Digital Commons Network^™

Longitudinal Association Between Midlife Cardiovascular Health And Cognitive Change In A Bi-Ethnic Cohort, Janette Vazquez, Rebecca Bernal, Luis Aguirre, Jesus D. Melgarejo, Gladys Maestre, Sudha Seshadri, Helen P. Hazuda, Chen-Pin Wang, Claudia Satizabal

School of Medicine Publications

Introduction: Midlife cardiovascular burden contributes to cognitive decline and dementia. However, research in diverse populations remains scarce.

Methods: We included 402 San Antonio Heart Study participants (1979–1988; midlife mean age 57.9 ± 3.8, 58.5% women, 52% Mexican American) later enrolled in the San Antonio Longitudinal Study of Aging (1992–2004). Midlife cardiovascular health was assessed using Life's Simple 7. Cognition was measured up to four times with the Mini-Mental State Examination. Generalized estimating equation models adjusted for age, sex, income, and education were used to relate cardiovascular factors to cognitive change. Sensitivity analyses evaluated attrition bias.

Results: Physical activity was associated …

Erratum: Genetic Variations In Extracellular Matrix Degradation Pathways Linking To Major Depressive Disorder: Evidence From A Large-Scale Genetic Association Study, Halliru Zailani, Daniel Tzu-Li Chen, Sheng-Che Lin, Jia-Hau Lee, Mei-Ling Li, Bing-Fang Huang, Jane Pei-Chen Chang, Kuan-Pin Su

BioMedicine

No abstract provided.

Pneumoperitoneum As A Rare Complication Of Percutaneous Vertebroplasty: A Case Report, Chen-Ting Yang, I-Han Hsiao, Chun-Chung Chen, Der-Yang Cho, Hui-Shan Lu, Po-Fan Chiu

BioMedicine

A 70-year-old woman with a history of hepatocellular carcinoma and bone metastasis underwent percutaneous vertebroplasty for multilevel pathological vertebral compression fractures due to back pain persisting despite conservative treatment. Subsequently, she reported significant pain relief; however, on postoperative day 1, she complained of intermittent, diffuse, and severe abdominal pain. Imaging examination revealed free air in the retroperitoneum and paraspinal space, suggesting hollow organ perforation. She refused exploratory surgery and was consequently discharged against medical advice with only oral antibiotics. Two weeks later, she returned for follow-up. She was in good condition with stable vital signs and no signs of toxic …

Tracking The Course Of Fibrodysplasia Ossificans Progressiva In A Patient With The Classic Acvr1 Mutation, Mohamed Mostafa Kotb, Usama Farghaly Omar, Bishoy Raafat Zaky, Arun-Kumar Kaliya-Perumal

BioMedicine

Fibrodysplasia Ossificans Progressiva (FOP) is an extremely rare and debilitating genetic disease affecting approximately 1 in 2 million people. It is caused by a heterozygous gain-of-function mutation in the gene encoding activin A receptor type I (ACVR1), leading to dysregulated bone morphogenetic protein (BMP) signaling. Clinically, the disease features progressive heterotopic ossification, with bone forming in sites of soft tissue inflammation. We report a 7-year-old boy with two isolated ectopic bone masses in the paraspinal muscles of the neck and lumbar spine, resulting in pain and restricted spinal mobility. Genetic analysis revealed the classic c.617G>A mutation in the gene …

Physalin A Protects Against Diabetes-Like Retinal Neurodegeneration Via Autophagy, Mitophagy, And Antioxidant Pathways In Drosophila Melanogaster, Yan-Ru Xiao, Wei-Yong Lin, Wen-Zhen Lee, Yu-Sheng Hsieh, Wei-Cheng Jiang, Fu-Shin Chueh, Yueh-Hsiung Kuo, Sheng-Yao Hsu, Yu-Jung Lin, Wen-Tsong Hsieh

BioMedicine

Background: Diabetic retinopathy begins with neuroretinal dysfunction driven by oxidative stress, mitochondrial injury, and impaired proteostasis before microvascular pathology emerges. Drosophila provides a tractable neuron-centric model to interrogate these early events. Physalin A (PA), a withanolide, has antioxidative and anti-inflammatory activities, yet its retina-specific mitochondrial actions in vivo remain incompletely defined.

Purpose: To determine whether PA rescues visual function and neuronal integrity in insulin receptor mutant Drosophila with DR-like retinal injury, and to delineate associated pathways in autophagy, mitophagy, and antioxidant defense.

Methods: Adult w^{1118; P{GMR-InR.A1325D}3} Drosophila received dietary PA (6–24 μM) for seven days. Visual function was …

Neuroinflammatory And Neuronal Damage Biomarkers In Depression: A Meta-Analysis Of Hmgb1, S100Β, And Nse Levels, Ikbal Andrian Malau, Suet-Kei Wu, Jane Pei-Chen Chang, Cheng-Ho Chang, Chun-Hung Chang, Ming-Jun Tsai, Yung-Chih Chiang, Kuan-Pin Su

BioMedicine

Background: Depression is associated with neuroinflammation and dysfunction of neurons and glial cells. Immune activation and damage-associated signals such as S100 calcium-binding protein B (S100β) and high mobility group box 1 (HMGB1) amplify inflammation, leading to neuronal injury. Neuron-specific enolase (NSE) reflects such injury. These molecules may serve as potential biomarkers of depression.

Aims: This study compared levels of S100β, HMGB1, and NSE in individuals with depression versus non-depressed controls.

Methods: PubMed, Embase, and Web of Science were searched up to April 5, 2025, using the terms “S100B AND Depression”, “neuron specific enolase AND Depression”, and “HMGB1 …

Evaluation Of The Anti-Inflammatory Properties In Vitro, In Vivo And In Silico, Of The Snail Slime Helix Aspersa Müller, Marouane Aouji, Malak Zirari, Mariame Taibi, Meryem Lamdak, Amine Rkhaila, Rachid Bengueddour

BioMedicine

Background: The search for effective natural alternatives to synthetic non-steroidal antiinflammatory drugs (NSAIDs), which are often associated with undesirable side effects, is an important axis of current research. The slime of the snail Helix aspersa Müller, is a traditional remedy that deserves scientific investigation for its potential therapeutic properties.

Purpose: This study aimed to comprehensively evaluate the anti-inflammatory effects of Helix aspersa Müller slime using a combination of in vitro, in vivo, and in silico methodologies.

Methods: In vitro analyses included assays for inhibition of protein denaturation, antiprotease and antilipoxygenase activities, and membrane stabilization, with diclofenac and indomethacin as reference …

Traditional Chinese Medicine And Healthcare Utilization In Bipolar Disorder: A Population-Based Study With Propensity-Matched And Mirror-Image Analyses, Shu-Ping Chen, Su-Tso Yang, Kai-Chieh Hu, Hui-Chih Chang, Jane Pei-Chen Chang, Kuan-Pin Su

BioMedicine

Background: Bipolar disorder (BD) is a chronic relapsing illness associated with high rates of acute psychiatric hospitalizations (APH) and emergency services (ES) use, placing burdens on healthcare systems. Many patients seek complementary modalities, including traditional Chinese medicine (TCM), alongside standard pharmacotherapy. However, population-based evidence regarding TCM’s effect on acute healthcare utilization in BD is lacking.

Methods: Using data from Taiwan’s Longitudinal Health Insurance Database 2000 (LHID 2000), this population-based study employed propensity score matching (PSM) based on age, gender, the index year (defined as the calendar year of the index date for TCM users and their matched nonTCM counterparts), and …

Topical Peony And Licorice Decoction Attenuates Exercise-Induced Muscle Pain: A Randomized Double-Blind Self-Controlled Trial In Taiwan, Daniel Tzu-Li Chen, Chang-Wei Hsieh, Chia-Han Tsai, Tzung-Yan Lee, Pin-Chun Chen, Pu-Wei Hou, Kuan-Pin Su, Hen-Hong Chang

BioMedicine

Background

Delayed onset muscle soreness (DOMS) is a common phenomenon that occurs after exercise training, resulting in pain and reduced muscle performance. Previous basic and animal studies have reported that oral use of Peony and Licorice Decoction (PLD), a traditional Chinese formula with anti-inflammatory and muscle-relaxing properties, may be safe and effective for DOMS. However, there have been no clinical studies, particularly on the topical use of PLD, in this field to date.

Material and Methods

Our study is a double-blind, randomized, placebo-controlled trial. We recruited healthy male athletes to assess the effect of external PLD, whose bioactive compounds were …

A Causal Association Between Alkaline Phosphatase And Natural-Cause Mortality: A Mendelian Randomization Study In East Asians And Europeans., Hung-Lin Chen, Ping-Hsun Wu, Yi-Ting Lin, Amrita Chattopadhyay, Hsiu-Yin Chiang, Yu-Ting Lin, Ya-Chi Lin, Che-Chen Lin, Min-Yu Chiang, Hung-Chieh Yeh, I-Wen Ting, Yu-Cyuan Hong, David Ray Chang, Jenq-Wen Huang, Yu-Ting Lin, Wei-Chi Syu, Tzu-Pin Lu, Yi-Chun Tsai, Fuu-Jen Tsai, Chin-Chi Kuo

BioMedicine

Background: Although observational studies show a positive association between alkaline phosphatase (ALP) levels and mortality, a causal study is not yet available.

Objective: We conducted a retrospective cohort study and a systematic one-sample Mendelian randomization (MR) study to investigate the causality of ALP on natural-cause mortality.

Methods: The study used a hospital-based cohort of Asian patients recruited from the China Medical University Hospital (CMUH) and a community-based cohort of white European participants from the UK Biobank (UKB). Two retrospective cohorts included 43,994 patients from CMUH and 80,941 participants from UKB, all aged 50–55 years, with ALP measurements. For the MR …

Linking Institutional Ai Capability With Workforce Ai Fluency In Academic Health Institutions, Chin-Chi Kuo, Yu-Ting Lin, Cheng-Chieh Lin, Long-Bin Jeng, Bradley Chen

BioMedicine

No abstract provided.

Flaxseed Ethanolic Extract Modulates Β-Catenin And Dkk1 Expressions During Osteoblast Differentiation Of Dental Pulp-Derived Stem Cells, Nur Sazwi Nordin, Khairani Idah Mokhtar, Omar Abdul Jabbar Abdul Qader, Basma Ezzat Mustafa, Widya Lestari, Deny Susanti Darnis, Thirumulu Ponnuraj Kannan, Azlina Ahmad, Solachuddin Jauhari Arief Ichwan

Journal of Dentistry Indonesia

Background: WNT signaling regulates osteogenic differentiation of mesenchymal stem cells (MSC) through the canonical WNT pathway. β-catenin; an important molecule of WNT pathway, and DKK1; a WNT antagonist, play important roles in regulating bone formation. Although flaxseed (Linum usitatissimum) has various health benefits, including promoting bone health, our previous study showed that flaxseed ethanolic extract (FEE) reduced the osteoblast differentiation potential of stem cells from human exfoliated deciduous teeth (SHED). This study aimed to determine the effects of FEE on WNT pathway-related molecules, β-catenin and DKK1, during osteoblast differentiation of SHED.

Methods: RNA at Day 7, 14, …

The Correlation Between Medication Adherence, Blood Glucose Levels, And Quality Of Life In Patients With Type 2 Diabetes Mellitus At Ciamis Regional Hospital, Amyla Putri Nurul Nazmi, Nur Rahayuningsih, Lusi N

Pharmacology and Clinical Pharmacy Research

Type 2 diabetes mellitus is a chronic condition requiring continuous treatment, including patient adherence to prescribed medication. This study aimed to explore the relationship between medication adherence, blood glucose levels, and quality of life in patients with type 2 diabetes mellitus at Ciamis Regional Hospital, conducted from January to March 2025, the research employed a quantitative, prospective cross-sectional design involving 49 hospitalized patients. Data included blood glucose levels (RPG, FPG, 2hPG), medication adherence measured using the Medication Adherence Report Scale (MARS-5), and quality of life assessed via the Diabetes Quality of Life-Brief Clinical Inventory (DQOL-BCI). The chi-square test was used …

The Phytochemical Content And Antibacterial Activity Of Purified Extract Of Mangifera Indica L. Against Gram Positive Pathogen, Dewi Andini Kunti Mulangsri, Masduki Faqih, Sugar Arifin, Mutiara Trie Sieya Agustin

Pharmacology and Clinical Pharmacy Research

The purified extract of arum manis mango leaves contained flavonoid compounds by TLC methods and antibacterial activity against Gram-positive and negative pathogens. This research aimed to identify and determine the phytochemical content (mangiferin and flavonoids content) and antibacterial activity against other Gram-positive pathogens. Purification of ethanol extract of arum manis mango leaves by liquid-liquid fraction method. Determination of total flavonoid content and identification of mangiferin used respectively by aluminum chloride and Thin Layer Chromatography method. The disk diffusion method was used to assay antibacterial activity against S. epidermidis, and B. subtilis bacteria with the concentration of the sample such …

Cost Effectiveness Analysis Of Psychopharmaca Therapy Combination Compared With Psychopharmaca Therapy And Ect Combination In Schizoaffective Inpatients At The Rsj Provinsi Jawa Barat, Yasmin Fadillah, Sani Asmi Ramdani Lestari, Ardilla Kemala Dewi

Pharmacology and Clinical Pharmacy Research

Mental disorders constitute an economic burden on health, estimated at USD 2.5 trillion in 2010 and expected to increase to USD 6 trillion by 2030. Treatment of schizoaffective disorder involves a combination of medication and psychotherapy. Pharmacoeconomics is an important consideration in drug selection. This study aims to determine the cost-effectiveness of psychopharmaca therapy combination compared with psychopharmaca therapy and ECT combination in schizoaffective inpatients at the RSJ Provinsi Jawa Barat. Data collection was conducted retrospectively from patient medical records for the period December 2023–December 2024. Total costs, based on a health perspective, include psychopharmaca drug costs, inpatient care costs, …

Evaluation Of Antibiotic Use Using The Gyssens Method On Clinical Outcomes In Ischemic Stroke Patients, Juniarto Mende, Graciano A. Maturbongs, Yohana K. A. Mbulang

Pharmacology and Clinical Pharmacy Research

Ischemic stroke is a health problem that causes death and neurovascular disability worldwide. The inflammatory response due to infection can increase ischemic stroke and increase brain damage through changes in blood pressure, coagulation, immune response, and endothelial function. This study aims to evaluate the rationality of antibiotic use on clinical outcomes in ischemic stroke patients. This study used a cross-sectional design. Retrospective data were taken from the medical records of Jayapura Regional Hospital for the period January 1, 2023, to May 31, 2025. The study subjects were all patients who suffered ischemic stroke and received antibiotics. Evaluation of the rationality …

Retrospective Analysis Of Antimicrobial Resistance Patterns In Gram-Positive And Gram-Negative Blood Isolates, Helman Kurniadi, Timbul Partogi Haposan Simorangkir, Ros Sumarny, Fitria Heldiana

Pharmacology and Clinical Pharmacy Research

Bloodstream infections are an important cause of morbidity and mortality, while antimicrobial resistance limits treatment options. This retrospective study evaluated bacterial distribution and antimicrobial susceptibility in blood cultures at RSPAD Gatot Soebroto, Jakarta, using microbiology and medical record data from January-December 2019. Clinically significant isolates were included, while duplicates and contaminants were excluded. Identification and susceptibility testing followed standard procedures and CLSI 2019 guidelines. Data were analyzed descriptively. Among 482 isolates, 246 (51.0%) were Gram-positive and 236 (49.0%) were Gram-negative. The Gram-positive isolates were mainly coagulase-negative staphylococci, including Staphylococcus epidermidis (62, 25.2%), S. hominis (61, 24.8%), and S. haemolyticus (50, …

Analysis Of Pharmacotherapy And Non-Pharmacotherapy Burden From The Ina-Cbgs Package For Cesarean Section Surgery At The Regional General Hospital Dr. Soedarso In 2023, Ananda Rizky Awwaliyah, Nurmainah Nurmainah, Ridha Ulfah

Pharmacology and Clinical Pharmacy Research

The prevalence of cesarean sections has been increasing each year. Previous studies show that the cost of medications and medical supplies for cesarean patients accounts for one-third of the total care costs. In the era of National Health Insurance (NHI), medications and medical supplies are considered operational expenses for hospitals rather than sources of income. This condition requires proper medication management and the use of medical supplies. This study aims to analyze the percentage of pharmacotherapy and non-pharmacotherapy, including the types and quantities of medications as well as disposable medical supplies used on patients undergoing cesarean section procedures at the …

Alexithymia In Substance Use Disorders: A Scoping Review Of Therapeutic Approaches, Pratami Diah Herliani, Shelly Iskandar, Angela Vera Herman Efendi

Pharmacology and Clinical Pharmacy Research

Alexithymia, defined as the inability to recognize and express emotions, has a high prevalence (40–50%) among individuals with substance use disorders (SUD), particularly alcohol use disorder, and is associated with poorer clinical outcomes. Despite this, comprehensive mapping of psychotherapeutic interventions targeting this condition within the SUD population remains limited. This study aimed to systematically map the therapeutic approaches investigated to address alexithymia among individuals with substance use disorders and to summarize the reported outcomes. A scoping review was conducted in accordance with the PRISMA-ScR guidelines using systematic literature searches in the PubMed and Scopus databases. Relevant studies were screened based …

Variation In Meningioma Recurrence Risk Estimates Across Observational Cohorts: The Influence Of Calendar Time, Who Classifications, Geographical Settings, And Healthcare Systems, Christian Mirian, Lasse Rehné Jensen, Adam Gorm Hoffmann, Tareq A Juratli, Anders Broechner, Sverre H Torp, Helen A Shih, Ramin A Morshed, Jacob S Young, Stephen T Magill, Luca Bertero, Walter Stummer, Dorothee Cäcilia Spille, Benjamin Brokinkel, Soichi Oya, Satoru Miyawaki, Nobuhito Saito, Martin Proescholdt, Yasuhiro Kuroi, Konstantinos Gousias, Matthias Simon, Jennifer Moliterno, Ricardo Prat-Acin, Stéphane Goutagny, Vikram C Prabhu, John T Tsiang, Johannes Wach, Erdem Güresir, Junkoh Yamamoto, Young Zoon Kim, Joo Ho Lee, Daniel W Kim, Matthew Koshy, Karthikeyan Perumal, Mustafa K Baskaya, Donald M Cannon, Dennis C Shrieve, Chang-Ok Suh, Jong Hee Chang, Maria Kamenova, Sven Straumann, Jehuda Soleman, Ilker Y Eyüpoglu, Tony Catalan, Austin Lui, Philip V Theodosopoulos, Michael W Mcdermott, Fang Wang, Pedro Góes, Manoel Antonio De Paiva Neto, Ricardo Komotar, Michael E Ivan, Aria Jamshidi, Evan Luther, Luis Souhami, Marie-Christine Guiot, Tamás Csonka, Toshiki Endo, Olivia Claire Barrett, Randy Jensen, Tejpal Gupta, Akash J Patel, Tiemo J Klisch, Jun Won Kim, Francesco Maiuri, Valeria Barresi, María Dolores Tabernero, Simon Skyrman, Ian Law, Bjarne Winther Kristensen, Tina Nørgaard Munch, Torstein Meling, Kåre Fugleholm, Paul Blanche, Tiit Mathiesen, Andrea Daniela Maier

Duncan NRI Faculty and Staff Publications

Purpose: Recurrence risk estimates underpin meningioma research, including molecular classification and clinical trial benchmarking, yet are often based on retrospective or historical data. The aim of this study was to assess the variation of recurrence risk estimates across calendar periods, WHO classification editions, geographical settings, and healthcare systems.thetermine METHODS: We analyzed 4,111 patients with primary WHO-1/-2 meningiomas from 31 centers in 15 countries (1990-2019). Recurrence was defined according to local radiological assessment. The 5- and 10-year recurrence risks were estimated using regression standardization with inverse probability of censoring weights, adjusting for key clinical, surgical, and histopathological variables.

Results: Recurrence risk …

Translational Initiative To Minimize Childhood Hemiparesis After Asymmetrical Perinatal Brain Injury, Susan V. Duff, Emily Garavatti, Terrie Inder

Physical Therapy Faculty Articles and Research

The purpose of this perspective paper is to present a translational approach aimed at identifying the critical periods in brain development during which to provide neuroprotective and neurorestorative strategies, followed by prehensile training, to minimize hemiparesis and foster skill acquisition after asymmetrical perinatal brain injury (APBI). We contend that hemiparesis could be minimized after APBI through a multimodal sequential approach based on timely implementation of evidence-based intervention strategies. If APBI is identified early, neuroprotective techniques can be used in the first 10 days of life to minimize cell death. This can be followed in the next 3 months by the …

Identifying And Addressing Problematic Studies In Allergy And Asthma Research: A Commentary, Alexandro W L Chu, Gordon H Guyatt, Jason W Busse, Romina Brignardello-Petersen, Xiajing Chu, Daniel G Rayner, Paul Oykhman, Vanessa Wong, Yetiani Roldan, Diane R Baker, Leonard B Bacharier, Lisa A Beck, Moshe Ben-Shoshan, Bradley Chipps, Flavia Hoyte, Elliot Israel, David M Lang, Sameer K Mathur, Sharmilee M Nyenhuis, Paul M O'Byrne, Eric T Oliver, John Oppenheimer, Tamara T Perry, Katherine Rivera-Spoljaric, Sarbjit S Saini, Javed Sheikh, Kaharu Sumino, Susan Waserman, Elissa M Abrams, Aikaterini Anagnostou, Jonathan A Bernstein, Anne K Ellis, David B K Golden, Caroline C Horner, Dennis K Ledford, Jay Lieberman, Giselle Mosnaim, Matthew A Rank, Marcus Shaker, Julie Wang, David A Khan, Derek K Chu

Center for Medical Ethics and Health Policy Staff Publications

Randomized controlled trials underpin evidence-based medicine, but a growing proportion of trials contain implausible, inaccurate, or fabricated data. When such studies are incorporated into systematic reviews, they distort effect estimates, inflate evidence certainty, and can mislead the guideline recommendations that the reviews aim to inform. Within 8 recent American Academy of Allergy, Asthma & Immunology and American College of Allergy, Asthma and Immunology Joint Task Force on Practice Parameters (JTFPP) systematic reviews, 17% of trials published between 2021 and 2024 were problematic, and in a network meta-analysis of antihistamines for chronic urticaria, 39% of recent trials were excluded because of …

Studying What Matters: South Texas Community-Driven Dementia Research Priorities, Sara S. Masoud, Juana Escareño, Belinda Flores, Byeong Yeob Choi, Karla Daniela Lopez Lorenzo, Shanae L. Rhodes, Quetzaly Zenil, Carole L. White

School of Medicine Publications

South Texas has among the highest dementia prevalence rates in the United States, yet communities in the region remain consistently underrepresented in dementia research. Aligning research studies with what matters to communities most impacted by dementia is critical in addressing the crisis of research exclusion. This participatory study sought to identify community-driven dementia research priorities grounded in the experiences and needs of South Texas residents impacted by dementia. A two-year community-engaged study was conducted in partnership with a Community Council composed of individuals living with dementia, family caregivers, community health workers, and community-serving professionals. A plática program model was co-developed …

Intouch Week Of August 24, 2026, New York Medical College

InTouch

• Walking Tour of the William F. Bierer, M.D. ’62, Educational Medicinal Herbal Garden
• GSBMS Welcomes New Students During Welcome Luncheon
• New and Improved AEDs are Installed Across Campus
• New Partnership Opens Doors to Physical Therapy Careers for Westchester Students
• NYMC SOM Student Senate Hits the Ground Running with New Executive Board
• NYMC Faculty Mentor Future Dentists Through Immersive Summer Research Experience
• Inaugural Anesthesiology Summer Research Program Gives Students an Early Start in Academic Medicine
• TCDM Promotes Healthy Smiles in the Community
• Faculty Spotlight: 60 Seconds of Science | Episode 2: Cyclospora

Amyloid-Related Imaging Abnormalities Summit Special Proceedings: Cardiovascular And Stroke Considerations For Β-Amyloid Immunotherapy In Alzheimer Disease., Steven M Greenberg, Costantino Iadecola, Sherry H-Y Chou, Petrice M Cogswell, Mitchell S V Elkind, William J Hicks, Caitlin Le, Deborah A Levine, Richard Lipton, Lauren Massimo, Stephanie M Mohl, Sudha Seshadri, Heather M Snyder, Kristine Yaffe, Kori S Zachrison, Aria Summit Working Group

Neuroscience Articles

BACKGROUND: New antiamyloid therapies (AAT) for treating patients with early Alzheimer disease (AD) have become available in the past 3 years. Although AAT can be beneficial in slowing progression of AD, they also come with potentially serious side effects, particularly for patients requiring anticoagulation or thrombolysis for cardiovascular conditions. Given that most patients with AD are older and likely to have cardiovascular risk factors, there is urgent need for additional guidance for clinicians about potential risks and benefits associated with AAT for patients with cardiovascular comorbidities, best practices for management of these patients, and special considerations with respect to emergency …

Cells And Networks In Flux: Rethinking Ontogenesis And Pathogenesis, Mark L. Tykocinski

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Organ and tissue functions emerge from the coordinated activity of cell networks. Therapeutics that act on pathogenic cell networks, modulating their cellular interplay, follow naturally. Over several decades, our laboratory has developed a series of approaches for rewiring cell networks, culminating in a class of cell surface-directed signal converter proteins (SCPs) that do so by modulating juxtacrine and autocrine signaling in and among their nodal cells. A first such SCP has now produced encouraging clinical data for cancer immunotherapy. Yet, these early network-directed fusion proteins rest on a deliberately simplified picture: discrete end-cell types plugged into graphically tractable networks. That …

Selective Loss Of Primary Cilia And Neurotrophic Signaling In G51d Α-Synuclein Mice Highlights A Common Pathway To Parkinson’S Disease, Yu-En Lin, Ebsy Jaimon, Youngdoo Kim, Annabeth Loftman, Aaran Vijayakumaran, Benjamin D W Belfort, Claire Y Chiang, Benjamin R Arenkiel, Huda Y Zoghbi, Suzanne R Pfeffer

Duncan NRI Faculty and Staff Publications

Parkinson's disease is characterized by dopaminergic neuron loss and accumulation of α-synuclein aggregates in the brain. G51D α-synuclein knock-in mice provide a genetically and clinically relevant model of disease, exhibiting early olfactory deficits, age-dependent motor impairment, and progressive phospho-α-synuclein accumulation. In multiple Parkinson's disease models, striatal cholinergic and parvalbumin interneurons, as well as astrocytes, lose primary cilia and the neurotrophic signaling needed to sustain dopaminergic neurons. We show here that G51D α-synuclein mice share these phenotypes. Phospho-Ser129 α-synuclein accumulation correlates with cilia loss in cholinergic interneurons but not in spiny projection neurons that accumulate higher phospho-α-synuclein levels. In the piriform …

Data-Driven Staging Of Neurodegenerative Pathology Related To Alzheimer’S Disease, Thomas Earnest

McKelvey School of Engineering Graduate Student Theses & Dissertations

Alzheimer’s Disease (AD), the most common cause of dementia, is a dual proteinopathy exhibiting deposits of extracellular amyloid-beta (Aβ) and intracellular tau in brain tissue. Models which describe the spatial and temporal trajectories of these pathologies have been invaluable for understanding AD and have the potential to support diagnosis, disease monitoring, and treatment development. Disease staging systems, which provide protocols for assessing individual disease severity based on their extent of brain pathology, have been crucial for explaining and diagnosing AD. However, these systems have been primarily informed by post-mortem histological assessments and are not directly applicable to disease assessment in …

For Weight Loss: Why Do Glp-1 Agonists Work, And How Can We Make Them Work Better?, Charlise Giang, Jieyi Meng, Mahmoud Ali Mohammad, Zhenqi Liu, Xinle Wu, Yi Zhu

Children’s Nutrition Research Center Staff Publications

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have revolutionized the management of not only type 2 diabetes but also obesity. However, even with rapid therapeutic advances in GLP-1RAs, questions regarding the fundamental principles of GLP-1-mediated weight loss and the enhanced efficacy of next-generation therapies remain. In this comprehensive review article, we first examine the milestones of GLP-1, from its initial discovery and biological characterization to its successful translation into clinical therapy. Furthermore, this review highlights the latest clinical trial data, specifically HbA1c reduction, weight-loss efficacy, and safety profiles, while exploring current pipelines of major pharmaceutical companies. Additionally, we delineate the mechanistic …

Brain Perivascular Macrophages Regulate Endothelial Cell Function Via A Cmaf-Dependent Transcriptional Program In Mouse And Human, Simone Brioschi, Julia A Belk, Steffen E Storck, Yue Wu, Zhuoying Wang, Ziang Feng, Lynn Van Olst, Josie L Emery, Raki Sudan, Junjie Wu, Siling Du, Marco Genua, Federica La Terza, Alex J Edwards, Khai M Nguyen, Jessie Sanford, Daniel D Lee, Mattia Bugatti, Arnold J Federico, Yun Chen, Zuoxu Wang, Silvia Penati, Patrick Fernandes Rodrigues, Alina Ulezko Antonova, Hui Qi Loo, Igor Smirnov, Susan Gilfillan, Carmen M Halabi, Jennifer Ponce, Jun Yan, Howard Y Chang, Gwendalyn J Randolph, William Vermi, Marina Cella, Michael Meers, Renato Ostuni, David Gate, Aivi T Nguyen, Carlos Cruchaga, Song Hu, Jonathan Kipnis, Marco Colonna

The Brown Foundation: Institute of Molecular Medicine

Brain perivascular macrophages maintain brain physiology, yet their transcriptional regulators and functions in health and disease remain unclear. Using single-cell multi-omics and functional experiments, we identify cellular musculoaponeurotic fibrosarcoma oncogene (cMAF) as a key transcription factor for brain perivascular macrophages, and conditional deletion of cMAF disrupts their phenotype in vivo. Functionally, cMAF drives insulin-like growth factor-1 (IGF1) expression in perivascular macrophages, enabling communication with endothelial cells. Consistently, cMAF deletion in perivascular macrophages causes transcriptional alterations in cerebral arteries, affecting vascular functions. Notably, cMAF emerges as the main transcription factor for human perivascular macrophages, suggesting conservation of this transcriptional module. During …