Uninterrupted prolonged sitting and arterial stiffness: moderating effect of prior aerobic exercise in physically active adults.

PURPOSE: Prolonged sitting acutely increases arterial stiffness, with interruption strategies only providing limited success in offsetting these rises. Acute aerobic exercise is a potent stimulus to decrease arterial stiffness. However, limited information exists on the effectiveness of acute exercise to maintain arterial stiffness when performed prior to prolonged sitting, particularly within physically active individuals. METHODS: Using a randomized crossover design, 22 young, active individuals (50% female) performed two conditions 30 min of walking at 55-65% of heart rate reserve (EX) and 30 min of standing (STAND) followed by 2.5-h of sitting. Brachial-femoral (bfPWV) and femoral-ankle pulse wave velocity (faPWV) were assessed at Baseline, post-exercise and pre-sitting (Pre), and post-sitting (Post) as estimates of central and peripheral arterial stiffness, respectively. RESULTS: For bfPWV, no interaction, condition, or time effects were observed. For faPWV, an interaction was present (p < 0.001); compared to Baseline, there was a 6.1% decrease for EX (- 0.4 m/s, p < 0.001) and a 4.6% increase for STAND (0.3 m/s, p = 0.016) for STAND such that there was an 11.3% difference between conditions at Pre (0.7 m/s, p < 0.001). From Pre to Post, EX then increased by 11.7% (0.9 m/s p < 0.001) while STAND remained unchanged, resulting in no difference between conditions (0.1 m/s, p = 0.569). CONCLUSIONS: While aerobic exercise resulted in a significant decrease in faPWV prior to sitting, the prior exercise bout did not confer a protective effect against the deleterious effects of uninterrupted sitting. Future work should investigate the combined effect of prior exercise and sitting interruption strategies on markers of arterial stiffness.

Perfusion estimation using synthetic MRI-based measurements and a porous media flow model.

The measurement of perfusion and filtration of blood in biological tissue give rise to important clinical parameters used in diagnosis, follow-up, and therapy. In this paper, we address techniques for perfusion analysis using processed contrast agent concentration data from dynamic MRI acquisitions. A new methodology for analysis is evaluated and verified using synthetic data generated on a tissue geometry.

Detecting the vitamin D receptor (VDR) protein in mouse and human skeletal muscle: Strain-specific, species-specific and inter-individual variation.

Vitamin D, and its receptor (VDR), play roles in muscle development/function, however, VDR detection in muscle has been controversial. Using different sample preparation methods and antibodies, we examined differences in muscle VDR protein abundance between two mouse strains and between mice and humans. The mouse D-6 VDR antibody was not reliable for detecting VDR in mouse muscle, but was suitable for human muscle, while the rabbit D2K6W antibody was valid for mouse and human muscle. VDR protein was generally lower in muscles from C57 B l/6 than FVB/N mice and was higher in human than mouse muscle. Two putative VDR bands were detected in human muscle, possibly representing VDR isoforms/splice variants, with marked inter-individual differences. This study provides new information on detecting VDR in muscle and on inter-mouse strain and inter-human individual differences in VDR expression. These findings may have implications for future pre-clinical and clinical studies and prompt further investigation to confirm possible VDR isoforms in human muscle.

Plasma UCHL1, GFAP, Tau, and NfL Are Not Different in Young Healthy Persons With Mild COVID-19 Symptoms Early in the Pandemic: A Pilot Study.

Elevated levels of brain injury biomarkers have been found primarily in middle-aged or older persons experiencing moderate-to-severe COVID-19 symptoms. However, there is little research in young adults, and there is concern that COVID-19 causes brain injury even in the absence of moderate-to-severe symptoms. Therefore, the purpose of our study was to investigate whether neurofilament light (NfL), glial fibrillary acidic protein (GFAP), tau, or ubiquitin carboxyl-terminal esterase L1 (UCHL1) are elevated in the plasma of young adults with mild COVID-19 symptoms. Twelve participants diagnosed with COVID-19 had plasma collected 1, 2, 3, and 4 months after diagnosis to determine whether NfL, GFAP, tau, and UCHL1 concentrations increased over time or whether plasma concentrations were elevated compared with COVID-19-naïve participants. We also compared plasma NfL, GFAP, tau, and UCHL1 concentrations between sexes. Our results showed no difference between NfL, GFAP, tau, and UCHL1 concentrations in COVID-19-naïve participants and COVID-19-positive participants at any of the four time points (p = 0.771). Within the COVID-19-positive participants, UCHL1 levels were higher at month 3 after diagnosis compared to month 1 or month 2 (p = 0.027). Between sexes, females were found to have higher UCHL1 (p = 0.003) and NfL (p = 0.037) plasma concentrations compared to males, whereas males had higher plasma tau concentrations than females (p = 0.024). Based on our data, it appears that mild COVID-19 in young adults does not increase plasma NfL, GFAP, tau, or UCHL1.

Acute exercise induces distinct quantitative and phenotypical T cell profiles in men with prostate cancer.

Background: Reduced testosterone levels can influence immune system function, particularly T cells. Exercise during cancer reduces treatment-related side effects and provide a stimulus to mobilize and redistribute immune cells. However, it is unclear how conventional and unconventional T cells (UTC) respond to acute exercise in prostate cancer survivors compared to healthy controls. Methods: Age-matched prostate cancer survivors on androgen deprivation therapy (ADT) and those without ADT (PCa) along with non-cancer controls (CON) completed ∼45 min of intermittent cycling with 3 min at 60% of peak power interspersed by 1.5 min of rest. Fresh, unstimulated immune cell populations and intracellular perforin were assessed before (baseline), immediately following (0 h), 2 h, and 24 h post-exercise. Results: At 0 h, conventional T cell counts increased by 45%-64% with no differences between groups. T cell frequency decreased by -3.5% for CD3+ and -4.5% for CD4+ cells relative to base at 0 h with CD8+ cells experiencing a delayed decrease of -4.5% at 2 h with no group differences. Compared to CON, the frequency of CD8+CD57+ cells was -18.1% lower in ADT. Despite a potential decrease in maturity, ADT increased CD8+perforin+ GMFI. CD3+Vα7.2+CD161+ counts, but not frequencies, increased by 69% post-exercise while CD3+CD56+ cell counts increased by 127% and were preferentially mobilized (+1.7%) immediately following the acute cycling bout. There were no UTC group differences. Cell counts and frequencies returned to baseline by 24 h. Conclusion: Following acute exercise, prostate cancer survivors demonstrate normal T cell and UTC responses that were comparable to CON. Independent of exercise, ADT is associated with lower CD8+ cell maturity (CD57) and perforin frequency that suggests a less mature phenotype. However, higher perforin GMFI may attenuate these changes, with the functional implications of this yet to be determined.

Home-based exercise improves quality of life in breast and prostate cancer survivors: A meta-analysis.

BACKGROUND: Breast (BCa) and prostate (PCa) cancer are two of the most common but survivable cancers. One important component of survivorship that is impacted by treatment long term is diminished quality of life (QoL). Supervised exercise improves QoL and subsequent outcomes but is not accessible for all survivors. Additionally, many factors influence QoL including physical activity (PA), cardiorespiratory fitness (CRF), physical function, and fatigue. However, the COVID-19 pandemic has highlighted the need to increase access to exercise beyond supervised exercise facilities. Home-based exercise may provide a feasible alternative for cancer survivors especially for those living in rural communities. OBJECTIVES: The primary aim is to investigate the effects of home-based exercise training (Pre-training vs. Post-training) on QoL in BCa/PCa. A secondary aim is to investigate PA, CRF, physical function, and fatigue and potential moderators (age, cancer-type, intervention duration and type). Home-based exercise trials (randomized crossover or quasi-experimental design) with adults (aged 18 years and over) breast or prostate cancer survivors (not currently undergoing chemotherapy or radiation treatment) were eligible for inclusion. DATA SOURCES: Electronic databases were searched (inception-December 2022) for studies which included adult BCa or PCa survivors (not currently on chemotherapy/radiation), at least measured QoL, and undergoing unsupervised, home-based exercise training. APPRAISAL AND SYNTHESIS METHODS: Initially, 819 studies were identified, from which 17 studies (20 effects) involving 692 participants were extracted. Effect sizes were calculated as standardized mean differences (SMD). Data were pooled using a 3-level model with restricted maximum likelihood estimation. Pooled SMD was used to assess the magnitude of effect, where <0.2, 0.2, 0.5, and 0.8 was defined as trivial, small, moderate, and large respectively. RESULTS: Home-based exercise resulted in small improvements in QoL (SMD = 0.30, 95% CI 0.01, 0.60, p = 0.042), PA (SMD = 0.49, 95% CI 0.26, 0.75, p<0.001) and CRF (SMD = 0.45, 95% CI -0.01, 0.91, p = 0.056). Physical function (SMD = 0.00, 95% CI -0.21, 0.21, p = 1.000) and fatigue (SMD = -0.61, 95%CI -1.53, 0.32, p = 0.198) did not change. CONCLUSIONS: Home-based exercise results in small improves QoL in BCa/PCa survivors, independent of cancer type, intervention duration and type, or age. Home-based exercise also improves PA and CRF enhancing survivorship. Therefore, home-based exercise is an efficacious alternative option to improve QoL for BCa and PCa survivors especially for those who live in rural communities or lack access to exercise facilities.

Small-scale genetic structure of coral populations in Palau based on whole mitochondrial genomes: Implications for future coral resilience.

The ability of local populations to adapt to future climate conditions is facilitated by a balance between short range dispersal allowing local buildup of adaptively beneficial alleles, and longer dispersal moving these alleles throughout the species range. Reef building corals have relatively low dispersal larvae, but most population genetic studies show differentiation only over 100s of km. Here, we report full mitochondrial genome sequences from 284 tabletop corals (Acropora hyacinthus) from 39 patch reefs in Palau, and show two signals of genetic structure across reef scales from 1 to 55 km. First, divergent mitochondrial DNA haplotypes exist in different proportions from reef to reef, causing PhiST values of 0.02 (p = 0.02). Second, closely related sequences of mitochondrial Haplogroups are more likely to be co-located on the same reefs than expected by chance alone. We also compared these sequences to prior data on 155 colonies from American Samoa. In these comparisons, many Haplogroups in Palau were disproportionately represented or absent in American Samoa, and inter-regional PhiST = 0.259. However, we saw three instances of identical mitochondrial genomes between locations. Together, these data sets suggest two features of coral dispersal revealed by occurrence patterns in highly similar mitochondrial genomes. First, the Palau-American Samoa data suggest that long distance dispersal in corals is rare, as expected, but that it is common enough to deliver identical mitochondrial genomes across the Pacific. Second, higher than expected co-occurrence of Haplogroups on the same Palau reefs suggests greater retention of coral larvae on local reefs than predicted by many current oceanographic models of larval movement. Increased attention to local scales of coral genetic structure, dispersal, and selection may help increase the accuracy of models of future adaptation of corals and of assisted migration as a reef resilience intervention.

Mutations in coral soma and sperm imply lifelong stem cell renewal and cell lineage selection.

In many animals, the germline differentiates early in embryogenesis, so only mutations that accumulate in germ cells are inherited by offspring. Exceptions to this developmental process may indicate other mechanisms have evolved to limit the effects of deleterious mutation accumulation. Stony corals are animals that can live for hundreds of years and have been thought to produce gametes from somatic tissue. To clarify conflicting evidence about germline-soma distinction in corals, we sequenced high coverage, full genomes with technical replicates for parent coral branches and their sperm pools. We identified post-embryonic single nucleotide variants (SNVs) unique to each parent branch, then checked if each SNV was shared by the respective sperm pool. Twenty-six per cent of post-embryonic SNVs were shared by the sperm and 74% were not. We also identified germline SNVs, those that were present in the sperm but not in the parent. These data suggest that self-renewing stem cells differentiate into germ and soma throughout the adult life of the colony, with SNV rates and patterns differing markedly in stem, soma and germ lineages. In addition to informing the evolution of germlines in metazoans, these insights inform how corals may generate adaptive diversity necessary in the face of global climate change.

Feasibility of home-based exercise training in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Home-based training increases accessibility to exercise and mitigates the side effects of hormone therapy for prostate cancer (PC). However, it is unknown if men with more advanced disease are willing to partake in such interventions. PURPOSE: To determine the feasibility of a home-based exercise intervention in men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: mCRPC patients on androgen receptor signaling inhibitors (ARSI) were prescribed a 12-week, home-based exercise intervention using resistance bands and walking. Feasibility was assessed using recruitment, retention, adherence, and outcome capture. Physiological changes and patient reported outcomes were assessed before and after the intervention. RESULTS: Of the 62 referrals, 47 were eligible with 22 men performing baseline testing (47% recruitment rate) and 16 completing the intervention (73% retention). Task completion was >86% for all physiological tests. Walking adherence was 80% and resistance training was 63%, the latter falling short of the study target (75%). Training increased thigh muscle cross-sectional area by 22%, time to exhaustion by 19% (both p < 0.05) and peak oxygen uptake by 6% (p = 0.057). Improvements in short physical performance battery scores and 400 m walk demonstrated moderate effect sizes that did not reach significance. CONCLUSIONS: Home-based exercise is feasible during ARSI treatment for mCRPC. Greater endurance capacity and localized hypertrophy appear as the primary improvements following training. These preliminary findings suggest home-based training may increase exercise accessibility, with important lessons that will inform subsequent trials investigating the efficacy of home-based exercise interventions during mCRPC.

Protocol for a study on Sitting with Interruption and Whole-Body Cardiovascular Health (SWITCH) in middle-aged adults.

BACKGROUND: Sedentary behavior (SB) is a biologically distinct yet understudied cardiovascular disease risk (CVD) factor. However, specific public health policy regarding the optimal strategy for SB interruption is unavailable. This paper outlines the protocol for part I of the Sitting with Interruption and Whole-Body Cardiovascular Health (SWITCH) study, including the rationale, objectives, methodology, and next steps. We additionally detail practical considerations that went into the development of the NIH R01 grant supporting this research. METHODS: Healthy men and women (n = 56, aged 36-55) who are inactive (<90 min/wk. of moderate-to-vigorous intensity physical activities for past 3 months) and sedentary (sitting for >8 h/day), will be recruited for this randomized crossover trial. Specifically, participants will complete the following 4-h conditions: (i) SB with once/h 5 min walk break; (ii) SB with once/h 15 min stand break; (iii) SB with twice/h breaks (alternating 5 min walk and 15 min stand); and (iv) SB with no breaks (i.e., control). Focus group discussions will refine our socioecological SB reduction model. RESULTS: The primary outcome will be change in aortic arterial stiffness (i.e., pulse wave velocity; PWV, m/s) for each substitution strategy relative to the control (SB with no breaks) condition. CONCLUSIONS: The outcomes from this study will facilitate the design of a subsequent randomized controlled trial to test a mechanism-informed, feasible SB-reduction intervention and support the development of SB policy.

Effects of high-intensity interval training on health-related quality of life in chronic lymphocytic leukemia: A pilot study.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) is the most common incurable leukemia/lymphoma in the United States. Individuals with CLL are at risk for disability, frailty, and cancer-specific complications that negatively affect health-related quality of life (HRQOL). High-intensity interval training (HIIT) and resistance training (RT) are safe and feasible for individuals with chronic diseases and when combined, they may be beneficial for reducing cancer-related fatigue, symptom burden, and global quality of life. However, no studies have examined the impact of HIIT or RT on HRQOL in CLL. The purpose of this study was to investigate the effects of a 12-week HIIT and RT (HIIT+RT) intervention on HRQOL in adults with treatment naïve CLL. MATERIALS AND METHODS: Changes in HRQOL was a secondary outcome in this pilot study. Individuals with CLL (63.9 ± 8.5 yrs) were non-randomly assigned to 12 weeks of HIIT+RT or a control group. The HIIT+RT protocol consisted of three 30-min sessions/week of HIIT and two sessions/week of RT. The control group maintained usual daily activities. We assessed pre and post HRQOL using the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) questionnaire with domains of physical (PWB), social (SWB), emotional (EWB), functional (FWB), and general (FACT-G) well-being as well as a lymphoma-specific subscale (LymS). We used a two-way mixed analysis of variance to assess changes in HRQOL. We calculated effect size (ES) using Cohen's d. RESULTS: Fifteen participants (HIIT+RT: n = 9; Control: n = 6) completed the study and questionnaire. Scores for FWB improved following HIIT+RT (21.7 ± 3.4 to 23.9 ± 3.2; ES = 1.38) compared to controls (25.7 ± 2.2 to 25.7 ± 2.3). The HIIT+RT group experienced clinically meaningful improvements in total FACT-Lym, FWB, FACT-G, and LymS. The control group had clinically meaningful changes only in LymS. DISCUSSION: The large effect sizes and clinically meaningful improvements associated with 12 weeks of HIIT+RT support the potential benefits of this type of exercise program for FWB, lymphoma-specific symptoms, and general well-being in CLL. A future randomized trial with an adequately powered sample size is needed to evaluate these findings. TRIAL REGISTRATION: NCT04950452.

Associations of clinical and circulating metabolic biomarkers with low physical fitness and function in adults with chronic lymphocytic leukemia.

Many patients with chronic lymphocytic leukemia (CLL) experience physical dysfunction and low overall fitness. It remains unknown what factors drive CLL physical dysfunction. We assessed physical function and metabolic lipoprotein panels in 106 patients with CLL. In univariate analyses of clinical factors, a longer time since diagnosis was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 3.56, 95% CI: 1.37-9.22; p = 0.002) and physical performance (SPPB: OR = 2.03, 95% CI: 1.20-3.44; p = 0.004). Having received treatment was associated with a higher likelihood of dysfunctional aerobic fitness (OR = 1.57, 95% CI: 1.02-2.40; p = 0.036), SPPB (OR = 1.85, 95% CI: 1.13-3.03; p = 0.011) and grip strength (OR = 1.67, 95% CI: 1.10-2.55; p = 0.015). We found that several small HDL particle parameters, higher levels of citrate (OR = 2.01, 95% CI: 1.22-3.31; p = 0.030), and lower levels of hemoglobin (OR = 0.50, 95% CI: 0.31-0.82; p = 0.030) were associated with a higher likelihood of dysfunctional aerobic fitness. Multivariable least absolute shrinkage and selection operator (LASSO)-penalized regression analyses using variable importance measures (VIM) showed that 7.8-nm HDL particles (VIM = 1.000) and total HDL particle levels (VIM = 1.000) were more informative than clinical measures for the odds of dysfunctional aerobic fitness and 6-min walk functional fitness, respectively, while 10.3-nm HDL particles (VIM = 0.383) were more informative for grip strength. Time since diagnosis (VIM = 0.680) and having received treatment (VIM = 0.490) were more informative than lipoprotein measures for the odds of having dysfunctional SPPB. Taken together, we establish significant relationships between clinical and metabolic factors and physical characteristics that might prompt early use of ancillary support services.

Impact of community-based exercise on fatigue in early breast cancer survivors: identifying potential determinants of change.

BACKGROUND: Exercise has been shown to reduce fatigue in early breast cancer survivors (EBCS), though it is unclear if these results translate to community-based exercise settings. Mechanisms that influence changes in fatigue seen after exercise are also poorly understood. This study sought to evaluate the impact of community-based exercise and identify associations of fatigue in EBCS. METHODS: Twenty-nine EBCS and 13 non-cancer controls (CON) enrolled. Pre/post-intervention measurements included measures of fitness/function, balance, and adherence/compliance as well as self-reported measures of fatigue, health-related quality of life (HRQOL), well-being, self-efficacy, and physical activity. Both groups participated in a supervised 16-week aerobic + resistance exercise intervention. A mixed model ANOVA and Cohen's D effect size assessed fatigue changes, and univariable linear regressions identified fatigue associations. RESULTS: Fatigue improved for EBCS (- 2.6, Cohen's D = 0.51) but not CON (0.0, Cohen's D = 0.02); no interaction effect was observed. Post-intervention fatigue in EBCS was associated with better QOL (R2 = 0.387; p < 0.01), depression (R2 = 0.251; p < 0.01), self-efficacy, (R2 = 0.453; p < 0.01), outcome expectations from exercise (R2 = 0.254; p < 0.01), balance (R2 = 0.167; p < 0.05), and the 6-minute walk test (R2 = 0.193; p < 0.05). EBCS improvements in fatigue were associated with improvements in self-reported physical health (R2 = 0.425; p < 0.01), depression (R2 = 0.233; p < 0.01), pain (R2 = 0.157; p < 0.05), outcome expectations from exercise (R2 = 0.420; p < 0.01), and the 6-minute walk test (R2 = 0.172; p < 0.05). Less fatigue in the CON group was shown be associated with better sleep quality (R2 = 0.309; p < 0.05) and pain (R2 = 0.259; p < 0.05). CONCLUSION: Community-based exercise appears beneficial for alleviating fatigue in EBCS. These improvements may be driven by parallel improvements in psychosocial outcomes and objectively measured functional outcomes.

Heat Acclimation with or without Normobaric Hypoxia Exposure Leads to Similar Improvements in Endurance Performance in the Heat.

BACKGROUND: Combining the key adaptation of plasma volume (PV) expansion with synergistic physiological effects of other acclimation interventions to maximise endurance performance in the heat has potential. The current study investigated the effects of heat acclimation alone (H), combined with normobaric hypoxia exposure (H+NH), on endurance athletic performance. METHODS: Well-trained participants completed a heat-stress trial (30 °C, 80% relative humidity (RH), 20.8% fraction of inspired oxygen (FiO2)) of a 75 min steady-state cycling (fixed workload) and a subsequent 15 min cycling time trial for distance before and after intervention. Participants completed 12 consecutive indoor training days with either heat acclimation (H; 60 min·day-1, 30 °C, 80% RH; 20.8% FiO2) or heat acclimation and overnight hypoxic environment (H+NH; ~12 h, 60% RH; 16% FiO2 simulating altitude of ~2500 m). Control (CON) group trained outdoors with average maximum daily temperature of 16.5 °C and 60% RH. RESULTS: Both H and H+NH significantly improved time trial cycling distance by ~5.5% compared to CON, with no difference between environmental exposures. PV increased (+3.8%) and decreased (-4.1%) following H and H+NH, respectively, whereas haemoglobin concentration decreased (-2%) and increased (+3%) in H and H+NH, respectively. CONCLUSION: Our results show that despite contrasting physiological adaptations to different environmental acclimation protocols, heat acclimation with or without hypoxic exposure demonstrated similar improvements in short-duration exercise performance in a hot environment.

Baseline fatigue in early breast cancer survivors: understanding its prevalence in community-based exercise.

PURPOSE: Examine baseline fatigue levels in early-breast cancer survivors (EBCS) compared to inactive controls (CON) and identify associated physical and psychosocial factors with fatigue prior to community-based exercise. METHODS: A total of 33 EBCS (53.9 ± 11.4 years) and 21 CON (54.0 ± 8.0 years) were recruited. Participants completed questionnaires for demographics and patient-reported outcome measures pertaining to fatigue, quality of life, mental health, and physical activity, and completed a 6-min walk test, balance assessment, cardiopulmonary exercise test (VO2peak), and muscular strength test. A Mann-Whitney U test compared fatigue between groups and unadjusted univariable linear regressions were used to explore relationships with fatigue. RESULTS: Fatigue in EBCS was not statistically different from CON (EBCS: 16.9 ± 5.75; CON: 14.2 ± 3.4, p = 0.121). Univariable analyses showed lower fatigue in EBCS was associated with better Physical and Mental Health (both R2 = 0.435; p < 0.01), better outcome expectations for exercise (R2 = 0.237; p < 0.01), better self-efficacy (R2 = 0.407; p < 0.01), lower depression (R2 = 0.383; p < 0.001), lower anxiety (R2 = 0.104; p < 0.05), and better balance (R2 = 0.265; p < 0.01). Lower fatigue in the CON group was associated with better sleep quality (R2 = 0.263; p < 0.05) and self-efficacy (R2 = 0.417; p < 0.05). CONCLUSIONS: Mild fatigue was prevalent in EBCS, whereas moderate/severe fatigue was not. This discrepancy should be explored provided the benefits of exercise for fatigue management. Further, fatigue in EBCS was associated with multiple psychosocial and functional outcomes, which emphasized both its multi-factorial nature and uniqueness to the EBCS population. CLINICALTRIALS: gov Number: NCT03760536.

Associations between estimated and measured carotid-femoral pulse wave velocity in older Black and White adults: the atherosclerosis risk in communities (ARIC) study.

Introduction: Aortic stiffness offers important insight into vascular aging and cardiovascular disease (CVD) risk. The referent measure of aortic stiffness is carotid-femoral pulse wave velocity (cfPWV). cfPWV can be estimated (ePWV) from age and mean arterial pressure. Few studies have directly compared the association of ePWV to measured cfPWV, particularly in non-White adults. Moreover, whether ePWV and cfPWV correlate similarly with CVD risk remains unexplored. Aim: (1) To estimate the strength of the agreement between ePWV and cfPWV in both Black and White older adults; and (2) to compare the associations of ePWV and cfPWV with CVD risk factors and determine whether these associations were consistent across races. Methods and Results: We evaluated 4478 [75.2 (SD 5.0) years] Black and White older adults in the Atherosclerosis Risk in Communities (ARIC) Study. cfPWV was measured using an automated pulse waveform analyzer. ePWV was derived from an equation based on age and mean arterial pressure. Association and agreement between the two measurements were determined using Pearson's correlation coefficient (r), standard error of estimate (SEE), and Bland-Altman analysis. Associations between traditional risk factors with ePWV and cfPWV were evaluated using linear mixed regression models. We observed weak correlations between ePWV and cfPWV within White adults (r = 0.36) and Black adults (r = 0.31). The mean bias for Bland-Altman analysis was low at -0.17 m/s (95%CI: -0.25 to -0.09). However, the inspection of the Bland-Altman plots indicated systematic bias (P < 0.001), which was consistent across race strata. The SEE, or typical absolute error, was 2.8 m/s suggesting high variability across measures. In models adjusted for sex, prevalent diabetes, the number of prevalent cardiovascular diseases, and medication count, both cfPWV and ePWV were positively associated with heart rate, triglycerides, and fasting glucose, and negatively associated with body mass index (BMI) and smoking status in White adults (P < 0.05). cfPWV and ePWV were not associated with heart rate, triglycerides, and fasting glucose in Black adults, while both measures were negatively associated with BMI in Black adults. Conclusions: Findings suggest a weak association between ePWV and cfPWV in older White and Black adults from ARIC. There were similar weak associations between CVD risk factors with ePWV and cfPWV in White adults with subtle differences in associations in Black adults.

A pilot study of high-intensity interval training in older adults with treatment naïve chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common leukemia in the USA, affecting predominantly older adults. CLL is characterized by low physical fitness, reduced immunity, and increased risk of secondary malignancies and infections. One approach to improving CLL patients' physical fitness and immune functions may be participation in a structured exercise program. The aims of this pilot study were to examine physical and immunological changes, and feasibility of a 12-week high-intensity interval training (HIIT) combined with muscle endurance-based resistance training on older adults with treatment naïve CLL. We enrolled eighteen participants with CLL aged 64.9 ± 9.1 years and assigned them to groups depending on distance lived from our fitness center. Ten participants (4 M/6F) completed HIIT and six participants (4 M/2F) completed a non-exercising control group (Controls). HIIT consisted of three 30-min treadmill sessions/week plus two concurrent 30-min strength training sessions/week. Physical and immunological outcomes included aerobic capacity, muscle strength and endurance, and natural killer (NK) cell recognition and killing of tumor cells. We confirmed feasibility if > 70% of HIIT participants completed > 75% of prescribed sessions and prescribed minutes, and if > 80% of high-intensity intervals were at a heart rate corresponding to at least 80% of peak aerobic capacity (VO2peak). Results are presented as Hedge's G effect sizes (g), with 0.2, 0.5 and 0.8 representing small, medium and large effects, respectively. Following HIIT, leg strength (g = 2.52), chest strength (g = 1.15) and seated row strength (g = 3.07) were 35.4%, 56.1% and 39.5% higher than Controls, respectively, while aerobic capacity was 3.8% lower (g = 0.49) than Controls. Similarly, following HIIT, in vitro NK-cell cytolytic activity against the K562 cell line (g = 1.43), OSU-CLL cell line (g = 0.95), and autologous B-cells (g = 1.30) were 20.3%, 3.0% and 14.6% higher than Controls, respectively. Feasibility was achieved, with HIIT completing 5.0 ± 0.2 sessions/week and 99 ± 3.6% of the prescribed minutes/week at heart rates corresponding to 89 ± 2.8% of VO2peak. We demonstrate that 12-weeks of supervised HIIT combined with muscle endurance-based resistance training is feasible, and that high adherence and compliance are associated with large effects on muscle strength and immune function in older adults with treatment naïve CLL.Trial registration: NCT04950452.

A nonlinear multi-scale model for blood circulation in a realistic vascular system.

In the last decade, numerical models have become an increasingly important tool in biological and medical science. Numerical simulations contribute to a deeper understanding of physiology and are a powerful tool for better diagnostics and treatment. In this paper, a nonlinear multi-scale model framework is developed for blood flow distribution in the full vascular system of an organ. We couple a quasi one-dimensional vascular graph model to represent blood flow in larger vessels and a porous media model to describe flow in smaller vessels and capillary bed. The vascular model is based on Poiseuille's Law, with pressure correction by elasticity and pressure drop estimation at vessels' junctions. The porous capillary bed is modelled as a two-compartment domain (artery and venous) using Darcy's Law. The fluid exchange between the artery and venous capillary bed compartments is defined as blood perfusion. The numerical experiments show that the proposed model for blood circulation: (i) is closely dependent on the structure and parameters of both the larger vessels and of the capillary bed, and (ii) provides a realistic blood circulation in the organ. The advantage of the proposed model is that it is complex enough to reliably capture the main underlying physiological function, yet highly flexible as it offers the possibility of incorporating various local effects. Furthermore, the numerical implementation of the model is straightforward and allows for simulations on a regular desktop computer.