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1.
Animals (Basel) ; 14(17)2024 Sep 09.
Article in English | MEDLINE | ID: mdl-39272407

ABSTRACT

Effective communication is a hallmark of successful veterinary clinical practice [...].

2.
Glob Adv Integr Med Health ; 13: 27536130241278970, 2024.
Article in English | MEDLINE | ID: mdl-39219712

ABSTRACT

Background: Surf therapy combines physical activity with social support to provide a healing environment. Objective: This exploratory pre-to post-intervention study examined the effects of a novel surf therapy program for women who experienced abuse, trauma, and/or mental illness on emotional regulation, resilience, body acceptance, and gratitude. Methods: Twenty-seven women (ages 25 to 54; mean 36.32 + SD 7.79) participated in an 8-week Groundswell Surf Therapy Program held in four different coastal cities in California. Standardized self-report questionnaires were administered prior to and following the therapy program, including the Body Acceptance Scale, the Connor-Davidson Resilience Scale (CD-RISC), the Affective Style Questionnaire, and the Gratitude Questionnaire-Six-Item Form (GQ-6) in a pre-post study design. Data were analyzed by repeated measures analysis of variance (ANOVA). Results: Body acceptance [P < 0.001; partial Eta squared = 0.472] and resilience were increased [P = 0.005; partial Eta squared = 0.319] following the surf therapy intervention. Emotional regulation was examined according to three subscales, with the adjust [P < 0.001; partial Eta squared = 0.397] and tolerate [P < 0.001; partial Eta squared = 0.299] subscales increasing following the intervention, and the conceal subscale [P = 0.459; partial Eta squared = 0.031] remaining unchanged. Gratitude scores were unchanged [P = 0.425; partial Eta squared = 0.026]. Conclusion: A surf therapy program rooted in somatic and trauma-informed models was associated with improved resilience, emotional regulation, and body acceptance in at-risk women.

3.
Am J Epidemiol ; 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39191647

ABSTRACT

COVID-19 vaccine efficacy has been evaluated in controlled clinical trials and serves as a benchmark for evaluating the protection acquired from prior COVID-19 infection ("natural immunity"). A cohort of persons with a prior COVID-19 infection was matched to a cohort of COVID-19 vaccinated persons and the risk of reinfection post-COVID-19 infection was compared to the risk of a COVID-19 infection post-vaccination. The hazard ratio (HR) for risk of reinfection from day 90 to 300 after initial COVID-19 infection vs. vaccine breakthrough infection was 0.48, 95% Confidence Interval (CI) 0.31-0.73). Thus from 90 to 300 days after COVID-19 infection, the post-COVID-19 infection cohort had a lower risk of COVID-19 infection compared with those fully vaccinated. The risk of death associated with the initial COVID-19 infection requisite for acquiring post-COVID-19 immunity was also assessed. The hazard ratio (HR) for deaths from all causes among those acquiring immunity via COVID-19 infection vs. vaccination was 14.9 (95% CI 7.27-30.4). Thus, while post-COVID-19 immunity was on a level comparable to that of vaccination, there was a 15-fold higher mortality resulting from achieving "natural immunity" versus acquiring vaccine-provided immunity.

4.
Clin Hypertens ; 30(1): 14, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822391

ABSTRACT

BACKGROUND: Obstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy. METHODS AND RESULTS: Forty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal. CONCLUSIONS: OSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea. TRIAL REGISTRATION: NCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125 .

5.
Ann Surg ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38801247

ABSTRACT

OBJECTIVE: To implement the BREASTChoice decision tool into the electronic health record and evaluate its effectiveness. BACKGROUND: BREASTChoice , is a multilevel decision tool that: 1) educates patients about breast reconstruction; 2) estimates personalized risk of complications; 3) clarifies patient preferences; and 4) informs clinicians about patients' risk and preferences. METHODS: A multisite randomized controlled trial enrolled adult women with stage 0-III breast malignancy undergoing mastectomy. Participants were randomized to BREASTChoice or a control website. A survey assessed knowledge, preferences, decisional conflict, shared decision-making, preferred treatment, and usability. We conducted intent-to-treat (ITT), per-protocol (PP) analyses (those randomized to BREASTChoice who accessed the tool), and stratified analyses. RESULTS: 23/25 eligible clinicians enrolled. 369/761 (48%) contacted patients enrolled and were randomized. Patients' average age was 51 years; 15% were older than 65. BREASTChoice participants had higher knowledge than control participants (ITT: mean 70.6 vs. 67.4, P =0.08; PP: mean 71.4 vs. 67.4, P =0.03), especially when stratified by site (ITT: P =0.04, PP: P =0.01), age (ITT: P =0.04, PP: P =0.02), and race (ITT: P =0.04, PP: P =0.01). BREASTChoice did not improve decisional conflict, match between preferences and treatment, or shared decision-making. In PP analyses, fewer high-risk patients using BREASTChoice chose reconstruction. BREASTChoice had high usability. CONCLUSIONS: BREASTChoice is a novel decision tool incorporating risk prediction, patient education, and clinician engagement. Patients using BREASTChoice had higher knowledge; older adults and those from racially minoritized backgrounds especially benefitted. There was no impact on other decision outcomes. Future studies should overcome implementation barriers and specifically examine decision outcomes among high-risk patients.

6.
Pharmaceutics ; 16(5)2024 May 16.
Article in English | MEDLINE | ID: mdl-38794337

ABSTRACT

The transdermal delivery of non-steroidal anti-inflammatory drugs (NSAIDs) has the potential to overcome some of the major disadvantages relating to oral NSAID usage, such as gastrointestinal adverse events and compliance. However, the poor solubility of many of the newer NSAIDs creates challenges in incorporating the drugs into formulations suitable for application to skin and may limit transdermal permeation, particularly if the goal is therapeutic systemic drug concentrations. This review is an overview of the various strategies used to increase the solubility of poorly soluble NSAIDs and enhance their permeation through skin, such as the modification of the vehicle, the modification of or bypassing the barrier function of the skin, and using advanced nano-sized formulations. Furthermore, the simple yet highly versatile microemulsion system has been found to be a cost-effective and highly successful technology to deliver poorly water-soluble NSAIDs.

7.
Proteomics ; 24(14): e2300431, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38468111

ABSTRACT

SWATH is a data acquisition strategy acclaimed for generating quantitatively accurate and consistent measurements of proteins across multiple samples. Its utility for proteomics studies in nonlaboratory animals, however, is currently compromised by the lack of sufficiently comprehensive and reliable public libraries, either experimental or predicted, and relevant platforms that support their sharing and utilization in an intuitive manner. Here we describe the development of the Veterinary Proteome Browser, VPBrowse (http://browser.proteo.cloud/), an on-line platform for genome-based representation of the Bos taurus proteome, which is equipped with an interactive database and tools for searching, visualization, and building quantitative mass spectrometry assays. In its current version (VPBrowse 1.0), it contains high-quality fragmentation spectra acquired on QToF instrument for over 36,000 proteotypic peptides, the experimental evidence for over 10,000 proteins. Data can be downloaded in different formats to enable analysis using popular software packages for SWATH data processing whilst normalization to iRT scale ensures compatibility with diverse chromatography systems. When applied to published blood plasma dataset from the biomarker discovery study, the resource supported label-free quantification of additional proteins not reported by the authors previously including PSMA4, a tissue leakage protein and a promising candidate biomarker of animal's response to dehorning-related injury.


Subject(s)
Proteome , Proteomics , Software , Tandem Mass Spectrometry , Cattle , Animals , Tandem Mass Spectrometry/methods , Proteomics/methods , Proteome/analysis , Databases, Protein , Genome/genetics
8.
J Wound Care ; 33(Sup2a): xiv-xix, 2024 Feb 01.
Article in English | MEDLINE | ID: mdl-38324421

ABSTRACT

OBJECTIVE: Thermal burn is a serious cause of morbidity and mortality that affects millions of people worldwide. The aim of this experimental study was to investigate the efficacy of Arnebia euchroma (AE) to treat burn wounds in a rat model. METHOD: A total of 80 male rats (200-250g) were shaved over the back of the neck (2×3cm2) and a second-degree burn wound was induced at this site under general anaesthesia. The rats were then randomly assigned to one of four groups (each n=20) and the burns were treated daily for 14 days as follows: (1) dressed with animal fat; (2) dressed with sulfadiazine; (3) dressed with a mixture of AE and animal fat; (4) no treatment (control). Five rats from each group were sacrificed on days 3, 5, 9 and 14 post-burn and the wounds were evaluated histologically and immunohistochemically for the expression of interleukin (IL)-1 and IL-6. RESULTS: There was a significant increase at day 3 and decrease on day 5 samples for the expression of IL-1 in the AE plus fat group and IL-6 in the AE plus fat and sulfadiazine groups, compared to the control and fat treatment groups, respectively. Both AE plus fat and sulfadiazine treatments reduced inflammation and granulation tissue formation by day 5 post-burn, while re-epithelialisation commenced by day 9 post-burn. In addition, burns treated with AE plus fat exhibited keratinised epidermis, associated with regular collagen fibres, compared to moderately dense collagen fibres without vascularisation in the sulfadiazine group. CONCLUSION: These findings suggested that AE plus fat was superior to sulfadiazine in enhancing burn wound healing in rats.


Subject(s)
Boraginaceae , Sulfadiazine , Humans , Rats , Male , Animals , Sulfadiazine/pharmacology , Interleukin-6/pharmacology , Wound Healing , Collagen/pharmacology , Silver Sulfadiazine/pharmacology , Silver Sulfadiazine/therapeutic use
9.
Biosensors (Basel) ; 14(1)2024 Jan 09.
Article in English | MEDLINE | ID: mdl-38248409

ABSTRACT

Non-invasive deep brain stimulation using transcranial magnetic stimulation is a promising technique for treating several neurological disorders, such as Alzheimer's and Parkinson's diseases. However, the currently used coils do not demonstrate the required stimulation performance in deep regions of the brain, such as the hippocampus, due to the rapid decay of the field inside the head. This study proposes an array that uses the cone coil method for deep stimulation. This study investigates the impact of magnetic core and shielding on field strength, focality, decay rate, and safety. The coil's size and shape effects on the electric field distribution in deep brain areas are also examined. The finite element method is used to calculate the induced electric field in a realistic human head model. The simulation results indicate that the magnetic core and shielding increase the electric field intensity and enhance focality but do not improve the field decay rate. However, the decay rate can be reduced by increasing the coil size at the expense of focality. By adopting an optimum cone structure, the proposed five-coil array reduces the electric field attenuation rate to reach the stimulation threshold in deep regions while keeping all other regions within safety limits. In vitro and in vivo experimental results using a head phantom and a dead pig's head validate the simulated results and confirm that the proposed design is a reliable and efficient candidate for non-invasive deep brain magnetic stimulation.


Subject(s)
Brain , Parkinson Disease , Humans , Computer Simulation , Electricity , Phantoms, Imaging
10.
Vet J ; 296-297: 105985, 2023.
Article in English | MEDLINE | ID: mdl-37127134

ABSTRACT

Behaviour-related issues are common in horses. Many 'undesirable behaviours' pose important safety concerns for the human handlers / riders / carers, as well as welfare concerns for the horse. Undesirable behaviours can also devalue a horse, or result in the horse being re-homed, relinquished, or euthanased. Undesirable behaviours occur for a range of reasons. These include physiological causes, poor management, and the use of inappropriate or poorly applied handling and training techniques. The potential contribution of each of these aspects must be considered when attempting to reduce or eliminate undesirable behaviours. Effectively modifying the existing behaviour includes investigation and treatment of potential physiological causes, assessing and adjusting existing handling, husbandry and management, and undertaking behaviour modifying training. Unlike in the treatment of dogs and cats, the use of psychotropic agents is uncommon in equine behaviour medicine but the benefits of using these agents in appropriate cases is gaining recognition. This review discusses potential causes for the development and maintenance of undesirable behaviours in horses and highlights the various considerations involved in determining the most appropriate course for reducing or eliminating these behaviours. There is also a brief discussion about the potential role of psychotropic agents as an additional component of an overall behaviour modification plan to reduce or eliminate undesirable behaviours in horses.


Subject(s)
Cat Diseases , Dog Diseases , Horse Diseases , Problem Behavior , Horses , Animals , Humans , Dogs , Cats , Behavior, Animal/physiology , Horse Diseases/therapy
11.
J Proteome Res ; 22(6): 2018-2029, 2023 06 02.
Article in English | MEDLINE | ID: mdl-37219895

ABSTRACT

Sequential window acquisition of all theoretical mass spectra-mass spectrometry underpinned by advanced bioinformatics offers a framework for comprehensive analysis of proteomes and the discovery of robust biomarkers. However, the lack of a generic sample preparation platform to tackle the heterogeneity of material collected from different sources may be a limiting factor to the broad application of this technique. We have developed universal and fully automated workflows using a robotic sample preparation platform, which enabled in-depth and reproducible proteome coverage and characterization of bovine and ovine specimens representing healthy animals and a model of myocardial infarction. High correlation (R2 = 0.85) between sheep proteomics and transcriptomics datasets validated the developments. The findings suggest that automated workflows can be employed for various clinical applications across different animal species and animal models of health and disease.


Subject(s)
Proteome , Proteomics , Animals , Cattle , Sheep , Proteomics/methods , Workflow , Mass Spectrometry/methods , Biomarkers , Proteome/analysis
12.
Environ Health Perspect ; 131(3): 37001, 2023 03.
Article in English | MEDLINE | ID: mdl-36856429

ABSTRACT

BACKGROUND: The prevalence of liver disorders and metabolic syndrome has increased among youth. Glyphosate, the most widely used herbicide worldwide, could contribute to the development of these conditions. OBJECTIVE: We aimed to assess whether lifetime exposure to glyphosate and its degradation product, aminomethylphosphonic acid (AMPA), is associated with elevated liver transaminases and metabolic syndrome among young adults. METHODS: We conducted a prospective cohort study (n=480 mother-child dyads) and a nested case-control study (n=60 cases with elevated liver transaminases and 91 controls) using data from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS). We measured glyphosate and AMPA concentrations in urine samples collected during pregnancy and at child ages 5, 14, and 18 y from cases and controls. We calculated glyphosate residue concentrations: [glyphosate + (1.5×AMPA)]. We estimated the amount of agricultural-use glyphosate applied within a 1-km radius of every residence from pregnancy to age 5 y for the full cohort using California Pesticide Use Reporting data. We assessed liver transaminases and metabolic syndrome at 18 y of age. RESULTS: Urinary AMPA at age 5 y was associated with elevated transaminases [relative risk (RR) per 2-fold increase=1.27, 95% confidence interval (CI): 1.06, 1.53] and metabolic syndrome (RR=2.07, 95% CI: 1.38, 3.11). Urinary AMPA and glyphosate residues at age 14 y were associated with metabolic syndrome [RR=1.80 (95% CI: 1.10, 2.93) and RR=1.88 (95% CI: 1.03, 3.42), respectively]. Overall, a 2-fold increase in urinary AMPA during childhood was associated with a 14% and a 55% increased risk of elevated liver transaminases and metabolic syndrome, respectively. Living near agricultural glyphosate applications during early childhood (birth to 5 y of age) was also associated with metabolic syndrome at age 18 y in the case-control group (RR=1.53, 95% CI: 1.16, 2.02). DISCUSSION: Childhood exposure to glyphosate and AMPA may increase risk of liver and cardiometabolic disorders in early adulthood, which could lead to more serious diseases later in life. https://doi.org/10.1289/EHP11721.


Subject(s)
Metabolic Syndrome , Female , Pregnancy , Young Adult , Adolescent , Child, Preschool , Humans , Adult , Case-Control Studies , Prospective Studies , alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid , Liver , Inflammation , Glyphosate
13.
Explore (NY) ; 19(5): 689-694, 2023.
Article in English | MEDLINE | ID: mdl-36710104

ABSTRACT

CONTEXT: While advances in the Western sciences have increased our understanding of the human biofield, few studies have examined the potential effects of sacred objects on its functioning. DESIGN AND STUDY PARTICIPANTS: This exploratory study examined the effects of a sacred object called the Sri Yantra / Durga Stone on the human biofield. Twelve women and five men were studied on three separate occasions using the Bio-Well device, which purportedly measures aspects of the biofield: baseline (the day before exposure to the sacred object), pre-exposure (immediately prior to exposure to the sacred object), and post-exposure (immediately following exposure to the sacred object). A set of a priori hypotheses examined outcome effects on a set of variables, including multiple physiological systems. RESULTS: The overall Bio-Well energy state (Bio-Well variables are in units of joules) was significantly changed following exposure to the sacred object (p = 0.001). In addition, the cardiovascular, endocrine, musculoskeletal, digestive, urinogenital, and immune system readings showed significant changes (p's<0.003) while the nervous and respiratory system assessments were unchanged. Chakra (defined as a center of vital prana) energy was changed following exposure to the stone (p = 0.001), while chakra alignment was not (p = 0.145). CONCLUSIONS: The findings from this exploratory study suggest that short-term human exposure to this particular sacred object had significant effects on aspects of the human biofield.


Subject(s)
Spirituality , Female , Humans , Male
14.
J Vet Pharmacol Ther ; 46(1): 70, 2023 01.
Article in English | MEDLINE | ID: mdl-36621862
15.
Animals (Basel) ; 12(21)2022 Oct 24.
Article in English | MEDLINE | ID: mdl-36359031

ABSTRACT

Husbandry and veterinary procedures have the potential to generate fear and stress in animals. In horses, the associated responses can pose a significant safety risk to the human personnel involved in the procedure, as well as to the animal itself. Traditionally, physical restraint, punishment, and/or threat of an aversive, have been the most common strategies used to achieve compliance from the horse. However, from a welfare perspective, this is less than ideal. This approach also has the potential for creating a more dangerous response from the horse in future similar situations. When caring for companion animals, and captive animals within zoological facilities, there has been a steady transition away from this approach, and toward strategies aimed at reducing fear and stress during veterinary visits and when undertaking routine husbandry procedures. This review discusses the current approaches to horse care and training, the strategies being used in other animal sectors, and potential strategies for improving human safety, as well as the horse's experience, during husbandry and veterinary procedures.

17.
J Vet Pharmacol Ther ; 45(6): 530-542, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36057922

ABSTRACT

Ketoprofen is registered in many countries for injectable administration in cattle. Because it is soluble in a wide range of excipients, development of a novel transdermal (TD) ketoprofen formulation was pursued to provide a convenient and pain-free route of administration in cattle. One hundred and six excipient combinations were screened using in vitro techniques (Franz diffusion cells), with a 20%(w/v) ketoprofen formulation dissolved in a combination of 45%:45%(v/v) ethanol and isopropyl myristate (IPM) and 10%(v/v) eucalyptus oil achieving maximal penetration of ketoprofen through bovine skin. A bioavailability study was then conducted using a randomized cross-over design (n = 12), including IV, IM (both 3 mg/kg) and TD (10 mg/kg) ketoprofen formulations administered with a one-week washout period between administrations. The IV and IM formulation pharmacokinetic results were as expected. The CMAX , Tmax and AUC0-Last were significantly higher (arithmetic mean ± SD) after TD administration (20.0 ± 6.5 µg/ml, 115 ± 17 min and 3940 ± 1324 µg*min/ml, respectively), compared to IM (11.0 ± 4.0 µg/ml, 74 ± 43 min and 2376 ± 738 µg*min/ml, respectively), although there were no significant differences for T½ß . However, dose corrected values CMAX and AUCinf were significantly higher for IM compared to TD. The arithmetic mean bioavailability (F) of the transdermal formulation was 50%. The plasma concentration of the TD formulation at a dose of 10 mg/kg was similar to the IM formulation at 3 mg/kg by 30 min post-dosing with an arithmetic mean ± SD of 7.97 ± 4.38 vs. 8.02 ± 3.55 µg/ml, respectively. The TD formulation was generally well tolerated by cattle, although some local irritation along the site of application was noted after 12 h of exposure during the bioavailability study. Results indicate that this novel TD formulation provides a substantial improvement in administration convenience, may improve animal welfare and end-user safety through needle-free administration, and achieves similar plasma pharmacokinetics to the IM product when administered at 10 mg/kg.


Subject(s)
Analgesia , Ketoprofen , Cattle , Animals , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Administration, Cutaneous , Biological Availability , Cross-Over Studies , Analgesia/veterinary
18.
Article in English | MEDLINE | ID: mdl-36078632

ABSTRACT

Introduction: Cross-sectional association between the neighborhood-built environment and physical activity (PA) has been demonstrated previously, indicating the importance of neighborhood perception characteristics such as walkability, safety, and the connectivity of streets on PA levels. Our study aimed to assess the longitudinal data from participants of the Multi-Ethnic Study of Atherosclerosis (MESA) to evaluate the potential relationship between perceived environment and PA patterns. Methods: We analyzed data from a subset of participants (n = 3097) with available PA data who participated in a prospective cohort conducted from 2000 to 2018. The exposure variables were the perceived aspects of the neighborhood environment and the perception of safety, and the outcome was patterns of PA. Patterns were defined as categories reflecting meeting versus not meeting PA guidelines over time. We created the following categories: adopters (individuals who did not meet guidelines at baseline but met guidelines at Exam 6), relapsers (individuals who met guidelines at baseline but did not meet guidelines at Exam 6), maintainers (individuals who met guidelines both at baseline and Exam 6), and insufficiently active (individuals who did not meet guidelines at either baseline or Exam 6). The maintainers' group was considered the reference category. We estimated the relative risk to assess the magnitude effect of the association between environmental perceptions and the outcome. Results: Individuals who reported that lack of parks and playgrounds was "not a problem" in their neighborhood had a 2.3-times higher risk of decreasing their physical activity (i.e., the "relapser" category) compared to maintainers. After full adjustment, perceiving poor sidewalks as "somewhat a serious problem" was associated with a 64% lower risk of becoming an adopter than a maintainer. When compared to those who perceive the neighborhood as "very safe", perception of the neighborhood as "safe" to "not at all safe" (ratings 3, 4, and 5, respectively, on the perceived safety scale) was significantly associated with being classified in the adopter category. Conclusions: As the first longitudinal study of the association of perceived environment and physical activity within the MESA cohort, we conclude that a few aspects are longitudinally associated with being physically active among adults.


Subject(s)
Atherosclerosis , Environment Design , Adult , Cross-Sectional Studies , Exercise , Follow-Up Studies , Humans , Longitudinal Studies , Prospective Studies , Residence Characteristics , Walking
19.
Commun Biol ; 5(1): 828, 2022 08 17.
Article in English | MEDLINE | ID: mdl-35978153

ABSTRACT

With planned deep space and commercial spaceflights, gaps remain to address health risks in astronauts. Multiple studies have shown associations between clonal expansion of hematopoietic cells with hematopoietic malignancies and cardiometabolic disease. This expansion of clones in the absence of overt hematopoietic disorders is termed clonal hematopoiesis (CH) of indeterminate potential (CHIP). Using deep, error-corrected, targeted DNA sequencing we assayed for somatic mutations in CH-driver genes in peripheral blood mononuclear cells isolated from de-identified blood samples collected from 14 astronauts who flew Shuttle missions between 1998-2001. We identified 34 nonsynonymous mutations of relatively low variant allele fraction in 17 CH-driver genes, with the most prevalent mutations in TP53 and DNMT3A. The presence of these small clones in the blood of relatively young astronaut cohort warrants further retrospective and prospective investigation of their clinical relevance and potential application in monitoring astronaut's health.


Subject(s)
Clonal Hematopoiesis , Hematopoiesis , Astronauts , Clonal Hematopoiesis/genetics , Hematopoiesis/genetics , Humans , Leukocytes, Mononuclear , Mutation , Prospective Studies , Retrospective Studies
20.
Front Cardiovasc Med ; 9: 855181, 2022.
Article in English | MEDLINE | ID: mdl-35783863

ABSTRACT

There are unique stressors in the spaceflight environment. Exposure to such stressors may be associated with adverse effects on astronauts' health, including increased cancer and cardiovascular disease risks. Small extracellular vesicles (sEVs, i.e., exosomes) play a vital role in intercellular communication and regulate various biological processes contributing to their role in disease pathogenesis. To assess whether spaceflight alters sEVs transcriptome profile, sEVs were isolated from the blood plasma of 3 astronauts at two different time points: 10 days before launch (L-10) and 3 days after return (R+3) from the Shuttle mission. AC16 cells (human cardiomyocyte cell line) were treated with L-10 and R+3 astronauts-derived exosomes for 24 h. Total RNA was isolated and analyzed for gene expression profiling using Affymetrix microarrays. Enrichment analysis was performed using Enrichr. Transcription factor (TF) enrichment analysis using the ENCODE/ChEA Consensus TF database identified gene sets related to the polycomb repressive complex 2 (PRC2) and Vitamin D receptor (VDR) in AC16 cells treated with R+3 compared to cells treated with L-10 astronauts-derived exosomes. Further analysis of the histone modifications using datasets from the Roadmap Epigenomics Project confirmed enrichment in gene sets related to the H3K27me3 repressive mark. Interestingly, analysis of previously published H3K27me3-chromatin immunoprecipitation sequencing (ChIP-Seq) ENCODE datasets showed enrichment of H3K27me3 in the VDR promoter. Collectively, our results suggest that astronaut-derived sEVs may epigenetically repress the expression of the VDR in human adult cardiomyocytes by promoting the activation of the PRC2 complex and H3K27me3 levels.

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