Open Access. Powered by Scholars. Published by Universities.®

Digital Commons Network™

Open Access. Powered by Scholars. Published by Universities.®

Articles 5731 - 5760 of 7516

Full-Text Articles in Entire DC Network

The Evolution, Current Indications And Outcomes Of Cementless Total Knee Arthroplasty, Maria T Schwabe, Charles P Hannon Nov 2022

The Evolution, Current Indications And Outcomes Of Cementless Total Knee Arthroplasty, Maria T Schwabe, Charles P Hannon

2020-Current year OA Pubs

Total knee arthroplasty (TKA) has been performed by orthopedic surgeons for decades, but the cementless TKA has only recently gained much interest in the world of arthroplasty. Initially, early designs had multiple complications, particularly with aseptic loosening due to osteolysis and micromotion. However, modifications have shown good outcomes and excellent survivorship. Over the last several decades, changes in implant designs as well as implant materials/coatings have helped with bone in growth and stability. Furthermore, surgeons have been performing TKA in younger and more obese patients as these populations have been increasing. Good results from the cementless TKA compared to cemented …


Ornithine Decarboxylase Supports Ilc3 Responses In Infectious And Autoimmune Colitis Through Positive Regulation Of Il-22 Transcription, Vincent Peng, Siyan Cao, Tihana Trsan, Jennifer K Bando, Julian Avila-Pacheco, John L Cleveland, Clary Clish, Ramnik J Xavier, Marco Colonna Nov 2022

Ornithine Decarboxylase Supports Ilc3 Responses In Infectious And Autoimmune Colitis Through Positive Regulation Of Il-22 Transcription, Vincent Peng, Siyan Cao, Tihana Trsan, Jennifer K Bando, Julian Avila-Pacheco, John L Cleveland, Clary Clish, Ramnik J Xavier, Marco Colonna

2020-Current year OA Pubs

Group 3 innate lymphoid cells (ILC3s) are RORγT


Genetic Addiction Risk Severity Assessment Identifies Polymorphic Reward Genes As Antecedents To Reward Deficiency Syndrome (Rds) Hypodopaminergia's Effect On Addictive And Non-Addictive Behaviors In A Nuclear Family, Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Panayotis K Thanos, Igor Elman, Mauro Ceccanti, Rajendra D Badgaiyan, Thomas Mclaughlin, Ashim Gupta, Anish Bajaj, David Baron, B William Downs, Debasis Bagchi, Mark S Gold Nov 2022

Genetic Addiction Risk Severity Assessment Identifies Polymorphic Reward Genes As Antecedents To Reward Deficiency Syndrome (Rds) Hypodopaminergia's Effect On Addictive And Non-Addictive Behaviors In A Nuclear Family, Catherine A Dennen, Kenneth Blum, Abdalla Bowirrat, Panayotis K Thanos, Igor Elman, Mauro Ceccanti, Rajendra D Badgaiyan, Thomas Mclaughlin, Ashim Gupta, Anish Bajaj, David Baron, B William Downs, Debasis Bagchi, Mark S Gold

2020-Current year OA Pubs

This case series presents the novel genetic addiction risk score (GARS), which shows a high prevalence of polymorphic risk alleles of reward genes in a nuclear family with multiple reward deficiency syndrome (RDS) behavioral issues expressing a hypodopaminergic antecedent. The family consists of a mother, father, son, and daughter. The mother experienced issues with focus, memory, anger, and amotivational syndrome. The father experienced weight issues and depression. The son experienced heavy drinking, along with some drug abuse and anxiety. The daughter experienced depression, lethargy, brain fog, focus issues, and anxiety, among others. A major clinical outcome of the results presented …


High-Throughput Analysis Of Tissue Microarrays Using Automated Desorption Electrospray Ionization Mass Spectrometry, Nicolás M Morato, Hannah Marie Brown, Diogo Garcia, Erik H Middlebrooks, Mark Jentoft, Kaisorn Chaichana, Alfredo Quiñones-Hinojosa, R Graham Cooks Nov 2022

High-Throughput Analysis Of Tissue Microarrays Using Automated Desorption Electrospray Ionization Mass Spectrometry, Nicolás M Morato, Hannah Marie Brown, Diogo Garcia, Erik H Middlebrooks, Mark Jentoft, Kaisorn Chaichana, Alfredo Quiñones-Hinojosa, R Graham Cooks

2020-Current year OA Pubs

Tissue microarrays (TMAs) are commonly used for the rapid analysis of large numbers of tissue samples, often in morphological assessments but increasingly in spectroscopic analysis, where specific molecular markers are targeted via immunostaining. Here we report the use of an automated high-throughput system based on desorption electrospray ionization (DESI) mass spectrometry (MS) for the rapid generation and online analysis of high-density (6144 samples/array) TMAs, at rates better than 1 sample/second. Direct open-air analysis of tissue samples (hundreds of nanograms) not subjected to prior preparation, plus the ability to provide molecular characterization by tandem mass spectrometry (MS/MS), make this experiment versatile …


Socioeconomic Status And Modification Of Atherosclerotic Cardiovascular Disease Risk Prediction: Epidemiological Analysis Using Data From The Atherosclerosis Risk In Communities Study, Kamal Henderson, Brystana Kaufman, Jason S. Rotter, Sally Stearns, Carla A A Sueta, Randi Foraker, P Michael Ho, Patricia P Chang Nov 2022

Socioeconomic Status And Modification Of Atherosclerotic Cardiovascular Disease Risk Prediction: Epidemiological Analysis Using Data From The Atherosclerosis Risk In Communities Study, Kamal Henderson, Brystana Kaufman, Jason S. Rotter, Sally Stearns, Carla A A Sueta, Randi Foraker, P Michael Ho, Patricia P Chang

2020-Current year OA Pubs

OBJECTIVE: Examine whether the relationship between the pooled cohort equations (PCE) predicted 10-year risk for atherosclerotic cardiovascular disease (ASCVD) and absolute risk for ASCVD is modified by socioeconomic status (SES).

DESIGN: Population-based longitudinal cohort study-Atherosclerosis Risk in Communities (ARIC)-investigating the development of cardiovascular disease across demographic subgroups.

SETTING: Four communities in the USA-Forsyth County, North Carolina, Jackson, Mississippi, suburbs of Minneapolis, Minnesota and Washington County, Maryland.

PARTICIPANTS: We identified 9782 ARIC men and women aged 54-73 without ASCVD at study visit 4 (1996-1998).

PRIMARY OUTCOME MEASURES: Risk ratio (RR) differences in 10-year incident hospitalisations or death for ASCVD by SES …


Oxidative Stress-Induced Cellular Senescence In Aging Retina And Age-Related Macular Degeneration, Ryo Terao, Tazbir Ahmed, Ayana Suzumura, Hiroko Terasaki Nov 2022

Oxidative Stress-Induced Cellular Senescence In Aging Retina And Age-Related Macular Degeneration, Ryo Terao, Tazbir Ahmed, Ayana Suzumura, Hiroko Terasaki

2020-Current year OA Pubs

Aging leads to a gradual decline of function in multiple organs. Cataract, glaucoma, diabetic retinopathy, and age-related macular degeneration (AMD) are age-related ocular diseases. Because their pathogenesis is unclear, it is challenging to combat age-related diseases. Cellular senescence is a cellular response characterized by cell cycle arrest. Cellular senescence is an important contributor to aging and age-related diseases through the alteration of cellular function and the secretion of senescence-associated secretory phenotypes. As a driver of stress-induced premature senescence, oxidative stress triggers cellular senescence and age-related diseases by inducing senescence markers via reactive oxygen species and mitochondrial dysfunction. In this review, …


Single-Cell Multiomics Identifies Clinically Relevant Mesenchymal Stem-Like Cells And Key Regulators For Mpnst Malignancy, Lai Man Natalie Wu, Joshua Rubin, Et Al. Nov 2022

Single-Cell Multiomics Identifies Clinically Relevant Mesenchymal Stem-Like Cells And Key Regulators For Mpnst Malignancy, Lai Man Natalie Wu, Joshua Rubin, Et Al.

2020-Current year OA Pubs

Malignant peripheral nerve sheath tumor (MPNST), a highly aggressive Schwann cell (SC)-derived soft tissue sarcoma, arises from benign neurofibroma (NF); however, the identity, heterogeneity and origins of tumor populations remain elusive. Nestin


Preventive Behaviors And Information Sources During Covid-19 Pandemic: A Cross-Sectional Study In Japan, Manae Uchibori, Cyrus Ghaznavi, Michio Murakami, Akifumi Eguchi, Hiroyuki Kunishima, Satoshi Kaneko, Keiko Maruyama-Sakurai, Hiroaki Miyata, Shuhei Nomura Nov 2022

Preventive Behaviors And Information Sources During Covid-19 Pandemic: A Cross-Sectional Study In Japan, Manae Uchibori, Cyrus Ghaznavi, Michio Murakami, Akifumi Eguchi, Hiroyuki Kunishima, Satoshi Kaneko, Keiko Maruyama-Sakurai, Hiroaki Miyata, Shuhei Nomura

2020-Current year OA Pubs

BACKGROUND: individual preventive behaviors are one of the key measures needed to prevent the spread of COVID-19. This study sought to identify the factors associated with the adoption of COVID-19 preventive measures, focusing specifically on information sources.

METHODS: we conducted a nationally representative cross-sectional survey of 30,053 Japanese adults in February 2021. The survey asked about socioeconomic, health-related, and psychological characteristics, attitudes toward immunization, and the use of information sources regarding COVID-19. We have constructed multivariable logistic regression to estimate the factors associated with the adoption of three preventive measures: 3Cs avoidance, hand hygiene and respiratory hygiene.

RESULTS: socioeconomic variables, …


Bi-Allelic Camsap1 Variants Cause A Clinically Recognizable Neuronal Migration Disorder, Reham Khalaf-Nazzal, Jennifer L Griffith, Joseph R Walsh, Amber Neilson, Evguenia Kouranova, Xiaoxia Cui, David T Curiel, Et Al. Nov 2022

Bi-Allelic Camsap1 Variants Cause A Clinically Recognizable Neuronal Migration Disorder, Reham Khalaf-Nazzal, Jennifer L Griffith, Joseph R Walsh, Amber Neilson, Evguenia Kouranova, Xiaoxia Cui, David T Curiel, Et Al.

2020-Current year OA Pubs

Non-centrosomal microtubules are essential cytoskeletal filaments that are important for neurite formation, axonal transport, and neuronal migration. They require stabilization by microtubule minus-end-targeting proteins including the CAMSAP family of molecules. Using exome sequencing on samples from five unrelated families, we show that bi-allelic CAMSAP1 loss-of-function variants cause a clinically recognizable, syndromic neuronal migration disorder. The cardinal clinical features of the syndrome include a characteristic craniofacial appearance, primary microcephaly, severe neurodevelopmental delay, cortical visual impairment, and seizures. The neuroradiological phenotype comprises a highly recognizable combination of classic lissencephaly with a posterior more severe than anterior gradient similar to PAFAH1B1(LIS1)-related lissencephaly and …


Phenome-Wide Analysis Of Taiwan Biobank Reveals Novel Glycemia-Related Loci And Genetic Risks For Diabetes, Chia-Jung Lee, Ting-Huei Chen, Aylwin Ming Wee Lim, Chien-Ching Chang, Jia-Jyun Sie, Pei-Lung Chen, Su-Wei Chang, Shang-Jung Wu, Chia-Lin Hsu, Ai-Ru Hsieh, Wei-Shiung Yang, Cathy S J Fann Nov 2022

Phenome-Wide Analysis Of Taiwan Biobank Reveals Novel Glycemia-Related Loci And Genetic Risks For Diabetes, Chia-Jung Lee, Ting-Huei Chen, Aylwin Ming Wee Lim, Chien-Ching Chang, Jia-Jyun Sie, Pei-Lung Chen, Su-Wei Chang, Shang-Jung Wu, Chia-Lin Hsu, Ai-Ru Hsieh, Wei-Shiung Yang, Cathy S J Fann

2020-Current year OA Pubs

To explore the complex genetic architecture of common diseases and traits, we conducted comprehensive PheWAS of ten diseases and 34 quantitative traits in the community-based Taiwan Biobank (TWB). We identified 995 significantly associated loci with 135 novel loci specific to Taiwanese population. Further analyses highlighted the genetic pleiotropy of loci related to complex disease and associated quantitative traits. Extensive analysis on glycaemic phenotypes (T2D, fasting glucose and HbA


Phase Iii Trial Of Chemoradiotherapy With Temozolomide Plus Nivolumab Or Placebo For Newly Diagnosed Glioblastoma With Methylated Mgmt Promoter, Michael Lim, George Ansstas, Et Al. Nov 2022

Phase Iii Trial Of Chemoradiotherapy With Temozolomide Plus Nivolumab Or Placebo For Newly Diagnosed Glioblastoma With Methylated Mgmt Promoter, Michael Lim, George Ansstas, Et Al.

2020-Current year OA Pubs

BACKGROUND: Nearly all patients with newly diagnosed glioblastoma experience recurrence following standard-of-care radiotherapy (RT) + temozolomide (TMZ). The purpose of the phase III randomized CheckMate 548 study was to evaluate RT + TMZ combined with the immune checkpoint inhibitor nivolumab (NIVO) or placebo (PBO) in patients with newly diagnosed glioblastoma with methylated MGMT promoter (NCT02667587).

METHODS: Patients (N = 716) were randomized 1:1 to NIVO [(240 mg every 2 weeks × 8, then 480 mg every 4 weeks) + RT (60 Gy over 6 weeks) + TMZ (75 mg/m2 once daily during RT, then 150-200 mg/m2 once daily on days …


Proteogenomic Markers Of Chemotherapy Resistance And Response In Triple-Negative Breast Cancer, Meenakshi Anurag, Shunqiang Li, Ian S Hagemann, Jeremy Hoog, Foluso O Ademuyiwa, Et Al. Nov 2022

Proteogenomic Markers Of Chemotherapy Resistance And Response In Triple-Negative Breast Cancer, Meenakshi Anurag, Shunqiang Li, Ian S Hagemann, Jeremy Hoog, Foluso O Ademuyiwa, Et Al.

2020-Current year OA Pubs

UNLABELLED: Microscaled proteogenomics was deployed to probe the molecular basis for differential response to neoadjuvant carboplatin and docetaxel combination chemotherapy for triple-negative breast cancer (TNBC). Proteomic analyses of pretreatment patient biopsies uniquely revealed metabolic pathways, including oxidative phosphorylation, adipogenesis, and fatty acid metabolism, that were associated with resistance. Both proteomics and transcriptomics revealed that sensitivity was marked by elevation of DNA repair, E2F targets, G2-M checkpoint, interferon-gamma signaling, and immune-checkpoint components. Proteogenomic analyses of somatic copy-number aberrations identified a resistance-associated 19q13.31-33 deletion where LIG1, POLD1, and XRCC1 are located. In orthogonal datasets, LIG1 (DNA ligase I) gene deletion and/or low …


The 5-Hydroxymethylcytosine Landscape Of Prostate Cancer, Martin Sjöström, Nupam P Mahajan, Christopher A Maher, Et Al. Nov 2022

The 5-Hydroxymethylcytosine Landscape Of Prostate Cancer, Martin Sjöström, Nupam P Mahajan, Christopher A Maher, Et Al.

2020-Current year OA Pubs

UNLABELLED: Analysis of DNA methylation is a valuable tool to understand disease progression and is increasingly being used to create diagnostic and prognostic clinical biomarkers. While conversion of cytosine to 5-methylcytosine (5mC) commonly results in transcriptional repression, further conversion to 5-hydroxymethylcytosine (5hmC) is associated with transcriptional activation. Here we perform the first study integrating whole-genome 5hmC with DNA, 5mC, and transcriptome sequencing in clinical samples of benign, localized, and advanced prostate cancer. 5hmC is shown to mark activation of cancer drivers and downstream targets. Furthermore, 5hmC sequencing revealed profoundly altered cell states throughout the disease course, characterized by increased proliferation, …


A New Mouse Model Of Charcot-Marie-Tooth 2j Neuropathy Replicates Human Axonopathy And Suggest Alteration In Axo-Glia Communication, Ghjuvan'ghjacumu Shackleford, Yo Sasaki, Et Al. Nov 2022

A New Mouse Model Of Charcot-Marie-Tooth 2j Neuropathy Replicates Human Axonopathy And Suggest Alteration In Axo-Glia Communication, Ghjuvan'ghjacumu Shackleford, Yo Sasaki, Et Al.

2020-Current year OA Pubs

Myelin is essential for rapid nerve impulse propagation and axon protection. Accordingly, defects in myelination or myelin maintenance lead to secondary axonal damage and subsequent degeneration. Studies utilizing genetic (CNPase-, MAG-, and PLP-null mice) and naturally occurring neuropathy models suggest that myelinating glia also support axons independently from myelin. Myelin protein zero (MPZ or P0), which is expressed only by Schwann cells, is critical for myelin formation and maintenance in the peripheral nervous system. Many mutations in MPZ are associated with demyelinating neuropathies (Charcot-Marie-Tooth disease type 1B [CMT1B]). Surprisingly, the substitution of threonine by methionine at position 124 of P0 …


International Consensus Guidelines For Adjuvant Radiation Therapy For Bladder Cancer After Radical Cystectomy: Update From An Ibis Workgroup, Flor Verghote, Paul Sargos, John P Christodouleas, Vedang Murthy, Brian C Baumann, Piet Dirix, Charlien Berghen, Leen Paelinck, Tom Vercauteren, Valérie Fonteyne Nov 2022

International Consensus Guidelines For Adjuvant Radiation Therapy For Bladder Cancer After Radical Cystectomy: Update From An Ibis Workgroup, Flor Verghote, Paul Sargos, John P Christodouleas, Vedang Murthy, Brian C Baumann, Piet Dirix, Charlien Berghen, Leen Paelinck, Tom Vercauteren, Valérie Fonteyne

2020-Current year OA Pubs

PURPOSE: In 2016, international consensus clinical target volume (CTV) guidelines for adjuvant radiation treatment after radical cystectomy in patients with muscle-invasive bladder cancer with high risk for locoregional failure (LRF) were published. A subsequent external validation study recommended several CTV optimizations (CTV-OPT). This study aimed to update international consensus guidelines based on new clinical experiences.

METHODS AND MATERIALS: Phase 1 (delineation interobserver variability): Four observers delineated the CTV of 9 patients post radical cystectomy, as in clinical practice. Interobserver agreement in contouring was evaluated using volume- and κ-statistics. Phase 2 (pattern of failure analysis): Among a prospective cohort of 72 …


The Programmed Death-1 Signaling Axis Modulates Inflammation And Lv Structure/Function In A Stress-Induced Cardiomyopathy Model, Tomohiro Hayashi, Sajal K Tiwary, Kory J Lavine, Sandeep Acharya, Michael Brent, Luigi Adamo, Attila Kovacs, Douglas L Mann Nov 2022

The Programmed Death-1 Signaling Axis Modulates Inflammation And Lv Structure/Function In A Stress-Induced Cardiomyopathy Model, Tomohiro Hayashi, Sajal K Tiwary, Kory J Lavine, Sandeep Acharya, Michael Brent, Luigi Adamo, Attila Kovacs, Douglas L Mann

2020-Current year OA Pubs

The role of immune checkpoints in the setting of tissue injury remains unknown. Using an experimental model of isoproterenol (ISO)-induced stress cardiomyopathy, we show that ISO-induced myocardial injury provokes tissue-autonomous up-regulation of the programmed death-1 (PD-1):programmed death ligand (PD-L) axis in cardiac resident innate immune cells and T cells. PD-1 signaling was responsible for modulating the acute inflammatory response, as well as normalization of impaired left ventricular structure and function after ISO injection. Necrotic cardiac extracts were sufficient to increase the expression of PD-1 in macrophages and T cells in vitro. Viewed together these studies suggest that the PD-1:PD-L signaling …


The Serotonin Receptor 3e Variant Is A Risk Factor For Female Ibs-D, Nikola Fritz, Gregory Sayuk, Et Al. Nov 2022

The Serotonin Receptor 3e Variant Is A Risk Factor For Female Ibs-D, Nikola Fritz, Gregory Sayuk, Et Al.

2020-Current year OA Pubs

Irritable bowel syndrome (IBS) is a gut-brain disorder of multifactorial origin. Evidence of disturbed serotonergic function in IBS accumulated for the 5-HT


Manufacturing-Dependent Change In Biological Activity Of The Tlr4 Agonist Gsk1795091 And Implications For Lipid A Analog Development, Neeltje Steeghs, Haeseong Park, Et Al. Nov 2022

Manufacturing-Dependent Change In Biological Activity Of The Tlr4 Agonist Gsk1795091 And Implications For Lipid A Analog Development, Neeltje Steeghs, Haeseong Park, Et Al.

2020-Current year OA Pubs

A phase I trial (NCT03447314; 204686) evaluated the safety and efficacy of GSK1795091, a Toll-like receptor 4 (TLR4) agonist, in combination with immunotherapy (GSK3174998 [anti-OX40 monoclonal antibody], GSK3359609 [anti-ICOS monoclonal antibody], or pembrolizumab) in patients with solid tumors. The primary endpoint was safety; other endpoints included efficacy, pharmacokinetics, and pharmacodynamics (PD). Manufacturing of GSK1795091 formulation was modified during the trial to streamline production and administration, resulting in reduced PD (cytokine) activity. Fifty-four patients received GSK1795091 with a combination partner; 32 received only the modified GSK1795091 formulation, 15 received only the original formulation, and seven switched mid-study from the original to …


Comparison Of Plasma And Csf Biomarkers In Predicting Cognitive Decline, Andrew J Aschenbrenner, Yan Li, Rachel L Henson, Katherine Volluz, Jason Hassenstab, Philip Verghese, Tim West, Matthew R Meyer, Kristopher M Kirmess, Anne M Fagan, Chengjie Xiong, David Holtzman, John C Morris, Randall J Bateman, Suzanne E Schindler Nov 2022

Comparison Of Plasma And Csf Biomarkers In Predicting Cognitive Decline, Andrew J Aschenbrenner, Yan Li, Rachel L Henson, Katherine Volluz, Jason Hassenstab, Philip Verghese, Tim West, Matthew R Meyer, Kristopher M Kirmess, Anne M Fagan, Chengjie Xiong, David Holtzman, John C Morris, Randall J Bateman, Suzanne E Schindler

2020-Current year OA Pubs

OBJECTIVES: Concentrations of amyloid-β peptides (Aβ42/Aβ40) and neurofilament light (NfL) can be measured in plasma or cerebrospinal fluid (CSF) and are associated with Alzheimer's disease brain pathology and cognitive impairment. This study directly compared plasma and CSF measures of Aβ42/Aβ40 and NfL as predictors of cognitive decline.

METHODS: Participants were 65 years or older and cognitively normal at baseline with at least one follow-up cognitive assessment. Analytes were measured with the following types of assays: plasma Aβ42/Aβ40, immunoprecipitation-mass spectrometry; plasma NfL, Simoa; CSF Aβ42/Aβ40, automated immunoassay; CSF NfL plate-based immunoassay. Mixed effects models evaluated the global cognitive composite score over …


Brain-Wide Versus Genome-Wide Vulnerability Biomarkers For Severe Mental Illnesses, Peter Kochunov, Aris Sotiras, Et Al. Nov 2022

Brain-Wide Versus Genome-Wide Vulnerability Biomarkers For Severe Mental Illnesses, Peter Kochunov, Aris Sotiras, Et Al.

2020-Current year OA Pubs

Severe mental illnesses (SMI), including major depressive (MDD), bipolar (BD), and schizophrenia spectrum (SSD) disorders have multifactorial risk factors and capturing their complex etiopathophysiology in an individual remains challenging. Regional vulnerability index (RVI) was used to measure individual's brain-wide similarity to the expected SMI patterns derived from meta-analytical studies. It is analogous to polygenic risk scores (PRS) that measure individual's similarity to genome-wide patterns in SMI. We hypothesized that RVI is an intermediary phenotype between genome and symptoms and is sensitive to both genetic and environmental risks for SMI. UK Biobank sample of N = 17,053/19,265 M/F (age = 64.8 …


Acute-Onset, Painful, Acral Granuloma Annulare In A 52-Year-Old Female, Faisal S Ahmad, Michael R Vittori, William H Mccoy Iv Nov 2022

Acute-Onset, Painful, Acral Granuloma Annulare In A 52-Year-Old Female, Faisal S Ahmad, Michael R Vittori, William H Mccoy Iv

2020-Current year OA Pubs

No abstract provided.


Mitochondrial Dysfunction And Pharmacodynamics Of Mitofusin Activation In Murine Charcot-Marie-Tooth Disease Type 2a, Antonietta Franco, Xiawei Dang, Lihong Zhang, Perry B Molinoff, Gerald W Dorn 2nd Nov 2022

Mitochondrial Dysfunction And Pharmacodynamics Of Mitofusin Activation In Murine Charcot-Marie-Tooth Disease Type 2a, Antonietta Franco, Xiawei Dang, Lihong Zhang, Perry B Molinoff, Gerald W Dorn 2nd

2020-Current year OA Pubs

Mitofusin (MFN) 1 and MFN2 are dynamin GTPase family mitochondrial proteins that mediate mitochondrial fusion requiring MFN conformational shifts, formation of macromolecular complexes on and between mitochondria, and GTP hydrolysis. Damaging MFN2 mutations cause an untreatable, largely pediatric progressive peripheral neuropathy, Charcot-Marie-Tooth (CMT) disease type 2A. We used small molecule allosteric mitofusin activators that promote MFN conformations favoring fusion to interrogate the effects of MFN2 conformation and GTPase activity on MFN2-mediated mitochondrial fusion and motility in vitro. We translated these findings in vivo by defining dose-dependent pharmacodynamic and disease-modifying effects of mitofusin activators in murine CMT2A. MFN2 catalytic GTPase activity …


Amyloid-Β And Tau Deposition Influences Cognitive And Functional Decline In Down Syndrome, Monika Grigorova, Beau Ances, Et Al. Nov 2022

Amyloid-Β And Tau Deposition Influences Cognitive And Functional Decline In Down Syndrome, Monika Grigorova, Beau Ances, Et Al.

2020-Current year OA Pubs

This study investigates whether tau has (i) an independent effect from amyloid-β on changes in cognitive and functional performance and (ii) a synergistic relationship with amyloid-β in the exacerbation of decline in aging Down syndrome (DS). 105 participants with DS underwent baseline PET [


Covariance-Based Vs. Correlation-Based Functional Connectivity Dissociates Healthy Aging From Alzheimer Disease, Jeremy F. Strain, Matthew R. Brier, Aaron Tanenbaum, Brian A. Gordon, John E. Mccarthy, Aylin Dincer, Daniel S. Marcus, Richard J. Perrin, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances, Abraham Z. Snyder, Et Al. Nov 2022

Covariance-Based Vs. Correlation-Based Functional Connectivity Dissociates Healthy Aging From Alzheimer Disease, Jeremy F. Strain, Matthew R. Brier, Aaron Tanenbaum, Brian A. Gordon, John E. Mccarthy, Aylin Dincer, Daniel S. Marcus, Richard J. Perrin, John C. Morris, Tammie L. S. Benzinger, Randall J. Bateman, Beau M. Ances, Abraham Z. Snyder, Et Al.

2020-Current year OA Pubs

Prior studies of aging and Alzheimer disease have evaluated resting state functional connectivity (FC) using either seed-based correlation (SBC) or independent component analysis (ICA), with a focus on particular functional systems. SBC and ICA both are insensitive to differences in signal amplitude. At the same time, accumulating evidence indicates that the amplitude of spontaneous BOLD signal fluctuations is physiologically meaningful. We systematically compared covariance-based FC, which is sensitive to amplitude, vs. correlation-based FC, which is not, in affected individuals and controls drawn from two cohorts of participants including autosomal dominant Alzheimer disease (ADAD), late onset Alzheimer disease (LOAD), and age-matched …


Transgenic Force Sensors And Software To Measure Force Transmission Across The Mammalian Nuclear Envelope In Vivo, Kelli D Fenelon, Evan Thomas, Mohammad Samani, Min Zhu, Hirotaka Tao, Yu Sun, Helen Mcneill, Sevan Hopyan Nov 2022

Transgenic Force Sensors And Software To Measure Force Transmission Across The Mammalian Nuclear Envelope In Vivo, Kelli D Fenelon, Evan Thomas, Mohammad Samani, Min Zhu, Hirotaka Tao, Yu Sun, Helen Mcneill, Sevan Hopyan

2020-Current year OA Pubs

Nuclear mechanotransduction is a growing field with exciting implications for the regulation of gene expression and cellular function. Mechanical signals may be transduced to the nuclear interior biochemically or physically through connections between the cell surface and chromatin. To define mechanical stresses upon the nucleus in physiological settings, we generated transgenic mouse strains that harbour FRET-based tension sensors or control constructs in the outer and inner aspects of the nuclear envelope. We knocked-in a published esprin-2G sensor to measure tensions across the LINC complex and generated a new sensor that links the inner nuclear membrane to chromatin. To mitigate challenges …


Associations Between Transcranial Doppler Vasospasm And Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study, Abhijit V. Lele, Rafael Wabl, Sarah Wahlster, Jade Keen, Andrew M. Walters, Christine T. Fong, Vasu B. Dhulipala, Umeshkumar Athiraman, Anne Moore, Monica S. Vavilala, Louis J. Kim, Michael R. Levitt Nov 2022

Associations Between Transcranial Doppler Vasospasm And Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage: A Retrospective Observational Study, Abhijit V. Lele, Rafael Wabl, Sarah Wahlster, Jade Keen, Andrew M. Walters, Christine T. Fong, Vasu B. Dhulipala, Umeshkumar Athiraman, Anne Moore, Monica S. Vavilala, Louis J. Kim, Michael R. Levitt

2020-Current year OA Pubs

OBJECTIVE: The objective is to examine the relationship between transcranial Doppler cerebral vasospasm (TCD-vasospasm), and clinical outcomes in aneurysmal subarachnoid hemorrhage (aSAH).

METHODS: In a retrospective cohort study, using univariate and multivariate analysis, we examined the association between TCD-vasospasm (defined as Lindegaard ratio >3) and patient's ability to ambulate without assistance, the need for tracheostomy and gastrostomy tube placement, and the likelihood of being discharged home from the hospital.

RESULTS: We studied 346 patients with aSAH; median age 55 years (Interquartile range IQR 46,64), median Hunt and Hess 3 [IQR 1-5]. Overall, 68.6% (n=238) had TCD-vasospasm, and 28% (n=97) had …


Quantitative Tumor Depth Determination Using Dual Wavelength Excitation Fluorescence, Christine M. O'Brien, Kevin W. Bishop, Haini Zhang, Xiao Xu, Leo Shmuylovich, Elizabeth Conley, Karen Nwosu, Kathleen Duncan, Suman B. Mondal, Gail Sudlow Nov 2022

Quantitative Tumor Depth Determination Using Dual Wavelength Excitation Fluorescence, Christine M. O'Brien, Kevin W. Bishop, Haini Zhang, Xiao Xu, Leo Shmuylovich, Elizabeth Conley, Karen Nwosu, Kathleen Duncan, Suman B. Mondal, Gail Sudlow

2020-Current year OA Pubs

No abstract provided.


Self-Care Management Of Bothersome Symptoms As Recommended By Clinicians For Patients With A Chronic Condition: A Delphi Study, Heleen Westland, Shayleigh Dickson Page, Michelle Van Rijn, Subhash Aryal, Kenneth E Freedland, Christopher Lee, Anna Strömberg, Ercole Vellone, Douglas J Wiebe, Tiny Jaarsma, Barbara Riegel Nov 2022

Self-Care Management Of Bothersome Symptoms As Recommended By Clinicians For Patients With A Chronic Condition: A Delphi Study, Heleen Westland, Shayleigh Dickson Page, Michelle Van Rijn, Subhash Aryal, Kenneth E Freedland, Christopher Lee, Anna Strömberg, Ercole Vellone, Douglas J Wiebe, Tiny Jaarsma, Barbara Riegel

2020-Current year OA Pubs

BACKGROUND: Chronically medically ill patients often need clinical assistance with symptom management, as well as self-care interventions that can help to reduce the impact of bothersome symptoms. Experienced clinicians can help to guide the development of more effective self-care interventions.

OBJECTIVE: To create a consensus-based list of common bothersome symptoms of chronic conditions and of self-care management behaviors recommended to patients by clinicians to reduce the impact of these symptoms.

METHODS: A two-round Delphi study was performed among an international panel of 47 clinicians using online surveys to identify common and bothersome symptoms and related self-care management behaviors recommended to …


Guidance For The Diagnosis And Treatment Of Hypolipidemia Disorders, Cindy Bredefeld, Nicholas O Davidson, Et Al. Nov 2022

Guidance For The Diagnosis And Treatment Of Hypolipidemia Disorders, Cindy Bredefeld, Nicholas O Davidson, Et Al.

2020-Current year OA Pubs

The Abetalipoproteinemia and Related Disorders Foundation was established in 2019 to provide guidance and support for the life-long management of inherited hypocholesterolemia disorders. Our mission is "to improve the lives of individuals and families affected by abetalipoproteinemia and related disorders". This review explains the molecular mechanisms behind the monogenic hypobetalipoproteinemia disorders and details their specific pathophysiology, clinical presentation and management throughout the lifespan. In this review, we focus on abetalipoproteinemia, homozygous hypobetalipoproteinemia and chylomicron retention disease; rare genetic conditions that manifest early in life and cause severe complications without appropriate treatment. Absent to low plasma lipid levels, in particular cholesterol …


To Calibrate Or Not To Calibrate? A Methodological Dilemma In Experimental Pain Research, Waclaw M Adamczyk, Tibor M Szikszay, Hadas Nahman-Averbuch, Jacek Skalski, Jakub Nastaj, Philip Gouverneur, Kerstin Luedtke Nov 2022

To Calibrate Or Not To Calibrate? A Methodological Dilemma In Experimental Pain Research, Waclaw M Adamczyk, Tibor M Szikszay, Hadas Nahman-Averbuch, Jacek Skalski, Jakub Nastaj, Philip Gouverneur, Kerstin Luedtke

2020-Current year OA Pubs

To calibrate or not to calibrate? This question is raised by almost everyone designing an experimental pain study with supra-threshold stimulation. The dilemma is whether to individualize stimulus intensity to the pain threshold / supra-threshold pain level of each participant or whether to provide the noxious stimulus at a fixed intensity so that everyone receives the identical input. Each approach has unique pros and cons which need to be considered to i) accurately design an experiment, ii) enhance statistical inference in the given data and, iii) reduce bias and the influence of confounding factors in the individual study e.g., body …