Elevated PSA is associated with decreased physical function in men with prostate cancer

Studies have reported an association between cortisol and fatigue in multiple clinical populations, including prostate cancer (PCa). Treatment options for men with PCa, such as androgen deprivation therapy (ADT), come with a wide variety of adverse effects, including cancer-related fatigue, which greatly impacts quality of life (QoL). PURPOSE: Conduct a preliminary analysis on the association between cortisol, fatigue and QoL in men with PCa. METHODS: This study is part of an ongoing study to determine the impact of PCa and PCa treatment on fatigue and QoL approved by the University of Texas Health Science Center at San Antonio Intuitional Review Board. Twenty-one men (age: 69.1±11.55; BMI 28.99±4.78) with PCa were recruited from the Urology Clinic at the Medical Arts and Research Center in San Antonio, Texas. Participants provided ~2 mL of saliva for cortisol quantification using the passive drool technique. Saliva was immediately placed on ice and transferred within 4 hours to a freezer at -80oC until analysis. Cortisol was quantified using a commercially available salivary cortisol ELISA assay kit (Salimetrics, College Park, PA). Participants also completed three questionnaires: the Brief Fatigue Inventory, the Functional Assessment of Chronic Illness Therapy-Fatigue, and the SF-36. Pearson product moment correlation was performed to determine association between outcome variables. Student t-test was used to determine differences in cortisol, fatigue and QoL between men treated with ADT and men not treated with ADT. Significance was set at pRESULTS: Of the 21 participants, 9.5% (n=2) of participants had metastatic PCa, 4.8% (n=1) had castration-resistant PCa, 4.8% (n=1) had high-grade prostatic intraepithelial neoplasia, and 81% (n=17) had localized PCa. Twelve of the participants were being treated with ADT (57.14%). Significant correlation was observed between prostate specific antigen (PSA) and physical function (r=-0.728; p=.001), physical health (r=-0.729; p=.001), and emotional problems (r=-0.765; p=.001). No correlation was found between fatigue and cortisol levels. A comparison between groups revealed no significant difference in fatigue level between those on ADT versus those not on ADT. However, men not on ADT had a 28% higher average general health score. CONCLUSION: The results of this study suggest cortisol is not a strong physiological measure of fatigue in men with PCa. Furthermore, these preliminary data suggest that advanced cancer, as evident by elevated PSA, significantly impacts physical function and QoL in men with PCa. Further study for a more reliable biomarker of fatigue and interventions to improve QoL in men with PCa is warranted

COVID-19 Pandemic Effects on Individuals Physical Activity Levels and Emotional Health: A Descriptive Study

Texas is among one of the leading states of COVID-19 cases and fatalities which has impacted both healthy individuals and those living with preexisting chronic illnesses. Maintaining a healthy lifestyle and remaining physically active during a pandemic has challenged most, if not all, local residents. PURPOSE: to describe physical activity and mental health status in Texas residents with preexisting comorbidities and those without preexisting illnesses. METHODS: On July 2020, four months after the declaration of the global pandemic, an online survey was developed and distributed to various regions in Texas. A total of 156 respondents answered questions regarding their demographics, current health status, physical activity level, and mental health status prior to and after the COVID-19 pandemic declaration. A frequency distribution and descriptive statistical analyses was completed. A paired sample t-test was used to calculate means of responses pre- and post- the pandemic with significance level set at p\u3c0.05. RESULTS: Majority of respondents were white (84%), non Hispanic or Latino (54%), female (87%), under the age of 45 (57%) and reported having 1 or more diagnosed medical condition (61%). Physical activity levels were not significantly impacted in either subgroup. Although not significant, participants with 1 or more preexisting conditions decreased their activity level by 10% after declaration of the pandemic. Those without preexisting conditions increased their overall physical activity level by 9%. While physical activity level did not report significant changes after the COVID-19 pandemic, the psychological health of individuals, however, was significantly impacted. A significant increase in emotional distress such as feelings of nervousness and anxiousness were highly evident after the declared pandemic (p\u3c0.001). CONCLUSION: The present analysis confirms significant levels of stress after the declared current pandemic. Prolonged stress can lead to harm and disease and make a person more susceptible to infection which is why promoting physical activity and improving psychological health strategies for all Texas residents with emphasis to those with preexisting conditions should be a public health priority

Synergistic Effect of Exercise and Phellodendron Amurense on Muscle Mass Preservation in a Prostate Cancer Mouse Model

Muscle loss has detrimental effects on the body. It leads to a reduction in physical function, strength, endurance, and quality of life. In men with prostate cancer (PCa), a large percentage of men will suffer from muscle loss, a debilitating adverse effect caused by both the chronic illnesses or from the treatment of these illnesses. Studies have shown that the implementation of a routine exercise elicits muscle preservation in patients with PCa. Previously, our group has found that the natural product phellodendron amurense (PA) preserves muscle mass similar to exercise. PURPOSE: The purpose of this study is to test the hypothesis that combining PA and exercise will have a synergistic effect on muscle preservation and strength. METHOD: Twenty-four, 10-week-old transgenic adenocarcinoma of the mouse prostate (TRAMP) mice were randomized into one of four study groups: Exercise (running wheel) group, PA group, exercise plus PA, or no treatment control. PA was pelleted into the feed at a dose of 600 mg/kg and provided ad lib. Body mass was measured each week. Fore limb and all limb grip strength was measured at baseline and end of study (Columbus Instruments, Columbus, OH). Mice completed 10 repetitions on the apparatus with the first five repetitions using only the forelimbs and the last five repetitions using all four limbs. After euthanasia, the right gastrocnemius and soleus were collected, cleaned and weighted. One way and two-way analysis of variance was performed with tukey’s post-hoc test. Significance was set at pRESULTS: Analysis of body weight revealed significant differences between groups (F(3,20) = 2.93, P = 0.0311). Post hoc analysis revealed significantly lower body mass at the end of the study in the combination exercise plus PA group (25.83 ± 1.72 g) compared to the control group (28.70 ± 1.70 g; p=0.03). Higher soleus mass was found in the mice from the exercise only (11.6 ± 5 mg) and combination exercise plus PA (11.5 ± 3.271 mg) groups compared to the no treatment control group (10.33 ± 3.445 mg), however, these results did not reach significance. No statistical significance was found in the measurement of forelimb or all limb grip strength. CONCLUSION: Our initial hypothesis of synergy was not supported, however, there is preliminary evidence that exercise and PA independently reduces the loss of slow twitch skeletal muscle induced by cancer. Future research is required to validate these results

Effects of a Home-Based Exercise Program on Inflammatory Cytokines and Functional Capacity in Men with Prostate Cancer Under Active Surveillance

Regular exercise can improve physical fitness, functional performance, and quality of life in men with prostate cancer (PCa); however, few men with PCa meet national physical activity guidelines. Structured, home-based exercise programs may bridge this gap and increase physical activity in men with PCa. PURPOSE: This pilot study aimed to investigate the impact of a home-based exercise program on cytokines associated with tumor progression in men with PCa. METHODS: A single group, self-controlled study design was used. Fifteen men with PCa under active surveillance were recruited to complete 24 weeks of a home-based exercise program, combining aerobic and body-weight based exercises. The aerobic portion of the intervention included 5 days of light-to-moderate intensity walking for 30 minutes at 40-60% of the participant’s heart rate reserve as calculated using the Karvonen formula. Body-weight based exercises were performed 3 times per week consisting of 3 sets of 15 reps of bodyweight squats, inclined push-ups, and hip thrusts. Serum was collected at baseline and end of study to measure circulating eotaxin, interferon (IFN)γ, interleukin (IL)-12, IL-1a, IL-5, IL-6, tumor necrosis factor (TNF)-α, and vascular endothelial growth factor (VEGF) cytokines using an 8-protein multiplex (Millipore Sigma, Billerica, MA). A 6-minute walk test (MWT)was completed at the beginning and end of study to measure physical function. T-tests were performed with significance set to p \u3c0.05. RESULTS: A total of 15 men were consented with 9 men completing the intervention (40% attrition due to COVID). At baseline, participants were 70.11 ± 5.42 years of age, weighted 85.31 ± 6.41 kg with a body mass index of 27.77 ± 2.93 kg/m2. A non-significant tendency was observed for improved 6MWT distance (meters) (Pre: 382.7 ± 108.1; Post: 466.7 ± 73.78; p=0.08). Analysis of circulating cytokines showed tendencies for reduced circulating concentrations (pg/mL) of IFNγ (Pre: 152.9 ± 312.7; Post: 118.9 ± 258.8; p=0.08), and VEGF (Pre: 125.2 ± 198.7; Post: 80.29 ± 124.3; p=0.06) following the intervention. Several other biomarkers showed relevant, though not significant, decreases as well, including IL-12 (Pre: 28.69 ± 32.06; Post: 23.92 ± 19.38; -16.6%), IL-1a (Pre: 78.76 ± 183.3; Post: 65.55 ± 147.7; -16.8%), IL-6 (Pre: 23.71 ± 45.64; Post: 21.24 ± 45.18; -10.4%), and TNF-α (Pre: 24.58 ± 35.4; Post: 19.71 ± 20.76; -19.8%). CONCLUSION: Due to institutional COVID-19 protocols limiting in person research visits, six participants declined to continue the study. The small sample size likely accounts for the lack of statistically significant findings. Although the study did not yield statistically significant outcomes, the results of this study show promising indications that a home-based exercise program could be effective in reducing inflammatory cytokines and increasing functional capacity in men with PCa. Further investigation is needed to confirm these results with a powered sample

Impact of a Home-Based Exercise Program on Cardiovascular Disease Biomarkers in Men with Prostate Cancer

Patients with prostate cancer (PCa) tend to live a sedentary lifestyle and fail to meet national physical activity requirements putting them at a greater risk for developing weight-related co-morbidities and cancer recurrence. Physical activity after cancer diagnosis is known to improve body composition, physical function, and overall quality of life. The inclusion of a home-based exercise regimen may increase their physical activity and reduce the risk of weight-related illness. PURPOSE: To gather preliminary data regarding the impact of a home-based exercise program on body composition and cardiovascular disease (CVD) biomarkers. METHODS: A single group self-controlled study design was used to test the hypothesis that a home-based exercise program can reduce CVD risk in men with PCa. Fifteen men with PCa under active surveillance were recruited to complete a 24-week home-based exercise program consisting of both aerobic and strength-based exercises. Each week, participants were asked to complete 5 days of light-to-moderate intensity walking at a heart rate reserve of 40-60% and 3 days of bodyweight-based exercises including 3 sets of 15 reps of squats, incline push-ups, and hip thrusts. Serum was collected at baseline and end of study to quantify circulating CVD biomarkers: a-2 macroglobulin (A2M), C-reactive protein (CRP), fetuin-A, a-1 acid glycoprotein (AGP), fibrinogen, L-selectin, serum amyloid P (SAP), platelet factor 4 (PF4/CXCL4), and adipsin using an 8-protein multiplex (Millipore Sigma, Billerica, MA). T-tests were performed with significance established at pRESULTS: A total of 15 men consented and 9 men saw the trial to completion (Age: 72.0 ± 8.52; Weight: 85.31 ± 6.41 kg; BMI: 27.77 ± 2.93 kg/m2). There was a 40% rate of attrition observed due to COVID-19. No significant changes occurred in average weights and BMI from pre to post trial visits. Though not significant, tendencies for increased concentrations of the anticoagulant, A2M (Pre: 99.83 ± 81.19 pg/mL; Post: 126.7 ± 102.5; p=0.064) and the inflammatory protein, SAP (Pre: 0.63 ± 0.32 pg/mL; Post: 0.86 ± 0.46; p=0.09) were seen. We also observed a 1.5-fold increase in CRP (Pre: 0.47 ± 0.38 pg/mL; Post: 1.19 ± 2.209) perhaps, as a result of an increase in SAP, or indicative of increased levels of stress due to COVID-19. No other significant differences were found. CONCLUSION: The reduced sample size may have contributed to the lack of significance found in the analysis. Although there were no statistically significant findings, the tendencies seen in A2M suggest that a home-based exercise program may protect against certain facets of CVD in this overweight population. However, our enthusiasm is blunted by the observed increases in SAP and CRP. Further investigation is necessary to validate these results

Exercise Does not Stimulate Citrate Synthase Activity in Cachectic Muscle

Cachexia causes metabolic alterations in skeletal muscle mitochondria stimulated by inflammatory imbalance towards pro-inflammatory signaling. Previous work by our group has demonstrated that exercise significantly increases muscle mass in cases of advanced tumors in transgenic mice. Furthermore, we have discovered that the natural product Nexrutine® has anti-inflammatory properties which can be beneficial in protecting mitochondria. PURPOSE: To compare the effects of exercise and Nexrutine® on mitochondrial density in skeletal muscle taken from transgenic adenocarcinoma of the mouse prostate (TRAMP) models. METHODS: This project is a continuation of a larger study investigating the effects of exercise and Nexrutine® on the attenuation of muscle wasting in TRAMP mice. For this analysis, gastrocnemius from 14 TRAMP mice from control (n=5), Nexrutine® (600 mg/kg; n=5), and voluntary wheel running (VWR) groups (n=4) that completed 20 weeks of intervention were used. Mitochondrial activity was quantified using a commercially available citrate synthase assay (Cayman Chemical, USA). An analysis of variance (ANOVA) with Tukey’s post-hoc was performed. Correlations between muscle mass and citrate synthase activity was performed for each group. Alpha was set at p ≤ 0.05. RESULTS: All mice presented with tumors upon necropsy. VWR mice ran on average 6.67 kilometers per day. Nexrutine® group consumed 1.49 mg Nexrutine® per day on average. No significant differences in muscle mass or citrate synthase were observed between groups. Briefly, the control group had 7.31% and 20.75% greater citrate synthase compared to Nexrutine® and exercise groups, respectively. Exercise group was observed to have 35.25% higher than Nexrutine® group. When all samples were combined, a significant positive correlation was observed between muscle mass and citrate synthase (p= 0.04). CONCLUSION: Contrary to our hypothesis, the results suggest neither exercise nor Nexrutine® positively affect citrate synthase activity in cachectic muscle. Future work by our group will focus on reactive oxygen species and mitochondrial complex activity to further understand how cachexia affects skeletal muscle mitochondrial efficiency

Effectiveness of exercise interventions in animal models of multiple sclerosis

Multiple sclerosis (MS) is associated with an impaired immune system that severely affects the spinal cord and brain, and which is marked by progressive inflammatory demyelination. Patients with MS may benefit from exercise training as a suggested course of treatment. The most commonly used animal models of studies on MS are experimental autoimmune/allergic encephalomyelitis (EAE) models. The present review intends to concisely discuss the interventions using EAE models to understand the effectiveness of exercise as treatment for MS patients and thereby provide clear perspective for future research and MS management. For the present literature review, relevant published articles on EAE animal models that reported the impacts of exercise on MS, were extracted from various databases. Existing literature support the concept that an exercise regimen can reduce the severity of some of the clinical manifestations of EAE, including neurological signs, motor function, pain, and cognitive deficits. Further results demonstrate the mechanisms of EAE suppression with information relating to the immune system, demyelination, regeneration, and exercise in EAE. The role for neurotrophic factors has also been investigated. Analyzing the existing reports, this literature review infers that EAE is a suitable animal model that can help researchers develop further understanding and treatments for MS. Besides, findings from previous animal studies supports the contention that exercise assists in ameliorating MS progression

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

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