonomous AEC2 reprogramming to the transitional state in the absence of an exogenous lung injury. Using two clinical SP-C mutation models we discovered that AEC2s experiencing significant ER stress lose quintessential AEC2 features and develop the recently identified transitional cell state. Using single cell RNA sequencing of the epithelium in our murine models we identify that UPR activated AEC2s develop the transitional cell phenotype in the absence of an exogenous lung injury. Through organoid based modeling we validated that this state arises de novo from intrinsic AEC2 dysfunction. The cell autonomous AEC2 reprogramming is mediated through IRE1 signaling as use of a novel IRE1 inhibitor attenuated the development of the transitional cell state and diminished AEC2 driven recruitment of granulocytes, alveolitis, and lung injury arising from the loss of proteostasis. We further show that this transitional state persists into the fibrotic phase of our murine models and is enriched in pro-fibrotic mediators. These findings identify AEC2 proteostasis, and specifically IRE1 signaling, as a driver of a key AEC2 phenotypic change that has been identified in lung fibrosis.

Our emerging conceptual understanding of Idiopathic Pulmonary Fibrosis (IPF) highlights the significant role of alveolar epithelial type II cell (AT2) cell dysfunction in underlying susceptibility, disease severity, and disease progression. This multifunctional cell is solely responsible for the synthesis and secretion of pulmonary surfactant, a highly metabolically taxing process. Though mutations in surfactant component genes are one of the recognized etiological causes of IPF, the relationship between the metabolic program of the AT2 cell and IPF is poorly understood. Leveraging a novel preclinical model of IPF, the IER‐SP‐CI73T mouse, we aimed to characterize the role of altered AT2 metabolism in IPF fibrogenesis and remodeling.

This pilot study sought to evaluate the impact of pharmacist involvement in the preexisting telehealth transitional care management (TCM) program at Atrium Health on the quality and safety of the medication discharge process for high medication risk patients. Eligible participants were those 18 years of age or older with moderate-to-high risk for hospital readmission who were contacted by a TCM Nurse, identified as high medication risk patients, and referred to the TCM Pharmacist from September 2018 through February 2019. The TCM Pharmacist contacted patients by phone, completed a comprehensive medication review, identified medication list discrepancies (MLDs) and medication-related problems (MRPs), and made interventions or recommendations to primary care providers. Primary endpoints included the number and types of MLDs identified, number and types of MRPs identified, and the rate of unplanned 30-day hospital readmissions. Seventy-six patients were enrolled, and 78 MLDs and 108 MRPs were identified. Of the identified MRPs, 74.1% were resolved. A relative risk reduction of 36.8% was achieved for 30-day hospital readmissions for those with high medication risk contacted by the TCM Pharmacist compared to those only contacted by the TCM Nurse. Overall, TCM Pharmacists identified and resolved 80 medication-related problems, improved access to medication therapy, provided comprehensive medication counseling, and bridged gaps in care following hospital discharge.

........................................................................................................ 3 Postpartum Depression and Anxiety Disorders........................................................ 4 Temporal, Behavioral, and Neurological Distinctiveness of PMDs................................ 7 The Biology of Postpartum.............................................................................. 11 A Unique Neurobiological Approach for Studying PMD.......................................... 17 Summary of the Rationale for the Present Study.................................................... 30 The Present Study......................................................................................... 31 Methods....................................................................................................... 33 Transgenic Mice........................................................................................... 33 Procedure.................................................................................................. 34 Results......................................................................................................... 39 Behavioral Results....................................................................................... 39 Neurological Results..................................................................................... 41 Discussion......................................................................................................42 Sample Limitations....................................................................................... 43 No Change in Anxiety Behaviors Between Hormone Conditions................................. 43 ∆FosB Expression in Dopamine MSNs within the NAc Core and Shell......................... 44 Interpreting the Behavioral and Neurological Results Together.................................. 54 Future Directions............................................................................................ 56 Accounting for Limitations in the Present Study.................................................... 56 Additional Future Research Considerations.......................................................... 57 Concluding Remarks....................................................................................... 58 References.................................................................................................... 59 Tables and Figures.......................................................................................... 77 ∆FOSB INDUCTION IN NAc POSTPARTUM 3 Abstract Postpartum mood disorders (PMD) are a worldwide health concern, yet the neurobiological etiology is still widely unknown. In the present study we replicated the hormone-simulated pregnancy method developed by Liisa Galea in a novel transgenic mouse model. This approach allowed us to measure long-term genomic changes in dopaminergic plasticity in medium spiny neurons (MSNs) within the nucleus accumbens (NAc) through the transcription factor ∆FosB. We used 16 ovariectomized female transgenic mice that had fluorescent reporter moleculesPostpartum mood disorders (PMD) are a worldwide health concern, yet the neurobiological etiology is still widely unknown. In the present study we replicated the hormone-simulated pregnancy method developed by Liisa Galea in a novel transgenic mouse model. This approach allowed us to measure long-term genomic changes in dopaminergic plasticity in medium spiny neurons (MSNs) within the nucleus accumbens (NAc) through the transcription factor ∆FosB. We used 16 ovariectomized female transgenic mice that had fluorescent reporter molecules coupled to either D1 or D2 receptor-containing neurons; this allowed us to differentially visualize the activity of ∆FosB in each of the neuronal subtypes following a hormone-simulated pregnancy. We found a significant increase in the expression of ∆FosB in D2-MSNs in the NAc core of hormone-withdrawn animals relative to hormone-sustained animals. These neurobiological changes did not correspond with measures of anxiety in either an Elevated Plus Maze or Open Field Test. Furthermore, we found no significant changes in ∆FosB expression in D2-MSNs in the NAc shell nor in D1-MSNs in the NAc core and shell. By further understanding the influence that hormonal changes throughout pregnancy have on neurological systems, we can identify the systems that may be involved in pathological cases to develop better and more direct treatment and diagnosis options for PMD.