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Trial Of Early Minimally Invasive Removal Of Intracerebral Hemorrhage, Gustavo Pradilla, Salah G Keyrouz, Et Al. Apr 2024

Trial Of Early Minimally Invasive Removal Of Intracerebral Hemorrhage, Gustavo Pradilla, Salah G Keyrouz, Et Al.

2020-Current year OA Pubs

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known.

METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical …


Chemotherapy Activates Inflammasomes To Cause Inflammation-Associated Bone Loss, Chun Wang, Khushpreet Kaur, Canxin Xu, Yousef Abu-Amer, Gabriel Mbalaviele Apr 2024

Chemotherapy Activates Inflammasomes To Cause Inflammation-Associated Bone Loss, Chun Wang, Khushpreet Kaur, Canxin Xu, Yousef Abu-Amer, Gabriel Mbalaviele

2020-Current year OA Pubs

Chemotherapy is a widely used treatment for a variety of solid and hematological malignancies. Despite its success in improving the survival rate of cancer patients, chemotherapy causes significant toxicity to multiple organs, including the skeleton, but the underlying mechanisms have yet to be elucidated. Using tumor-free mouse models, which are commonly used to assess direct off-target effects of anti-neoplastic therapies, we found that doxorubicin caused massive bone loss in wild-type mice, a phenotype associated with increased number of osteoclasts, leukopenia, elevated serum levels of danger-associated molecular patterns (DAMPs; e.g. cell-free DNA and ATP) and cytokines (e.g. IL-1β and IL-18). Accordingly, …


Impact Of Self-Reported Loss Of Balance And Gait Disturbance On Outcomes Following Adult Spinal Deformity Surgery, Bassel G Diebo, Munish C Gupta, Et Al. Apr 2024

Impact Of Self-Reported Loss Of Balance And Gait Disturbance On Outcomes Following Adult Spinal Deformity Surgery, Bassel G Diebo, Munish C Gupta, Et Al.

2020-Current year OA Pubs

No abstract provided.


Innovation In Non-Invasive Diagnosis And Disease Monitoring For Meningiomas, Brianna Korte, Dimitrios Mathios Apr 2024

Innovation In Non-Invasive Diagnosis And Disease Monitoring For Meningiomas, Brianna Korte, Dimitrios Mathios

2020-Current year OA Pubs

Meningiomas are tumors of the central nervous system that vary in their presentation, ranging from benign and slow-growing to highly aggressive. The standard method for diagnosing and classifying meningiomas involves invasive surgery and can fail to provide accurate prognostic information. Liquid biopsy methods, which exploit circulating tumor biomarkers such as DNA, extracellular vesicles, micro-RNA, proteins, and more, offer a non-invasive and dynamic approach for tumor classification, prognostication, and evaluating treatment response. Currently, a clinically approved liquid biopsy test for meningiomas does not exist. This review provides a discussion of current research and the challenges of implementing liquid biopsy techniques for …


Bone Canonical Wnt Signaling Is Downregulated In Type 2 Diabetes And Associates With Higher Advanced Glycation End-Products (Ages) Content And Reduced Bone Strength, Giulia Leanza, Alec T Beeve, Erica L Scheller, Simon Y Tang, Roberto Civitelli, Nicola Napoli, Et Al. Apr 2024

Bone Canonical Wnt Signaling Is Downregulated In Type 2 Diabetes And Associates With Higher Advanced Glycation End-Products (Ages) Content And Reduced Bone Strength, Giulia Leanza, Alec T Beeve, Erica L Scheller, Simon Y Tang, Roberto Civitelli, Nicola Napoli, Et Al.

2020-Current year OA Pubs

Type 2 diabetes (T2D) is associated with higher fracture risk, despite normal or high bone mineral density. We reported that bone formation genes (


Constant-Ph Simulations With The Polarizable Atomic Multipole Amoeba Force Field, Andrew C Thiel, Matthew J Speranza, Sanika Jadhav, Lewis L Stevens, Daniel K Unruh, Pengyu Ren, Jay W Ponder, Jana Shen, Michael J Schnieders Apr 2024

Constant-Ph Simulations With The Polarizable Atomic Multipole Amoeba Force Field, Andrew C Thiel, Matthew J Speranza, Sanika Jadhav, Lewis L Stevens, Daniel K Unruh, Pengyu Ren, Jay W Ponder, Jana Shen, Michael J Schnieders

2020-Current year OA Pubs

Accurately predicting protein behavior across diverse pH environments remains a significant challenge in biomolecular simulations. Existing constant-pH molecular dynamics (CpHMD) algorithms are limited to fixed-charge force fields, hindering their application to biomolecular systems described by permanent atomic multipoles or induced dipoles. This work overcomes these limitations by introducing the first polarizable CpHMD algorithm in the context of the Atomic Multipole Optimized Energetics for Biomolecular Applications (AMOEBA) force field. Additionally, our implementation in the open-source Force Field X (FFX) software has the unique ability to handle titration state changes for crystalline systems including flexible support for all 230 space groups. The …


A Macrophage-Cell Model Of Hiv Latency Reveals The Unusual Importance Of The Bromodomain Axis, Javan K Kisaka, Daniel Rauch, Malachi Griffith, George B Kyei Apr 2024

A Macrophage-Cell Model Of Hiv Latency Reveals The Unusual Importance Of The Bromodomain Axis, Javan K Kisaka, Daniel Rauch, Malachi Griffith, George B Kyei

2020-Current year OA Pubs

BACKGROUND: Although macrophages are now recognized as an essential part of the HIV latent reservoir, whether and how viral latency is established and reactivated in these cell types is poorly understood. To understand the fundamental mechanisms of viral latency in macrophages, there is an urgent need to develop latency models amenable to genetic manipulations and screening for appropriate latency-reversing agents (LRAs). Given that differentiated THP-1 cells resemble monocyte-derived macrophages in HIV replication mechanisms, we set out to establish a macrophage cell model for HIV latency using THP-1 cells.

METHODS: We created single-cell clones of THP-1 cells infected with a single …


Blocking Senescence And Tolerogenic Function Of Dendritic Cells Induced By Γδ Treg Cells Enhances Tumor-Specific Immunity For Cancer Immunotherapy, Fusheng Si, Xia Liu, Yan Tao, Yuanqin Zhang, Feiya Ma, Eddy C Hsueh, Sidharth V Puram, Guangyong Peng Apr 2024

Blocking Senescence And Tolerogenic Function Of Dendritic Cells Induced By Γδ Treg Cells Enhances Tumor-Specific Immunity For Cancer Immunotherapy, Fusheng Si, Xia Liu, Yan Tao, Yuanqin Zhang, Feiya Ma, Eddy C Hsueh, Sidharth V Puram, Guangyong Peng

2020-Current year OA Pubs

BACKGROUND: Regulatory T (Treg) cells are a key component in maintaining the suppressive tumor microenvironment and immune suppression in different types of cancers. A precise understanding of the molecular mechanisms used by Treg cells for immune suppression is critical for the development of effective strategies for cancer immunotherapy.

METHODS: Senescence development and tolerogenic functions of dendritic cells (DCs) induced by breast cancer tumor-derived γδ Treg cells were fully characterized using real-time PCR, flow cytometry, western blot, and functional assays. Loss-of-function strategies with pharmacological inhibitor and/or neutralizing antibody were used to identify the potential molecule(s) and pathway(s) involved in DC senescence …


Perioperative Mental Health Intervention For Depression And Anxiety Symptoms In Older Adults Study Protocol: Design And Methods For Three Linked Randomised Controlled Trials, Katherine J Holzer, Kimberly A Bartosiak, Ryan P Calfee, Chet W Hammill, Simon Haroutounian, Benjamin D Kozower, Theresa A Cordner, Emily M Lenard, Kenneth E Freedland, Bethany R Tellor Pennington, J Philip Miller, Mary C Politi, Yi Zhang, Michael D Yingling, Ana A Baumann, Thomas Kannampallil, Julia A Schweiger, Sherry L Mckinnon, Michael S Avidan, Eric J Lenze, Joanna Abraham, Et Al. Apr 2024

Perioperative Mental Health Intervention For Depression And Anxiety Symptoms In Older Adults Study Protocol: Design And Methods For Three Linked Randomised Controlled Trials, Katherine J Holzer, Kimberly A Bartosiak, Ryan P Calfee, Chet W Hammill, Simon Haroutounian, Benjamin D Kozower, Theresa A Cordner, Emily M Lenard, Kenneth E Freedland, Bethany R Tellor Pennington, J Philip Miller, Mary C Politi, Yi Zhang, Michael D Yingling, Ana A Baumann, Thomas Kannampallil, Julia A Schweiger, Sherry L Mckinnon, Michael S Avidan, Eric J Lenze, Joanna Abraham, Et Al.

2020-Current year OA Pubs

INTRODUCTION: Preoperative anxiety and depression symptoms among older surgical patients are associated with poor postoperative outcomes, yet evidence-based interventions for anxiety and depression have not been applied within this setting. We present a protocol for randomised controlled trials (RCTs) in three surgical cohorts: cardiac, oncological and orthopaedic, investigating whether a perioperative mental health intervention, with psychological and pharmacological components, reduces perioperative symptoms of depression and anxiety in older surgical patients.

METHODS AND ANALYSIS: Adults ≥60 years undergoing cardiac, orthopaedic or oncological surgery will be enrolled in one of three-linked type 1 hybrid effectiveness/implementation RCTs that will be conducted in tandem …


Health Factors Associated With Development And Severity Of Poststroke Dysphagia: An Epidemiological Investigation, Brittany N Krekeler, Opeolu Adeoye, Et Al. Apr 2024

Health Factors Associated With Development And Severity Of Poststroke Dysphagia: An Epidemiological Investigation, Brittany N Krekeler, Opeolu Adeoye, Et Al.

2020-Current year OA Pubs

BACKGROUND: Dysphagia after stroke is common and can impact morbidity and death. The purpose of this population-based study was to determine specific epidemiological and health risk factors that impact development of dysphagia after acute stroke.

METHODS AND RESULTS: Ischemic and hemorrhagic stroke cases from 2010 and 2015 were identified via chart review from the GCNKSS (Greater Cincinnati Northern Kentucky Stroke Study), a representative sample of ≈1.3 million adults from southwestern Ohio and northern Kentucky. Dysphagia status was determined on the basis of clinical assessments and necessity for alternative access to nutrition via nasogastric or percutaneous endoscopic gastrostomy tube placement. Comparisons …


Nfĸb Signaling Drives Myocardial Injury Via Ccr2+ Macrophages In A Preclinical Model Of Arrhythmogenic Cardiomyopathy, Stephen P. Chelko, Vinay R. Penna, Morgan Engel, Emily A. Shiel, Ann M. Centner, Waleed Farra, Elisa N. Cannon, Maicon Landim-Vieira, Niccole Schaible, Kory Lavine, Jeffrey E. Saffitz Apr 2024

Nfĸb Signaling Drives Myocardial Injury Via Ccr2+ Macrophages In A Preclinical Model Of Arrhythmogenic Cardiomyopathy, Stephen P. Chelko, Vinay R. Penna, Morgan Engel, Emily A. Shiel, Ann M. Centner, Waleed Farra, Elisa N. Cannon, Maicon Landim-Vieira, Niccole Schaible, Kory Lavine, Jeffrey E. Saffitz

2020-Current year OA Pubs

Nuclear factor κ-B (NFκB) is activated in iPSC-cardiac myocytes from patients with arrhythmogenic cardiomyopathy (ACM) under basal conditions, and inhibition of NFκB signaling prevents disease in Dsg2mut/mut mice, a robust mouse model of ACM. Here, we used genetic approaches and single-cell RNA-Seq to define the contributions of immune signaling in cardiac myocytes and macrophages in the natural progression of ACM using Dsg2mut/mut mice. We found that NFκB signaling in cardiac myocytes drives myocardial injury, contractile dysfunction, and arrhythmias in Dsg2mut/mut mice. NFκB signaling in cardiac myocytes mobilizes macrophages expressing C-C motif chemokine receptor-2 (CCR2+ cells) to affected areas within the …


Using The Consolidated Framework For Implementation Research (Cfir) To Guide Implementation Of Cardio-Oncology Services, Jessica Miller Clouser, Colleen A Mcmullen, Akosua K Adu, Gretchen Wells, Amit Arbune, Jing Li Apr 2024

Using The Consolidated Framework For Implementation Research (Cfir) To Guide Implementation Of Cardio-Oncology Services, Jessica Miller Clouser, Colleen A Mcmullen, Akosua K Adu, Gretchen Wells, Amit Arbune, Jing Li

2020-Current year OA Pubs

INTRODUCTION: Cardio-oncology focuses on diagnosing and preventing adverse cardiovascular outcomes in cancer patients. Interdisciplinary cardio-oncology services address the spectrum of prevention, detection, monitoring, and treatment of cancer patients at risk of cardio-toxicity and aim to improve the continuum of cardiac care for oncology patients. The goal of this study was to engage clinician and administrative stakeholders to assess multilevel needs, barriers, and expectations regarding cardio oncology services.

METHODS: We interviewed clinicians and administrators at an academic medical center using the Consolidated Framework for Implementation Research (CFIR) to understand multilevel determinants influencing cardio-oncology service implementation. We also conducted a web-based survey …


A Targeted Proteomics Method For Quantifying Plasma Apolipoprotein Kinetics In Individual Mice Using Stable Isotope Labeling, Baohai Shao, Masami Shimizu-Albergine, Farah Kramer, Jenny E Kanter, Jay W Heinecke, Tomas Vaisar, Bettina Mittendorfer, Bruce W Patterson, Karin E Bornfeldt Apr 2024

A Targeted Proteomics Method For Quantifying Plasma Apolipoprotein Kinetics In Individual Mice Using Stable Isotope Labeling, Baohai Shao, Masami Shimizu-Albergine, Farah Kramer, Jenny E Kanter, Jay W Heinecke, Tomas Vaisar, Bettina Mittendorfer, Bruce W Patterson, Karin E Bornfeldt

2020-Current year OA Pubs

Altered apolipoprotein kinetics play a critical role in promoting dyslipidemia and atherogenesis. Human apolipoprotein kinetics have been extensively evaluated, but similar studies in mice are hampered by the lack of robust methods suitable for the small amounts of blood that can be collected at sequential time points from individual mice. We describe a targeted liquid chromatography tandem mass spectrometry method for simultaneously quantifying the stable isotope enrichment of several apolipoproteins represented by multiple peptides in serial blood samples (15 μl each) obtained after retro-orbital injection of


Trapdoor Endarterectomy For Coral Reef Plaque Of The Paravisceral Aorta In The Modern Era, Jackson S Burton, Nathan M Droz, Vipul Khetarpaul, Luis A Sanchez, J Westley Ohman Apr 2024

Trapdoor Endarterectomy For Coral Reef Plaque Of The Paravisceral Aorta In The Modern Era, Jackson S Burton, Nathan M Droz, Vipul Khetarpaul, Luis A Sanchez, J Westley Ohman

2020-Current year OA Pubs

Coral reef atherosclerosis of the paravisceral aorta is a rare disease whose description is confined to before contemporary vascular surgical techniques. This study aims to describe the characteristics and outcomes of patients with coral reef aorta treated with trapdoor endarterectomy at a single high-volume quaternary referral center since 2010. From 2010 to 2022, 14 patients with coral reef aorta were treated with trapdoor endarterectomy. The patient data were obtained via a retrospective medical record review. The patients were predominantly women (79%) with a median age of 65 years (interquartile range [IQR], 60-70 years). The patients universally had a tobacco smoking …


Safety And Effectiveness Of Diazepam Nasal Spray In Male And Female Patients: Post Hoc Analysis Of Data From A Phase 3 Safety Study, James W Wheless, Robert Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz Apr 2024

Safety And Effectiveness Of Diazepam Nasal Spray In Male And Female Patients: Post Hoc Analysis Of Data From A Phase 3 Safety Study, James W Wheless, Robert Edward Hogan, Charles S Davis, Enrique Carrazana, Adrian L Rabinowicz

2020-Current year OA Pubs

Sex differences in drug pharmacokinetics include variations in the expression of the cytochrome P450 enzymes, which are involved in the metabolism of benzodiazepines. It is unclear whether sex influences outcomes associated with intranasally administered drugs. A post hoc analysis of sex differences was conducted to evaluate the effectiveness and safety of diazepam nasal spray, which included examining changes in the number of days between seizure clusters over time (SEIzure interVAL [SEIVAL]). Diazepam nasal spray is approved for acute treatment of seizure clusters in patients with epilepsy aged ≥6 years. Data from a phase 3 safety study were used to determine …


Anatomical Registration Of Intracranial Electrodes. Robust Model-Based Localization And Deformable Smooth Brain-Shift Compensation Methods, Alejandro Omar Blenkmann, Sabine Liliana Leske, Anaïs Llorens, Jack J Lin, Edward F Chang, Peter Brunner, Gerwin Schalk, Jugoslav Ivanovic, Pål Gunnar Larsson, Robert Thomas Knight, Tor Endestad, Anne-Kristin Solbakk Apr 2024

Anatomical Registration Of Intracranial Electrodes. Robust Model-Based Localization And Deformable Smooth Brain-Shift Compensation Methods, Alejandro Omar Blenkmann, Sabine Liliana Leske, Anaïs Llorens, Jack J Lin, Edward F Chang, Peter Brunner, Gerwin Schalk, Jugoslav Ivanovic, Pål Gunnar Larsson, Robert Thomas Knight, Tor Endestad, Anne-Kristin Solbakk

2020-Current year OA Pubs

BACKGROUND: Intracranial electrodes are typically localized from post-implantation CT artifacts. Automatic algorithms localizing low signal-to-noise ratio artifacts and high-density electrode arrays are missing. Additionally, implantation of grids/strips introduces brain deformations, resulting in registration errors when fusing post-implantation CT and pre-implantation MR images. Brain-shift compensation methods project electrode coordinates to cortex, but either fail to produce smooth solutions or do not account for brain deformations.

NEW METHODS: We first introduce GridFit, a model-based fitting approach that simultaneously localizes all electrodes' CT artifacts in grids, strips, or depth arrays. Second, we present CEPA, a brain-shift compensation algorithm combining orthogonal-based projections, spring-mesh models, …


Neutrophils Are Indispensable For Adverse Cardiac Remodeling In Heart Failure, Sergey Antipenko, Nicolas Mayfield, Miki Jinno, Matthias Gunzer, Mohamed Ameen Ismahil, Tariq Hamid, Sumanth D Prabhu, Gregg Rokosh Apr 2024

Neutrophils Are Indispensable For Adverse Cardiac Remodeling In Heart Failure, Sergey Antipenko, Nicolas Mayfield, Miki Jinno, Matthias Gunzer, Mohamed Ameen Ismahil, Tariq Hamid, Sumanth D Prabhu, Gregg Rokosh

2020-Current year OA Pubs

Persistent immune activation contributes significantly to left ventricular (LV) dysfunction and adverse remodeling in heart failure (HF). In contrast to their well-known essential role in acute myocardial infarction (MI) as first responders that clear dead cells and facilitate subsequent reparative macrophage polarization, the role of neutrophils in the pathobiology of chronic ischemic HF is poorly defined. To determine the importance of neutrophils in the progression of ischemic cardiomyopathy, we measured their production, levels, and activation in a mouse model of chronic HF 8 weeks after permanent coronary artery ligation and large MI. In HF mice, neutrophils were more abundant both …


Feasibility Of Surface-Guidance Combined With Cbct For Intra-Fractional Breath-Hold Motion Management During Ethos Rt, Taeho Kim, Eric Laugeman, Kendall Kiser, Joshua Schiff, Shanti Marasini, Alex Price, H Michael Gach, Nels Knutson, Pamela Samson, Clifford Robinson, Casey Hatscher, Lauren Henke Apr 2024

Feasibility Of Surface-Guidance Combined With Cbct For Intra-Fractional Breath-Hold Motion Management During Ethos Rt, Taeho Kim, Eric Laugeman, Kendall Kiser, Joshua Schiff, Shanti Marasini, Alex Price, H Michael Gach, Nels Knutson, Pamela Samson, Clifford Robinson, Casey Hatscher, Lauren Henke

2020-Current year OA Pubs

PURPOSE: High-quality CBCT and AI-enhanced adaptive planning techniques allow CBCT-guided stereotactic adaptive radiotherapy (CT-STAR) to account for inter-fractional anatomic changes. Studies of intra-fractional respiratory motion management with a surface imaging solution for CT-STAR have not been fully conducted. We investigated intra-fractional motion management in breath-hold Ethos-based CT-STAR and CT-SBRT (stereotactic body non-adaptive radiotherapy) using optical surface imaging combined with onboard CBCTs.

METHODS: Ten cancer patients with mobile lower lung or upper abdominal malignancies participated in an IRB-approved clinical trial (Phase I) of optical surface image-guided Ethos CT-STAR/SBRT. In the clinical trial, a pre-configured gating window (± 2 mm in AP …


Exploring The Association Between Weight Loss-Inducing Medications And Multiple Sclerosis: Insights From The Fda Adverse Event Reporting System Database, Afsaneh Shirani, Anne H Cross, Olaf Stuve Apr 2024

Exploring The Association Between Weight Loss-Inducing Medications And Multiple Sclerosis: Insights From The Fda Adverse Event Reporting System Database, Afsaneh Shirani, Anne H Cross, Olaf Stuve

2020-Current year OA Pubs

BACKGROUND: Several studies have demonstrated that early childhood and adolescent obesity are risk factors for multiple sclerosis (MS) susceptibility. Obesity is thought to share inflammatory components with MS through overproduction of pro-inflammatory adipokines (e.g., leptin) and reduction of anti-inflammatory adipokines (e.g, adiponectin). Recently, drug repurposing (i.e. identifying new indications for existing drugs) has garnered significant attention. The US Food and Drug Administration Adverse Event Reporting System (FAERS) database serves not only as a resource for mining adverse drug reactions and safety signals but also for identifying inverse associations and potential medication repurposing opportunities.

OBJECTIVE: We aimed to explore the association …


Novel Sgce Mutation In A Patient With Myoclonus-Dystonia: A Case Report, Eva Klinman, Catherine Gooch, Joel S. Perlmutter, Albert A. Davis, Baijayanta Maiti Apr 2024

Novel Sgce Mutation In A Patient With Myoclonus-Dystonia: A Case Report, Eva Klinman, Catherine Gooch, Joel S. Perlmutter, Albert A. Davis, Baijayanta Maiti

2020-Current year OA Pubs

OBJECTIVES: Characterize the presentation, workup, and management of

METHODS: A woman with myoclonus and dystonia was identified based on clinical history and physical examination. Workup was conducted to determine the cause of her symptoms, including whole-exome sequencing. Myoclonus-dystonia is associated with more than 100 distinct mutations in MYC/DYT

RESULTS: Childhood onset myoclonus and worsening dystonia with age were identified in a young woman. She underwent screening for common causes of twitching movements, followed by whole-exome sequencing which identified a de novo novel variant in the

DISCUSSION: Myoclonus-dystonia should be considered in patients with symptoms of head and upper extremity myoclonus …


Cholesterol 25-Hydroxylase Mediates Neuroinflammation And Neurodegeneration In A Mouse Model Of Tauopathy, Danira Toral-Rios, Justin M Long, Jason D Ulrich, Jinsheng Yu, Michael R Strickland, Xianlin Han, David M Holtzman, Anil G Cashikar, Steven M Paul Apr 2024

Cholesterol 25-Hydroxylase Mediates Neuroinflammation And Neurodegeneration In A Mouse Model Of Tauopathy, Danira Toral-Rios, Justin M Long, Jason D Ulrich, Jinsheng Yu, Michael R Strickland, Xianlin Han, David M Holtzman, Anil G Cashikar, Steven M Paul

2020-Current year OA Pubs

Alzheimer's disease (AD) is characterized by amyloid plaques and neurofibrillary tangles, in addition to neuroinflammation and changes in brain lipid metabolism. 25-Hydroxycholesterol (25-HC), a known modulator of both inflammation and lipid metabolism, is produced by cholesterol 25-hydroxylase encoded by Ch25h expressed as a "disease-associated microglia" signature gene. However, whether Ch25h influences tau-mediated neuroinflammation and neurodegeneration is unknown. Here, we show that in the absence of Ch25h and the resultant reduction in 25-HC, there is strikingly reduced age-dependent neurodegeneration and neuroinflammation in the hippocampus and entorhinal/piriform cortex of PS19 mice, which express the P301S mutant human tau transgene. Transcriptomic analyses of …


Mysm1 Attenuates Dna Damage Signals Triggered By Physiologic And Genotoxic Dna Breaks, Brendan Mathias, David O'Leary, Nermina Saucier, Faiz Ahmad, Lynn S White, Le'mark Russell, Marwan Shinawi, Matthew J Smith, Roshini S Abraham, Megan A Cooper, Maleewan Kitcharoensakkul, Abby M Green, Jeffrey J Bednarski Apr 2024

Mysm1 Attenuates Dna Damage Signals Triggered By Physiologic And Genotoxic Dna Breaks, Brendan Mathias, David O'Leary, Nermina Saucier, Faiz Ahmad, Lynn S White, Le'mark Russell, Marwan Shinawi, Matthew J Smith, Roshini S Abraham, Megan A Cooper, Maleewan Kitcharoensakkul, Abby M Green, Jeffrey J Bednarski

2020-Current year OA Pubs

BACKGROUND: Patients with deleterious variants in MYSM1 have an immune deficiency characterized by B-cell lymphopenia, hypogammaglobulinemia, and increased radiosensitivity. MYSM1 is a histone deubiquitinase with established activity in regulating gene expression. MYSM1 also localizes to sites of DNA injury but its function in cellular responses to DNA breaks has not been elucidated.

OBJECTIVES: This study sought to determine the activity of MYSM1 in regulating DNA damage responses (DDRs) to DNA double-stranded breaks (DSBs) generated during immunoglobulin receptor gene (Ig) recombination and by ionizing radiation.

METHODS: MYSM1-deficient pre- and non-B cells were used to determine the role of MYSM1 in DSB …


Cannabis Oil Extracts For Chronic Pain: What Else Can Be Learned From Another Structured Prospective Cohort?, Dorit Pud, Suhail Aamar, Bareket Schiff-Keren, Roee Sheinfeld, Silviu Brill, Dror Robinson, Yaakov Fogelman, George Habib, Haggai Sharon, Howard Amital, Boris Boltyansky, Simon Haroutounian, Elon Eisenberg Apr 2024

Cannabis Oil Extracts For Chronic Pain: What Else Can Be Learned From Another Structured Prospective Cohort?, Dorit Pud, Suhail Aamar, Bareket Schiff-Keren, Roee Sheinfeld, Silviu Brill, Dror Robinson, Yaakov Fogelman, George Habib, Haggai Sharon, Howard Amital, Boris Boltyansky, Simon Haroutounian, Elon Eisenberg

2020-Current year OA Pubs

INTRODUCTION: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials.

OBJECTIVES: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain.

METHODS: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 …


Brain High-Throughput Multi-Omics Data Reveal Molecular Heterogeneity In Alzheimer's Disease, Abdallah M. Eteleeb, Brenna C. Novotny, Carolina Soriano Tarraga, Christopher Sohn, Eliza Dhungel, Logan Brase, Aasritha Nallapu, Jared Buss, Fabiana Farias, Kristy Bergmann, Joseph Bradley, Joanne Norton, Jen Gentsch, Fengxian Wang, Albert A. Davis, John C. Morris, Celeste M. Karch, Richard J. Perrin, Bruno A. Benitez, Oscar Harari Apr 2024

Brain High-Throughput Multi-Omics Data Reveal Molecular Heterogeneity In Alzheimer's Disease, Abdallah M. Eteleeb, Brenna C. Novotny, Carolina Soriano Tarraga, Christopher Sohn, Eliza Dhungel, Logan Brase, Aasritha Nallapu, Jared Buss, Fabiana Farias, Kristy Bergmann, Joseph Bradley, Joanne Norton, Jen Gentsch, Fengxian Wang, Albert A. Davis, John C. Morris, Celeste M. Karch, Richard J. Perrin, Bruno A. Benitez, Oscar Harari

2020-Current year OA Pubs

Unbiased data-driven omic approaches are revealing the molecular heterogeneity of Alzheimer disease. Here, we used machine learning approaches to integrate high-throughput transcriptomic, proteomic, metabolomic, and lipidomic profiles with clinical and neuropathological data from multiple human AD cohorts. We discovered 4 unique multimodal molecular profiles, one of them showing signs of poor cognitive function, a faster pace of disease progression, shorter survival with the disease, severe neurodegeneration and astrogliosis, and reduced levels of metabolomic profiles. We found this molecular profile to be present in multiple affected cortical regions associated with higher Braak tau scores and significant dysregulation of synapse-related genes, endocytosis, …


Neurosteroids And Their Potential As A Safer Class Of General Anesthetics, Hiroki Tateiwa, Alex S Evers Apr 2024

Neurosteroids And Their Potential As A Safer Class Of General Anesthetics, Hiroki Tateiwa, Alex S Evers

2020-Current year OA Pubs

Neurosteroids (NS) are a class of steroids that are synthesized within the central nervous system (CNS). Various NS can either enhance or inhibit CNS excitability and they play important biological roles in brain development, brain function and as mediators of mood. One class of NS, 3α-hydroxy-pregnane steroids such as allopregnanolone (AlloP) or pregnanolone (Preg), inhibits neuronal excitability; these endogenous NS and their analogues have been therapeutically applied as anti-depressants, anti-epileptics and general anesthetics. While NS have many favorable properties as anesthetics (e.g. rapid onset, rapid recovery, minimal cardiorespiratory depression, neuroprotection), they are not currently in clinical use, largely due to …


Dna Combing Versus Dna Spreading And The Separation Of Sister Chromatids, Alice Meroni, Sophie E Wells, Carmen Fonseca, Arnab Ray Chaudhuri, Keith W Caldecott, Alessandro Vindigni Apr 2024

Dna Combing Versus Dna Spreading And The Separation Of Sister Chromatids, Alice Meroni, Sophie E Wells, Carmen Fonseca, Arnab Ray Chaudhuri, Keith W Caldecott, Alessandro Vindigni

2020-Current year OA Pubs

DNA combing and DNA spreading are two central approaches for studying DNA replication fork dynamics genome-wide at single-molecule resolution by distributing labeled genomic DNA on coverslips or slides for immunodetection. Perturbations in DNA replication fork dynamics can differentially affect either leading or lagging strand synthesis, for example, in instances where replication is blocked by a lesion or obstacle on only one of the two strands. Thus, we sought to investigate whether the DNA combing and/or spreading approaches are suitable for resolving adjacent sister chromatids during DNA replication, thereby enabling the detection of DNA replication dynamics within individual nascent strands. To …


Cognitive Flexibility Training For Chronic Pain: A Randomized Clinical Study, Katherine J. Holzer, Marko S. Todorovic, Elizabeth A. Wilson, Aaron Steinberg, Michael S. Avidan, Simon Haroutounian Apr 2024

Cognitive Flexibility Training For Chronic Pain: A Randomized Clinical Study, Katherine J. Holzer, Marko S. Todorovic, Elizabeth A. Wilson, Aaron Steinberg, Michael S. Avidan, Simon Haroutounian

2020-Current year OA Pubs

INTRODUCTION: Previous studies suggest an association between cognitive flexibility and development of chronic pain after surgery. It is not known whether cognitive flexibility can be improved in patients with chronic pain.

OBJECTIVES: This study tested whether a neurocognitive training program results in improved cognitive flexibility and pain in patients with chronic pain.

METHODS: We conducted a single-center, prospective, randomized study investigating 5-week daily neurocognitive training in patients with chronic pain. Participants (n = 145) were randomized into neurocognitive training or care as usual, and they completed assessments at baseline, posttreatment, and 3 months. The treatment group was asked to spend …


The Dmptool Nih Dmsp Templates Project, Nina Exner, Seonyoung Kim, Katy Smith Apr 2024

The Dmptool Nih Dmsp Templates Project, Nina Exner, Seonyoung Kim, Katy Smith

2020-Current year OA Pubs

The DMPTool NIH Data Management and Sharing Plan (DMSP) Templates Project was launched in response to the 2023 NIH Data Management and Sharing (DMS) Policy. This new policy introduced a more structured framework for DMS Plans, featuring six key elements, a departure from the 2003 NIH DMS policy. The project aimed to simplify the process for data librarians, research administrators, and researchers by providing a template with curated guidance, eliminating the need to navigate various policies and guidelines. The template breaks out each Plan section and subsection and provides related guidance and examples at the point of need. This effort …


2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al. Mar 2024

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society Expert Consensus Statement On Catheter And Surgical Ablation Of Atrial Fibrillation, Stylianos Tzeis, Ralph J Damiano, Et Al.

2020-Current year OA Pubs

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a …


Next Generation Microfluidics: Fulfilling The Promise Of Lab-On-A-Chip Technologies, Umut A Gurkan, Jorge Di Paola, Et Al. Mar 2024

Next Generation Microfluidics: Fulfilling The Promise Of Lab-On-A-Chip Technologies, Umut A Gurkan, Jorge Di Paola, Et Al.

2020-Current year OA Pubs

Microfluidic lab-on-a-chip technologies enable the analysis and manipulation of small fluid volumes and particles at small scales and the control of fluid flow and transport processes at the microscale, leading to the development of new methods to address a broad range of scientific and medical challenges. Microfluidic and lab-on-a-chip technologies have made a noteworthy impact in basic, preclinical, and clinical research, especially in hematology and vascular biology due to the inherent ability of microfluidics to mimic physiologic flow conditions in blood vessels and capillaries. With the potential to significantly impact translational research and clinical diagnostics, technical issues and incentive mismatches …