A Novel Mechanistic Model for Future Research in the Elements of the ERAS Program in Patients With Sickle Cell Disease.

Enhanced recovery after surgery (ERAS) is a patient-centered, evidence-based, multidisciplinary team-developed approach to a surgical stress response that is implemented to optimize physiological function and facilitate recovery for the best possible outcomes from surgery. Although there are currently well-known published guidelines for the perioperative management of patients with sickle cell disease, there are currently no specific and evidencebased ERAS protocols that address the needs of these patients. A novel mechanistic model has recently been found that could change ERAS protocols for patients with sickle cell disease with regard to a current preoperative carbohydrate loading drink recommendation, nutrition and intravenous fluid management. ERAS has great benefits for most patient populations, but emerging research suggests that patients with sickle cell disease may process and respond differently to varying concentrations of serum glucose and serum cations (hyperglycemia and hypertonic states). This adverse response involves actin, a cytoskeletal protein, in the red blood cell and how increased hemoglobin glycosylation may lead to a malfunction in this protein and a transition to vaso-occlusive crises in patients with sickle cell disease. Further research is warranted with this new mechanistic model to develop more meticulous and customized perioperative management plans to address risk mitigation in patients with sickle cell disease.

Cast Removal: Pearls and Methods.

Cast removal is a common procedure that can involve risks to the patient and should be done by a qualified and experienced provider. Indications for removal, assessment parameters, and careful procedural steps should be understood by all technicians, practitioners, and physicians who will participate in the removal of casting materials. Because this procedure can also produce anxiety for the patient and their family members, it is good practice to thoroughly inform the patient and answer any questions in advance to help reduce anxiety and promote cooperation from all during the process. This article describes common techniques for cast removal and provides tips to facilitate safe and efficient outcomes during this procedure.

Novel hydration and nutritional strategies for sickle cell disease.

Introduction: Sickle cell disease and sickle cell trait affect over 300 million people worldwide. Vaso-occlusive crises (VOCs) are the most common reason that these patients seek medical care. Objectives: Recently, a newly identified "trigger" (involving glucose and electrolytes) for a mechanism of abnormal actin polymerization may offer further understanding with regard to the sequence of events that cascade to complications such as VOCs in those with sickle cell disease (SCD) and as well as those with sickle cell trait. Methods: A literature review to identify the current standard of care guidelines for hydration and nutritional strategies during VOCs in patients with SCD and sickle cell trait was conducted in PubMed, OVID, and Google Scholar. Results: This review suggested that current rationales for hydration and nutritional strategies for these patients during periods of crisis are generally based on consensus and have remained largely undefined to date. Conclusion: This new trigger, along with this literature review, suggests investigations related to serum glucose and cation (electrolyte) levels may help define novel strategies for the development of protocols/standard of care with regard to intravenous and oral hydration/nutritional guidelines in these patients during both clinical and perioperative management periods.

Bio-Field Array: The Influence of Junction Mediating and Regulatory Protein Expression on Cytoskeletal Filament Behavior During Apoptosis in Triple-Negative Breast Cancer.

INTRODUCTION: The Bio-Field Array (BFA) is a device that generates a dielectrophoretic electromagnetic field (DEP-EMF) when placed in a hypotonic saline solution and a direct current (dc) of ~3 amperes is applied. Human triple-negative breast cancer (MDA-MB-231 cells) is known to have a high percentage of apoptotic (P53) deficient cells and some patients can have poor outcomes with current treatments. OBJECTIVES: Previously, we reported a strong upregulation of the apoptotic arm of the unfolded protein response, via reverse transcription-quantitative polymerase chain reaction (RT-qPCR), as well as positive annexin staining in this human breast carcinoma, when grown in media prepared with BFA's dc DEP-EMF treated saline. Here we will examine and discuss cytoskeletal microtubule changes that were noted in the treated breast carcinoma that are strongly suggestive of apoptosis and the possible correlation of these microtubule changes to the upregulation of Junction Mediating and Regulatory Protein (JMY, a P53/TP53 cofactor) that is known to drive cytoskeleton microfilaments (actin) function. METHODS: In addition to microarray and RT-qPCR analyses, we conducted 7 days of fluorescent microscopic analyses of tubulin assays in these treated versus control MDA-MB-231 cells. RESULTS: These data suggest 2 possible forms of apoptosis, rounded and irregular, may be occurring and possibly facilitated by the significant upregulation (via microarray and RT-qPCR) of an important but poorly understood Nucleation-Promoting Factor (NPF), JMY. CONCLUSIONS: The ability of the BFA dc DEP-EMF to significantly upregulate JMY and possibly influence the regulation of unbranched (nucleation-microtubule spikes) and branched forms (autophagy) of actin in the cytoplasmic domains may facilitate a "two coffins" or round and irregular necrosis-like apoptosis for this highly aggressive and often apoptotic-deficient breast cancer cell line.

The interaction of valine and glucose and the influence on the spectrin-actin complex in sickle cell disease.

Sickle cell disease (SCD), the most common severe monogenic disease in the world, is known for the hallmark vaso-occlusive crises that cause great suffering and degradation of health for these patients. In 1949, the discovery of the abnormal sickle cell hemoglobin protein (HbS) ß-globin chain revealed a mutation where glutamic acid is replaced with a valine (ß6Glu→Val). From this discovery came the pathophysiological mechanism based on the abnormal polymerization of deoxy-HbS. While an important discovery, this initial mechanism has yet been able to account for the cascade of events that trigger these crises and has therefore offered few treatment options for these patients. In red blood cells, alterations to membrane structure lead to changes in their biomechanical behaviors. A literature review has been conducted and a possible sickle cell pathophysiological mechanism that involves the potential for abnormal polymerization of the critical actin protein (in the spectrin-actin complex) within the red blood cell cytoskeleton has been identified. This review will discuss the interaction of valine and glucose on the HbS molecule and how it may lead to a destabilization of the HbS red blood cell cytoskeleton and SCD crises.

Modulation of endoplasmic reticulum stress and the unfolded protein response in cancerous and noncancerous cells.

OBJECTIVES: The bio-field array is a device that generates a dielectrophoretic electromagnetic field when placed in a hypotonic saline solution and a direct current of approximately 3 A is applied. It is known that cell physiology is guided by bioelectrical properties, and there is a significant growth inhibition in cancerous (MDA-MB-231) cells that are grown in media that has been reconstituted with the saline that has been exposed to the bio-field array direct current dielectrophoretic electromagnetic field, alternatively there is no growth inhibition noted in noncancerous cells (MCF-10A) when grown in the bio-field array direct current dielectrophoretic electromagnetic field treated versus control media. METHODS: To examine the basis for selective growth inhibition in human breast carcinoma, we employed cell death assays, cell cycle assays, microarray analysis and reverse transcription-quantitative polymerase chain reaction. RESULTS: We found a large transcriptional reprogramming in the cell lines and of the genes affected, those involved in endoplasmic reticulum stress and the unfolded protein response pathways showed some of the most dramatic changes. Cancerous cells grown in media that has been reconstituted with a hypotonic saline solution that has been exposed to the bio-field array direct current dielectrophoretic electromagnetic field show a significant and strong upregulation of the apoptotic arms of the unfolded protein response while the noncancerous cells show a decrease in endoplasmic reticulum stress via microarray analyses and reverse transcription-quantitative polymerase chain reaction. CONCLUSION: The bio-field array shows potential to initiate apoptosis in cancerous cells while relieving cell stress in noncancerous cells in vitro. These studies lay a foundation for nurses to conduct future in vivo models for the possible development of future adjunct treatments in chronic disease.

Bio-field array: a dielectrophoretic electromagnetic toroidal excitation to restore and maintain the golden ratio in human erythrocytes.

Erythrocytes must maintain a biconcave discoid shape in order to efficiently deliver oxygen (O2 ) molecules and to recycle carbon dioxide (CO2 ) molecules. The erythrocyte is a small toroidal dielectrophoretic (DEP) electromagnetic field (EMF) driven cell that maintains its zeta potential (ζ) with a dielectric constant (ԑ) between a negatively charged plasma membrane surface and the positively charged adjacent Stern layer. Here, we propose that zeta potential is also driven by both ferroelectric influences (chloride ion) and ferromagnetic influences (serum iron driven). The Golden Ratio, a function of Phi φ, offers a geometrical mathematical measure within the distinct and desired curvature of the red blood cell that is governed by this zeta potential and is required for the efficient recycling of CO2 in our bodies. The Bio-Field Array (BFA) shows potential to both drive/fuel the zeta potential and restore the Golden Ratio in human erythrocytes thereby leading to more efficient recycling of CO2 . Live Blood Analyses and serum CO2 levels from twenty human subjects that participated in immersion therapy sessions with the BFA for 2 weeks (six sessions) were analyzed. Live Blood Analyses (LBA) and serum blood analyses performed before and after the BFA immersion therapy sessions in the BFA pilot study participants showed reversal of erythrocyte rheological alterations (per RBC metric; P = 0.00000075), a morphological return to the Golden Ratio and a significant decrease in serum CO2 (P = 0.017) in these participants. Immersion therapy sessions with the BFA show potential to modulate zeta potential, restore this newly defined Golden Ratio and reduce rheological alterations in human erythrocytes.

Bio-electric field enhancement: the influence on hyaluronan mediated motility receptors in human breast carcinoma.

Mechanisms that regulate cancer cell metastasis are often intricately linked to mechanisms that control cell migration in wound repair. Hyaluronan Mediated Motility Receptor (HMMR) encodes a receptor for hyaluronan-mediated motility (RHAMM), a non-integral cell surface hyaluronan receptor and intracellular protein that promotes mitotic spindle formation and cell motility. RHAMM has been found to have increased expression in both cancers and wounds, and when cancers show increased RHAMM expression poor outcomes have occurred. Therefore, RHAMM has been shown to contribute to both natural healing mechanisms and cancer cell pathology. RHAMM is expressed in breast tissue and forms a polarity normalizing complex with BRCA1. Mutations of BRCA1 have been associated with a loss of apicobasal cell polarity along with a subsequent increased expression of RHAMM. Here we show how a human breast carcinoma cell line was maintained in media prepared with a dilute saline solution that had been exposed to a dielectrophoretic (DEP) electromagnetic field (EMF) generated by 3 amperes of direct current (dc) to a device housing an array of conductive rings. This Bio-electric Field Enhancement (BEFE) device has been available commercially for use in baths/footbaths since 1996 and consumers claim that it provides health benefits ranging from lowering blood pressure to faster wound healing. Our studies showed a significant inhibition of growth of human breast carcinoma MDA-MB-231 cells when they were maintained in media prepared with dc-DEP EMF force treated dilute saline while no growth inhibition occurred when the same cells were maintained in identically prepared but untreated media. Importantly, no growth inhibition was observed in human epithelial MCF-10A cells when grown in either treated or untreated media. Also, mitotic spindle formation was inhibited in the human breast carcinoma when they were grown in dc-DEP EMF force treated media. To determine if any gene expression changes contributed to the selective growth inhibition and absent mitotic spindle formation in the human breast carcinoma grown in the treated media, we employed microarray analysis and found that there was large-scale transcriptional reprogramming of the tumor cells grown in the treated media with over 1,000 genes up- or down-regulated over 2-fold, whereas the non-cancerous MCF-10A cells showed relatively modest changes in gene expression. Of the genes affected in the MDA-MB-231 cells, the significance of down-regulation of HMMR is discussed. The ability to enhance cell polarity through the application of this dc-DEP EMF force may offer another way to stabilize HMMR and differentially modulate its expression in cancerous and noncancerous cells.

The dielectrophoretic disassociation of chloride ions and the influence on diamagnetic anisotropy in cell membranes.

Chloride channels represent ubiquitously expressed proteins that regulate fundamental cellular processes including membrane potential, maintenance of intracellular pH, and regulation of cell volume. However, mechanisms to modulate this large family of ion channels have remained elusive to date. This large chloride channel family does not appear to operate with selectivity similar to the sodium and potassium channels. These unique channels appear to be bi-directional cotransporters of two or more different molecules or ions across a bilayer phospholipid membrane. Here we show how 3 amperes of direct current from a device that generates an electromagnetic field in a 3 mM hypotonic saline solution leads to a dielectrophoretic disassociation of the chloride ion from its chloro-metabolites transforming it into a polymorphic diamagnetically disassociated bio-chloride (bCl-). This field treated aqueous solution appears to continue to induce a magnetic moment change in solution for some hours when no longer under the influence of the direct current; for when this field influenced solution is used to reconstitute growth media of human breast carcinoma (MDA-MB-231) and human breast epithelial (MCF-10A) cells in vitro, significant changes in chloride ion channel expression, membrane potential, cell volume, and a massive transcriptional reprogramming of 2,468 genes expressions by Human Genome U133 Plus 2.0 Gene Chip Array (Affymetrix) analyses occur. We will highlight how the strong changes in chloride ion channel expression and cell physiology could be intricately linked to enhanced diamagnetic anisotropy in cell membranes that occur under the influence of this disassociated polymorphic bCl-.

Bioelectric Field Enhancement: The Influence on Membrane Potential and Cell Migration In Vitro.

Objective: The extracellular matrix consists of critical components that affect fibroblast polarization and migration. The existence of both intrinsic and extrinsic electrical signals that play essential roles in the development, physiology, regeneration, and pathology of cells was discovered over a century ago. In this study, we study how the Bioelectric Field Enhancement (BEFE) device and its generated electromagnetic field (EMF) by continuous direct current (DC) significantly affect the membrane potential and cell migration of fibroblasts in vitro. Approach: This is an experimental analysis of membrane potential and cell migration of murine fibroblasts when grown in treated media that has been reconstituted with an aqueous solution that has been exposed to an EMF, which is generated by this device versus fibroblasts grown in identically prepared control media that has not been exposed to the EMF. Results: The growth of fibroblasts in the treated media shows a strong percent change in polarization of the plasma membrane and significant increase in cell migration compared to control groups. Innovation: These experiments show the potential for an adjunct wound care therapy using a continuous DC EMF application through a medium of water. Conclusion: Growth media that was reconstituted with an aqueous solution that had been exposed to this DC derived EMF shows significant changes in cell polarity and cell migration of fibroblasts in vitro. The BEFE device has shown enhanced chronic wound healing in anecdotal reports from patients globally for decades when used as a footbath/bath and could lead to a novel EMF application in wound healing.

Bioelectrodynamics: A New Patient Care Strategy for Nursing, Health, and Wellness.

Bioelectrodynamics is an interdisciplinary subject that offers a pathway for nursing to develop a new patient care strategy in health care. The application of bioenergy to living organisms has the potential to advance medical science in the areas of prevention, cancer, wound care, pain, and many other chronic diseases.