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  • Springer (CrossRef)  (4)
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  • 1
    In: Clinical Orthopaedics and Related Research, 2015, Vol.473(9), pp.2856-2864
    Description: BACKGROUND: Effective treatments for implant-associated infections are often lacking. Cathodic voltage-controlled electrical stimulation has shown potential as a treatment of implant-associated infections of methicillin-resistant Staphylococcus aureus (MRSA). QUESTIONS/PURPOSES: The primary purpose of this study was to (1) determine if cathodic voltage-controlled electrical stimulation combined with vancomycin therapy is more effective at reducing the MRSA bacterial burden on the implant, bone, and synovial fluid in comparison to either treatment alone or no treatment controls. We also sought to (2) evaluate the histologic effects of the various treatments on the surrounding bone; and to (3) determine if the cathodic voltage-controlled electrical stimulation treatment had an effect on the mechanical properties of the titanium implant as a result of possible hydrogen embrittlement. METHODS: Thirty-two adult male Long-Evans rats (Harlan Laboratories, Indianapolis, IN, USA) with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, eight animals received a treatment of cathodic voltage-controlled electrical stimulation at −1.8 V versus Ag/AgCl for 1 hour (STIM), eight received vancomycin twice daily for 1 week (VANCO), eight received the cathodic voltage-controlled electrical stimulation and vancomycin therapy combined (STIM + VANCO), and eight served as controls with no treatment (CONT). Two weeks after initial infection, the implant, bone, and synovial fluid were collected for colony-forming unit (CFU) enumeration, qualitative histological analysis by a pathologist blinded to the treatments each animal received, and implant three-point bend testing. RESULTS: The implant-associated CFU enumerated from the STIM + VANCO (mean, 3.7 × 10; SD, 6.3 × 10) group were less than those from the CONT (mean, 1.3 × 10; SD, 2.8 × 10; 95% confidence interval [CI] of difference, −4.3 × 10 to −9.9 × 10; p 〈 0.001), STIM (mean, 1.4 × 10; SD, 2.0 × 10; 95% CI of difference, −2.1 × 10 to −1.8 × 10; p = 0.002), and VANCO (mean, 5.8 × 10; SD, 5.7 × 10; 95% CI of difference, −6.4 × 10 to −1.7 × 10; p 〈 0.001) group. The bone-associated CFU enumerated from the STIM + VANCO group (6.3 × 10; SD, 1.1 × 10) were less than those from the CONT (mean, 2.8 × 10; SD, 4.8 × 10; 95% CI of difference, −9.4 × 10 to −5.0 × 10; p 〈 0.001) and STIM (mean, 2.6 × 10; SD, 2.5 × 10; 95% CI of difference, −4.1 × 10 to −1.6 × 10; p 〈 0.001) groups. The VANCO group (4.3 × 10; SD, 6.3 × 10) also had lower bone-associated CFU as compared with the CONT (mean 95% CI of difference, −9.3 × 10 to −4.5 × 10; p 〈 0.001) and STIM (95% CI of difference, −4.0 × 10 to −1.5 × 10; p 〈 0.001) groups. In comparison to the synovial fluid CFU enumerated from the CONT group (mean, 3.3 × 10; SD, 6.0 × 10), lower synovial CFU were reported for both the STIM + VANCO group (mean, 4.6 × 10; SD, 1.2 × 10; 95% CI of difference, −4.9 × 10 to −3.0 × 10; p 〈 0.001) and the VANCO group (mean, 6.8 × 10; SD, 9.2 × 10; 95% CI of difference, −4.9 × 10 to −2.8 × 10; p = 0.007). The histological analysis showed no discernable deleterious effects on the surrounding tissue as a result of the treatments. No brittle fracture occurred during mechanical testing and with the numbers available, no differences in implant flexural yield strength were detected between the groups. CONCLUSIONS: In this rodent model, cathodic voltage-controlled electrical stimulation combined with vancomycin is an effective treatment for titanium implant-associated infections showing greater than 99.8% reduction in bacterial burden on the implant, surrounding bone, and synovial fluid as compared with the controls and the stimulation alone groups. CLINICAL RELEVANCE: Cathodic voltage-controlled electrical stimulation combined with vancomycin may enable successful treatment of titanium orthopaedic implant-associated infections with implant retention. Future studies will focus on optimization of the stimulation parameters for complete eradication of infection and the ability to promote beneficial host tissue responses.
    Keywords: Staphylococcus Aureus Infections – Care and Treatment ; Staphylococcus Aureus Infections – Analysis ; Staphylococcus Aureus Infections – Health Aspects ; Vancomycin – Analysis ; Vancomycin – Health Aspects ; Staphylococcus Aureus – Analysis ; Staphylococcus Aureus – Health Aspects ; Microbial Drug Resistance – Care and Treatment ; Microbial Drug Resistance – Analysis ; Microbial Drug Resistance – Health Aspects;
    ISSN: 0009-921X
    E-ISSN: 15281132
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  • 2
    Language: English
    In: Clinical Orthopaedics and Related Research®, 2016, Vol.474(7), pp.1668-1675
    Description: To access, purchase, authenticate, or subscribe to the full-text of this article, please visit this link: http://dx.doi.org/10.1007/s11999-016-4705-7 Byline: Scott R. Nodzo (1), Menachem Tobias (1), Richard Ahn (1), Lisa Hansen (2), Nicole R. Luke-Marshall (2), Craig Howard (1), Linda Wild (3), Anthony A. Campagnari (2), Mark T. Ehrensberger (4) Abstract: Background Cathodic voltage-controlled electrical stimulation (CVCES) of titanium implants, either alone or combined with a short course of vancomycin, has previously been shown to reduce the bone and implant bacterial burden in a rodent model of methicillin-resistant Staphylococcus aureus (MRSA) implant-associated infection (IAI). Clinically, the goal is to achieve complete eradication of the IAI therefore, the rationale for the present study was to evaluate the antimicrobial effects of combining CVCES with prolonged antibiotic therapy with the goal of decreasing the colony-forming units (CFUs) to undetectable levels. Questions/purposes (1) In an animal MRSA IAI model, does combining CVCES with prolonged vancomycin therapy decrease bacteria burden on the implant and surrounding bone to undetectable levels? (2) When used with prolonged vancomycin therapy, are two CVCES treatments more effective than one? (3) What are the longer term histologic effects (inflammation and granulation tissue) of CVCES on the surrounding tissue? Methods Twenty adult male Long-Evans rats with surgically placed shoulder titanium implants were infected with a clinical strain of MRSA (NRS70). One week after infection, the rats were randomly divided into four groups of five: (1) VANCO: only vancomycin treatment (150 mg/kg, subcutaneous, twice daily for 5 weeks) (2) VANCO + 1STIM: vancomycin treatment (same as the VANCO group) coupled with one CVCES treatment (-1.8 V for 1 hour on postoperative day [POD] 7) (3) VANCO + 2STIM: vancomycin treatment (same as the VANCO group) coupled with two CVCES treatments (-1.8 V for 1 hour on POD 7 and POD 21) or (4) CONT: no treatment. On POD 42, the implant, bone, and peripheral blood were collected for CFU enumeration and histological analysis, where we compared CFU/mL on the implants and bone among the groups. A pathologist, blinded to the experimental conditions, performed a semiquantitative analysis of inflammation and granulation tissue present in serial sections of the humeral head for animals in each experimental group. Results The VANCO + 1STIM decreased the implant bacterial burden (median = 0, range = 0--10 CFU/mL) when compared with CONT (median = 5.7 x 10.sup.4, range = 4.0 x 10.sup.3-8.0 x 10.sup.5 CFU/mL difference of medians = -5.6 x 10.sup.4 p 〈 0.001) and VANCO (median = 4.9 x 10.sup.3, range = 9.0 x 10.sup.2-2.1 x 10.sup.4 CFU/mL difference of medians = -4.9 x 10.sup.3 p 〈 0.001). The VANCO + 1STIM decreased the bone bacterial burden (median = 0, range = 0--0 CFU/mL) when compared with CONT (median = 1.3 x 10.sup.2, range = 0--9.4 x 10.sup.2 CFU/mL difference of medians = -1.3 x 10.sup.2 p 〈 0.001) but was not different from VANCO (median = 0, range = 0--1.3 x 10.sup.2 CFU/mL difference of medians = 0 p = 0.210). The VANCO + 2STIM group had implant CFU (median = 0, range = 0--8.0 x 10.sup.1 CFU/mL) and bone CFU (median = 0, range = 0--2.0 x 10.sup.1 CFU/mL) that were not different from the VANCO + 1STIM treatment group implant CFU (median = 0, range = 0--10 CFU/mL difference of medians = 0 p = 0.334) and bone CFU (median = 0, range = 0--0 CFU/mL difference of medians = 0 p = 0.473). The histological analysis showed no deleterious effects on the surrounding tissue as a result of the treatments. Conclusions Using CVCES in combination with prolonged vancomycin resulted in decreased MRSA bacterial burden, and it may be beneficial in treating biofilm-related implant infections. Clinical Relevance CVCES combined with clinically relevant lengths of vancomycin therapy may be a treatment option for IAI and allow for component retention in certain clinical scenarios. However, more animal research and human trials confirming the efficacy of this approach are needed before such a clinical recommendation could be made. Author Affiliation: (1) Department of Orthopedics, State University of New York at Buffalo, Buffalo, NY, USA (2) Department of Microbiology and Immunology, State University of New York at Buffalo, Buffalo, NY, USA (3) Department of Pathology and Anatomical Sciences, State University of New York at Buffalo, Buffalo, NY, USA (4) Department of Biomedical Engineering, State University of New York at Buffalo, 162 Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA Article History: Registration Date: 08/01/2016 Online Date: 22/01/2016 Article note: The institution of one or more of the authors (MTE) has received, during the study period, funding from the Congressionally Directed Medical Research Program, Peer Reviewed Orthopedic Research Program, and the Bruce Holm Memorial Catalyst Fund. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research [R] editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research [R] neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDA-approval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research. A comment to this article is available at http://dx.doi.org/10.1007/s11999-016-4744-0.
    Keywords: Vancomycin – Health Aspects ; Vancomycin – Analysis;
    ISSN: 0009-921X
    E-ISSN: 1528-1132
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  • 3
    Language: English
    In: Journal of Developmental and Physical Disabilities, 2017, Vol.29(2), pp.341-351
    Description: The present study sought to examine the relationships between two language assessments and a psychometrically validated adaptive behavior scale. The assessments evaluated included the Promoting the Emergence of Advanced Knowledge Relational Training System - Direct Training Module (PEAK-DT), the Assessment of Basic Language and Learning Skills – Revised (ABLLS-R), and the Vineland Adaptive Behavior Scales, second edition (VABS-II). The assessments were completed for 21 children diagnosed with autism. Results indicate a significant correlation between scores on the PEAK-DT and ABLLS-R ( r  = 0.951, p  〈 0.001, PEAK-DT and VABS-II ( r  = 0.453, p 〈 .05 ), as well as the ABLLS-R and VABS-II ( r  = 0.563, p  〈 0.05). The results did not indicate any ceiling effects amongst any of the assessments. These results extend research on the psychometric properties of these assessment tools and provide implications for practitioner choice of curricula.
    Keywords: Autism ; Assessment ; Curriculum guide ; Peak ; ABLLS-R ; VABS-ii
    ISSN: 1056-263X
    E-ISSN: 1573-3580
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  • 4
    Language: English
    In: Molecular Neurobiology, 2018, Vol.55(2), pp.1795-1813
    Description: Lipids are essential components of the nervous system. However, the functions of very long-chain fatty acids (VLC-FA; ≥ 28 carbons) in the brain are unknown. The enzyme ELOngation of Very Long-chain fatty acids-4 (ELOVL4) catalyzes the rate-limiting step in the biosynthesis of VLC-FA (Agbaga et al., Proc Natl Acad Sci USA 105(35): 12843–12848, 2008; Logan et al., J Lipid Res 55(4): 698–708, 2014), which we identified in the brain as saturated fatty acids (VLC-SFA). Homozygous mutations in ELOVL4 cause severe neuropathology in humans (Ozaki et al., JAMA Neurol 72(7): 797–805, 2015; Mir et al., BMC Med Genet 15: 25, 2014; Cadieux-Dion et al., JAMA Neurol 71(4): 470–475, 2014; Bourassa et al., JAMA Neurol 72(8): 942–943, 2015; Aldahmesh et al., Am J Hum Genet 89(6): 745–750, 2011) and are post-natal lethal in mice (Cameron et al., Int J Biol Sci 3(2): 111–119, 2007; Li et al., Int J Biol Sci 3(2): 120–128, 2007; McMahon et al., Molecular Vision 13: 258–272, 2007; Vasireddy et al., Hum Mol Genet 16(5): 471–482, 2007) from dehydration due to loss of VLC-SFA that comprise the skin permeability barrier. Double transgenic mice with homozygous knock-in of the Stargardt-like macular dystrophy (STDG3; 797-801_AACTT) mutation of Elovl4 with skin-specific rescue of wild-type Elovl4 expression ( S + Elovl4 mut/mut mice) develop seizures by P19 and die by P21. Electrophysiological analyses of hippocampal slices showed aberrant epileptogenic activity in S + Elovl4 mut/mut mice. FM1-43 dye release studies showed that synapses made by cultured hippocampal neurons from S + Elovl4 mut/mut mice exhibited accelerated synaptic release kinetics. Supplementation of VLC-SFA to cultured hippocampal neurons from mutant mice rescued defective synaptic release to wild-type rates. Together, these studies establish a critical, novel role for ELOVL4 and its VLC-SFA products in regulating synaptic release kinetics and epileptogenesis. Future studies aimed at understanding the molecular mechanisms by which VLC-SFA regulate synaptic function may provide new targets for improved seizure therapies.
    Keywords: ELOVL4 ; Very long-chain saturated fatty acids ; Synaptic vesicle fusion kinetics ; Synaptic dysregulation ; Seizure ; Brain lipids
    ISSN: 0893-7648
    E-ISSN: 1559-1182
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