Akron, OH, United States
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Callahan L.A.S.,University of Akron | Ganios A.M.,University of Akron | McBurney D.L.,Northeast Ohio Medical University | Dilisio M.F.,Summa Health Systems | And 4 more authors.
Biomacromolecules | Year: 2012

The development of advanced materials that facilitate hyaline cartilage formation and regeneration in aging populations is imperative. Critical to the success of this endeavor is the optimization of ECM production from clinically relevant cells. However, much of the current literature focuses on the investigation of primary bovine chondrocytes from young calves, which differ significantly than osteoarthritic cells from human sources. This study examines the levels of extracellular matrix (ECM) production using various levels of type I collagen and hyaluronic acid in poly(ethylene glycol) dimethacrylate (PEGDM) hydrogels in total knee arthroplasties, compared with the results from bovine chondrocytes. The addition of type 1 collagen in both the presence and absence of low levels of hyaluronic acid increased ECM production and/or retention in scaffolds containing either bovine or human chondrocytes. These findings are supported consistently with colorimetric quantification, whole mount extracellular matrix staining for both cell types, and histological staining for glycoaminoglycans and collagen of human chondrocyte containing samples. While exhibiting similar trends, the relative ECM productions levels for the primary human chondrocytes are significantly less than the bovine chondrocytes which reinforces the need for additional optimization. © 2012 American Chemical Society.


Smith Callahan L.A.,University of Akron | Ganios A.M.,University of Akron | Childers E.P.,University of Akron | Weiner S.D.,Summa Health Systems | And 3 more authors.
Acta Biomaterialia | Year: 2013

Efficient ex vivo methods for expanding primary human chondrocytes while maintaining the phenotype is critical to advancing the sourcing of autologous cells for tissue engineering applications. While there has been significant research reported in the literature, systematic approaches are necessary to determine and optimize the chemical and mechanical scaffold properties for hyaline cartilage generation using limited cell numbers. Functionalized hydrogels possessing continuous variations in physico-chemical properties are, therefore, an efficient three-dimensional platform for studying several properties simultaneously. Herein we describe a polyethylene glycol dimethacrylate (PEGDM) hydrogel system with a modulus gradient (∼27,000-3800 Pa) containing a uniform concentration of arginine-glycine-aspartic acid (RGD) peptide to enhance cell adhesion in order to correlate primary human osteoarthritic chondrocyte proliferation, phenotype maintenance, and extracellular matrix (ECM) production with hydrogel properties. Cell number and chondrogenic phenotype (CD14:CD90 ratios) were found to decline in regions with a higher storage modulus (>13,100 Pa), while regions with a lower storage modulus maintained their cell number and phenotype. Over 3 weeks culture hydrogel regions possessing a lower Young's modulus experienced an increase in ECM content (∼200%) compared with regions with a higher storage modulus. Variations in the amount and organization of the cytoskeletal markers actin and vinculin were observed within the modulus gradient, which are indicative of differences in chondrogenic phenotype maintenance and ECM expression. Thus scaffold mechanical properties have a significant impact in modulating human osteoarthritic chondrocyte behavior and tissue formation. © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Smith Callahan L.A.,University of Akron | Childers E.P.,University of Akron | Bernard S.L.,University of Akron | Weiner S.D.,Summa Health Systems | And 2 more authors.
Acta Biomaterialia | Year: 2013

New systematic approaches are necessary to determine and optimize the chemical and mechanical scaffold properties for hyaline cartilage generation using the limited cell numbers obtained from primary human sources. Peptide functionalized hydrogels possessing continuous variations in physico-chemical properties are an efficient three-dimensional platform for studying several properties simultaneously. Herein, we describe a polyethylene glycol dimethacrylate (PEGDM) hydrogel system possessing a gradient of arginine-glycine-aspartic acid peptide (RGD) concentrations from 0 mM to 10 mM. The system is used to correlate primary human osteoarthritic chondrocyte proliferation, phenotype maintenance and extracellular matrix (ECM) production to the gradient hydrogel properties. Cell number and chondrogenic phenotype (CD14:CD90 ratios) were found to decline in regions with higher RGD concentrations, while regions with lower RGD concentrations maintained cell number and phenotype. Over three weeks of culture, hydrogel regions containing lower RGD concentrations experience an increase in ECM content compared to regions with higher RGD concentrations. Variations in actin amounts and vinculin organization were observed within the RGD concentration gradients that contribute to the differences in chondrogenic phenotype maintenance and ECM expression. © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.


Nazir A.,Indiana University | Smucker W.D.,Summa Health Systems | Smucker W.D.,Northeastern University
Journal of the American Medical Directors Association | Year: 2015

Heart failure (HF) is highly prevalent among older patients in skilled nursing facilities (SNFs). HF outcomes for SNF patients suffer because of many factors, including staff training, lack of physician availability, and failure to implement evidence-based care. AMDA - The Society for Post-Acute and Long-Term Care Medicine has recently updated the Clinical Practice Guidelines for Heart Failure Management in SNFs. This review supplements the Guidelines with a robust focus on best practices for transitional care, symptom management, treatment and monitoring, and palliative care in patients with HF. © 2015 AMDA - The Society for Post-Acute and Long-Term Care Medicine.


Gallagher K.M.,Kent State University | Updegraff J.A.,Kent State University | Rothman A.J.,University of Minnesota | Sims L.,SUMMA Health Systems
Health Psychology | Year: 2011

Objective: This study examined the role of three distinct beliefs about risk (risks associated with screening, construal of the function of screening as health-affirming or illness-detecting, and perceived susceptibility to breast cancer) in moderating women's responses to framed messages that promote mammography. Design: Three hundred fifty-five women recruited from an inner city hospital, nonadherent to guidelines for receiving annual screening mammograms, were randomly assigned to view a gain- or loss-framed video message about the importance of mammography. Main Outcome Measure: Mammography screening was self-reported at a 3-month follow-up. Results: Only perceived susceptibility to breast cancer significantly moderated the effect of message framing on screening. Women with average and higher levels of perceived susceptibility for breast cancer were significantly more likely to report screening after viewing a loss-framed message compared to a gain-framed message. No effects of framing on reported screening were observed for women with lower levels of perceived susceptibility. Conclusion: The study identifies a key role for perceived susceptibility in shaping responses to framed messages that promote cancer screenings. © 2011 American Psychological Association.


Garcia-Effron G.,Public Health Research Institute | Chua D.J.,Summa Health Systems | Tomada J.R.,Summa Health Systems | DiPersio J.,Summa Health Systems | And 3 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2010

We studied three clinical isolates of Candida spp. (one C. tropicalis isolate and two C. glabrata isolates) from patients with invasive candidiasis. The first isolate emerged during echinocandin treatment, while the others emerged after the same treatment. These strains harbored an amino acid substitution in Fksp never linked before with reduced echinocandin susceptibility in C. tropicalis or in C. glabrata. The molecular mechanism of reduced susceptibility was confirmed using a 1,3-β-D-glucan synthase inhibition assay. Copyright © 2010, American Society for Microbiology. All Rights Reserved.


Unsdorfer G.L.,Cleveland Clinic | Unsdorfer G.L.,Summa Health Systems | Unsdorfer K.M.L.,Ohio State University
Journal of Foot and Ankle Surgery | Year: 2011

Combined transverse and sagittal plane deformities of the second toe represent a common painful condition encountered by the foot surgeon. After a period of conservative management, surgical intervention is often required. Historically, a number of surgical options have been described for the treatment of this condition, with the universal acknowledgment that an ideal surgical outcome is difficult to achieve and prone to failure. In this report, a review of previously described surgical techniques is presented, along with a retrospective analysis of 20 second toe surgical reconstructions, in 16 patients, performed between June 2003 and October 2010. Subjective outcomes were assessed by means of a mailed questionnaire, and a subset (15 second toes in 11 patients) returned for follow-up evaluation, including ascertainment of American Orthopaedic Foot & Ankle Society Clinical Rating System for Lesser Metatarsophalangeal-Interphalangeal Joint Surgery scores. Overall, the duration of follow-up was 38.25 ± 25.82 months, and the subset was followed up for 36.07 ± 27.95 months. The preoperative visual analog pain score was 4.9 ± 2.7, whereas the postoperative pain score was 1.6 ± 2.47 (p < .001). The preoperative American Orthopaedic Foot & Ankle Society score was 44.57 ± 17.76, whereas the postoperative score was 91.27 ± 12.27 (p < .001). Based on the results of this investigation, pairing a basilar proximal phalangeal osteotomy with arthrodesis of the proximal interphalangeal joint, for correction of combined transverse and sagittal plane deformities, appears to yield satisfactory long-term results. © 2011 American College of Foot and Ankle Surgeons.


Geldenhuys W.J.,Northeastern Ohio Universities Colleges of Medicine and Pharmacy | Nakamura H.,Summa Health Systems
Bioorganic and Medicinal Chemistry Letters | Year: 2010

The transforming growth factor-β (TGF-β) is part of a family of cytokines which regulate various signaling pathways such as cell development, growth, and tissue injury. Although several studies have been published describing the synthesis of small compounds which inhibit the receptor of TGF-β, especially the subtype 1 receptor (TGBR1) kinase, no 3D-quantitiative structure-activity relationship study has been published. Here we describe the development of a comparative molecular field analysis (CoMFA) model which yielded a partial least squares statistical cross validated r2 of >0.3. CoMFA maps agree with docking studies and pharmacophore analysis that hydrogen bonding is important for binding to ALK-5. These studies could enable the medicinal chemist to develop novel inhibitors which can be used in glaucoma filtration surgery.


Willett M.C.,Summa Health Systems | Edward D.P.,Summa Health Systems
Journal of Medical Case Reports | Year: 2011

Introduction: Topiramate is a sulphonamide derivative indicated in the treatment of epilepsy and migraine. A known adverse affect is an idiosyncratic reaction that results in angle-closure glaucoma. We describe a patient with bilateral glaucoma related to topiramate that showed some unusual clinical features. Case presentation: A 39-year-old Caucasian man presented with acute angle-closure glaucoma; he initially presented with intractable headaches after being treated with an escalating dose of topiramate. Clinical signs included elevated intraocular pressure that was initially refractory to treatment, shallow anterior chambers, and extensive bilateral choroidal effusions. After treatment with intravenous methylprednisolone, in conjunction with conventional glaucoma treatment, there was rapid reduction of intraocular pressure, gradual delayed resolution of the choroidal effusion and induced myopic shift; and eventually a good outcome without optic nerve damage. Conclusion: This case illustrates the importance of recognizing this entity in a non-ophthalmic setting and that intravenous methylprednisolone may be useful in the treatment of the condition when it is not responsive to conventional treatment. In addition, it is important to recognize that complete resolution of visual symptoms from the myopic shift may be delayed, despite normalization of intraocular pressure. © 2011 Willett and Edward; licensee BioMed Central Ltd.


PubMed | Summa Health Systems
Type: Journal Article | Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology | Year: 2016

3539 Background: MMR protein deficient CRC (15-20% of all CRC) can be sporadic or genetic (due to Lynch Syndrome). Loss of MMR proteins can be detected by absence of staining on immunohistochemistry (IHC). Previously, all MMR-deficient CRC were tested for LS by sequencing. With the advent of BRAF testing, genetic testing for LS can be avoided in a large subset of MMR-deficient CRC. In addition, detection of BRAF mutations (mut) may have therapeutic implications. We sought to investigate the contribution of BRAF V600E mut to MLH1 deficient CRC and incidence of LS among all newly diagnosed CRC.All CRC between 3/2010-12/2010 were tested for MMR protein (MLH1, MSH2, MSH6 and PMS2) deficiency by IHC. Absence of MLH1 prompted BRAF mut (V600E) testing. If BRAF was mut, further testing was stopped. Absence of MSH2, MSH6 and MLH1 with normal BRAF prompted genetic sequencing of the absent protein. If patients had MMR-proficient tumors but met modified Bethesda criteria, LS genetic testing was pursued.Results are shown in the table.BRAF was mutated in 77% of patients with absence of MLH1. These patients were elderly and solely women with right-sided CRC. [Table: see text].

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