Advances in Imaging of Inflammation, Fibrosis, and Cancer in the Gastrointestinal Tract.

Gastrointestinal disease is prevalent and broad, manifesting itself in a variety of ways, including inflammation, fibrosis, infection, and cancer. However, historically, diagnostic technologies have exhibited limitations, especially with regard to diagnostic uncertainty. Despite development of newly emerging technologies such as optoacoustic imaging, many recent advancements have focused on improving upon pre-existing modalities such as ultrasound, computed tomography, magnetic resonance imaging, and endoscopy. These advancements include utilization of machine learning models, biomarkers, new technological applications such as diffusion weighted imaging, and new techniques such as transrectal ultrasound. This review discusses assessment of disease processes using imaging strategies for the detection and monitoring of inflammation, fibrosis, and cancer in the context of gastrointestinal disease. Specifically, we include ulcerative colitis, Crohn's disease, diverticulitis, celiac disease, graft vs. host disease, intestinal fibrosis, colorectal stricture, gastric cancer, and colorectal cancer. We address some of the most recent and promising advancements for improvement of gastrointestinal imaging, including unique discussions of such advancements with regard to imaging of fibrosis and differentiation between similar disease processes.

Pharmaceutical and Supply Waste in Oculofacial Plastic Surgery at a Hospital-Based Outpatient Surgery Center.

PURPOSE: To investigate the financial and environmental waste burden of unused disposable surgical supplies and pharmaceutical products in oculofacial plastic surgery at a hospital-based outpatient surgery center. METHODS: This descriptive study was performed at a single academic hospital-based outpatient surgery center. Unused pharmaceuticals and disposable surgical materials were recorded for each of 34 consecutive oculofacial plastic surgeries performed by the same surgical team. Pharmaceutical products were grouped as local anesthetic (tetracaine, bupivacaine, lidocaine, and sodium bicarbonate), intraoperative (basic saline solution, methylene blue, and oxymetazoline hydrochloride), or antiseptic/antimicrobial (erythromycin ointment and hydrogen peroxide). Percentage of unused pharmaceutical product and disposable surgical material were calculated and extrapolated to direct costs to the institution and greenhouse gas emissions. RESULTS: The mean percentage of disposable surgical supply waste per case was 11.6% ($29.32). The mean percentage of pharmaceutical waste was 96.1% ($271.84) for local anesthetic, 71.0% ($163.47) for intraoperative medications, and 26.7% ($2.19) for antiseptic medication. The mean emissions per surgical case for unused disposable surgical equipment and unused pharmaceutical product were 10 and 103 kg of carbon equivalent gases (kg CO2-e), respectively. CONCLUSIONS: Surgical supply waste was nominal, but pharmaceutical waste was considerable in this single hospital-based outpatient surgery center study. There may exist opportunities for quality improvement in waste, especially pharmacologic burden, in oculofacial plastic surgery.

Label-Free Electrochemical Sensor for Rapid Bacterial Pathogen Detection Using Vancomycin-Modified Highly Branched Polymers.

Rapid point of care tests for bacterial infection diagnosis are of great importance to reduce the misuse of antibiotics and burden of antimicrobial resistance. Here, we have successfully combined a new class of non-biological binder molecules with electrochemical impedance spectroscopy (EIS)-based sensor detection for direct, label-free detection of Gram-positive bacteria making use of the specific coil-to-globule conformation change of the vancomycin-modified highly branched polymers immobilized on the surface of gold screen-printed electrodes upon binding to Gram-positive bacteria. Staphylococcus carnosus was detected after just 20 min incubation of the sample solution with the polymer-functionalized electrodes. The polymer conformation change was quantified with two simple 1 min EIS tests before and after incubation with the sample. Tests revealed a concentration dependent signal change within an OD600 range of Staphylococcus carnosus from 0.002 to 0.1 and a clear discrimination between Gram-positive Staphylococcus carnosus and Gram-negative Escherichia coli bacteria. This exhibits a clear advancement in terms of simplified test complexity compared to existing bacteria detection tests. In addition, the polymer-functionalized electrodes showed good storage and operational stability.

In vitro experimental models for examining the skeletal muscle cell biology of exercise: the possibilities, challenges and future developments.

Exercise provides a cornerstone in the prevention and treatment of several chronic diseases. The use of in vivo exercise models alone cannot fully establish the skeletal muscle-specific mechanisms involved in such health-promoting effects. As such, models that replicate exercise-like effects in vitro provide useful tools to allow investigations that are not otherwise possible in vivo. In this review, we provide an overview of experimental models currently used to induce exercise-like effects in skeletal muscle in vitro. In particular, the appropriateness of electrical pulse stimulation and several pharmacological compounds to resemble exercise, as well as important technical considerations, are addressed. Each model covered herein provides a useful tool to investigate different aspects of exercise with a level of abstraction not possible in vivo. That said, none of these models are perfect under all circumstances, and the choice of model (and terminology) used should be informed by the specific research question whilst accounting for the several inherent limitations of each model. Further work is required to develop and optimise the current experimental models used, such as combination with complementary techniques during treatment, and thereby improve their overall utility and impact within muscle biology research.

Temperature-dependent structure and dynamics of highly-branched poly(N-isopropylacrylamide) in aqueous solution.

Small-angle neutron scattering (SANS) and neutron spin-echo (NSE) have been used to investigate the temperature-dependent solution behaviour of highly-branched poly(N-isopropylacrylamide) (HB-PNIPAM). SANS experiments have shown that water is a good solvent for both HB-PNIPAM and a linear PNIPAM control at low temperatures where the small angle scattering is described by a single correlation length model. Increasing the temperature leads to a gradual collapse of HB-PNIPAM until above the lower critical solution temperature (LCST), at which point aggregation occurs, forming disperse spherical particles of up to 60 nm in diameter, independent of the degree of branching. However, SANS from linear PNIPAM above the LCST is described by a model that combines particulate structure and a contribution from solvated chains. NSE was used to study the internal and translational solution dynamics of HB-PNIPAM chains below the LCST. Internal HB-PNIPAM dynamics is described well by the Rouse model for non-entangled chains.

Probing the Effect of Physiological Concentrations of IL-6 on Insulin Secretion by INS-1 832/3 Insulinoma Cells under Diabetic-Like Conditions.

Exercise improves insulin secretion by pancreatic beta cells (ß-cells) in patients with type 2 diabetes, but molecular mechanisms of this effect are yet to be determined. Given that contracting skeletal muscle causes a spike in circulating interleukin-6 (IL-6) levels during exercise, muscle-derived IL-6 is a possible endocrine signal associated with skeletal muscle to ß-cell crosstalk. Evidence to support a role of IL-6 in regulating the health and function of ß-cells is currently inconsistent and studies investigating the role of IL-6 on the function of ß-cells exposed to type 2 diabetic-like conditions are limited and often confounded by supraphysiological IL-6 concentrations. The purpose of this study is to explore the extent by which an exercise-relevant concentration of IL-6 influences the function of pancreatic ß-cells exposed to type 2 diabetic-like conditions. Using insulin-secreting INS-1 832/3 cells as an experimental ß-cell model, we show that 1-h IL-6 (10 pg/mL) has no effect on insulin secretion under normal conditions and does not restore the loss of insulin secretion caused by elevated glucose ± palmitate or IL-1ß. Moreover, treatment of INS-1 832/3 cells to medium collected from C2C12 myotubes conditioned with electrical pulse stimulation does not alter insulin secretion despite significant increases in IL-6. Since insulin secretory defects caused by diabetic-like conditions are neither improved nor worsened by exposure to physiological IL-6 levels, we conclude that the beneficial effect of exercise on ß-cell function is unlikely to be driven by muscle-derived IL-6.

The real-time fMRI neurofeedback based stratification of Default Network Regulation Neuroimaging data repository.

This data descriptor describes a repository of openly shared data from an experiment to assess inter-individual differences in default mode network (DMN) activity. This repository includes cross-sectional functional magnetic resonance imaging (fMRI) data from the Multi Source Interference Task, to assess DMN deactivation, the Moral Dilemma Task, to assess DMN activation, a resting state fMRI scan, and a DMN neurofeedback paradigm, to assess DMN modulation, along with accompanying behavioral and cognitive measures. We report technical validation from n=125 participants of the final targeted sample of 180 participants. Each session includes acquisition of one whole-brain anatomical scan and whole-brain echo-planar imaging (EPI) scans, acquired during the aforementioned tasks and resting state. The data includes several self-report measures related to perseverative thinking, emotion regulation, and imaginative processes, along with a behavioral measure of rapid visual information processing. Technical validation of the data confirms that the tasks deactivate and activate the DMN as expected. Group level analysis of the neurofeedback data indicates that the participants are able to modulate their DMN with considerable inter-subject variability. Preliminary analysis of behavioral responses and specifically self-reported sleep indicate that as many as 73 participants may need to be excluded from an analysis depending on the hypothesis being tested. The present data are linked to the enhanced Nathan Kline Institute, Rockland Sample and builds on the comprehensive neuroimaging and deep phenotyping available therein. As limited information is presently available about individual differences in the capacity to directly modulate the default mode network, these data provide a unique opportunity to examine DMN modulation ability in relation to numerous phenotypic characteristics.

Frictional properties of a polycationic brush.

The frictional behaviour of end-grafted poly[2-(dimethyl amino)ethyl methacrylate] films (brushes) has been shown by friction force microscopy to be a strong function of pH in aqueous solution. Data were acquired using bare silicon nitride and gold-coated tips, and gold coated probes that were functionalized by the deposition of self-assembled monolayers. At the extremes of pH (pH = 1, 2, and 12), the friction-load relationship was found to be linear, in agreement with Amontons' law of macroscopic friction. However, at intermediate pH values, the data were fitted by single asperity contact mechanics models; both Johnson-Kendall-Roberts (JKR) and Derjaguin-Muller-Toporov models were observed, with JKR behaviour fitting the data better at relatively neutral pH.

Development of a Web-based surgical booking and informed consent system to reduce the potential for error and improve communication.

BACKGROUND: The decision to perform an elective procedure often originates during an office visit between surgeon and patient. Several administrative tasks follow, including scheduling or "booking" of the case and obtaining informed consent. These processes require communicating accurate information regarding diagnosis, procedure, and other patient-specific details necessary for the safe and effective performance of an operation. Nonstandardized and paper-based consents pose difficulty with legibility, portability, and consistency, thereby representing a source of potential error and inefficiency. There are numerous barriers to efficiently booking elective surgical procedures and obtaining a legible, complete, and easily retrievable informed consent. An integrated Web-based booking and consent system was developed at a multisite university-affiliated community hospital system to improve the speed and quality of work flow, as well as communication with both the patients and staff. METHODS: A booking and consent system was developed and made available over the intranet. This customized system was created by leveraging existing information systems. RESULTS: The electronic consent system uses surgeon-specific templates and allows for a consistent approach to each procedure. A printed consent form can be generated at any time from any of the health care system's three campuses and is commonly stored in the electronic medical record. Integration into our perioperative system allows for coordination with the operating room staff, administrative personal, financial coordinators, and central supply. Total systems expenditure for development was estimated at $40,000 (US). CONCLUSIONS: Organizations considering standardizing their own consent and operating room booking processes can review this experience in making their own "make or buy" decision for their own settings.

SMALL-GAUGE TECHNIQUES FOR REMOVING A FLUOCINOLONE ACETONIDE IMPLANT.

PURPOSE: Long-acting injectable fluocinolone releasing implants are used in clinical practice. Although limited in scope, situations may arise where removal of the implant is warranted. We set out to describe possible explantation techniques and to determine whether these implants can be safely removed from a standard sclerotomy or eliminated using a vitrectomy system. METHODS: A vitreoretinal surgery system was designed using a porcine eye model. A fluocinolone implant was injected into the vitreous cavity. Pars plana vitrectomy was performed and the vitreous cavity was infused with balanced salt solution. The injected implants were removed from 23-Gauge (G) and 25-Gauge (G) vitrectomy cannulas with 27-G forceps. The implants were examined under the microscope for induced defects. Implants were injected into the eye model and eliminated using a 23-G and 25-G vitrector system. RESULTS: The implant was removed from both the 23-G and 25-G vitrectomy cannulas with only mild structural damage to the implant. During implant extraction through the 25-G sclerotomy, the cannula was dislodged from the incision along with the implant. The most technically challenging portion involved aligning the implant coaxially to allow for removal en bloc through the sclerotomy site. Implants could be eliminated using both the 23-G and 25-G vitrector using a low-cut rate. CONCLUSION: The fluocinolone implant was removed safely via standard 23-G or 25-G vitrectomy systems. It is unknown whether intraocular manipulation will affect pharmacokinetics of drug delivery if the implant is not explanted.

The Effect of Body Mass Index on the Creation of an End-Colostomy in Rectal Cancer Patients.

With the increasing prevalence of obesity, there has been a parallel increase in the incidence of rectal cancer. The association of body mass index (BMI) and end-colostomy creation versus primary anastomosis in patients undergoing proctectomy for rectal cancer has not been described. This is a retrospective study of patients with rectal cancer from 2012 to 2018 using data from the National Surgical Quality Improvement Project. 16,446 (92.1%) underwent primary anastomosis and 1,418 (7.9%) underwent creation of an end-colostomy. Patients with a BMI of 25-29.9 (overweight) comprised the most frequent group to have a proctectomy (reference group), but the least likely to have an end-colostomy. Patients with severe obesity (BMI 50+) had an adjusted odds ratio for end-colostomy of 2.7 (95% CI 1.5-4.7) compared to the reference group. Patients who have severe obesity should be counseled regarding the likelihood of an end-colostomy and may benefit from medical weight management or weight-loss surgery.

Risk Factors for Meibomian Gland Disease Assessed by Meibography.

Purpose: To elucidate risk factors for meibomian gland disease (MGD) and understand associated changes in meibography and in relation to ocular surface disease. Patients and Methods: As part of the standard workup for ocular surface disease at a tertiary academic center, 203 patients received an ocular history and lifestyle questionnaire. The questionnaire included detailed inquiries about ocular health and lifestyle, including makeup use, cosmetic eyelid procedures, screen time, and contact lens habits. Subjects also took the standardized patient evaluation of eye dryness (SPEED) II questionnaire. Meibomian gland (MG) dropout and structural changes were evaluated on meibography and scored by three independent graders using meiboscores. Statistical analysis was conducted to identify significant risk factors associated with MG loss. Results: This retrospective, cross-sectional study included 189 patients (378 eyes) with high-quality images for grading, and the average age was 67 years (77% female). Patients older than 45 years had significantly more dropout than younger patients (p < 0.01). Self-reported eye makeup use did not significantly impact MG loss. Patients with a history of blepharoplasty trended toward higher meiboscores, but the difference was not statistically significant. Self-reported screen time did not affect meiboscores. Contact lens use over 20 years was associated with significant MG loss (p < 0.05). SPEED II scores had no relationship to meiboscores (p = 0.75). Conclusion: Older age is a significant risk factor for MG loss. Any contact lens use over 20 years also impacted MG dropout. Highlighting the incongruence of symptoms to signs, SPEED II scores showed no relationship to the structural integrity of MGs.

Plasma FGF21 concentrations are regulated by glucose independently of insulin and GLP-1 in lean, healthy humans.

BACKGROUND: Fibroblast growth factor 21 (FGF21) treatment improves metabolic homeostasis in diverse species, including humans. Physiologically, plasma FGF21 levels increase modestly after glucose ingestion, but it is unclear whether this is mediated by glucose itself or due to a secondary effect of postprandial endocrine responses. A refined understanding of the mechanisms that control FGF21 release in humans may accelerate the development of small-molecule FGF21 secretagogues to treat metabolic disease. This study aimed to determine whether FGF21 secretion is stimulated by elevations in plasma glucose, insulin, or glucagon-like peptide-1 (GLP-1) in humans. METHODS: Three groups of ten healthy participants were included in a parallel-group observational study. Group A underwent a hyperglycemic infusion; Group B underwent a 40 mU/m2/min hyperinsulinemic euglycemic clamp; Group C underwent two pancreatic clamps (to suppress endogenous insulin secretion) with euglycemic and hyperglycemic stages with an infusion of either saline or 0.5 pmol/kg/min GLP-1. Plasma FGF21 concentrations were measured at baseline and during each clamp stage by ELISA. RESULTS: Plasma FGF21 was unaltered during hyperglycemic infusion and hyperinsulinemic euglycemic clamps, compared to baseline. FGF21 was, however, increased by hyperglycemia under pancreatic clamp conditions (P < 0.05), while GLP-1 infusion under pancreatic clamp conditions did not change circulating FGF21 levels. CONCLUSION: Increases in plasma FGF21 are likely driven directly by changes in plasma glucose independent of changes in insulin or GLP-1 secretion. Ecologically valid postprandial investigations are now needed to confirm our observations from basic science infusion models.

(-)-Epicatechin and its colonic metabolite hippuric acid protect against dexamethasone-induced atrophy in skeletal muscle cells.

Cocoa flavanols have been shown to improve muscle function and may offer a novel approach to protect against muscle atrophy. Hippuric acid (HA) is a colonic metabolite of (-)-epicatechin (EPI), the primary bioactive compound of cocoa, and may be responsible for the associations between cocoa supplementation and muscle metabolic alterations. Accordingly, we investigated the effects of EPI and HA upon skeletal muscle morphology and metabolism within an in vitro model of muscle atrophy. Under atrophy-like conditions (24h 100µM dexamethasone (DEX)), C2C12 myotube diameter was significantly greater following co-incubation with either 25µM HA (11.19±0.39µm) or 25µM EPI (11.01±0.21µm) compared to the vehicle control (VC; 7.61±0.16µm, both P < .001). In basal and leucine-stimulated states, there was a significant reduction in myotube protein synthesis (MPS) rates following DEX treatment in VC (P = .024). Interestingly, co-incubation with EPI or HA abrogated the DEX-induced reductions in MPS rates, whereas no significant differences versus control treated myotubes (CTL) were noted. Furthermore, co-incubation with EPI or HA partially attenuated the increase in proteolysis seen in DEX-treated cells, preserving LC3 α/ß II:I and caspase-3 protein expression in atrophy-like conditions. The protein content of PGC1α, ACC, and TFAM (regulators of mitochondrial function) were significantly lower in DEX-treated versus. CTL cells (all P < .050). However, co-incubation with EPI or HA was unable to prevent these DEX-induced alterations. For the first time we demonstrate that EPI and HA exert anti-atrophic effects on C2C12 myotubes, providing novel insight into the association between flavanol supplementation and favourable effects on muscle health.

An analysis of sexual dimorphism in the tumor microenvironment of colorectal cancer.

Women with colorectal cancer (CRC) have survival advantages over men, yet the underlying mechanisms are unclear. T cell infiltration within the CRC tumor microenvironment (TME) correlates strongly with survival. We hypothesized that women with CRC have increased T cell infiltration and differential gene expression in the TME compared to men. Tissue microarrays comprising primary tumor, tumor infiltrated lymph nodes, and uninvolved colon were created from CRC patients. Proportions of CD4 positive (CD4+) and CD8 positive (CD8+) T cells were identified using immunohistochemistry. TME immune- and cancer-related genetic expression from primary and metastatic CRC tumor were also evaluated via the NanoStringIO360 panel and The Cancer Genome Atlas Project database. CD4+ was higher in tumor samples from women compared to men (22.04% vs. 10.26%, p=0.002) and also in lymph node samples (39.54% vs. 8.56%, p=0.001). CD8+ was increased in uninvolved colon from women compared to men (59.40% vs. 43.61%, p=0.015), and in stage I/II tumors compared to III/IV in all patients (37.01% vs. 23.91%, p=0.009). Top CD8+ tertile patients survived longer compared to the bottom (43.9 months vs. 25.3 months, p=0.007). Differential gene expression was observed in pathways related to Treg function, T cell activity, and T cell exhaustion, amongst several others, in women compared to men. Thus, significant sexual dimorphism exists in the TME that could contribute to survival advantages observed in female patients with CRC.

Molecular Imaging of Inflammatory Disease.

Inflammatory diseases include a wide variety of highly prevalent conditions with high mortality rates in severe cases ranging from cardiovascular disease, to rheumatoid arthritis, to chronic obstructive pulmonary disease, to graft vs. host disease, to a number of gastrointestinal disorders. Many diseases that are not considered inflammatory per se are associated with varying levels of inflammation. Imaging of the immune system and inflammatory response is of interest as it can give insight into disease progression and severity. Clinical imaging technologies such as computed tomography (CT) and magnetic resonance imaging (MRI) are traditionally limited to the visualization of anatomical information; then, the presence or absence of an inflammatory state must be inferred from the structural abnormalities. Improvement in available contrast agents has made it possible to obtain functional information as well as anatomical. In vivo imaging of inflammation ultimately facilitates an improved accuracy of diagnostics and monitoring of patients to allow for better patient care. Highly specific molecular imaging of inflammatory biomarkers allows for earlier diagnosis to prevent irreversible damage. Advancements in imaging instruments, targeted tracers, and contrast agents represent a rapidly growing area of preclinical research with the hopes of quick translation to the clinic.

Exercise-Induced Improvements in Postprandial Glucose Response Are Blunted by Pre-Exercise Hyperglycemia: A Randomized Crossover Trial in Healthy Individuals.

Background: Exercise improves glycemic control but the magnitude, and in some cases, the direction of this effect is variable. Ambient hyperglycemia has been implicated in this exercise response heterogeneity. The current study investigated whether pre-exercise hyperglycemia directly impacts the effect of exercise on glycemic control. Methods: Twelve healthy normal glucose-tolerant males completed four trials in a randomized, crossover design. Each trial consisted of 24-h pre-intervention monitoring, a 7-h intervention, and 24-h post-intervention monitoring. Glycemic control was measured throughout the study by continuous glucose monitoring. The four interventions were no exercise (CON) or 45 min of cycling exercise (70%HRmax) preceded by 3.5 h of either normoglycemia (NG-Ex), steady-state hyperglycemia induced by constant glucose infusion (HG-Ex) or fluctuating glycemia induced by repeated glucose bolus infusions (FG-Ex). Results: Physical activity and diet were similar between trials, and energy expenditure during exercise was matched between exercise trials (all P > 0.05). Mean glucose during the 3.5 h ± infusion period was higher in HG-Ex (mean ± SEM; 7.2 ± 0.4 mmol/L) and FG-Ex (7.3 ± 0.3 mmol/L) compared to CON (4.8 ± 0.2 mmol/L) and NG-Ex (5.0 ± 0.2 mmol/L) trials (P < 0.01). Glycemic variability was greatest in FG-Ex (P < 0.01). Following the interventions, the postprandial glucose response (iAUC) was reduced by exercise in NG-Ex compared to CON (321.1 ± 38.6 vs. 445.5 ± 49.7 mmol/L.8h, P < 0.05, d=0.81). This benefit was blunted when exercise was preceded by steady-state (HG-Ex, 425.3 ± 45.7 mmol/L.8h) and fluctuating (FG-Ex, 465.5 ± 39.3 mmol/L.8h) hyperglycemia (both P > 0.05 vs. CON). Conclusion: Pre-exercise hyperglycemia blunted the glucoregulatory benefits of acute exercise upon postprandial glucose response, suggesting that exposure to hyperglycemia contributes to exercise response heterogeneity. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03284216.

A potential shift from adaptive immune activity to nonspecific inflammatory activation associated with higher depression symptoms in chronic heart failure patients.

BACKGROUND: Chronic heart failure (CHF) patients with elevated depression symptoms are at greater risk of morbidity and mortality. The mechanisms linking symptoms of depression with disease progression in CHF are unclear. However, research studies have found evidence of alterations in immune activity associated with depression symptoms that may influence heart function. The present study sought to determine the relationship between depression symptoms and chemotaxis of peripheral blood mononuclear cells (PBMCs) in CHF patients, both at rest and in response to moderate exercise. METHODS AND RESULTS: Sixty-five patients diagnosed with CHF (mean age, 59.8 +/- 14.5 years) and 45 non-CHF control subjects (mean age, 52.1 +/- 11.6) completed the Beck Depression Inventory (BDI) before undergoing a moderate 20-minute bicycle exercise task. Chemotaxis of PBMCs was examined in vitro to a bacterial peptide f-met leu phe (fMLP) and a physiologic chemokine, stromal cell derived factor-1 (SDF-1) immediately before and after exercise. CHF patients had reduced chemotaxis to SDF-1 (P = .025) compared with non-CHF subjects. Higher BDI scores were associated with reduced baseline chemotaxis to SDF-1 in both CHF and non-CHF subjects (P = .027). In contrast, higher BDI scores were associated with increased chemotaxis to fMLP (P = .049) and SDF-1 (P = .018) in response to exercise in the CHF patients. CONCLUSION: The present study suggests a shift in immune cell mobility in CHF patients with greater depression symptom severity, with reduced chemotaxis to a physiologically specific chemokine at rest but increased chemotaxis to both nonspecific and specific chemical attractants in response to physical activity. This could have implications for cardiac repair and remodeling in CHF patients and therefore may affect disease progression.