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  1. Article ; Online: VLDL receptor gene therapy for reducing atherogenic lipoproteins

    Ronald M. Krauss / Jonathan T. Lu / Joseph J. Higgins / Cathryn M. Clary / Ray Tabibiazar

    Molecular Metabolism, Vol 69, Iss , Pp 101685- (2023)

    2023  

    Abstract: Over the past 40 years, there has been considerable research into the management and treatment of atherogenic lipid disorders. Although the majority of treatments and management strategies for cardiovascular disease (CVD) center around targeting low- ... ...

    Abstract Over the past 40 years, there has been considerable research into the management and treatment of atherogenic lipid disorders. Although the majority of treatments and management strategies for cardiovascular disease (CVD) center around targeting low-density lipoprotein cholesterol (LDL-C), there is mounting evidence for the residual CVD risk attributed to high triglyceride (TG) and lipoprotein(a) (Lp(a)) levels despite the presence of lowered LDL-C levels. Among the biological mechanisms for clearing TG-rich lipoproteins, the VLDL receptor (VLDLR) plays a key role in the trafficking and metabolism of lipoprotein particles in multiple tissues, but it is not ordinarily expressed in the liver. Since VLDLR is capable of binding and internalizing apoE-containing TG-rich lipoproteins as well as Lp(a), hepatic VLDLR expression has the potential for promoting clearance of these atherogenic particles from the circulation and managing the residual CVD risk not addressed by current lipid lowering therapies. This review provides an overview of VLDLR function and the potential for developing a genetic medicine based on liver-targeted VLDLR gene expression.
    Keywords Lipid disorders ; VLDL ; VLDL receptor ; Triglycerides ; lipoprotein(a) ; Gene therapy ; Internal medicine ; RC31-1245
    Subject code 616
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Dementia assessment and management in primary care settings

    Alissa Bernstein / Kirsten M. Rogers / Katherine L. Possin / Natasha Z.R. Steele / Christine S. Ritchie / Joel H. Kramer / Michael Geschwind / Joseph J. Higgins / Jay Wohlgemuth / Rick Pesano / Bruce L. Miller / Katherine P. Rankin

    BMC Health Services Research, Vol 19, Iss 1, Pp 1-

    a survey of current provider practices in the United States

    2019  Volume 10

    Abstract: Abstract Background Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management ... ...

    Abstract Abstract Background Primary care providers (PCPs) are typically the first to screen and evaluate patients for neurocognitive disorders (NCDs), including mild cognitive impairment and dementia. However, data on PCP attitudes and evaluation and management practices are sparse. Our objective was to quantify perspectives and behaviors of PCPs and neurologists with respect to NCD evaluation and management. Methods A cross-sectional survey with 150 PCPs and 50 neurologists in the United States who evaluated more than 10 patients over age 55 per month. The 51-item survey assessed clinical practice characteristics, and confidence, perceived barriers, and typical practices when diagnosing and managing patients with NCDs. Results PCPs and neurologists reported similar confidence and approaches to general medical care and laboratory testing. Though over half of PCPs performed cognitive screening or referred patients for cognitive testing in over 50% of their patients, only 20% reported high confidence in interpreting results of cognitive tests. PCPs were more likely to order CT scans than MRIs, and only 14% of PCPs reported high confidence interpreting brain imaging findings, compared to 70% of specialists. Only 21% of PCPs were highly confident that they correctly recognized when a patient had an NCD, and only 13% were highly confident in making a specific NCD diagnosis (compared to 72 and 44% for neurologists, both p < 0.001). A quarter of all providers identified lack of familiarity with diagnostic criteria for NCD syndromes as a barrier to clinical practice. Conclusions This study demonstrates how PCPs approach diagnosis and management of patients with NCDs, and identified areas for improvement in regards to cognitive testing and neuroimaging. This study also identified all providers’ lack of familiarity with published diagnostic criteria for NCD syndromes. These findings may inform the development of new policies and interventions to help providers improve the efficacy of their decision processes and deliver better ...
    Keywords Primary care ; Dementia ; Neurocognitive disorders ; Diagnosis ; Care management ; Public aspects of medicine ; RA1-1270
    Subject code 610
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: A brief review of recent Charcot-Marie-Tooth research and priorities [v1; ref status

    Sean Ekins / Nadia K. Litterman / Renée J.G. Arnold / Robert W. Burgess / Joel S. Freundlich / Steven J. Gray / Joseph J. Higgins / Brett Langley / Dianna E. Willis / Lucia Notterpek / David Pleasure / Michael W. Sereda / Allison Moore

    F1000Research, Vol

    indexed, http://f1000r.es/53g]

    2015  Volume 4

    Abstract: This brief review of current research progress on Charcot-Marie-Tooth (CMT) disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF) scientific advisory board meeting on November 7, 2014. It covers recent published and ... ...

    Abstract This brief review of current research progress on Charcot-Marie-Tooth (CMT) disease is a summary of discussions initiated at the Hereditary Neuropathy Foundation (HNF) scientific advisory board meeting on November 7, 2014. It covers recent published and unpublished in vitro and in vivo research. We discuss recent promising preclinical work for CMT1A, the development of new biomarkers, the characterization of different animal models, and the analysis of the frequency of gene mutations in patients with CMT. We also describe how progress in related fields may benefit CMT therapeutic development, including the potential of gene therapy and stem cell research. We also discuss the potential to assess and improve the quality of life of CMT patients. This summary of CMT research identifies some of the gaps which may have an impact on upcoming clinical trials. We provide some priorities for CMT research and areas which HNF can support. The goal of this review is to inform the scientific community about ongoing research and to avoid unnecessary overlap, while also highlighting areas ripe for further investigation. The general collaborative approach we have taken may be useful for other rare neurological diseases.
    Keywords Bioinformatics ; Genomics ; Molecular Pharmacology ; Musculoskeletal Pharmacology ; Neuropharmacology & Psychopharmacology ; Medicine ; R ; Science ; Q
    Subject code 306
    Language English
    Publishing date 2015-02-01T00:00:00Z
    Publisher F1000 Research Ltd
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Markers of Celiac Disease and Gluten Sensitivity in Children with Autism.

    Nga M Lau / Peter H R Green / Annette K Taylor / Dan Hellberg / Mary Ajamian / Caroline Z Tan / Barry E Kosofsky / Joseph J Higgins / Anjali M Rajadhyaksha / Armin Alaedini

    PLoS ONE, Vol 8, Iss 6, p e

    2013  Volume 66155

    Abstract: Gastrointestinal symptoms are a common feature in children with autism, drawing attention to a potential association with celiac disease or gluten sensitivity. However, studies to date regarding the immune response to gluten in autism and its association ...

    Abstract Gastrointestinal symptoms are a common feature in children with autism, drawing attention to a potential association with celiac disease or gluten sensitivity. However, studies to date regarding the immune response to gluten in autism and its association with celiac disease have been inconsistent. The aim of this study was to assess immune reactivity to gluten in pediatric patients diagnosed with autism according to strict criteria and to evaluate the potential link between autism and celiac disease.Study participants included children (with or without gastrointestinal symptoms) diagnosed with autism according to both the Autism Diagnostic Observation Schedule (ADOS) and the Autism Diagnostic Interview, Revised (ADI-R) (n = 37), their unaffected siblings (n = 27), and age-matched healthy controls (n = 76). Serum specimens were tested for antibodies to native gliadin, deamidated gliadin, and transglutaminase 2 (TG2). Affected children were genotyped for celiac disease associated HLA-DQ2 and -DQ8 alleles.Children with autism had significantly higher levels of IgG antibody to gliadin compared with unrelated healthy controls (p<0.01). The IgG levels were also higher compared to the unaffected siblings, but did not reach statistical significance. The IgG anti-gliadin antibody response was significantly greater in the autistic children with gastrointestinal symptoms in comparison to those without them (p<0.01). There was no difference in IgA response to gliadin across groups. The levels of celiac disease-specific serologic markers, i.e., antibodies to deamidated gliadin and TG2, did not differ between patients and controls. An association between increased anti-gliadin antibody and presence of HLA-DQ2 and/or -DQ8 was not observed.A subset of children with autism displays increased immune reactivity to gluten, the mechanism of which appears to be distinct from that in celiac disease. The increased anti-gliadin antibody response and its association with GI symptoms points to a potential mechanism involving ...
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2013-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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