Darpan I. Patel

Cytokine responses to acute and chronic exercise in multiple sclerosis

Regular exercise reduces functional loss associated with multiple sclerosis (MS). However, the impact of exercise on inflammatory mediators associated with disease activity remains relatively unexplored. The purpose of this study was to determine whether ambulatory MS subjects would respond similarly to aerobic cycle training compared with matched controls on circulating immune variables, interleukin (IL)-6, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma. Eleven MS and 11 non-MS control subjects (8 women and 3 men in both groups) matched in age, height, body mass, body fat, and peak O(2) uptake completed the study. Subjects completed 30 min of cycle ergometry at 60% of peak O(2) uptake, 3 day/wk for 8 wk. Plasma cytokine concentrations were determined before and after exercise at weeks 0, 4, and 8. MS and control subjects showed a similar cytokine responses to exercise. IL-6 at rest tended to decrease (P = 0.08) with training in both groups. Resting plasma TNF-alpha tended to be higher in MS compared with controls throughout the study (P = 0.08). MS subjects showed elevated resting TNF-alpha in MS at the end of the 8-wk program (P = 0.04), whereas resting TNF-alpha remained unchanged in controls (P > 0.05). Resting plasma IFN-gamma at rest was elevated in MS subjects (P = 0.008) and unchanged in controls at the end of the intervention (P > 0.05). The response of plasma IL-6, TNF-alpha, and IFN-gamma after a single bout of exercise was similar between MS and control subjects (P > 0.05). Additional research to understand the impact of exercise on immune variables in MS is warranted.

Effect of 10-day forced treadmill training on neurotrophic factors in experimental autoimmune encephalomyelitis.

The impact of exercise on disease progression in multiple sclerosis (MS) is unclear. In the present study, we evaluated the clinical effects of forced wheel running on rats induced with experimental autoimmune encephalomyelitis (EAE), a model of MS. Female Lewis rats (n = 40) were randomly assigned to 1 of 4 groups prior to inoculation: EAE exercise (EAE-Ex), EAE sedentary (EAE-Sed), control exercise (Con-Ex), or control sedentary (Con-Sed). Exercise training was composed of forced treadmill running at increasing intensity across 10 consecutive days. No significant differences in clinical disability were observed in the EAE groups at the conclusion of this study. Furthermore, no significant differences in brain mass were observed across groups. Analysis of brain tissue proteins revealed that tumour necrosis factor-α (TNF-α) concentrations were higher in both EAE groups compared with the control groups (p < 0.05); however, no significant differences were seen between the EAE-Ex and EAE-Sed groups. The Con-Ex group had lower whole-brain TNF-α compared with the Con-Sed group (p < 0.05). Nerve growth factor concentrations were greater in the EAE-Ex animals compared with both control groups (p < 0.05 for both). No differences were seen in brain-derived neurotrophic factor. Our results indicate that aerobic exercise can modulate the proteins associated with disability in EAE; however, further research is required to understand the total impact of exercise on EAE disability and disease progression.

Effect of aerobic interval training on serum IL-10, TNFα, and adipokines levels in women with multiple sclerosis: possible relations with fatigue and quality of life

PurposeMultiple sclerosis is associated with immune system dysfunction and chronic inflammation; however, possible relations between immunologic and metabolic factors and some psychological indexes such as fatigue and quality of life, especially in relation to exercise training, have not yet been investigated. The present study was designed to investigate the effect of aerobic interval training on interleukin-10/tumor necrosis factor ratio and adipokine (leptin and adiponectin) concentrations in women with multiple sclerosis. Furthermore, the relationship between these factors with fatigue and quality of life were assessed.MethodsForty women with multiple sclerosis (Expanded Disability Status Scale ≤3) were randomized into either a non-exercising control or training group. The training group performed 8-weeks of upper and lower limb aerobic interval training. Serum concentrations of tumor necrosis factorα, interleukin-10, leptin, and adiponectin were measured before and after the 8-week intervention. Moreover, antropometric measures and measures for fatigue and quality of life were determined at the onset of and after exercise training.ResultsThe results revealed that leptin and tumor necrosis factorα levels significantly decreased subsequent to the aerobic interval training. Although blood adiponectin levels considerably increased in the training group, interleukin-10 and interleukin-10/tumor necrosis factorα ratio underwent no substantial change after the exercise training. In addition, the aerobic interval training was associated with improvement in fatigue, quality of life, and maximal oxygen consumption.ConclusionsOur findings suggested that aerobic interval training can be an effective strategy for managing the immune system at least by its significant impact on inflammatory cytokines and adipokines levels in women with multiple sclerosis. Additionally, this positive impact improved fatigue and adipose tissue indicators.

Variations in Institutional Review Board Approval in the Implementation of an Improvement Research Study

The purpose of this paper is to report the variance in institutional review board (IRB) reviews as part of the implementation of a multisite, quality improvement study through the Improvement Science Research Network (ISRN) and recommend strategies successful in procuring timely IRB approval. Using correspondence documents as data sources, the level of review was identified and time to submission, time to approval, and time to study start were analyzed. Thirteen of the 14 IRBs conducted independent reviews of the project. Twelve IRBs approved the study through expedited review while two IRBs reviewed the project at a full board meeting. Lastly, 11 of the 14 sites required documented consent. The greatest delay in approval was seen early on in the IRB process with site PIs averaging 45.1 ± 31.8 days to submit the study to the IRB. IRB approvals were relatively quick with an average of 14 ± 5.7 days to approval. The delay in study submission may be attributed to a lack of clear definitions and differing interpretations of the regulations that challenge researchers.

Adopting Best Practices from Team Science in a Healthcare Improvement Research Network: The Impact on Dissemination and Implementation

Healthcare is a complex adaptive system, and efforts to improve through the implementation of best practice are well served by various interacting disciplines within the system. As a transdisciplinary model is new to clinicians, an infrastructure that creates academic-practice partnerships and builds capacity for scientific collaboration is necessary to test, spread, and implement improvement strategies. This paper describes the adoption of best practices from the science of team science in a healthcare improvement research network and the impact on conducting a large-scale network study. Key components of the research network infrastructure were mapped to a team science framework and evaluated in terms of their effectiveness and impact on a national study of nursing operations. Results from this study revealed an effective integration of the team science principles which facilitated the rapid collection of a large dataset. Implications of this study support a collaborative model for improvement research and stress a need for future research and funding to further evaluate the impact on dissemination and implementation.

Extracting the Benefit of Nexrutine® for Cancer Prevention

The current standard of care for prostate cancer includes hormone therapy, radiation therapy, and radical prostatectomy, each with its own set of undesirable side effects. In this regard, there is an unmet need to develop strategies that can prevent or delay the development of clinical prostate cancer. One potential area involves the use of natural compounds involving botanicals. Along these lines, we have found that Nexrutine®, a dietary supplement derived from Phellodendron amurense bark extract, has prostate cancer prevention activity. The “extract” nature of this botanical, which constitutes a blend of several active protoberberine alkaloids, allows it to target several pathways deregulated in prostate cancer simultaneously. In this review, we will emphasize the prospective translational benefit of Nexrutine® as a chemopreventive agent for prostate cancer management. The potential of Nexrutine® was first identified and has subsequently been most exhaustively studied with reference to prostate cancer. Therefore, the focus of this review is on the use of Nexrutine® in prostate cancer. In addition, we have summarized the emerging evidence regarding the use of Nexrutine® in other tumor models to demonstrate the potential benefits of Nexrutine®.

Advancing Care for Family Caregivers of persons with dementia through caregiver and community partnerships

BackgroundThere are currently 15 million Americans who provide over 80% of the care required by their family members with Alzheimer’s disease and other dementias. Yet care for caregivers continues to be fragmented and few evidence-based interventions have been translated into routine clinical care and therefore remain inaccessible to most family caregivers. To address this gap, the Caring for the Caregiver program is being developed at UT Health San Antonio, School of Nursing to improve support services and health outcomes for family caregivers. Our purpose is to describe the engagement process undertaken to assess caregiver and community needs and how findings are informing program development.MethodsWe are using a model of public engagement that consists of communication of information, collection of information from stakeholders, and collaboration where stakeholders are partners in an exchange of information to guide program activities. An assessment of the community was undertaken to identify resources/services for family caregivers. Subsequently, stakeholders were invited to a community-academic forum to discuss strategies to build on existing strengths for family caregiving and to identify gaps in care. Detailed notes were taken and all discussions were recorded and transcribed for analysis. Data were analyzed using thematic content analysis.ResultsWe conducted site visits with 15 community agencies, interviewed 13 family caregivers, and attended community events including support groups and health and senior fairs. Fifty-three diverse stakeholders attended the community-academic forum. Participants identified existing assets within our community to support family caregivers. Consistent among groups was the need to increase awareness in our community about family caregivers. Themes identified from the discussion were: making the invisible visible, you don’t know what you don’t know, learning too late, and anticipating and preparing for the future.ConclusionsIncorporating caregiver and community stakeholders was critical to ensure that the priorities of our community are addressed in a culturally responsive accessible program for family caregivers. The forum served as important mechanism to partner with the community and will be an annual event where we can continue to work with our stakeholders around needs for practice, education, and research.

Exercise-induced changes in neurotrophic factors and markers of blood-brain barrier permeability are moderated by weight status in multiple sclerosis

Blood-brain barrier (BBB) and neurotrophic factors seemingly have an important role in multiple sclerosis pathology. Physical activity may influence blood-brain barrier function and levels of neurotrophic factors, and such effects might be moderated by body weight status. This study investigated the effect of exercise training on markers of blood-brain barrier permeability and neurotrophic factors as a function of weight status in multiple sclerosis patients. Sixty three persons with relapsing remitting multiple sclerosis who were normal weight (n: 33) or overweight (n: 33) were randomly assigned into groups of exercise (normal weight training, n: 18; overweight training group, n: 18) or no exercise (normal weight control, n: 15; overweight control group, n: 15). The intervention consisted of 8 weeks (3 days per week) of cycling undertaken at 60-70% peak power. Resting blood concentrations of s100 calcium-binding protein B (s100b) and neuron-specific enolase as BBB permeability markers, neurotrophic factors and cytokines (Interleukin-10 and tumor necrosis factor alpha) were evaluated before and after the intervention. There were significant weight, training, and interaction effects on brain-derived neurotrophic factor and platelet-derived growth factor; however, ciliary neurotrophic factor and nerve growth factor did not demonstrate any effect. Brain-derived neurotrophic factor and platelet-derived growth factor were significantly increased from pre-post in normal weight exercise. Significant weight, training, and interaction effects were found for s100b. In detail, s100b was significantly increased from pre-post in normal weight exercise. In contrast, neuron-specific enolase and cytokines did not demonstrate any effect. Generally, Exercise training may alter markers of BBB permeability and neurotrophic factor status in normal weight persons with multiple sclerosis; however, overweight participants may be more resistant to these effects of exercise.

Nursing Research, CER, PICO and PCORI

Community and public health nurse researchers encompass a unique cohort of nurse researchers that have the skills and capacity to lead projects and programs of science centered on improvement of patient outcomes through methods of comparative effectiveness research (CER). CER, as a general method, has been taught to all nurses in the form of the PICO question to improve evidence-based practices. As the climate for funding becomes more and more competitive, nurse researchers are primed to lead the change in improving patient outcomes through patient centered outcomes research (PCOR). However, the number of projects funded by agencies like the Patient Centered Outcomes Research Institute, fall well below the capabilities of the field. The purpose of this commentary is to promote the field of PCOR and encourage novice and experienced nurse researchers to apply for funding from the PCORI by introducing different methods for building capacity and promoting engagement in the national conversations of PCOR and CER.

Effect of Short-Term Interval Exercise Training on Fatigue, Depression, and Fitness in Normal Weight vs. Overweight Person With Multiple Sclerosis

Context: Excessive weight is a health problem that can exacerbate multiple sclerosis (MS) symptoms and its associated comorbidities such as depression and fatigue. In addition, weight may be a moderator of exercise effects on depression and fatigue symptoms. Objective: This study aimed to investigate the effects of exercise training on fatigue and depression in normal and overweight individuals with MS. Methods: Sixty‐six persons with MS were randomly assigned into an exercise or control condition based on body weight status (overweight vs. normal weight). The exercise conditions involved 8‐weeks of interval exercise at 60%–75% Wattpeak, while the control condition did not involve any exercise. Fatigue, depression, aerobic capacity, time up and go (TUG) and body mass index were measured before and following the 8‐week period. Results: There were no significant relationships revealed for weight status interactions for any of the variables examined. There were significant condition main effects for fatigue, depression, aerobic capacity and TUG, and significant improvements were noted for the exercise conditions, but not in the non‐exercising control group. Conclusion: The results from this study confirm that exercise is an effective therapeutic intervention for improving fatigue, depression and functional parameters, independent of initial weight status, in persons with MS.