Modeling, synthesis and cell-based evaluation of pyridine-substituted analogs of CD3254 and fluorinated analogs of CBt-PMN as novel therapeutics.

Six pyridine analogs of (E)-3-(3-(1,2,3,4-tetrahydro-1,1,4,4,6-pentamethylnaphthalen-7-yl)-4-hydroxyphenyl)acrylic acid-or CD3254 (11)-in addition to two novel analogs of 1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)-1H-benzo[d][1,2,3]triazole-5-carboxylic acid (CBt-PMN or 23) were prepared and evaluated for selective retinoid-X-receptor (RXR) agonism alongside bexarotene (1), an FDA-approved drug for cutaneous T-cell lymphoma (CTCL). Treatment with 1 often elicits side-effects by disrupting or provoking other RXR-dependent nuclear receptors and cellular pathways. All analogs were assessed through modeling for their ability to bind RXR and then evaluated in human colon and kidney cells employing an RXR-RXR mammalian-2-hybrid (M2H) system and in an RXRE-controlled transcriptional assay.

Synergistic Activation of VDR-RXR Heterodimers by Vitamin D and Rexinoids in Human Kidney and Brain Cells.

The active form of vitamin D, 1,25-dihydroxyvitamin D (1,25D), binds to the vitamin D receptor (VDR) with high affinity. The VDR then heterodimerizes with the retinoid X receptor (RXR) and associates with vitamin D response elements (VDREs) to regulate the transcription of target genes. Bexarotene (Bex) is an RXR ligand (rexinoid) developed to treat cutaneous T-cell lymphoma and is a putative therapeutic for other diseases.

Equity-Focused Evaluation of a Medicaid-Funded Statewide Diabetes Quality Improvement Project Collaborative.

Objective: To evaluate the Ohio Diabetes Quality Improvement Project (QIP) equity aim to reduce the percentage of Non-Hispanic Black (NHB) and Hispanic patients with A1C >9% by ≥20% over 2 years.

Research Design And Methods: The Ohio Department of Medicaid, Ohio Colleges of Medicine Government Resource Center, Ohio Medicaid managed care plans, and seven medical schools in Ohio formed the Diabetes QIP collaborative using the collective impact model to improve diabetes outcomes and equity in 20 practices across 11 health systems. The quality improvement (QI) strategies included data audit and feedback, peer-to-peer learning, QI coaching/practice facilitation, and subject matter expert consultation through coaching calls, monthly webinars, and annual virtual learning sessions.

Rexinoids Induce Differential Gene Expression in Human Glioblastoma Cells and Protein-Protein Interactions in a Yeast Two-Hybrid System.

Rexinoids are compounds that bind to the rexinoid X receptor (RXR) to modulate gene expression and have been proposed as a new class of therapeutics to treat Alzheimer's disease. Different rexinoids will initiate downstream effects that can be quite marked even though such compounds can be structurally similar and have comparable RXR binding affinities. RXR can both homo- and heterodimerize, and these protein-protein interactions and subsequent transactivating potential lead to differential gene expression, depending on the RXR dimeric partner, additional cofactors recruited, and downstream transcription factors that are up- or downregulated.

Developing a career and education framework for advanced clinical practice in midwifery.

Introduction: This study outlines the nature of Advanced Clinical Practice in Midwifery (ACPiM), reporting on a stakeholder analysis as part of a national project to develop a career framework for advanced practice in midwifery on behalf of the National Health Service (NHS) in England.

Methods: Between June and July 2022, 31 advanced practice midwives were recruited across England within the NHS settings. Convenience sampling was used to identify midwives working as advanced practitioners, and those pursuing this career route.

Development of Bexarotene Analogs for Treating Cutaneous T-Cell Lymphomas.

Bexarotene, a drug approved for treatment of cutaneous T-cell lymphoma (CTCL), is classified as a rexinoid by its ability to act as a retinoid X receptor (RXR) agonist with high specificity. Rexinoids are capable of inducing RXR homodimerization leading to the induction of apoptosis and inhibition of proliferation in human cancers. Numerous studies have shown that bexarotene is effective in reducing viability and proliferation in CTCL cell lines.

A Medicaid-Funded Statewide Diabetes Quality Improvement Collaborative: Ohio 2020‒2022.

We used a collective impact model to form a statewide diabetes quality improvement collaborative to improve diabetes outcomes and advance diabetes health equity. Between 2020 and 2022, in collaboration with the Ohio Department of Medicaid, Medicaid Managed Care Plans, and Ohio's seven medical schools, we recruited 20 primary care practices across the state. The percentage of patients with hemoglobin A1c greater than 9% improved from 25% to 20% over two years.

Topography of inputs into the hippocampal formation of a food-caching bird.

The mammalian hippocampal formation (HF) is organized into domains associated with different functions. These differences are driven in part by the pattern of input along the hippocampal long axis, such as visual input to the septal hippocampus and amygdalar input to the temporal hippocampus. HF is also organized along the transverse axis, with different patterns of neural activity in the hippocampus and the entorhinal cortex.

Evaluating adaptiveness of an active back exosuit for dynamic lifting and maximum range of motion.

Back exosuits deliver mechanical assistance to reduce the risk of back injury, however, minimising restriction is critical for adoption. We developed the adaptive impedance controller to minimise restriction while maintaining assistance by modulating impedance based on the user's movement direction and nonlinear sine curves. The objective of this study was to compare active assistance, delivered by a back exosuit via our adaptive impedance controller, to three levels of assistance from passive elastics.

Trends in Use of Medication to Treat Opioid Use Disorder During the COVID-19 Pandemic in 10 State Medicaid Programs.

Importance: Federal and state agencies granted temporary regulatory waivers to prevent disruptions in access to medication for opioid use disorder (MOUD) during the COVID-19 pandemic, including expanding access to telehealth for MOUD. Little is known about changes in MOUD receipt and initiation among Medicaid enrollees during the pandemic.

Objectives: To examine changes in receipt of any MOUD, initiation of MOUD (in-person vs telehealth), and the proportion of days covered (PDC) with MOUD after initiation from before to after declaration of the COVID-19 public health emergency (PHE).

An entorhinal-like region in food-caching birds.

The mammalian entorhinal cortex routes inputs from diverse sources into the hippocampus. This information is mixed and expressed in the activity of many specialized entorhinal cell types, which are considered indispensable for hippocampal function. However, functionally similar hippocampi exist even in non-mammals that lack an obvious entorhinal cortex or, generally, any layered cortex.

A Medicaid Statewide Hypertension Quality Improvement Project: Initial Results.

Background Hypertension control is critical to reducing cardiovascular disease, challenging to achieve, and exacerbated by socioeconomic inequities. Few states have established statewide quality improvement (QI) infrastructures to improve blood pressure (BP) control across economically disadvantaged populations. In this study, we aimed to improve BP control by 15% for all Medicaid recipients and by 20% for non-Hispanic Black participants.

Topography of inputs into the hippocampal formation of a food-caching bird.

The mammalian hippocampal formation (HF) is organized into domains associated with different functions. These differences are driven in part by the pattern of input along the hippocampal long axis, such as visual input to the septal hippocampus and amygdalar input to temporal hippocampus. HF is also organized along the transverse axis, with different patterns of neural activity in the hippocampus and the entorhinal cortex.

Self-supervised denoising of Nyquist-sampled volumetric images via deep learning.

Purpose: Deep learning has demonstrated excellent performance enhancing noisy or degraded biomedical images. However, many of these models require access to a noise-free version of the images to provide supervision during training, which limits their utility. Here, we develop an algorithm (noise2Nyquist) that leverages the fact that Nyquist sampling provides guarantees about the maximum difference between adjacent slices in a volumetric image, which allows denoising to be performed without access to clean images.

An entorhinal-like region in food-caching birds.

The mammalian entorhinal cortex routes inputs from diverse sources into the hippocampus. This information is mixed and expressed in the activity of many specialized entorhinal cell types, which are considered indispensable for hippocampal function. However, functionally similar hippocampi exist even in non-mammals that lack an obvious entorhinal cortex, or generally any layered cortex.

Forming Cardi-OH: A Statewide Collaborative to Improve Cardiovascular Health in Ohio.

Background Cardiovascular risk factor control is challenging, especially in disadvantaged populations. However, few statewide efforts exist to tackle this challenge. Therefore, our objective is to describe the formation of a unique statewide cardiovascular health collaborative so others may learn from this approach.

Optical coherence tomography holds promise to transform the diagnostic anatomic pathology gross evaluation process.

Significance: Real-time histology can close a variety of gaps in tissue diagnostics. Currently, gross pathology analysis of excised tissue is dependent upon visual inspection and palpation to identify regions of interest for histopathological processing. Such analysis is limited by the variable correlation between macroscopic and microscopic findings.

Opioid Use Disorder Among Ohio's Medicaid Population: Prevalence Estimates From 19 Counties Using a Multiplier Method.

The decades-long overdose epidemic in the United States is driven by opioid misuse. Overdoses commonly, although not exclusively, occur in individuals with opioid use disorder (OUD). To allocate adequate resources and develop appropriately scaled public health responses, accurate estimation of the prevalence of OUD is needed.

Flexible use of memory by food-caching birds.

Animals use memory-guided and memory-independent strategies to make navigational decisions. Disentangling the contribution of these strategies to navigation is critical for understanding how memory influences behavioral output. To address this issue, we studied spatial behaviors of the chickadee, a food-caching bird.

Hemodynamics of the sternocleidomastoid measured with frequency domain near-infrared spectroscopy towards non-invasive monitoring during mechanical ventilation.

Mechanical ventilation (MV) is used to assist spontaneous breathing in critically ill patients in the intensive care unit (ICU). MV is a cornerstone of critical care medicine but it is now known that inspiratory muscle dysfunction due to injury, disuse, and/or atrophy during MV plays a major role in outcomes for these patients. For example, prolonged MV is strongly correlated with dysfunction of the sternocleidomastoid (SCM), an accessory inspiratory muscle that has been linked to weaning failure from MV.

Real-Time Handheld Probe Tracking and Image Formation Using Digital Frequency-Domain Diffuse Optical Spectroscopy.

Objective: Frequency-domain diffuse optical spectroscopic imaging (FD-DOS) is a non-invasive method for measuring absolute concentrations of tissue chromophores such as oxy- and deoxy-hemoglobin in vivo. The utility of FD-DOS for clinical applications such as monitoring chemotherapy response in breast cancer has previously been demonstrated, but challenges for further clinical translation, such as slow acquisition speed and lack of user feedback, remain. Here, we propose a new high speed FD-DOS instrument that allows users to freely acquire measurements over the tissue surface, and is capable of rapidly imaging large volumes of tissue.

Modulation frequency selection and efficient look-up table inversion for frequency domain diffuse optical spectroscopy.

Significance: Frequency domain diffuse optical spectroscopy (FD-DOS) uses intensity modulated light to measure the absorption and reduced scattering coefficients of turbid media such as biological tissue. Some FD-DOS instruments utilize a single modulation frequency, whereas others use hundreds of frequencies. The effect of modulation frequency choice and measurement bandwidth on optical property (OP) extraction accuracy has not yet been fully characterized.

Dual-DMD hyperspectral spatial frequency domain imaging (SFDI) using dispersed broadband illumination with a demonstration of blood stain spectral monitoring.

Spatial frequency domain imaging (SFDI) is a widefield diffuse optical measurement technique capable of generating 2D maps of sub-surface absorption and scattering in biological tissue. We developed a new hyperspectral SFDI instrument capable of collecting images at wavelengths from the visible to the near infrared. The system utilizes a custom-built monochromator with a digital micromirror device (DMD) that can dynamically select illumination wavelength bands from a broadband quartz tungsten halogen lamp, and a second DMD to provide spatially modulated sample illumination.

Project ACTIVE: a Randomized Controlled Trial of Personalized and Patient-Centered Preventive Care in an Urban Safety-Net Setting.

Background: Evidence-based preventive care in the USA is underutilized, diminishing population health and worsening health disparities. We developed Project ACTIVE, a program to improve adherence with preventive care goals through personalized and patient-centered care.

Objective: To determine whether Project ACTIVE improved utilization of preventive care and/or estimated life expectancy compared to usual care.