Miami Veterans Affairs Healthcare System

Miami, FL, United States

Miami Veterans Affairs Healthcare System

Miami, FL, United States
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Presynaptic short-term plasticity (STP) dynamically modulates synaptic strength in a reversible manner on a timescale of milliseconds to minutes. For low basal vesicular release probability (prob0), four components of enhancement, F1 and F2 facilitation, augmentation (A), and potentiation (P), increase synaptic strength during repetitive nerve activity. For release rates that exceed the rate of replenishment of the readily releasable pool (RRP) of synaptic vesicles, depression of synaptic strength, observed as a rundown of postsynaptic potential amplitudes, can also develop. To understand the relationship between enhancement and depression at the frog (Rana pipiens) neuromuscular synapse, data obtained over a wide range of prob0 using patterned stimulation are analyzed with a hybrid model to reveal the components of STP. We find that F1, F2, A, P, and depletion of the RRP all contribute to STP during repetitive nerve activity at low prob0. As prob0 is increased by raising Ca2+o (extracellular Ca2+), specific components of enhancement no longer contribute, with first P, then A, and then F2 becoming undetectable, even though F1 continues to enhance release. For levels of prob0 that lead to appreciable depression, only F1 and depletion of the RRP contribute to STP during rundown, and for low stimulation rates, F2 can also contribute. These observations place prob0-dependent limitations on which components of enhancement contribute to STP and suggest some fundamental mechanistic differences among the components. The presented model can serve as a tool to readily characterize the components of STP over wide ranges of prob0. © 2011 the authors.

Gauthier T.P.,Miami Veterans Affairs Healthcare System | Sherman E.M.,Nova Southeastern University | Unger N.R.,Nova Southeastern University
American Journal of Pharmaceutical Education | Year: 2015

Objective. To implement an antimicrobial stewardship (AS) elective course for second-year and thirdyear pharmacy students and to assess its impact on students’ perceptions regarding the application of AS principles. Design. A 2-credit elective course focusing on principles of AS incorporated prelecture didactic recordings with primary literature and guideline-based reading assignments, in-class active-learning group work and student-led presentations, and student-generated examination items. Assessment. Perceptions were assessed by precourse and postcourse survey items. Graded course assessments included completion of preclass assignments (readings, prerecorded lecture and writing assessment items), in-class active participation and group presentations, a midpoint examination, and a final examination. Conclusion. An AS-themed elective course in a doctor of pharmacy curriculum incorporating preclass, self-directed learning and in-class group-based active-learning strategies positively impacted students’ perceived understanding of AS strategies. © 2015, American Association of Colleges of Pharmacy. All rights reserved.

Gaunaurd I.,Miami Veterans Affairs Healthcare System
Prosthetics and orthotics international | Year: 2011

Postural asymmetries are thought to lead to impairment of body structure and function such as muscle imbalance, gait asymmetry and possible chronic conditions, which result in limitation of mobility and restriction of daily activity for transfemoral amputees (TFAs). Despite the potential clinical impact, postural asymmetries have not been confirmed or quantified in TFAs. To identify the presence of postural asymmetries in TFAs utilizing clinical evaluation measures. An observational cross-sectional study in which participants were evaluated at a single time point without intervention or follow-up. Forty-seven unilateral TFAs were measured for standing limb length, pelvic innominate inclination (PII), lateral trunk flexion and hip extension. Limb length discrepancy was present in 66% of participants and 57% had a short prosthetic limb. PII was greater than has been reported in the literature, and the shorter the prosthetic lower limb, the greater the PII on the amputated side (r = -0.422, p = 0.004). Limb length discrepancy and decreased lateral trunk flexion accounted for 26% of the variance in amputated side PII. Three postural measurements, namely leg length, pelvic innominate inclination and hip extension, were found to differ between the intact and amputated limb in this study sample. Clinicians should include postural assessment as part of their routine evaluation of TFAs in an effort to achieve postural symmetry and reduce the risk of chronic conditions associated with impairment of body structure and function.

Kanashiro-Takeuchi R.M.,University of Miami | Schulman I.H.,University of Miami | Schulman I.H.,Miami Veterans Affairs Healthcare System | Hare J.M.,University of Miami
Journal of Molecular and Cellular Cardiology | Year: 2011

Cell-based therapy is emerging as an exciting potential therapeutic approach for cardiac regeneration following myocardial infarction (MI). As heart failure (HF) prevalence increases over time, development of new interventions designed to aid cardiac recovery from injury are crucial and should be considered more broadly. In this regard, substantial efforts to enhance the efficacy and safety of cell therapy are continuously growing along several fronts, including modifications to improve the reprogramming efficiency of inducible pluripotent stem cells (iPS), genetic engineering of adult stem cells, and administration of growth factors or small molecules to activate regenerative pathways in the injured heart. These interventions are emerging as potential therapeutic alternatives and/or adjuncts based on their potential to promote stem cell homing, proliferation, differentiation, and/or survival. Given the promise of therapeutic interventions to enhance the regenerative capacity of multipotent stem cells as well as specifically guide endogenous or exogenous stem cells into a cardiac lineage, their application in cardiac regenerative medicine should be the focus of future clinical research. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure.". © 2011 Elsevier Ltd.

Schulman I.H.,University of Miami | Schulman I.H.,Miami Veterans Affairs Healthcare System | Hare J.M.,University of Miami
Biochimica et Biophysica Acta - General Subjects | Year: 2012

Background: Nitric oxide (NO), a highly versatile signaling molecule, exerts a broad range of regulatory influences in the cardiovascular system that extends from vasodilation to myocardial contractility, angiogenesis, inflammation, and energy metabolism. Considerable attention has been paid to deciphering the mechanisms for such diversity in signaling. S-nitrosylation of cysteine thiols is a major signaling pathway through which NO exerts its actions. An emerging concept of NO pathophysiology is that the interplay between NO and reactive oxygen species (ROS), the nitroso/redox balance, is an important regulator of cardiovascular homeostasis. Scope of review: ROS react with NO, limit its bioavailability, and compete with NO for binding to the same thiol in effector molecules. The interplay between NO and ROS appears to be tightly regulated and spatially confined based on the co-localization of specific NO synthase (NOS) isoforms and oxidative enzymes in unique subcellular compartments. NOS isoforms are also in close contact with denitrosylases, leading to crucial regulation of S-nitrosylation. Major conclusions: Nitroso/redox balance is an emerging regulatory pathway for multiple cells and tissues, including the cardiovascular system. Studies using relevant knockout models, isoform specific NOS inhibitors, and both in vitro and in vivo methods have provided novel insights into NO- and ROS-based signaling interactions responsible for numerous cardiovascular disorders. General significance: An integrated view of the role of nitroso/redox balance in cardiovascular pathophysiology has significant therapeutic implications. This is highlighted by human studies where pharmacologic manipulation of oxidative and nitrosative pathways exerted salutary effects in patients with advanced heart failure. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation. © 2011 Published by Elsevier B.V.

Brescian N.E.,Eastern Colorado Veterans Affairs Healthcare System | Curiel R.E.,University of Miami | Gass C.S.,Miami Veterans Affairs Healthcare System
Neurocase | Year: 2014

This is a case study of an 88-year-old man who presented with agenesis of the corpus callosum and colpocephaly. Symptomatically, he reported a sudden onset of mild, intermittent left hand apraxia, but denied any previous manifestations consistent with this type of brain malformation. The patient underwent neuroimaging, evaluation by neurology, and comprehensive neuropsychological testing to determine the nature of any other associated impairments. Test results indicated that he was, with a few exceptions, neuropsychologically normal. He performed well on tests that are highly sensitive to acquired brain dysfunction. His most notable deficit was failed performance in the simultaneous and coordinated use of both hands in using tactile and proprioceptive feedback on the Tactual Performance Test. This case is discussed in terms of plasticity of the developing brain, including compensatory mechanisms, highlighting the variability in clinical outcome in the context of congenital brain malformation. This case study illustrates the strong influence of cerebral plasticity as well as a possible circumscribed manifestation of interhemispheric disconnection. © 2013 © 2013 Taylor & Francis.

Karantalis V.,University of Miami | Balkan W.,University of Miami | Schulman I.H.,University of Miami | Schulman I.H.,Miami Veterans Affairs Healthcare System | And 2 more authors.
American Journal of Physiology - Heart and Circulatory Physiology | Year: 2012

Although pharmacological and interventional advances have reduced the morbidity and mortality of ischemic heart disease, there is an ongoing need for novel therapeutic strategies that prevent or reverse progressive ventricular remodeling following myocardial infarction, the process that forms the substrate for ventricular failure. The development of cell-based therapy as a strategy to repair or regenerate injured tissue offers extraordinary promise for a powerful anti-remodeling therapy. In this regard, the field of cell therapy has made major advancements in the past decade. Accumulating data from preclinical studies have provided novel insights into stem cell engraftment, differentiation, and interactions with host cellular elements, as well as the effectiveness of various methods of cell delivery and accuracy of diverse imaging modalities to assess therapeutic efficacy. These findings have in turn guided rationally designed translational clinical investigations. Collectively, there is a growing understanding of the parameters that underlie successful cell-based approaches for improving heart structure and function in ischemic and other cardiomyopathies. © 2012 the American Physiological Society.

Schulman I.H.,University of Miami | Schulman I.H.,Miami Veterans Affairs Healthcare System | Hare J.M.,University of Miami
Regenerative Medicine | Year: 2012

A novel therapeutic strategy to prevent or reverse ventricular remodeling, the substrate for heart failure and arrhythmias following a myocardial infarction, is the use of cell-based therapy. Successful cell-based tissue regeneration involves a complex orchestration of cellular and molecular events that include stem cell engraftment and differentiation, secretion of anti-inflammatory and angiogenic mediators, and proliferation of endogenous cardiac stem cells. Recent therapeutic approaches involve bone marrow-derived mononuclear cells and mesenchymal stem cells, adipose tissue-derived stem cells, cardiac-derived stem cells and cell combinations. Clinical trials employing mesenchymal stem cells and cardiac-derived stem cells have demonstrated efficacy in infarct size reduction and regional wall contractility improvement. Regarding delivery methods, the safety of catheter-based, transendocardial stem cell injection has been established. These proof-of-concept studies have paved the way for ongoing pivotal trials. Future studies will focus on determining the most efficacious cell type(s) and/or cell combinations and the mechanisms underlying their therapeutic effects. © 2012 Future Medicine Ltd.

Suncion V.Y.,University of Miami | Schulman I.H.,University of Miami | Schulman I.H.,Miami Veterans Affairs Healthcare System | Hare J.M.,University of Miami
Stem Cells Translational Medicine | Year: 2012

Although the initial promise of cardiac cell-based therapy was based on the concept that stem cells engraft into diseased tissue and differentiate into beating cardiomyocytes, it is now clear that successful cell-based tissue repair involves a more complex orchestration of cellular and molecular events. Many lessons about successful tissue repair can be gleaned from the results of early-stage clinical trials. This body of work shows that cell-based therapy (with various cell sources and delivery methods) effectively prevents and reverses the remodeling process, the sine qua non of the myocardial injury reaction and anatomic substrate for subsequent clinical events. The potentially favorable remodeling responses to cell therapy have prompted a search for mechanisms of action beyond cell repopulation and guided future clinical trial design by providing more clear focus on pathophysiological endpoints signifying favorable responses to cell-based therapy. Perhaps the most important mechanistic insight is that endogenous stem/precursor cells have the potential to participate in tissue healing. With regard to the phenotype of cellular response, it is clear that parameters of remodeling, such as infarct size and ventricular dimensions, should be directly measured, thereby necessitating the use of sophisticated imaging modalities, such as cardiac magnetic resonance imaging or multidetector computed tomography. These new insights offer an optimistic outlook on the state of cell-based therapeutics for cardiac disease and suggest that pivotal clinical trials are warranted. Here, we review lessons learned from clinical trials and evaluate the choice and assessment of endpoints to best predict efficacy of cell therapy. ©AlphaMed Press.

Nole K.L.B.,University of Miami | Yim E.,University of Miami | Keri J.E.,University of Miami | Keri J.E.,Miami Veterans Affairs Healthcare System
Journal of the American Academy of Dermatology | Year: 2014

The rapid increase in the medical use of probiotics and prebiotics in recent years has confirmed their excellent safety profile. As immune modulators, they have been used in inflammatory skin conditions, such as atopic dermatitis. We review the literature regarding the use of probiotics and prebiotics in dermatology. Probiotics and prebiotics appear to be effective in reducing the incidence of atopic dermatitis in infants, but their role in atopic dermatitis treatment is controversial. Their role in acne, wound healing, and photoprotection is promising, but larger trials are needed before a final recommendation can be made.

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