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

Links between white matter microstructure and cortisol reactivity to stress in early childhood: evidence for moderation by parenting.

Activity of the hypothalamic-pituitary-adrenal axis (measured via cortisol reactivity) may be a biological marker of risk for depression and anxiety, possibly even early in development. However, the structural neural correlates of early cortisol reactivity are not well known, although these would potentially inform broader models of mechanisms of risk, especially if the early environment further shapes these relationships. Therefore, we examined links between white matter architecture and young girls\u27 cortisol reactivity and whether early caregiving moderated these links. We recruited 45 6-year-old girls based on whether they had previously shown high or low cortisol reactivity to a stress task at age 3. White matter integrity was assessed by calculating fractional anisotropy (FA) of diffusion-weighted magnetic resonance imaging scans. Parenting styles were measured via a standardized parent-child interaction task. Significant associations were found between FA in white matter regions adjacent to the left thalamus, the right anterior cingulate cortex, and the right superior frontal gyrus (all ps \u3c .001). Further, positive early caregiving moderated the effect of high cortisol reactivity on white matter FA (all ps ≤ .05), with high stress reactive girls who received greater parent positive affect showing white matter structure more similar to that of low stress reactive girls. Results show associations between white matter integrity of various limbic regions of the brain and early cortisol reactivity to stress and provide preliminary support for the notion that parenting may moderate associations

Free-breathing Pulmonary (1)H and Hyperpolarized (3)He MRI: Comparison in COPD and Bronchiectasis.

RATIONALE AND OBJECTIVES: In this proof-of-concept demonstration, we aimed to quantitatively and qualitatively compare pulmonary ventilation abnormalities derived from Fourier decomposition of free-breathing (1)H magnetic resonance imaging (FDMRI) to hyperpolarized (3)He MRI in subjects with chronic obstructive pulmonary disease (COPD) and bronchiectasis. MATERIALS AND METHODS: All subjects provided written informed consent to a protocol approved by a local research ethics board and Health, Canada, and they underwent MRI, computed tomography (CT), spirometry, and plethysmography during a single 2-hour visit. Semiautomated segmentation was used to generate ventilation defect measurements derived from FDMRI and (3)He MRI, and these were compared using analysis of variance and Pearson correlations. RESULTS: Twenty-six subjects were evaluated including 12 COPD subjects (67 ± 9 years) and 14 bronchiectasis subjects (70 ± 11 years). For COPD subjects, FDMRI and (3)He MRI ventilation defect percent (VDP) was 7 ± 6% and 24 ± 14%, respectively (P \u3c .001; bias = -16 ± 9%). In COPD subjects, FDMRI was significantly correlated with (3)He MRI VDP (r = .88; P = .0001), (3)He MRI apparent diffusion coefficient (r = .71; P \u3c .05), airways resistance (r = .60; P \u3c .05), and RA950 (r = .80; P \u3c .01). In subjects with bronchiectasis, FDMRI VDP (5 ± 3%) and (3)He MRI VDP (18 ± 9%) were significantly different (P \u3c .001) and not correlated (P \u3e .05). The Dice similarity coefficient (DSC) for FDMRI and (3)He MRI ventilation was 86 ± 7% for COPD and 86 ± 4% for bronchiectasis subjects (P \u3e .05); the DSC for FDMRI ventilation defects and CT RA950 was 19 ± 20% in COPD and 2 ± 3% in bronchiectasis subjects (P \u3c .01). CONCLUSIONS: FDMRI and (3)He MRI VDP were strongly related in COPD but not in bronchiectasis subjects. In COPD only, FDMRI ventilation defects were spatially related with (3)He ventilation defects and emphysema

Parental depression and child cognitive vulnerability predict children\u27s cortisol reactivity

Risk for depression is expressed across multiple levels of analysis. For example, parental depression and cognitive vulnerability are known markers of depression risk, but no study has examined their interactive effects on children\u27s cortisol reactivity, a likely mediator of early depression risk. We examined relations across these different levels of vulnerability using cross-sectional and longitudinal methods in two community samples of children. Children were assessed for cognitive vulnerability using self-reports (Study 1; n = 244) and tasks tapping memory and attentional bias (Study 2; n = 205), and their parents were assessed for depression history using structured clinical interviews. In both samples, children participated in standardized stress tasks and cortisol reactivity was assessed. Cross-sectionally and longitudinally, parental depression history and child cognitive vulnerability interacted to predict children\u27s cortisol reactivity; associations between parent depression and elevated child cortisol activity were found when children also showed elevated depressotypic attributions as well as attentional and memory biases. Findings indicate that models of children\u27s emerging depression risk may benefit from the examination of the interactive effects of multiple sources of vulnerability across levels of analysis

Prevalence of Panton-Valentine Leukocidin (PVL) and Antimicrobial Resistance in Community-Acquired Clinical Staphylococcus aureus in an Urban Gambian Hospital : A 11-Year Period Retrospective Pilot Study

This work is supported by MRCG. The source of funding has no role in the design and writing of the manuscript.Peer reviewedPublisher PD

Global, regional, and national burden of chronic kidney disease, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background Health system planning requires careful assessment of chronic kidney disease (CKD) epidemiology, but data for morbidity and mortality of this disease are scarce or non-existent in many countries. We estimated the global, regional, and national burden of CKD, as well as the burden of cardiovascular disease and gout attributable to impaired kidney function, for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017. We use the term CKD to refer to the morbidity and mortality that can be directly attributed to all stages of CKD, and we use the term impaired kidney function to refer to the additional risk of CKD from cardiovascular disease and gout. Methods The main data sources we used were published literature, vital registration systems, end-stage kidney disease registries, and household surveys. Estimates of CKD burden were produced using a Cause of Death Ensemble model and a Bayesian meta-regression analytical tool, and included incidence, prevalence, years lived with disability, mortality, years of life lost, and disability-adjusted life-years (DALYs). A comparative risk assessment approach was used to estimate the proportion of cardiovascular diseases and gout burden attributable to impaired kidney function. Findings Globally, in 2017, 1·2 million (95% uncertainty interval [UI] 1·2 to 1·3) people died from CKD. The global all-age mortality rate from CKD increased 41·5% (95% UI 35·2 to 46·5) between 1990 and 2017, although there was no significant change in the age-standardised mortality rate (2·8%, −1·5 to 6·3). In 2017, 697·5 million (95% UI 649·2 to 752·0) cases of all-stage CKD were recorded, for a global prevalence of 9·1% (8·5 to 9·8). The global all-age prevalence of CKD increased 29·3% (95% UI 26·4 to 32·6) since 1990, whereas the age-standardised prevalence remained stable (1·2%, −1·1 to 3·5). CKD resulted in 35·8 million (95% UI 33·7 to 38·0) DALYs in 2017, with diabetic nephropathy accounting for almost a third of DALYs. Most of the burden of CKD was concentrated in the three lowest quintiles of Socio-demographic Index (SDI). In several regions, particularly Oceania, sub-Saharan Africa, and Latin America, the burden of CKD was much higher than expected for the level of development, whereas the disease burden in western, eastern, and central sub-Saharan Africa, east Asia, south Asia, central and eastern Europe, Australasia, and western Europe was lower than expected. 1·4 million (95% UI 1·2 to 1·6) cardiovascular disease-related deaths and 25·3 million (22·2 to 28·9) cardiovascular disease DALYs were attributable to impaired kidney function. Interpretation Kidney disease has a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for cardiovascular disease. CKD is largely preventable and treatable and deserves greater attention in global health policy decision making, particularly in locations with low and middle SDI

Association between microbiome and the development of adverse posttraumatic neuropsychiatric sequelae after traumatic stress exposure

Patients exposed to trauma often experience high rates of adverse post-traumatic neuropsychiatric sequelae (APNS). The biological mechanisms promoting APNS are currently unknown, but the microbiota-gut-brain axis offers an avenue to understanding mechanisms as well as possibilities for intervention. Microbiome composition after trauma exposure has been poorly examined regarding neuropsychiatric outcomes. We aimed to determine whether the gut microbiomes of trauma-exposed emergency department patients who develop APNS have dysfunctional gut microbiome profiles and discover potential associated mechanisms. We performed metagenomic analysis on stool samples (n = 51) from a subset of adults enrolled in the Advancing Understanding of RecOvery afteR traumA (AURORA) study. Two-, eight- and twelve-week post-trauma outcomes for post-traumatic stress disorder (PTSD) (PTSD checklist for DSM-5), normalized depression scores (PROMIS Depression Short Form 8b) and somatic symptom counts were collected. Generalized linear models were created for each outcome using microbial abundances and relevant demographics. Mixed-effect random forest machine learning models were used to identify associations between APNS outcomes and microbial features and encoded metabolic pathways from stool metagenomics. Microbial species, including Flavonifractor plautii, Ruminococcus gnavus and, Bifidobacterium species, which are prevalent commensal gut microbes, were found to be important in predicting worse APNS outcomes from microbial abundance data. Notably, through APNS outcome modeling using microbial metabolic pathways, worse APNS outcomes were highly predicted by decreased L-arginine related pathway genes and increased citrulline and ornithine pathways. Common commensal microbial species are enriched in individuals who develop APNS. More notably, we identified a biological mechanism through which the gut microbiome reduces global arginine bioavailability, a metabolic change that has also been demonstrated in the plasma of patients with PTSD

Disentangling sex differences in PTSD risk factors

Despite extensive research on sex/gender differences in posttraumatic stress disorder (PTSD), underlying mechanisms are still not fully understood. Here we present a systematic overview of three sex/gender-related risk pathways. We assessed 16 risk factors as well as 3 month PTSD severity in a prospective cohort study (n = 2924) of acutely traumatized individuals and investigated potential mediators in the pathway between sex assigned at birth and PTSD severity using multiple mediation analysis with regularization. Six risk factors were more prevalent/severe in women, and none was more pronounced in men. Analyses showed that acute stress disorder, neuroticism, lifetime sexual assault exposure, anxiety sensitivity and pretrauma anxiety symptoms fully mediated and uniquely contributed to the relationship between sex assigned at birth and PTSD severity. Our results demonstrate different risk mechanisms for women and men. Such knowledge can inform targeted interventions. Our systematic approach to differential risk pathways can be transferred to other mental disorders to guide sex- and gender-sensitive mental health research

Socio-demographic and trauma-related predictors of depression within eight weeks of motor vehicle collision in the AURORA study

BACKGROUND: This is the first report on the association between trauma exposure and depression from the Advancing Understanding of RecOvery afteR traumA(AURORA) multisite longitudinal study of adverse post-traumatic neuropsychiatric sequelae (APNS) among participants seeking emergency department (ED) treatment in the aftermath of a traumatic life experience. METHODS: We focus on participants presenting at EDs after a motor vehicle collision (MVC), which characterizes most AURORA participants, and examine associations of participant socio-demographics and MVC characteristics with 8-week depression as mediated through peritraumatic symptoms and 2-week depression. RESULTS: Eight-week depression prevalence was relatively high (27.8%) and associated with several MVC characteristics (being passenger v. driver; injuries to other people). Peritraumatic distress was associated with 2-week but not 8-week depression. Most of these associations held when controlling for peritraumatic symptoms and, to a lesser degree, depressive symptoms at 2-weeks post-trauma. CONCLUSIONS: These observations, coupled with substantial variation in the relative strength of the mediating pathways across predictors, raises the possibility of diverse and potentially complex underlying biological and psychological processes that remain to be elucidated in more in-depth analyses of the rich and evolving AURORA database to find new targets for intervention and new tools for risk-based stratification following trauma exposure