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1.
Cancer Res Commun ; 4(5): 1211-1226, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38530195

ABSTRACT

PURPOSE: Among patients with breast cancer undergoing radiotherapy, posttreatment cardiovascular disease and worsened quality of life (QoL) are leading causes of morbidity and mortality. To overcome these negative radiotherapy effects, this prospective, randomized clinical trial pilots a 12-week Stay on Track exercise and diet intervention for overweight patients with nonmetastatic breast cancer undergoing whole-breast radiotherapy. EXPERIMENTAL DESIGN: The intervention group (n = 22) participated in three personal exercise and dietary counseling sessions, and received three text reminders/week to adhere to recommendations. The control group (n = 22) was administered a diet/exercise information binder. All patients received a Fitbit, and at baseline, 3 months, and 6 months, measurements of biomarkers, dual-energy X-ray absorptiometry scans, QoL and physical activity surveys, and food frequency questionnaires were obtained. A satisfaction survey was administered at 3 months. RESULTS: Stay on Track was well received, with high rates of adherence and satisfaction. The intervention group showed an increase in self-reported physical activity and preserved QoL, a decrease in body mass index and visceral fat, and higher American Cancer Society/American Institute of Cancer Research dietary adherence. The control participants had reduced QoL, anti-inflammatory markers, and increased metabolic syndrome markers. Both groups had decreased overall body mass. These changes were within group effects. When comparing the intervention and control groups over time, there were notable improvements in dietary adherence in the intervention group. CONCLUSIONS: Targeted lifestyle interventions during radiotherapy are feasible and could decrease cardiovascular comorbidities in patients with breast cancer. Larger-scale implementation with longer follow-up can better determine interventions that influence cardiometabolic health and QoL. SIGNIFICANCE: This pilot study examines cardiometabolic benefits of a combined diet and exercise intervention for patients with breast cancer undergoing radiotherapy. The intervention included an activity tracker (FitBit) and text message reminders to promote adherence to lifestyle interventions. Large-scale implementation of such programs may improve cardiometabolic outcomes and overall QoL among patients with breast cancer.


Subject(s)
Breast Neoplasms , Feasibility Studies , Quality of Life , Adult , Aged , Female , Humans , Middle Aged , Breast Neoplasms/radiotherapy , Breast Neoplasms/diet therapy , Diet , Exercise , Exercise Therapy/methods , Patient Compliance , Pilot Projects , Prospective Studies , Quality of Life/psychology
2.
Med ; 4(12): 928-943.e5, 2023 Dec 08.
Article in English | MEDLINE | ID: mdl-38029754

ABSTRACT

BACKGROUND: Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. METHODS: In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. FINDINGS: In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. CONCLUSIONS: These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. FUNDING: NIH, ASTRO, AHA, Longer Life Foundation.


Subject(s)
Cardiomyopathies , Heart Failure , Humans , Mice , Animals , Ventricular Remodeling , Cardiomyopathies/complications , Heart Failure/radiotherapy , Heart Failure/drug therapy , Heart Failure/etiology , Myocytes, Cardiac/metabolism , Ventricular Function , Fibrosis
3.
Curr Cardiol Rep ; 25(11): 1589-1600, 2023 11.
Article in English | MEDLINE | ID: mdl-37796395

ABSTRACT

PURPOSE OF REVIEW: Radiation is foundational to the treatment of cancer and improves overall survival. Yet, it is important to recognize the potential cardiovascular effects of radiation therapy and how to best minimize or manage them. Screening-both through imaging and with biomarkers-can potentially identify cardiovascular effects early, allowing for prompt initiation of treatment to mitigate late effects. RECENT FINDINGS: Cardiac echocardiography, magnetic resonance imaging (MRI), computed tomography, and measurements of troponin and natriuretic peptides serve as the initial screening tests of choice for RICD. Novel imaging applications, including positron emission tomography and specific MRI parameters, and biomarker testing, including myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and metabolomics, hold promise for earlier detection and more specific characterization of RICD. Advances in imaging and novel applications of biomarkers have potential to identify subclinical RICD and may reveal opportunities for early intervention. Further research is needed to elucidate optimal imaging screening modalities, biomarkers, and surveillance strategies.


Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Cardiotoxicity/diagnostic imaging , Cardiotoxicity/etiology , Early Detection of Cancer , Neoplasms/radiotherapy , Neoplasms/drug therapy , Biomarkers , Echocardiography , Antineoplastic Agents/therapeutic use
4.
Methods Cell Biol ; 180: 127-146, 2023.
Article in English | MEDLINE | ID: mdl-37890926

ABSTRACT

Cancer survivors who have received thoracic radiation as part of their primary treatment are at risk for developing radiation-induced cardiotoxicity (RICT) due to incidental radiation delivered to the heart. In recent decades, advancements in radiation delivery have dramatically improved the therapeutic ratio of radiation therapy (RT)-efficiently targeting malignancies while sparing the heart; yet, in many patients, incidental radiation to the heart cannot be fully avoided. Cardiac radiation exposure can cause long-term morbidity and contribute to poorer survival in cancer patients. Severe cardiac effects can occur within 2years of treatment. Currently, there is no way to predict who is at higher or lower risk of developing cardiotoxicity from radiation, and the critical factors that alter RICT have not yet been clearly identified. Thus, pre-clinical investigations are an important step towards better prevention, detection, and management of RICT in cancer survivors. The overarching aim of this chapter is to provide researchers with foundational and technical knowledge in the use of mice and rats for RICT investigations. After a brief overview of RICT pathophysiology and clinical manifestations, we discuss important considerations of RICT study design, including animal selection and radiation planning. We then provide example protocols for murine tissue harvesting and processing that can support use in downstream applications of the reader's choosing.


Subject(s)
Cardiotoxicity , Neoplasms , Mice , Humans , Rats , Animals , Cardiotoxicity/etiology , Cardiotoxicity/diagnosis , Cardiotoxicity/prevention & control , Rodentia , Neoplasms/radiotherapy , Heart
6.
JACC Basic Transl Sci ; 8(3): 340-355, 2023 Mar.
Article in English | MEDLINE | ID: mdl-37034289

ABSTRACT

Apolipoprotein M (ApoM) binds sphingosine-1-phosphate (S1P) and is inversely associated with mortality in human heart failure (HF). Here, we show that anthracyclines such as doxorubicin (Dox) reduce circulating ApoM in mice and humans, that ApoM is inversely associated with mortality in patients with anthracycline-induced heart failure, and ApoM heterozygosity in mice increases Dox-induced mortality. In the setting of Dox stress, our studies suggest ApoM can help sustain myocardial autophagic flux in a post-transcriptional manner, attenuate Dox cardiotoxicity, and prevent lysosomal injury.

7.
Int J Radiat Biol ; 99(7): 1096-1108, 2023.
Article in English | MEDLINE | ID: mdl-36971580

ABSTRACT

PURPOSE: Radiation therapy remains part of the standard of care for breast, lung, and esophageal cancers. While radiotherapy improves local control and survival, radiation-induced heart dysfunction is a common side effect of thoracic radiotherapy. Cardiovascular dysfunction can also result from non-therapeutic total body radiation exposures. Numerous studies have evaluated the relationship between radiation dose to the heart and cardiotoxicity, but relatively little is known about whether there are differences based on biological sex in radiation-induced heart dysfunction (RIHD). MATERIALS AND METHODS: We evaluated whether male and female inbred Dahl SS rats display differences in RIHD following delivery of 24 Gy in a single fraction to the whole heart using a 1.5 cm beam size (collimater). We also compared the 2.0 cm vs. 1.5 cm collimator in males. Pleural and pericardial effusions and normalized heart weights were measured, and echocardiograms were performed. RESULTS: Female SS rats displayed more severe RIHD relative to age-matched SS male rats. Normalized heart weight was significantly increased in females, but not in males. A total of 94% (15/16) of males and 55% (6/11) of females survived 5 months after completion of radiotherapy (p < .01). Among surviving rats, 100% of females and 14% of males developed moderate-to-severe pericardial effusions at 5 months. Females demonstrated increased pleural effusions, with the mean normalized pleural fluid volume for females and males being 56.6 mL/kg ± 12.1 and 10.96 mL/kg ± 6.4 in males (p = .001), respectively. Echocardiogram findings showed evidence of heart failure, which was more pronounced in females. Because age-matched female rats have smaller lungs, a higher percentage of the total lung was treated with radiation in females than males using the same beam size. After using a larger 2 cm beam in males which results in higher lung exposure, there was not a significant difference between males and females in terms of the development of moderate-to-severe pericardial effusions or pleural effusions. Treatment of males with a 2 cm beam resulted in comparable increases in LV mass and reductions in stroke volume to female rats treated with a 1.5 cm beam. CONCLUSION: Together, these results illustrate that there are differences in radiation-induced cardiotoxicity between male and female SS rats and add to the data that lung radiation doses, in addition to other factors, may play an important role in cardiac dysfunction following heart radiation exposure. These factors may be important to factor into future mitigation studies of radiation-induced cardiotoxicity.


Subject(s)
Heart , Radiography, Thoracic , Animals , Rats , Male , Female , Radiography, Thoracic/adverse effects , Heart/radiation effects , Cardiotoxicity , Pericardial Effusion , Pleural Effusion , Rats, Inbred Dahl
8.
Curr Cardiol Rep ; 25(3): 133-146, 2023 03.
Article in English | MEDLINE | ID: mdl-36790618

ABSTRACT

PURPOSE OF REVIEW: Following significant advancements in cancer therapeutics and survival, the risk of cancer therapy-related cardiotoxicity (CTRC) is increasingly recognized. With ongoing efforts to reduce cardiovascular morbidity and mortality in cancer patients and survivors, cardiac biomarkers have been studied for both risk stratification and monitoring during and after therapy to detect subclinical disease. This article will review the utility for biomarker use throughout the cancer care continuum. RECENT FINDINGS: A recent meta-analysis shows utility for troponin in monitoring patients at risk for CTRC during cancer therapy. The role for natriuretic peptides is less clear but may be useful in patients receiving proteasome inhibitors. Early studies explore use of myeloperoxidase, growth differentiation factor 15, galectin 3, micro-RNA, and others as novel biomarkers in CTRC. Biomarkers have potential to identify subclinical CTRC and may reveal opportunities for early intervention. Further research is needed to elucidate optimal biomarkers and surveillance strategies.


Subject(s)
Antineoplastic Agents , Heart Diseases , Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/chemically induced , Biomarkers , Medical Oncology , Heart Diseases/chemically induced , Heart Diseases/diagnosis , Cardiotoxicity/diagnosis , Risk Assessment , Antineoplastic Agents/adverse effects
9.
Eur J Appl Physiol ; 123(5): 975-988, 2023 May.
Article in English | MEDLINE | ID: mdl-36607416

ABSTRACT

BACKGROUND: Elevated low-density lipoprotein (LDL) and triglyceride concentrations are associated with future cardiovascular risk in young adults. Conversely, chronic physical activity is generally accepted to reduce CVD risk. Atherosclerosis is a major underlying cause of CVD, and atherogenesis is mediated by peripheral monocytes and monocyte-derived macrophages. The study aimed to determine if an individual's physical activity level impacts the phenotype of monocytes and monocyte-derived macrophages when stimulated with LDL and fatty acid ex vivo. METHODS: Peripheral blood mononuclear cells (PBMCs) were obtained from healthy, young adults of differing physical activity levels before and after a single bout of moderate intensity exercise (25 min at 60% of VO2peak). PBMCs were stimulated with LDL and palmitate ex vivo prior to differentiation into macrophages. Monocyte subset percentages and monocyte-derived macrophage expression of phenotypic (CD86, CD206) and functional (CCR2, ERK 1/2) markers were evaluated by flow cytometry. RESULTS: Compared to baseline, ex vivo LDL and palmitate stimulation decreased (p = 0.038) non-classical monocyte percentage from 24.7 ± 3.2 to 21.5 ± 2.6% in all participants. When ex vivo lipid stimulation was preceded by acute exercise, non-classical monocyte percentage was similar to baseline levels (p = 0.670, 25.8 ± 2.15%). Macrophage CD86/CD206 was increased from 1.30 ± 0.14 to 1.68 ± 0.19 when preceded by acute exercise in all participants. No differences were observed between participants of differing physical activity levels. CONCLUSIONS: Findings suggest that acute exercise modulates monocyte phenotype after LDL and palmitate stimulation in a protective manner, however, chronic physical activity does not alter monocyte/macrophage responses to any experimental condition in this population.


Subject(s)
Cardiovascular Diseases , Monocytes , Humans , Monocytes/metabolism , Leukocytes, Mononuclear , Macrophages/metabolism , Exercise/physiology , Lipoproteins, LDL/pharmacology
10.
Curr Treat Options Oncol ; 23(10): 1388-1404, 2022 10.
Article in English | MEDLINE | ID: mdl-36087234

ABSTRACT

OPINION STATEMENT: Several seminal papers over the last decade have furthered our recognition of radiation-induced heart disease (RIHD) as an important potential toxicity following radiation therapy (RT) to the chest. Investigators continue to evaluate the subacute and long-term effects of RT. In addition, studies are determining whether certain cardiac substructures are more sensitive to radiation, working to identify risk factors for the development of RIHD, and testing screening and mitigation strategies for RIHD. Multiple groups and expert consensus guidelines have published whole-heart and cardiac substructure dose constraints based on available data and cancer type. The authors recommend readers to familiarize themselves with the guidelines for screening and mitigating RIHD in adults and children, which advocate for cardiovascular risk assessment and reduction before and following RT, as well as cardiovascular imaging at appropriate follow-up intervals for early recognition of subclinical cardiovascular disease. Referrals to cardiology or cardio-oncology can also be helpful in prevention, screening, and mitigation strategies.


Subject(s)
Cardiovascular Diseases , Heart Diseases , Neoplasms , Radiation Injuries , Adult , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/etiology , Child , Heart/radiation effects , Heart Diseases/diagnosis , Humans , Neoplasms/diagnosis , Neoplasms/etiology , Neoplasms/radiotherapy , Radiation Injuries/diagnosis , Radiation Injuries/epidemiology , Radiation Injuries/etiology
11.
Diabetes Res Clin Pract ; 191: 110077, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36089102

ABSTRACT

AIMS: Following ST-segment elevation myocardial infarction (STEMI), recruitment and activation of monocytes [classical (CD14++CD16-CCR2++), intermediate (CD14++CD16+CCR2+), non-classical (CD14LowCD16++CCR2Low)] are needed for myocardial wound healing. Monocyte surface receptor CC chemokine receptor type 2 (CCR2) is responsible for monocyte chemotaxis to sites of inflammation and the lipopolysaccharide (LPS)-binding protein co-receptor, CD14, is involved in pro-inflammatory monocyte activation. The purpose of this investigation was to determine the effects of ex-vivo LPS activation on monocyte subset CD14 and CCR2 expression in post-STEMI individuals with normal and elevated random blood glucose. METHODS: Post-STEMI subjects were identified as normal random glucose (NG, <98 mg/dL, n = 13) or impaired random glucose (IG, ≥98 mg/dL, n = 26) and monocytes were analyzed for non-activated and LPS-activated (1 µg/mL for 4 h) CCR2 and CD14 expression. RESULTS: Non-activated intermediate monocytes from IG showed decreased CD14 expression when compared to NG, which was maintained following LPS-activation. The NG group showed a larger absolute reduction in classical CCR2 expression, leading to a significant difference between NG and IG following LPS-activation. CONCLUSION: Results suggest a heightened response to pro-inflammatory activation in IG following STEMI, which may impair or delay post-STEMI myocardial healing, and thus increase the incidence of chronic heart failure. NIH 1R34HL121402.


Subject(s)
Hyperglycemia , Lipopolysaccharide Receptors/immunology , ST Elevation Myocardial Infarction , Blood Glucose/metabolism , Humans , Hyperglycemia/metabolism , Lipopolysaccharides/pharmacology , Monocytes/metabolism , Receptors, CCR/metabolism , Receptors, CCR2/metabolism , Receptors, IgG/metabolism
12.
Heart Fail Clin ; 18(3): 403-413, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35718415

ABSTRACT

Radiation therapy (RT) is part of standard-of-care treatment of many thoracic cancers. More than 60% of patients receiving thoracic RT may eventually develop radiation-induced cardiac dysfunction (RICD) secondary to collateral heart dose. This article reviews factors contributing to a thoracic cancer patient's risk for RICD, including RT dose to the heart and/or cardiac substructures, other anticancer treatments, and a patient's cardiometabolic health. It is also discussed how automated tracking of these factors within electronic medical record environments may aid radiation oncologists and other treating physicians in their ability to prevent, detect, and/or treat RICD in this expanding patient population.


Subject(s)
Heart Diseases , Radiotherapy Planning, Computer-Assisted , Heart , Heart Diseases/etiology , Heart Diseases/prevention & control , Humans
13.
Life Sci ; 299: 120557, 2022 Jun 15.
Article in English | MEDLINE | ID: mdl-35447130

ABSTRACT

Monocyte chemokine receptor 2 (CCR2) and phosphorylated extra-cellular regulated kinase 1 & 2 (ERK1/2) impact macrophage differentiation and progression of atherosclerosis. Whereas aerobic exercise favorably modulates the immune system and reduces atherosclerotic risk, it is unknown whether sex differences exist in the monocyte/macrophage response to acute aerobic exercise. AIMS: To determine the impact of an acute bout of moderate intensity aerobic exercise on monocyte and macrophage CCR2 expression, ERK1/2 phosphorylation, and macrophage polarization in pre-menopausal women and men. MATERIALS AND METHODS: Blood samples were collected in 24 people (Women/Men; n = 12) prior to (PRE), immediately after a bout of moderate intensity cycle ergometry (POST), and 2 h (2H) following exercise. Monocyte and macrophage CCR2 and phosphorylated ERK1/2 as well as macrophage CD86 and CD206 were analyzed by flow cytometry. KEY FINDINGS: PRE classical monocyte CCR2 expression was greater in women compared to men (Women: 20546.2 ± 2306.4 vs. Men: 14437.6 ± 1201.9 AUF; p = 0.028) and was reduced in women at 2H (PRE: 20546.2 ± 2306.4 vs. 2H: 15856.9 ± 1314.4 AUF; p = 0.027). POST classical monocyte CCR2 expression was inversely associated (r = -0.697, p = 0.012) with POST classical monocyte ERK1/2 phosphorylation in women only. The percentage of CCR2+ macrophages was lower in women at POST (Women: 62.0 ± 8.9 vs. Men: 83.6 ± 3.1; p = 0.031) and at 2H (Women: 60.3 ± 8.4 vs. Men: 83.5 ± 3.0%; p = 0.016). SIGNIFICANCE: These data suggest that a single bout of moderate intensity aerobic exercise differentially impacts monocyte CCR2 expression and macrophage polarization in women compared to men.


Subject(s)
Monocytes , Receptors, CCR2 , Exercise , Female , Humans , Macrophages/metabolism , Male , Monocytes/metabolism , Receptors, CCR2/metabolism , Sex Characteristics
14.
Kardiol Pol ; 80(3): 256-265, 2022.
Article in English | MEDLINE | ID: mdl-35238396

ABSTRACT

Radiation-induced cardiac dysfunction is a critical healthcare concern facing survivors of thoracic cancers treated with radiation therapy. Despite cardiac-sparing advances in radiation therapy delivery, many patients with thoracic cancers receiving modern radiation therapy will still have incidental radiation exposure to the heart. Therefore, it is imperative that cardiovascular healthcare providers take appropriate measures to prevent, screen, and manage radiation-induced cardiac dysfunction in patients with a history of thoracic radiation therapy. In this review, we aim to provide healthcare providers with foundational information about radiation-induced cardiac pathophysiology and a chronology of advances in radiation technology. Subsequently, we provide an up-to-date review of treatment- and host-related factors that can influence a patient's risk for radiation-induced cardiac dysfunction. Finally, we culminate our discussion by detailing current screening and management guidelines to aid healthcare providers in caring for their patients with a history of thoracic radiation therapy.


Subject(s)
Heart Diseases , Neoplasms , Heart , Heart Diseases/etiology , Humans
15.
Viruses ; 13(9)2021 08 31.
Article in English | MEDLINE | ID: mdl-34578323

ABSTRACT

HIV-associated neurocognitive disorders (HAND) persist despite the advent of antiretroviral therapy (ART), suggesting underlying systemic and central nervous system (CNS) inflammatory mechanisms. The endogenous cannabinoid receptors 1 and 2 (CB1 and CB2) modulate inflammatory gene expression and play an important role in maintaining neuronal homeostasis. Cannabis use is disproportionately high among people with HIV (PWH) and may provide a neuroprotective effect for those on ART due to its anti-inflammatory properties. However, expression profiles of CB1 and CB2 in the brains of PWH on ART with HAND have not been reported. In this study, biochemical and immunohistochemical analyses were performed to determine CB1 and CB2 expression in the brain specimens of HAND donors. Immunoblot revealed that CB1 and CB2 were differentially expressed in the frontal cortices of HAND brains compared to neurocognitively unimpaired (NUI) brains of PWH. CB1 expression levels negatively correlated with memory and information processing speed. CB1 was primarily localized to neuronal soma in HAND brains versus a more punctate distribution of neuronal processes in NUI brains. CB1 expression was increased in cells with glial morphology and showed increased colocalization with an astroglial marker. These results suggest that targeting the endocannabinoid system may be a potential therapeutic strategy for HAND.


Subject(s)
Brain/metabolism , Endocannabinoids/pharmacology , HIV Infections/metabolism , Neurocognitive Disorders/metabolism , Neurocognitive Disorders/therapy , Receptors, Cannabinoid/metabolism , Anti-Inflammatory Agents/pharmacology , Astrocytes , Central Nervous System , Endocannabinoids/therapeutic use , Humans , Immunohistochemistry , Neurocognitive Disorders/pathology , Neuroglia
16.
Transl Psychiatry ; 10(1): 289, 2020 08 17.
Article in English | MEDLINE | ID: mdl-32807767

ABSTRACT

Epidemiological studies consistently implicate traffic-related air pollution (TRAP) and/or proximity to heavily trafficked roads as risk factors for developmental delays and neurodevelopmental disorders (NDDs); however, there are limited preclinical data demonstrating a causal relationship. To test the effects of TRAP, pregnant rat dams were transported to a vivarium adjacent to a major freeway tunnel system in northern California where they were exposed to TRAP drawn directly from the face of the tunnel or filtered air (FA). Offspring remained housed under the exposure condition into which they were born and were tested in a variety of behavioral assays between postnatal day 4 and 50. To assess the effects of near roadway exposure, offspring of dams housed in a standard research vivarium were tested at the laboratory. An additional group of dams was transported halfway to the facility and then back to the laboratory to control for the effect of potential transport stress. Near roadway exposure delayed growth and development of psychomotor reflexes and elicited abnormal activity in open field locomotion. Near roadway exposure also reduced isolation-induced 40-kHz pup ultrasonic vocalizations, with the TRAP group having the lowest number of call emissions. TRAP affected some components of social communication, evidenced by reduced neonatal pup ultrasonic calling and altered juvenile reciprocal social interactions. These findings confirm that living in close proximity to highly trafficked roadways during early life alters neurodevelopment.


Subject(s)
Neurodevelopmental Disorders , Vehicle Emissions , Animals , Environmental Exposure , Female , Neurodevelopmental Disorders/etiology , Phenotype , Pregnancy , Rats , Risk Factors
17.
Brain Behav Immun Health ; 2: 100033, 2020 Feb.
Article in English | MEDLINE | ID: mdl-38377416

ABSTRACT

Coronary artery disease (CAD) is an immune-mediated disease in which CCR2 attracts classical, intermediate, and non-classical monocytes to the arterial intima where they differentiate to macrophages. Balance between pro-inflammatory M1 and anti-inflammatory M2 macrophages contributes to CAD prevention. Moderate to vigorous intensity physical activity (MVPA) elicits an immune response and reduces the incidence of CAD, however, the impact of prior MVPA on monocyte subset CCR2 expression and macrophage polarization following acute exercise is unknown. Purpose: To determine the impact of physical activity status on monocyte subset CCR2 surface expression and macrophage polarization in response to an acute bout of moderate intensity cycle ergometry. Methods: 24 healthy women and men (12 high physically active [HIACT]: ≥1500 METmin/wk MVPA & 12 low physically active [LOACT]: <600 METmin/wk MVPA) underwent an acute moderate intensity (60% VO2peak) bout of cycle ergometry for 30 â€‹min. Blood samples were collected prior to (PRE), immediately (POST), 1 â€‹h (1H), and 2 â€‹h (2H) following exercise. Monocyte CCR2 and macrophage CD86 (M1) and CD206 (M2) were analyzed by flow cytometry. Results: Intermediate monocyte CCR2 decreased in response to exercise in the HIACT group (PRE: 11409.0 â€‹± â€‹1084.0 vs. POST: 9524.3 â€‹± â€‹1062.4; p â€‹= â€‹0.034). Macrophage CD206 was lower in the LOACT compared to the HIACT group at 1H (HIACT: 67.2 â€‹± â€‹5.6 vs. LOACT: 50.1 â€‹± â€‹5.2%; p â€‹= â€‹0.040). Macrophage CD206 at 1H was associated with both PRE (r â€‹= â€‹0.446, p â€‹= â€‹0.043) and POST (r â€‹= â€‹0.464, p â€‹= â€‹0.034) non-classical monocyte CCR2. Conclusion: These data suggest that regular moderate to vigorous physical activity positively impacts both monocytes and macrophages following acute moderate intensity exercise and that this impact may contribute to the prevention of coronary artery disease.

18.
Iperception ; 10(4): 2041669519870553, 2019.
Article in English | MEDLINE | ID: mdl-31448073

ABSTRACT

A single experiment evaluated the haptic-visual cross-modal matching of solid object shape. One set of randomly shaped artificial objects was used (sinusoidally modulated spheres, SMS) as well as two sets of naturally shaped objects (bell peppers, Capsicum annuum and sweet potatoes, Ipomoea batatas). A total of 66 adults participated in the study. The participants' task was to haptically explore a single object on any particular trial and subsequently indicate which of 12 simultaneously visible objects possessed the same shape. The participants' performance for the natural objects was 60.9 and 78.7 percent correct for the bell peppers and sweet potatoes, respectively. The analogous performance for the SMS objects, while better than chance, was far worse (18.6 percent correct). All of these types of stimulus objects possess a rich geometrical structure (e.g., they all possess multiple elliptic, hyperbolic, and parabolic surface regions). Nevertheless, these three types of stimulus objects are perceived differently: Individual members of sweet potatoes and bell peppers are largely identifiable to human participants, while the individual SMS objects are not. Analyses of differential geometry indicate that these natural objects (e.g., bell peppers and sweet potatoes) possess heterogeneous spatial configurations of distinctly curved surface regions, and this heterogeneity is lacking in SMS objects. The current results therefore suggest that increases in surface structure heterogeneity facilitate human object recognition.

19.
Motor Control ; 23(1): 13-33, 2019 Jan 01.
Article in English | MEDLINE | ID: mdl-29902955

ABSTRACT

We examined whether or not coherence between chest wall intercostal and oblique muscles changed as a function of lung volume excursion, alveolar pressure, and muscular demand. We also assessed the effects of acute expiratory threshold loading (ETL) on chest wall muscular control. A total of 15 healthy adults (7 males; average age = 28 years) completed maximum performance and ETL tasks. Chest wall surface electromyographic and kinematic recordings were made. Participants also performed a session of acute ETL. We showed that corticomuscular control of the chest wall varied as a function of lung volume excursion and muscular effort. Acute ETL had some effect on respiratory kinematics but not coherence.


Subject(s)
Biomechanical Phenomena/physiology , Thoracic Wall/physiopathology , Adult , Female , Humans , Male
20.
Perception ; 47(12): 1166-1178, 2018 12.
Article in English | MEDLINE | ID: mdl-30373473

ABSTRACT

In the current study of haptic distance perception, 20 younger (median age: 22 years) and 20 older adults (median age: 72 years) used active touch to estimate distance ratios(one length relative to another). Nine tactile stimuli were created from wooden dowels; each consisted of two perpendicular dowels. The stimulus distance ratios ranged from 1.0 to 5.0. Each participant used both hands (without vision) to actively explore (30 s) a single stimulus object on every trial. The task was to numerically estimate the distance ratio. Overall, the participants' judgments were precise; the overall magnitude of the Pearson r correlation coefficient was 0.943 and did not differ for younger and older adults. While the participants' judgments were precise, they were not completely accurate: The average slope (of the relationship between actual and judged distance ratios) for all participants was significantly greater than 1.0 (1.15). Surprisingly, differences in manual dexterity had no apparent effect on distance ratio estimates. Older adults apparently retain an excellent ability to perceive distances using their sense of touch. Our results also demonstrate that the geometry of haptic space (at the scale of the hand) is approximately Euclidean in nature (and certainly not merely topological, projective, or affine).


Subject(s)
Aging , Distance Perception , Judgment , Space Perception , Touch Perception , Age Factors , Aged , Aging/physiology , Aging/psychology , Discrimination, Psychological , Female , Humans , Male , Physical Stimulation/methods , Research Design , Sex Factors , Young Adult
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