Neurology Commons^™

Levodopa Rescues Retinal Function In The Transgenic A53t Alpha-Synuclein Model Of Parkinson's Disease, Katie K N Tran, Vickie H Y Wong, Kirstan A Vessey, David I Finkelstein, Bang V Bui, Christine T O Nguyen

Faculty, Staff and Student Publications

BACKGROUND: Loss of substantia nigra dopaminergic cells and alpha-synuclein (α-syn)-rich intraneuronal deposits within the central nervous system are key hallmarks of Parkinson's disease (PD). Levodopa (L-DOPA) is the current gold-standard treatment for PD. This study aimed to evaluate

METHODS: Anaesthetised 6-month-old mice expressing human A53T alpha-synuclein (HOM) and wildtype (WT) control littermates were intraperitoneally given 20 mg/kg L-DOPA (50 mg levodopa, 2.5 mg benserazide) or vehicle saline (

RESULTS: We found that photoreceptor (a-wave) and bipolar cell (b-wave) ERG responses (

CONCLUSIONS: These findings deepen our understanding of dopamine and alpha-synuclein interactions in the retina and provide a high-throughput preclinical …

Vaccines: A Promising Therapy For Myelodysplastic Syndrome, Kriti Gera, Anjali Chauhan, Paul Castillo, Maryam Rahman, Akash Mathavan, Akshay Mathavan, Elizabeth Oganda-Rivas, Leighton Elliott, John R Wingard, Elias J Sayour

Faculty, Staff and Student Publications

Myelodysplastic neoplasms (MDS) define clonal hematopoietic malignancies characterized by heterogeneous mutational and clinical spectra typically seen in the elderly. Curative treatment entails allogeneic hematopoietic stem cell transplant, which is often not a feasible option due to older age and significant comorbidities. Immunotherapy has the cytotoxic capacity to elicit tumor-specific killing with long-term immunological memory. While a number of platforms have emerged, therapeutic vaccination presents as an appealing strategy for MDS given its promising safety profile and amenability for commercialization. Several preclinical and clinical trials have investigated the efficacy of vaccines in MDS; these include peptide vaccines targeting tumor antigens, whole …

Developmental Basis Of Shh Medulloblastoma Heterogeneity, Maxwell P Gold, Winnie Ong, Andrew M Masteller, David R Ghasemi, Julie Anne Galindo, Noel R Park, Nhan C Huynh, Aneesh Donde, Veronika Pister, Raul A Saurez, Maria C Vladoiu, Grace H Hwang, Tanja Eisemann, Laura K Donovan, Adam D Walker, Joseph Benetatos, Christelle Dufour, Livia Garzia, Rosalind A Segal, Robert J Wechsler-Reya, Jill P Mesirov, Andrey Korshunov, Kristian W Pajtler, Scott L Pomeroy, Olivier Ayrault, Shawn M Davidson, Jennifer A Cotter, Michael D Taylor, Ernest Fraenkel

Faculty, Staff and Students Publications

Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development. Through innovative computational approaches, we connect these results to published datasets and find that some established molecular subtypes of SHH MB appear arrested at different …

Development Of A Rabbit Human Glioblastoma Model For Testing Of Endovascular Selective Intra-Arterial Infusion (Esia) Of Novel Stem Cell-Based Therapeutics, Peter Kan, Visish M Srinivasan, Joy Gumin, Roberto Garcia, Stephen R Chen, Jeremiah N Johnson, Dalis E Collins, Melissa M Chen, Daniel Ledbetter, Jason Huse, Zean Aaron Evan Luna, Ariadna Robledo, Viren Vasandani, Abhijit Rao, Sanjay K Singh, Elizabeth J Shpall, Juan Fueyo, Candelaria Gomez-Manzano, Frederick F Lang

Faculty, Staff and Student Publications

BACKGROUND: Endovascular selective intra-arterial (ESIA) infusion of cellular oncotherapeutics is a rapidly evolving strategy for treating glioblastoma. Evaluation of ESIA infusion requires a unique animal model. Our goal was to create a rabbit human GBM model to test IA infusions of cellular therapies and to test its usefulness by employing clinical-grade microcatheters and infusion methods to deliver mesenchymal stem cells loaded with an oncolytic adenovirus, Delta-24-RGD (MSC-D24).

METHODS: Rabbits were immunosuppressed with mycophenolate mofetil, dexamethasone, and tacrolimus. They underwent stereotactic xenoimplantation of human GBM cell lines (U87, MDA-GSC-17, and MDA-GSC-8-11) into the right frontal lobe. Tumor formation was confirmed on …

A Retrospective Genomic Landscape Of 661 Young Adult Glioblastomas Diagnosed Using 2016 Who Guidelines For Central Nervous System Tumors, James F Haberberger, Worthy Pegram, Nicholas Britt, Kelsie Schiavone, Eric Severson, Radwa Sharaf, Lee A Albacker, Erik Williams, Mirna Lechpammer, Amanda Hemmerich, Douglas Lin, Richard S P Huang, Matthew Hiemenz, Julia Elvin, Ryon Graf, Glenn Lesser, David Kram, Roy Strowd, Wenya Linda Bi, Lori A Ramkissoon, Michael B Cohen, Prasanth Reddy, James Creeden, Jeffrey S Ross, Brian M Alexander, Shakti H Ramkissoon

Faculty, Staff and Student Publications

The authors present a cohort of 661 young adult glioblastomas diagnosed using 2016 WHO World Health Organization Classification of Tumors of the Central Nervous System, utilizing comprehensive genomic profiling (CGP) to explore their genomic landscape and assess their relationship to currently defined disease entities. This analysis explored variants with evidence of pathogenic function, common copy number variants (CNVs), and several novel fusion events not described in literature. Tumor mutational burden (TMB) mutational signatures, anatomic location, and tumor recurrence are further explored. Using data collected from CGP, unsupervised machine-learning techniques were leveraged to identify 10 genomic classes in previously assigned young …

Alzheimer’S Disease And Microorganisms: The Non-Coding Rnas Crosstalk, Hanieh Mohammadi-Pilehdarboni, Mohammad Shenagari, Farahnaz Joukar, Hamed Naziri, Fariborz Mansour-Ghanaei

Department of Neurology Faculty Papers

Alzheimer’s disease (AD) is a complex, multifactorial disorder, influenced by a multitude of variables ranging from genetic factors, age, and head injuries to vascular diseases, infections, and various other environmental and demographic determinants. Among the environmental factors, the role of the microbiome in the genesis of neurodegenerative disorders (NDs) is gaining increased recognition. This paradigm shift is substantiated by an extensive body of scientific literature, which underscores the significant contributions of microorganisms, encompassing viruses and gut-derived bacteria, to the pathogenesis of AD. The mechanism by which microbial infection exerts its influence on AD hinges primarily on inflammation. Neuroinflammation, activated in …

Doxycycline For Transgene Control Disrupts Gut Microbiome Diversity Without Compromising Acute Neuroinflammatory Response, Emily J Koller, Caleb A Wood, Zoe Lai, Ella Borgenheimer, Kristi L Hoffman, Joanna L Jankowsky

Faculty, Staff and Students Publications

The tetracycline transactivator (tTA) system provides controllable transgene expression through oral administration of the broad-spectrum antibiotic doxycycline. Antibiotic treatment for transgene control in mouse models of disease might have undesirable systemic effects resulting from changes in the gut microbiome. Here we assessed the impact of doxycycline on gut microbiome diversity in a tTA-controlled model of Alzheimer's disease and then examined neuroimmune effects of these microbiome alterations following acute LPS challenge. We show that doxycycline decreased microbiome diversity in both transgenic and wild-type mice and that these changes persisted long after drug withdrawal. Despite the change in microbiome composition, doxycycline treatment …

Pediatric Medical Subspecialist Use In Outpatient Settings, Christopher B Forrest, Candice P Chen, Eliana M Perrin, Christopher J Stille, Ruth Cooper, Katherine Harris, Qian Luo, Mitchell G Maltenfort, Lauren E Parlett

Faculty, Staff and Student Publications

Importance

A first step toward understanding whether pediatric medical subspecialists are meeting the needs of the nation’s children is describing rates of use and trends over time.

Objectives

To quantify rates of outpatient pediatric medical subspecialty use.

Design, Setting, and Participants

This repeated cross-sectional study of annual subspecialist use examined 3 complementary data sources: electronic health records from PEDSnet (8 large academic medical centers [January 1, 2010, to December 31, 2021]); administrative data from the Healthcare Integrated Research Database (HIRD) (14 commercial health plans [January 1, 2011, to December 31, 2021]); and administrative data from the Transformed Medicaid Statistical Information …

Gene Regulation And Speciation In A Migratory Divide Between Songbirds, Matthew I M Louder, Hannah Justen, Abigail A Kimmitt, Koedi S Lawley, Leslie M Turner, J David Dickman, Kira E Delmore

Faculty, Staff and Students Publications

Behavioral variation abounds in nature. This variation is important for adaptation and speciation, but its molecular basis remains elusive. Here, we use a hybrid zone between two subspecies of songbirds that differ in migration - an ecologically important and taxonomically widespread behavior---to gain insight into this topic. We measure gene expression in five brain regions. Differential expression between migratory states was dominated by circadian genes in all brain regions. The remaining patterns were largely brain-region specific. For example, expression differences between the subspecies that interact with migratory state likely help maintain reproductive isolation in this system and were documented in …

The Impact Of Telestroke Services On Diagnosis, Patient Outcomes, And Treatment, Dustin Baum

Theses, Dissertations and Capstones

Introduction: In 2011, an estimated 20% of U.S. residents lacked timely access to stroke care. As of 2019, that number plummeted to 4% of patients. A reason for this improved access was the implementation of telestroke services. Telestroke services have utilized remote stroke specialists to help guide local emergency department physicians in reviewing imaging, diagnosing, treating, or transferring patients appropriately.

Purpose: The purpose of this research was to analyze the impact of telestroke implementation in the hospital setting. The study hypothesized the implementation of telestroke services in the hospital setting maintained an accurate stroke diagnosis, decreased inappropriate hospital transfers, reduced …

Digital Clock Drawing As An Alzheimer's Disease Susceptibility Biomarker: Associations With Genetic Risk Score And Apoe In Older Adults, L I Thompson, M Cummings, S Emrani, David J. Libon, A Ang, C Karjadi, R Au, C Liu

Rowan-Virtua School of Osteopathic Medicine Departmental Research

BACKGROUND: Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.

OBJECTIVE: We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.

DESIGN: We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.

SETTING: We used existing data …

Mechanosensory Encoding In Ex Vivo Muscle–Nerve Preparations, Stephen N. Housley, Evelyn A. Gardolinski, Paul Nardelli, J'Ana Reed, Mark M. Rich, Timothy C. Cope

Neuroscience, Cell Biology & Physiology Faculty Publications

Our objective was to evaluate an ex vivo muscle-nerve preparation used to study mechanosensory signalling by low threshold mechanosensory receptors (LTMRs). Specifically, we aimed to assess how well the ex vivo preparation represents in vivo firing behaviours of the three major LTMR subtypes of muscle primary sensory afferents, namely type Ia and II muscle spindle (MS) afferents and type Ib tendon organ afferents. Using published procedures for ex vivo study of LTMRs in mouse hindlimb muscles, we replicated earlier reports on afferent firing in response to conventional stretch paradigms applied to non-contracting, that is passive, muscle. Relative to in vivo …

Case Report: A 28-Year-Old Male With Bilateral Lower Extremities Paresthesias, Characteristic Presentation Of Guillain-Barre Syndrome And Innovative Treatments, Petros Keoseyan, Ricky Oshakuade, Danielle Genov, Derek Draper, Nick Duff, Anna Belits, Dmitriy Scherbak

Continental, MidAmerica, & Mountain Divisions GME Research Day 2024

No abstract provided.

A Case Report Of Marburg Multiple Sclerosis Responding To Mitoxantrone, Aruna Souri, Athena Dao, Russell Bartt

Continental, MidAmerica, & Mountain Divisions GME Research Day 2024

No abstract provided.

Multiple Central Nervous System Cryptococcomas Masquerading As Lymphoma, Alexander V. Ortiz, Dhruven Mehta, Juli Horton, Adrian A. Jarquin-Valdivia

TriStar Division GME Research Day 2024

No abstract provided.

A Case Of Elevated Intracranial Pressure Following Acute Parotitis, Alexander V. Ortiz, Ashwini Kini, Adrian A. Jarquin-Valdivia

TriStar Division GME Research Day 2024

No abstract provided.

Cancer Research Provides A Model For Advancing Clinical Trials In Dementia In The Era Of Disease-Modifying Alzheimer’S-Type Dementia Therapies, Gregory Jicha, Thomas Tucker, Susanne Arnold, Peter T. Nelson

Neurology Faculty Publications

Dementia and cancer are multifactorial, widely-feared, age-associated clinical syndromes that are increasing in prevalence. There have been major breakthroughs in clinical cancer research leading to some effective treatments, whereas the field of dementia has achieved comparatively limited success in clinical research. The lessons of cancer research may help those in the dementia research field in confronting some of the dilemmas faced when the clinical care regimen is not entirely safe or efficacious. Cancer clinical trials have assumed that untreated individuals with cancer are at high risk for morbidity and mortality after primary diagnoses. Thus, patients deserve a choice of clinical …

Estimating Socio-Economic Status For Alzheimer’S Disease Trials, D. M. Rentz, J. D. Grill, D. P. Molina-Henry, Gregory Jicha, Michael S. Rafii, A. Liu, Reisa A. Sperling, Paul Aisen, R. Raman

Neurology Faculty Publications

INTRODUCTION: Metrics of a participant’s socioeconomic status (SES) are not routinely collected or standardized in clinical trials. This omission limits the ability to evaluate the generalizability of trial results and restricts clinicians from confidently interpreting the efficacy of new treatments across important sub-populations. METHODS: We adapted an SES measure of social disparity; the Hollingshead Two Factor Index of Social Position, which combines education and occupation into a single metric. We modernized the 1965 occupations to reflect the 2017 careers tabulated by the US Bureau of Labor Statistics. We currently use this adapted measure in Alzheimer’s Clinical Trials Consortium studies. RESULTS: …

Clinical Trial Protocol For Beach: A Phase 2a Study Of Mw189 In Patients With Acute Nontraumatic Intracerebral Hemorrhage, Radhika Avadhani, Wendy C. Ziai, Richard E. Thompson, W. Andrew Mould, Karen Lane, Angeline Nanni, Michael Lacobelli, Matthew F. Sharrock, Lauren H. Sansing, Linda J. Van Eldik, Daniel F. Hanley

Neurology Faculty Publications

Patients with acute spontaneous intracerebral hemorrhage (ICH) develop secondary neuroinflammation and cerebral edema that can further damage the brain and lead to increased risk of neurologic complications. Preclinical studies in animal models of acute brain injury have shown that a novel small-molecule drug candidate, MW01-6-189WH (MW189), decreases neuroinflammation and cerebral edema and improves functional outcomes. MW189 was also safe and well tolerated in phase 1 studies in healthy adults. The proof-of-concept phase 2a Biomarker and Edema Attenuation in IntraCerebral Hemorrhage (BEACH) clinical trial is a first-in-patient, multicenter, randomized, double-blind, placebo-controlled trial. It is designed to determine the safety and tolerability …

Multiomics Analysis To Explore Blood Metabolite Biomarkers In An Alzheimer’S Disease Neuroimaging Initiative Cohort, Takaki Oka, Yuki Matsuzawa, Momoka Tsuneyoshi, Yoshitaka Nakamura, Ken Aoshima, Hiroshi Tsugawa, Alzheimer’S Disease Metabolomics Consortium

Neurology Faculty Publications

Alzheimer’s disease (AD) is a neurodegenerative disease that commonly causes dementia. Identifying biomarkers for the early detection of AD is an emerging need, as brain dysfunction begins two decades before the onset of clinical symptoms. To this end, we reanalyzed untargeted metabolomic mass spectrometry data from 905 patients enrolled in the AD Neuroimaging Initiative (ADNI) cohort using MS-DIAL, with 1,304,633 spectra of 39,108 unique biomolecules. Metabolic profiles of 93 hydrophilic metabolites were determined. Additionally, we integrated targeted lipidomic data (4873 samples from 1524 patients) to explore candidate biomarkers for predicting progressive mild cognitive impairment (pMCI) in patients diagnosed with AD …

Nalfurafine Promotes Myelination In Vitro And Facilitates Recovery From Cuprizone + Rapamycin-Induced Demyelination In Mice, Ross Van De Wetering, Rabia Bibi, Andy Biggerstaff, Sheein Hong, Bria Pengelly, Thomas E. Prisinzano, Anne C. La Flamme, Bronwyn M. Kivell

Markey Cancer Center Faculty Publications

The kappa opioid receptor has been identified as a promising therapeutic target for promoting remyelination. In the current study, we evaluated the ability of nalfurafine to promote oligodendrocyte progenitor cell (OPC) differentiation and myelination in vitro, and its efficacy in an extended, cuprizone-induced demyelination model. Primary mouse (C57BL/6J) OPC-containing cultures were treated with nalfurafine (0.6–200 nM), clemastine (0.01–100 μM), T3 (30 ng/mL), or vehicle for 5 days. Using immunocytochemistry and confocal microscopy, we found that nalfurafine treatment increased OPC differentiation, oligodendrocyte (OL) morphological complexity, and myelination of nanofibers in vitro. Adult male mice (C57BL/6J) were given a diet con- taining …

Taste And Learning In The Gustatory Cortex, Martin Raymond

Alternative Theses and Dissertations (AETDs)

This research investigates the organization of taste representations in the gustatory cortex (GC) through two experiments utilizing miniscope imaging in mice. The first experiment focuses on conditioned taste aversion (CTA) and reveals that taste representations in GC are heavily dominated by palatability, with shifts in representational space occurring as a function of learning and extinction. The second experiment explores the interrelation of aversive stimuli, the impact of novelty on taste representations, and the role of somatosensory feedback. Findings suggest that familiarity and palatability emerge as positive signals with experience, shaping taste representations in GC. The study contributes to a nuanced …

Outpatient Fall Prevention In Ambulatory Adults 65 Years Old And Over, Dorothy L. Osborne-White

Doctor of Nursing Practice (DNP) Scholarly Projects - Archive

Background: In the United States (U.S.), falls are the leading cause of injury among adults 65 and over, resulting in 36 million falls yearly (Moreland et al., 2020). According to the Centers for Disease Control and Prevention (CDC, 2023), one in four older adults experiences a fall each year. Falls are the world's second most prominent cause of accidental deaths (World Health Organization [WHO], 2021). Falls are the leading cause of both fatal and non-fatal injuries among older adults (Moreland et al., 2020).

Methods: A quality improvement project that included a fall bundle was implemented in a primary clinic. A …

Association Between Encephalopathy And Clinical Outcomes Of Covid-19: Findings From The Philippine Corona Study, V. M.M. Anlacan, F. G.C. Gabriel, R. D.G. Jamora, E. Q. Villanueva, M. C.C. Sy, M. H.L. Lee Yu, A. I. Espiritu

Ateneo School of Medicine and Public Health Publications

Introduction

This study aimed to determine whether encephalopathy is associated with such COVID-19 outcomes as disease severity, mortality, respiratory failure, intensive care unit (ICU) admission, duration of ventilator dependence, and length of ICU and hospital stay.

Methods

We performed a subgroup analysis comparing outcomes in patients with and without encephalopathy, based on data from a nationwide retrospective cohort study among adult patients hospitalized with COVID-19 at 37 hospital sites in the Philippines. The patient outcomes included for analysis were disease severity, mortality, respiratory failure, ICU admission, duration of ventilator dependence, and length of ICU and hospital stay.

Results

Of a …

Non-Coding Rnas Involved In The Molecular Pathology Of Alzheimer’S Disease: A Systematic Review, Reynand Jay Canoy, Jenica Clarisse Sy, Christian Deo Deguit, Caitlin Bridgette Castro, Lyoneil James Dimaapi, Beatrice Gabrielle Panlaqui, Wenzel Perian, Justine Yu, John Mark Velasco, Jesus Emmanuel Sevilleja, Anna Gibson

Ateneo School of Medicine and Public Health Publications

Alzheimer’s disease (AD) is the leading cause of dementia globally, having a pathophysiology that is complex and multifactorial. Recent findings highlight the significant role of non-coding RNAs (ncRNAs), specifically microRNAs (miRNAs), long non-coding RNAs (lncRNAs), circular RNAs (circRNAs), and piwi-interacting RNAs (piRNAs) in the molecular mechanisms underlying AD. These ncRNAs are involved in critical biological processes such as cell proliferation, apoptosis, oxidative stress, amyloid-beta aggregation, tau phosphorylation, neuroinflammation, and autophagy, which are pivotal in AD development and progression. This systematic review aims to consolidate current scientific knowledge on the role of ncRNAs in AD, making it the first to encompass …

Developmental Profile Of Filipino Children Born During The Sars-Cov-2 Pandemic: Pilot Study, Angel Belle Dy, Michelle Alexandra Edillon, Mikhaela Francesca Marietta A. Malonzo, Glenda Darlene Garcia, Alane Blythe C. Dy, Clarisse Joyce S. Espiritu, Ma Bianca Carmela Aquino, Shannen Louise T. So, Nina Linly D. Capulong, Rizza Victoria C. Dagal, Lourdes Bernadette Tanchanco

Ateneo School of Medicine and Public Health Publications

Objective

The Philippines experienced one of the longest restriction periods during the COVID-19 pandemic. This study aimed to provide a developmental profile of 18-25 month-old children and identify factors associated with their development during their early years being born and raised during the pandemic.

Methods

The study population was recruited through convenience sampling among families living in proximity to the daycare centers in Cainta, Rizal, Philippines. 116 children qualified to participate and underwent developmental screening using the Early Childhood Care and Development (ECCD) Checklist and their parents were interviewed related to demographic and social factors.

Results

The mean score of …

Systemic Lupus Erythematosus Presenting As Aseptic Meningitis And Pancytopenia, Julia Collins, Roy Escobar, Vishnu Halthore, Ali Abu-Alya, Tanvir Khosla, Hamza Hansoti, Janita Sidhu, Elia Barraza, Zachary Charif, Azaam Mamoor, Ann Wierman, Venkatachalam Veerappan

Far West Division GME Research Day 2024

No abstract provided.

Two-Fraction Postoperative Spine Radiosurgery For Metastatic Spine Cancer, Elizabeth E. Obi, A Sanchez-Feliciano, G A. Smith, D J. Donnelly

TriStar Division GME Research Day 2024

No abstract provided.

Epidemiologic Profile And Treatment Analysis Of Cervicalgia In Patients With Migraine Vs. Tension-Type Headaches From A Multicenter Electronic Medical Record Database (Trinetx), Ethan J. Le, Victor S. Wang, Md, Hsiangkuo Yuan, Md, Phd

Alpha Omega Alpha Research Symposium Posters

BACKGROUND

• Cervicalgia, or chronic neck pain, remains an understudied and undertreated comorbid condition in patients with headache disorders that benefits from both pharmacologic and non-pharmacologic treatment profiles.

• Cervicogenic headaches present a significant global healthcare burden, with estimates projecting up to 4.1% of the global population and 20% of headache complaints are attributed to cervicalgia (Fernandez et al. 2020).

• What is the global demographic, treatment, and migraine preventive profile of cervicalgia in patients with either concurrent migraine (CM) or tension-type (CT) headaches?

Alternatives To The Squad Car: A Strategy Providing Hope For People With Mental Illness, Judy Ann Clausen, Joanmarie I. Davoli

UF Law Faculty Publications

Frontline healthcare providers and first responders have had enough of mental health care policy rooted in ideology and utopian visions instead of the practical realities of the nature of Serious Mental Illnesses (SMI). The current system of a severe shortage of mental health beds and strict criteria for administering mental health treatment in contravention of illness-induced treatment refusals has caused the real-world preventable tragedies of mass shootings, incarceration, homelessness, victimization, and death of people suffering from untreated SMI. Innovative programs and long-established protocols have been profiled by the media and examined by scholars. Momentum is brewing. Across the country, creative …