Publications by authors named "J Panos"

75 Publications

Alzheimer's disease: a step closer to understanding type 3 diabetes in African Americans.

Metab Brain Dis 2021 May 22. Epub 2021 May 22.

Division of Neurotoxicology, National Center for Toxicological Research/Food and Drug Administration, Jefferson, AR, 72079, USA.

Alzheimer's disease (AD) is the fourth leading cause of death in the United States and the most common cause of adult-onset dementia. Recent results suggest an increased prevalence and severity in African Americans compared to Caucasians. Our understanding of the potential mechanism(s) underlying this ethnicity difference is limited. We previously described ethnicity-related differences in levels of neurodegenerative proteins and cytokines/chemokines in the BA21 region of African Americans and Caucasians with AD. Here, similar multiplex assays were used to examine those endpoints in patient postmortem cerebrospinal fluid (CSF). Additionally, we measured levels of C-peptide, ghrelin, gastric inhibitory polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, insulin, leptin, PAI-1, resistin, and visfatin using a human diabetes 10-plex assay. The cytokine and chemokine assays revealed that levels of 26 chemokines or cytokines differed significantly with ethnicity, and three of those were significantly associated with gender. The neurodegenerative disease panel indicated that levels of soluble RAGE were significantly elevated in African Americans compared to Caucasians. All measures in the diabetes disease panel assay were significantly elevated in African Americans: ghrelin, GIP, GLP-1, glucagon, insulin, and visfatin. Through peripheral sample analysis, these results provide further evidence that ethnicity is critically involved in the manifestation of AD.
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http://dx.doi.org/10.1007/s11011-021-00754-zDOI Listing
May 2021

Gene therapy for bone healing: lessons learned and new approaches.

Transl Res 2021 May 5. Epub 2021 May 5.

Rehabilitation Medicine Research Center, Mayo Clinic, Rochester, Minnesota; Musculoskeletal Gene Therapy Research Laboratory, Mayo Clinic, Rochester, Minnesota; IBE, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, Maastricht, Netherlands.

Although gene therapy has its conceptual origins in the treatment of Mendelian disorders, it has potential applications in regenerative medicine, including bone healing. Research into the use of gene therapy for bone healing began in the 1990s. Prior to this period, the highly osteogenic proteins bone morphogenetic protein (BMP)-2 and -7 were cloned, produced in their recombinant forms and approved for clinical use. Despite their promising osteogenic properties, the clinical usefulness of recombinant BMPs is hindered by delivery problems that necessitate their application in vastly supraphysiological amounts. This generates adverse side effects, some of them severe, and raises costs; moreover, the clinical efficacy of the recombinant proteins is modest. Gene delivery offers a potential strategy for overcoming these limitations. Our research has focused on delivering a cDNA encoding human BMP-2, because the recombinant protein is Food and Drug Administration approved and there is a large body of data on its effects in people with broken bones. However, there is also a sizeable literature describing experimental results obtained with other transgenes that may directly or indirectly promote bone formation. Data from experiments in small animal models confirm that intralesional delivery of BMP-2 cDNA is able to heal defects efficiently and safely while generating transient, local BMP-2 concentrations 2-3 log orders less than those needed by recombinant BMP-2. The next challenge is to translate this information into a clinically expedient technology for bone healing. Our present research focuses on the use of genetically modified, allografted cells and chemically modified messenger RNA.
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http://dx.doi.org/10.1016/j.trsl.2021.04.009DOI Listing
May 2021

3-D printed spectacles: potential, challenges and the future.

Clin Exp Optom 2020 09 3;103(5):590-596. Epub 2020 Feb 3.

Public Health Division, Brien Holden Vision Institute, Sydney, Australia.

Three-dimensional (3-D) printing offers the potential to custom-produce a wide range of manufactured objects and improve manufacturing processes. The additive manufacturing process involves material (resin, metal, ceramics or biological cells) being deposited layer upon layer, which is fused to create a 3-D object. While 3-D printing has been readily available in the aerospace and automotive industries, and is being used increasingly in the medical field, its potential for optometry and ophthalmic optics has rarely been discussed in depth. 3-D printing of spectacles has the potential to provide customised experiences, to cater for those who do not fit standardised frames or for those with irregular prescriptions, and to reduce delivery times and inventory with the opportunity of increasing access to underserved populations. Here we review available 3-D printing technologies, and the current 3-D printed spectacle market, including testing three commercially available spectacle frames to assess compliance with ISO:12870 standards. The article then explores the challenges faced and environmental impact of implementing 3-D printing of spectacles.
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http://dx.doi.org/10.1111/cxo.13042DOI Listing
September 2020

Increased inflammation in BA21 brain tissue from African Americans with Alzheimer's disease.

Metab Brain Dis 2020 01 10;35(1):121-133. Epub 2019 Dec 10.

Division of Neurotoxicology, National Center for Toxicological Research/Food and Drug Administration, 3900 NCTR Road, Jefferson, AR, 72079, USA.

Chronic neuroinflammation is strongly associated with AD and altered peripheral and central levels of chemokines and cytokines have been frequently described in those with AD. Given the increasing evidence of ethnicity-related differences in AD, it was of interest to determine if those altered chemokine and cytokine levels are ethnicity-related. Because African Americans exhibit a higher incidence of AD and increased symptom severity, we explored chemokine and cytokine concentrations in post-mortem brain tissue from the BA21 region of African Americans and Caucasians with AD using multiplex assays. IL-1β, MIG, TRAIL, and FADD levels were significantly increased in African Americans while levels of IL-3 and IL-8 were significantly decreased. Those effects did not interact with gender; however, overall levels of CCL25, CCL26 and CX3CL1 were significantly decreased in women. The NLRP3 inflammasome is thought to be critically involved in AD. Increased activation of this inflammasome in African Americans is consistent with the current results.
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http://dx.doi.org/10.1007/s11011-019-00512-2DOI Listing
January 2020

Anterior cruciate ligament grafts display differential maturation patterns on magnetic resonance imaging following reconstruction: a systematic review.

Knee Surg Sports Traumatol Arthrosc 2020 Jul 13;28(7):2124-2138. Epub 2019 Sep 13.

Department of Physiology and Biomedical Engineering, Mayo Clinic, 200 First St. SW, Rochester, MN, 55902, USA.

Purpose: The appearance of anterior cruciate ligament (ACL) grafts on magnetic resonance imaging (MRI) is related to graft maturity and mechanical strength after ACL reconstruction (ACLR). Accordingly, the purpose of this review was to quantitatively analyze reports of serial MRI of the ACL graft during the first year following ACLR; the hypothesis tested was that normalized MRI signal intensity would differ significantly by ACL graft type, graft source, and postoperative time.

Methods: PubMed, Scopus, and CINAHL were searched for all studies published prior to June 2018 reporting MRI signal intensity of the ACL graft at multiple time points during the first postoperative year after ACLR. Signal intensity values at 6 and 12 months post-ACLR were normalized to initial measurements and analyzed using a least-squares regression model to study the independent variables of postoperative time, graft type, and graft source on the normalized MRI signal intensity.

Results: An effect of graft type (P = 0.001) with interactions of graft type * time (P = 0.012) and graft source * time (P = 0.001) were observed. Post hoc analyses revealed greater predicted normalized MRI signal intensity of patellar tendon autografts than both hamstring (P = 0.008) and hamstring with remnant preservation (P = 0.001) autografts at postoperative month 12.

Conclusion: MRI signal varies with graft type, graft source, and time after ACLR. Enhanced graft maturity during the first postoperative year was associated with hamstring autografts, with and without remnant preservation. Serial MRI imaging during the first postoperative year may be clinically useful to identify biologically or mechanically deficient ACL grafts at risk for failure.

Level Of Evidence: IV.
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http://dx.doi.org/10.1007/s00167-019-05685-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067650PMC
July 2020