43 research outputs found

    Servant or Service? The Problem and a Conceptual Solution

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    The present article addresses issues within U.S. collegiate sport as it pertains to the physical preparation and health and well-being of intercollegiate athletes. Specifically, the sport coach is often perceived as “all knowing” about every facet of their sport when, in fact, they typically are not formally educated or well-trained in current methods of enhancing sport performance. Often strength and conditioning coaches, who may also be poorly trained, are tied directly (financially and administratively) to the sport coach—a situation which has led to a subservient role heavily influenced by the wishes of the sport coach. This has unfortunately resulted in the multidimensional well-being of the athlete clearly not being a primary objective in many programs

    Significance of intraoperative testing in right-sided implantable cardioverter-defibrillators

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    BACKGROUND: Implantation of implantable cardioverter-defibrillators (ICD) from the left pectoral region is the standard therapeutical method. Increasing numbers of system revisions due to lead dysfunction and infections will consecutively increase the numbers of right-sided implantations. The reliability of devices implanted on the right pectoral side remains controversially discussed, and the question of testing these devices remains unanswered. METHODS: In a prospectively designed study all 870 patients (60.0 ± 14  years, 689 male) who were treated with a first ICD from July 2005 until May 2012 and tested intraoperatively according to the testing protocol were analyzed. The indication for implantation was primary prophylactic in 71.5%. Underlying diseases included ischemic cardiomyopathy (50%), dilative cardiomyopathy (37%), and others (13%). Mean ejection faction was 27 ± 12%. Implantation site was right in 4.5% and left in 95.5%. RESULTS: Five patients supplied with right-sided ICD (13%, p = 0.02 as compared to left-sided) failed initial intraoperative testing with 21 J. 3 patients were male. The age of the patients failing intraoperative testing with right-sided devices appeared higher than of patients with left-sided devices (p = 0.07). The ejection fraction was 28 ± 8%. All patients reached a sufficient DFT ≤ 21 J after corrective procedures. CONCLUSION: Implantation of ICDs on the right side results in significantly higher failure rate of successful termination of intraoperatively induced ventricular fibrillation. The data of our study suggest the necessity of intraoperative ICD testing in right-sided implanted ICDs

    Broad-Spectrum Antiherpes Activities of 4-Hydroxyquinoline Carboxamides, a Novel Class of Herpesvirus Polymerase Inhibitors

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    Through broad screening of the compound library at Pharmacia, a naphthalene carboxamide was identified as a nonnucleoside inhibitor of human cytomegalovirus (HCMV) polymerase. Structure-activity relationship studies demonstrated that a quinoline ring could be substituted for naphthalene, resulting in the discovery of a 4-hydroxyquinoline-3-carboxamide (4-HQC) class of antiviral agents with unique biological properties. In vitro assays with the 4-HQCs have demonstrated potent inhibition of HCMV, herpes simplex virus type 1 (HSV-1), and varicella-zoster virus (VZV) polymerases but no inhibition of human α, δ, and γ polymerases. Antiviral cell culture assays have further confirmed that these compounds are active against HCMV, HSV-1, HSV-2, VZV, and many animal herpesviruses. However, these compounds were not active against several nonherpesviruses representing different DNA and RNA virus families. A strong correlation between the viral DNA polymerase and antiviral activity for this class of compounds supports inhibition of the viral polymerase as the mechanism of antiviral activity. Northern blot analysis of immediate-early and late viral transcripts also pointed to a block in the viral life cycle consistent with inhibition of viral DNA replication. In vitro HCMV polymerase assays indicate that the 4-HQCs are competitive inhibitors of nucleoside binding. However, no cross-resistance could be detected with ganciclovir-resistant HCMV or acyclovir-resistant HSV-1 mutants. The unique, broad-spectrum activities of the 4-HQCs may offer new opportunities for treating many of the diseases caused by herpesviruses

    Global immune fingerprinting in glioblastoma patient peripheral blood reveals immune-suppression signatures associated with prognosis

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    Glioblastoma (GBM) remains uniformly lethal, and despite a large accumulation of immune cells in the microenvironment, there is limited antitumor immune response. To overcome these challenges, a comprehensive understanding of GBM systemic immune response during disease progression is required. Here, we integrated multiparameter flow cytometry and mass cytometry TOF (CyTOF) analysis of patient blood to determine changes in the immune system among tumor types and over disease progression. Utilizing flow cytometry analysis in a cohort of 259 patients ranging from benign to malignant primary and metastatic brain tumors, we found that GBM patients had a significant elevation in myeloid-derived suppressor cells (MDSCs) in peripheral blood but not immunosuppressive Tregs. In GBM patient tissue, we found that increased MDSC levels in recurrent GBM portended poor prognosis. CyTOF analysis of peripheral blood from newly diagnosed GBM patients revealed that reduced MDSCs over time were accompanied by a concomitant increase in DCs. GBM patients with extended survival also had reduced MDSCs, similar to the levels of low-grade glioma (LGG) patients. Our findings provide a rationale for developing strategies to target MDSCs, which are elevated in GBM patients and predict poor prognosis
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