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  1. Article ; Online: Vitamin C, lactoferrin and elastin-Advancing the science.

    Widgerow, Alan D / Ziegler, Mary E

    Journal of cosmetic dermatology

    2024  Volume 23, Issue 3, Page(s) 964–969

    Abstract: Background: This study follows an initial scientific validation linking sodium ascorbate (SAC) with elastin conservation and the clinical trial histology observation that the full formulation tested there stimulated elastin development. In an effort to ... ...

    Abstract Background: This study follows an initial scientific validation linking sodium ascorbate (SAC) with elastin conservation and the clinical trial histology observation that the full formulation tested there stimulated elastin development. In an effort to explain the increased elastin response, a candidate was sought that may provide synergy to SAC during elastin stimulation. Lactoferrin was the constituent chosen to explore in this realm.
    Materials and methods: Using the previously described ex vivo skin model, freshly collected discarded human skin from 2 donors was used to evaluate the effects of lactoferrin and SAC alone and together, and L-ascorbate CE Ferulic formulation (CEF) on elastogenesis. Four skin explants were topically subjected to the treatments daily for 7 days and one group was left untreated as a negative control. The tissue was fixed and embedded. Sections were evaluated by immunofluorescence using antibodies targeting Tropoelastin and CD44, with DAPI counterstaining to observe nuclei. Images were then analyzed using ImageJ.
    Results: Treatment with SAC and lactoferrin demonstrated a significant synergistic effect on tropoelastin stimulation compared to the single treatments. In addition, this combination demonstrated intact and increased elastin fibers in contrast to the CEF, which portrayed fragmented elastin fibers. In addition, an additive effect of SAC also contributed to the enhanced CD44, suggesting an increased presence of hyaluronic acid, a new observation for this compound.
    Conclusion: This study complements a series of studies that have been undertaken to validate the efficacy of a novel antioxidant formulation. Aside from its efficacy in ROS management, the SAC constituent is unique in the different forms of Vitamin C for its ability to conserve elastin. Prior clinical studies demonstrated additive elastin stimulation on histology, not just conservation. From this current study, the combination of SAC with lactoferrin may be responsible for this additive stimulatory effect on elastin. This presents a significant advance in topical antioxidant formulations where the Vitamin C component provides antioxidant and collagen stimulation with additional elastin stimulation rather than degradation.
    MeSH term(s) Humans ; Tropoelastin/metabolism ; Ascorbic Acid/pharmacology ; Lactoferrin ; Antioxidants/pharmacology ; Elastin/metabolism ; Vitamins
    Chemical Substances Tropoelastin ; Ascorbic Acid (PQ6CK8PD0R) ; Lactoferrin (EC 3.4.21.-) ; Antioxidants ; Elastin (9007-58-3) ; Vitamins
    Language English
    Publishing date 2024-02-08
    Publishing country England
    Document type Journal Article
    ZDB-ID 2280551-5
    ISSN 1473-2165 ; 1473-2130
    ISSN (online) 1473-2165
    ISSN 1473-2130
    DOI 10.1111/jocd.16217
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Antioxidants with proven efficacy and elastin-conserving vitamin C-A new approach to free radical defense.

    Widgerow, Alan D / Ziegler, Mary E / Garruto, John A / Shafiq, Faiza

    Journal of cosmetic dermatology

    2023  Volume 22, Issue 12, Page(s) 3320–3328

    Abstract: Background: This paper describes the background research and validation related to the formulation of a novel antioxidant product. Two defined outcomes were sought. Firstly, a combined efficacy of antioxidant ingredients in quenching free oxygen ... ...

    Abstract Background: This paper describes the background research and validation related to the formulation of a novel antioxidant product. Two defined outcomes were sought. Firstly, a combined efficacy of antioxidant ingredients in quenching free oxygen radicals. Secondly, the investigation into whether a vitamin C derivative sodium salt was elastin conserving in contrast to current vitamin C/l-ascorbic acid variations that have been reported to negatively affect elastin constitution and regeneration.
    Materials and methods: A leading l-ascorbic acid antioxidant available on the market was compared with the experimental new product in two studies. In the first experiment, the products were compared to assess their antioxidant properties. The evaluated products TOPICAL ANTIOXIDANT 1 and TOPICAL ANTIOXIDANT 2 were applied to human skin cultures (25-30 mg/cm
    Results: A full description of the different components selected for the new formulation is presented. In the first study, the experimental formulation performed with absolute equivalence to the comparator in its radical quenching capacity; both showed extremely effective antioxidant function. In the second study, the comparator negatively affected the existing elastin with areas of breakdown and diminished staining. In contrast, the new formulation showed good conservation of healthy elastin in all sections demonstrating elastin preservation.
    Conclusion: A new antioxidant formulation was carefully designed with multiple actives that show an equivalent antioxidant capacity to a leading product on the market. More importantly, the vitamin C component shows direct elastin conservation and improvement as opposed to the comparator, which had negative effects on elastin preservation. This is in keeping with little-known literature reports on vitamin C and its negative effects on elastin and validates the use of a sodium salt derivative, which appears to have protective effects on elastin. These findings support the overall regenerative extracellular matrix changes seen with TriHex® technology in other products.
    MeSH term(s) Humans ; Antioxidants ; Ascorbic Acid/pharmacology ; Elastin ; Vitamins ; Free Radicals ; Sodium
    Chemical Substances Antioxidants ; Ascorbic Acid (PQ6CK8PD0R) ; Elastin (9007-58-3) ; Vitamins ; Free Radicals ; Sodium (9NEZ333N27)
    Language English
    Publishing date 2023-10-18
    Publishing country England
    Document type Journal Article
    ZDB-ID 2280551-5
    ISSN 1473-2165 ; 1473-2130
    ISSN (online) 1473-2165
    ISSN 1473-2130
    DOI 10.1111/jocd.15999
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Tissue Engineering Auricular Cartilage: A Review of Auricular Cartilage Characteristics and Current Techniques for Auricular Reconstruction.

    Khan, Nawal / Zaki, Daniel P / Brown, Wendy E / Halaseh, Faris F / Willette, Dominique / Ziegler, Mary / Athanasiou, Kyriacos A / Widgerow, Alan D

    The Journal of craniofacial surgery

    2024  

    Abstract: Microtia and anotia are congenital auricular anomalies that negatively impact the psychosocial development of those affected. Because auricular cartilage is a type of elastic cartilage that lacks regenerative capacity, any notable defect in its structure ...

    Abstract Microtia and anotia are congenital auricular anomalies that negatively impact the psychosocial development of those affected. Because auricular cartilage is a type of elastic cartilage that lacks regenerative capacity, any notable defect in its structure requires a surgical approach to reconstructing the auricle. While there are several reconstructive options available between alloplastic and prosthetic implants, autologous rib cartilage grafts remain the most commonly used treatment modality. Still, this widely used technique is accompanied by significant patient discomfort in a young child and carries additional risks secondary to the traumatic process of rib cartilage extraction, such as pneumothorax and chest wall deformities, and the final esthetic results may not be ideal. To circumvent these limitations, tissue engineering approaches have been used to create a realistic-looking ear that mirrors the complex anatomy of the normal ear. This article reviews the biochemical and biomechanical properties of human auricular cartilage as they relate to design criteria. In addition, a variety of cell sources, biocompatible scaffolds, scaffold-free techniques, and mechanical and biological stimuli are discussed. This review aims to identify knowledge gaps in the literature related to auricular cartilage characteristics and make recommendations to drive the field of auricular tissue engineering.
    Language English
    Publishing date 2024-03-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1159501-2
    ISSN 1536-3732 ; 1049-2275
    ISSN (online) 1536-3732
    ISSN 1049-2275
    DOI 10.1097/SCS.0000000000010015
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Effects of a Topical Anti-aging Formulation on Skin Aging Biomarkers.

    Widgerow, Alan D / Ziegler, Mary E / Garruto, John A / Bell, Michaela

    The Journal of clinical and aesthetic dermatology

    2022  Volume 15, Issue 8, Page(s) E53–E60

    Abstract: Objective: Following previous clinical trials, an antiaging product (Restorative Skin complex [RSC]; Alastin Skin Care Carlsbad, a Galderma company), was investigated for its effects on Klotho gene regulation, telomere length, and histological biopsy ... ...

    Abstract Objective: Following previous clinical trials, an antiaging product (Restorative Skin complex [RSC]; Alastin Skin Care Carlsbad, a Galderma company), was investigated for its effects on Klotho gene regulation, telomere length, and histological biopsy changes to provide a comprehensive picture of the mechanism and efficacy of its anti-aging effect.
    Methods: Neonatal human fibroblasts were used for telomere length studies to examine the effect of the full RSC formulation and the amino acid components Tripeptide-1 and Hexapeptide-12 (TriHex™) on these cellular aging mechanisms. In addition, RNA sequencing was conducted using human keratinocytes specifically investigating Klotho and related genes. This was supplemented by a clinical study using biopsy samples.
    Results: TriHex™ significantly upregulated the Klotho gene and related FGF23, FGFR1 and FOXO3B anti-aging genes. Significant telomere shortening reduction over control was demonstrated with the RSC formulation at four weeks and with TriHex™ at six weeks for all percentiles tested. Previous clinical studies demonstrated that the use of the antiaging regimen for 12 weeks produced a statistically significant improvement in scores for all evaluated parameters. Restaining of previous biopsy blocks from the clinical trial revealed positive ECM changes, stimulation of collagen, fibrillin, CD44 and elastin.
    Limitations: The study was limited by a relatively small numbers of patients in the clinical trial and the non-competitive nature of the trial.
    Conclusion: RSC anti-aging formulation and its TriHex™ components demonstrated significant reduction in telomere shortening, upregulation of Klotho and FOXO3 genes and biopsy validation of anti-aging efficacy. This new science supplements previous trials that demonstrated clinical efficacy of the formulation.
    Language English
    Publishing date 2022-08-30
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2571623-2
    ISSN 1941-2789
    ISSN 1941-2789
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Topical Skin Treatment and Its Influence on Surgical Healing: Review of Literature and Underlying Physiology.

    Widgerow, Alan D / Ziegler, Mary E / Casas, Laurie A

    Aesthetic surgery journal. Open forum

    2021  Volume 3, Issue 3, Page(s) ojab029

    Abstract: TriHex Technology (Alastin Skincare, Carlsbad, CA) has been shown clinically to promote healing and outcomes post procedures and has been demonstrated clinically to improve lipid droplet dissolution and patient-reported outcomes post procedure. ... ...

    Abstract TriHex Technology (Alastin Skincare, Carlsbad, CA) has been shown clinically to promote healing and outcomes post procedures and has been demonstrated clinically to improve lipid droplet dissolution and patient-reported outcomes post procedure. Histologically, the formulations have proven to regenerate collagen and elastin. The use of the technology to prepare the skin for surgical procedures combined with its use post procedure was assessed through clinical study outcomes, histological evidence, and gene expression analyses and demonstrated remodeling of the extracellular matrix (ECM), accelerating healing, and initiation of anti-inflammatory genes. While the improvement in clinical signs and outcomes has been validated, the changes taking place at a molecular level need to be explored. The interaction of cells (adipocytes, macrophages, fibroblasts) and the ECM proteins (collagen, elastin) secondary to the effects of the topical agent application are discussed. It appears that the manipulation of fat during body contouring surgery and the resultant adipocytolysis precipitates a molecular profile that can be positively directed toward hastened healing by using adjuvant topical applications as preconditioning prior to surgery and after the surgical procedure. Here, we review the literature and underlying physiology relating to these products and describe how interleukin 6 appears to be the primary facilitator of these effects.
    Language English
    Publishing date 2021-08-07
    Publishing country England
    Document type Journal Article
    ISSN 2631-4797
    ISSN (online) 2631-4797
    DOI 10.1093/asjof/ojab029
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Reply: Improving In Vitro Cartilage Generation by Co-Culturing Adipose-Derived Stem Cells and Chondrocytes on an Allograft Adipose Matrix Framework.

    Ziegler, Mary E / Sorensen, Alexandria M / Banyard, Derek A / Evans, Gregory R D / Widgerow, Alan D

    Plastic and reconstructive surgery

    2022  Volume 148, Issue 6, Page(s) 1063e–1064e

    MeSH term(s) Adipose Tissue ; Allografts ; Cartilage ; Chondrocytes ; Coculture Techniques ; Stem Cells
    Language English
    Publishing date 2022-05-19
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 208012-6
    ISSN 1529-4242 ; 0032-1052 ; 0096-8501
    ISSN (online) 1529-4242
    ISSN 0032-1052 ; 0096-8501
    DOI 10.1097/PRS.0000000000008551
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  7. Article ; Online: Impact of 2018 allocation system change on outcomes in patients with durable left ventricular assist device as bridge to transplantation: A UNOS registry analysis.

    Hess, Nicholas R / Ziegler, Luke A / Keebler, Mary E / Hickey, Gavin W / Kaczorowski, David J

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2023  Volume 42, Issue 7, Page(s) 925–935

    Abstract: Background: This study compared outcomes of patients waitlisted for orthotopic heart transplantation with durable left ventricular assist devices (LVAD) before and after the October 18, 2018 heart allocation policy change.: Methods: The United ... ...

    Abstract Background: This study compared outcomes of patients waitlisted for orthotopic heart transplantation with durable left ventricular assist devices (LVAD) before and after the October 18, 2018 heart allocation policy change.
    Methods: The United Network of Organ Sharing database was queried to identify 2 cohorts of adult candidates with durable LVAD listed within seasonally-matched, equal-length periods before (old policy era [OPE]) and after the policy change (new policy era [NPE]). The primary outcomes were 2-year survival from the time of initial waitlisting, as well as 2-year post-transplant survival. Secondary outcomes included incidence of transplantation from the waitlist and de-listing due to either death or clinical deterioration.
    Results: A total of 2,512 candidates were waitlisted, 1,253 within the OPE and 1,259 within the NPE. Candidates under both policies had similar 2-year survival after waitlisting, as well as a similar cumulative incidence of transplantation and de-listing due to death and/or clinical deterioration. A total of 2,560 patients were transplanted within the study period, 1,418 OPE and 1,142 within the NPE. Two-year post-transplant survival was similar between policy eras, however, the NPE was associated with a higher incidence of post-transplant stroke, renal failure requiring dialysis, and a longer hospital length of stay.
    Conclusions: The 2018 heart allocation policy has conferred no significant impact on overall survival from the time of initial waitlisting among durable LVAD-supported candidates. Similarly, the cumulative incidence of transplantation and waitlist mortality have also been largely unchanged. For those undergoing transplantation, a higher degree of post-transplant morbidity was observed, though survival was not impacted.
    MeSH term(s) Adult ; Humans ; Heart Failure/surgery ; Heart Failure/epidemiology ; Heart-Assist Devices/adverse effects ; Clinical Deterioration ; Heart Transplantation/adverse effects ; Registries
    Language English
    Publishing date 2023-02-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2023.02.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Targeting Myofibroblasts as a Treatment Modality for Dupuytren Disease.

    Ziegler, Mary E / Staben, Andres / Lem, Melinda / Pham, Jason / Alaniz, Leonardo / Halaseh, Faris F / Obagi, Sabine / Leis, Amber / Widgerow, Alan D

    The Journal of hand surgery

    2023  Volume 48, Issue 9, Page(s) 914–922

    Abstract: Purpose: Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured ... ...

    Abstract Purpose: Currently, no treatment corrects the contractile nature of Dupuytren myofibroblasts (DMFs) or prevents recurrence following surgery. Antifibrotic and proadipogenic growth factors are released when adipose-derived stem cells (ASCs) are cultured with platelet-rich plasma (PRP), a platelet concentration from whole blood. Reprograming myofibroblasts into adipocytes via growth factors is proposed as a powerful potential tool to target fibrosis. We aimed to assess whether the combination of ASCs and PRP reprograms DMFs into adipocytes in vitro and alters their contractile nature in vivo.
    Methods: Normal human dermal fibroblasts (NHDFs) and DMFs from Dupuytren patients were isolated and cocultured with ASCs and PRP either alone or together. Adipocytes were detected by Oil Red O and perilipin staining. DMFs and NHDFs were transplanted into the forepaws of rats (Rowett Nude [rnu/rnu]) and treated with saline, PRP+ASCs, or collagenase Clostridium histolyticum (clinical comparison) 2 months later. After 2 weeks, the tissue was harvested and subjected to Masson trichrome staining, and collagen I and III and alpha-smooth muscle actin detection by immunohistochemistry.
    Results: Myofibroblasts transform into adipocytes upon coculture with PRP+ASCs. DMFs show increased alpha-smooth muscle actin expression in vivo compared with NHDFs, which is significantly decreased after PRP+ASCs and collagenase Clostridium histolyticum treatments. DMFs induce collagen I and III expressions in rat paws compared with NHDFs, with a type III to I ratio increase. Treatment with PRP+ASC reduced the ratio, but collagenase Clostridium histolyticum did not.
    Conclusions: Treating DMFs with PRP+ASCs provides factors that induce myofibroblast to adipocyte transformation. This treatment reduces the contractile phenotype and fibrosis markers in vivo. Future studies should detail the mechanism of this conversion.
    Clinical relevance: The combination of PRP and ASCs to induce the differentiation of DMFs into adipocytes may serve to limit surgery to a percutaneous contracture release and biological injection, rather than a moderate or radical fasciectomy, and reduce the recurrence of Dupuytren contracture.
    MeSH term(s) Humans ; Animals ; Rats ; Dupuytren Contracture/therapy ; Myofibroblasts ; Microbial Collagenase ; Actins ; Collagen Type I
    Chemical Substances Microbial Collagenase (EC 3.4.24.3) ; Actins ; Collagen Type I
    Language English
    Publishing date 2023-07-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 605716-0
    ISSN 1531-6564 ; 0363-5023
    ISSN (online) 1531-6564
    ISSN 0363-5023
    DOI 10.1016/j.jhsa.2023.06.007
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  9. Article ; Online: Impact of post-transplant stroke and subsequent functional independence on outcomes following heart transplantation under the 2018 United States heart allocation system.

    Hong, Yeahwa / Huckaby, Lauren V / Hess, Nicholas R / Ziegler, Luke A / Hickey, Gavin W / Huston, Jessica H / Mathier, Michael A / McNamara, Dennis M / Keebler, Mary E / Kaczorowski, David J

    The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation

    2024  

    Abstract: Background: This study evaluates the clinical trends, risk factors, and effects of post-transplant stroke and subsequent functional independence on outcomes following orthotopic heart transplantation under the 2018 heart allocation system.: Methods: ... ...

    Abstract Background: This study evaluates the clinical trends, risk factors, and effects of post-transplant stroke and subsequent functional independence on outcomes following orthotopic heart transplantation under the 2018 heart allocation system.
    Methods: The United Network for Organ Sharing registry was queried to identify adult recipients from October 18, 2018 to December 31, 2021. The cohort was stratified into 2 groups with and without post-transplant stroke. The incidence of post-transplant stroke was compared before and after the allocation policy change. Outcomes included post-transplant survival and complications. Multivariable logistic regression was performed to identify risk factors for post-transplant stroke. Sub-analysis was performed to evaluate the impact of functional independence among recipients with post-transplant stroke.
    Results: A total of 9,039 recipients were analyzed in this study. The incidence of post-transplant stroke was higher following the policy change (3.8% vs 3.1%, p = 0.017). Thirty-day (81.4% vs 97.7%) and 1-year (66.4% vs 92.5%) survival rates were substantially lower in the stroke cohort (p < 0.001). The stroke cohort had a higher rate of post-transplant renal failure, longer hospital length of stay, and worse functional status. Multivariable analysis identified extracorporeal membrane oxygenation, durable left ventricular assist device, blood type O, and redo heart transplantation as strong predictors of post-transplant stroke. Preserved functional independence considerably improved 30-day (99.2% vs 61.2%) and 1-year (97.7% vs 47.4%) survival rates among the recipients with post-transplant stroke (p < 0.001).
    Conclusions: There is a higher incidence of post-transplant stroke under the 2018 allocation system, and it is associated with significantly worse post-transplant outcomes. However, post-transplant stroke recipients with preserved functional independence have improved survival, similar to those without post-transplant stroke.
    Language English
    Publishing date 2024-01-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1062522-7
    ISSN 1557-3117 ; 1053-2498
    ISSN (online) 1557-3117
    ISSN 1053-2498
    DOI 10.1016/j.healun.2024.01.010
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: An Analysis of Patient-Reported Recovery Outcomes of Topical Tripeptide/Hexapeptide Formulations Utilized in a Prospective Randomized Double-Blind Split Neck and Body Study.

    Casas, Laurie A / Bell, Michaela / Claytor, Brannon / Ziegler, Mary E / Widgerow, Alan D

    Aesthetic surgery journal. Open forum

    2020  Volume 3, Issue 1, Page(s) ojaa052

    Language English
    Publishing date 2020-11-18
    Publishing country England
    Document type Journal Article
    ISSN 2631-4797
    ISSN (online) 2631-4797
    DOI 10.1093/asjof/ojaa052
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