The Effects of 15 Minutes vs. 30 Minutes of Moderate Intensity Exercise on Lymphocytes, Monocytes and Granulocytes

Vigorous intensity exercise lasting 30 minutes or longer is well known to increase white blood cells, including lymphocytes, monocytes, and granulocytes, in blood. White blood cells are cells of the immune system that provide protection against infection and disease. However, the relative effects of 15 minutes vs 30-minutes of moderate intensity exercise on these variables are not known. PURPOSE: Compare 15 minutes vs 30 minutes of moderate-intensity exercise on the mobilization of white blood cells including lymphocytes (LYM), monocytes (MONO), and granulocytes (GRAN). METHODS: 9 healthy men and women across physical fitness levels were recruited (4 female, (mean ± standard deviation): 28.1 ± 9.7 years old). Following a 5-minute warm-up, participants were prescribed a 30-minute (min) exercise on a stationary bike at a moderate intensity (55% of heart rate reserve, calculated by (maximum heart rate - resting heart rate) × 55% of resting heart rate). A blood sample taken before, after 15 min, and after 30 min of exercise. Blood samples were analyzed with a hematology analyzer. Paired T tests were used to compare LYM, MONO, and GRAN between pre-exercise and 15 min exercise, and between 15 min and 30 min exercise. RESULTS: The number of LYM was greater at 15 min compared to pre-exercise (pre mean ± standard deviation: 2.12 x 103 ± 0.68 x 103 cells/μl, 15 min: 2.88 x 103 ± 1.22 x 103 cells/μl, p=.007). The number of MONO was greater at 15 min compared to pre (pre: 0.43 x 103 ± 0.12 x 103 cells/μl, 15 min: 0.61 x 103 ± 0.19 x 103 cells/μl, p= .006). The number of GRAN was greater at 15 min compared to pre (pre: 2.86 x 103 ± 0.60 x 103 cells/μl, 15 min: 4.00 x 103 ± 0.82 x 103 cells/μl, p= .002). On the other hand, the number of LYM, MONO, and GRAN in blood did not differ between 15 min and 30 min (all p\u3e.05). CONCLUSION: Cycling for just 15 minutes at a moderate intensity showed mobilization of the white blood cells (lymphocytes, monocytes, and granulocytes) into blood circulation. If used in the clinical setting, this has the potential to complement current medical therapies, giving patients with diseases and infections a stronger chance for recovery. However, this requires further investigation

Rheological effects of micropolar slime on the gliding motility of bacteria with slip boundary condition

The gliding organisms are phylogenetically diverse with their hundreds of types, different shapes and several mechanism of motility. Gliding bacteria are rod-shaped bacteria without any flagella on their surface. They exhibit a creeping type of self-powered motion when nearly in contact with a solid surface. These bacteria leave an adhesive trail of slime and propel themselves by producing undulating waves in their body, which is one possible mode of motility for gliding bacteria. In the present study an undulating surface model is considered to discuss this type of bacterial locomotion. The classical Navier-Stokes equations are incapable of explaining the slime rheology at the microscopic level. Micropolar fluid dynamics however provides a solid framework for mimicking bacterial physical phenomena at both micro and nano-scales, and therefore in the present study, the constitutive equations of micropolar fluid are implemented to characterize the rheology of the slime. The flow equations are formulated under long wavelength and low Reynolds number assumptions. Exact expressions for stream function and pressure gradient are obtained. The speed of the gliding bacteria is numerically calculated by using a modified Newton-Raphson method. In addition, when the glider is fixed, the effects of micropolar slime parameters on the velocity, micro-rotation (angular velocity) of spherical slime particles, pressure rise per wavelength, pumping and trapping phenomena are also shown graphically and discussed in detail. The study is relevant to emerging biofuel cell technologies and also bacterial biophysics

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterisation and RALA complexation

DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity. Of these devices, dissolvable microneedles promise a safe, pain-free delivery system which may simultaneously improve DNA stability within a solid matrix and increase DNA delivery compared to solid arrays. However, to date little work has directly compared the suitability of different dissolvable matrices for formulation of DNA-loaded microneedles. Therefore, the current study examined the ability of 4 polymers to formulate mechanically robust, functional DNA loaded dissolvable microneedles. Additionally, complexation of DNA to a cationic delivery peptide, RALA, prior to incorporation into the dissolvable matrix was explored as a means to improve transfection efficacies following release from the polymer matrix. Our data demonstrates that DNA is degraded following incorporation into PVP, but not PVA matrices. The complexation of DNA to RALA prior to incorporation into polymers resulted in higher recovery from dissolvable matrices, and increased transfection efficiencies in vitro. Additionally, RALA/DNA nanoparticles released from dissolvable PVA matrices demonstrated up to 10-fold higher transfection efficiencies than the corresponding complexes released from PVP matrices, indicating that PVA is a superior polymer for this microneedle application

Computational homogenization of nano-materials accounting for size effects via surface elasticity

The objective of this contribution is to establish a first-order computational homogenization framework for micro-to-macro transitions of porous media that accounts for the size effects through the consideration of surface elasticity at the microscale. Although the classical (first-order) homogenization schemes are well established, they are not capable of capturing the well-known size effects in nano-porous materials. In this contribution we introduce surface elasticity as a remedy to account for size effects within a first-order homogenization scheme. This proposition is based on the fact that surfaces are no longer negligible at small scales. Following a standard first-order homogenization ansatz on the microscopic motion in terms of the macroscopic motion, a Hill-type averaging condition is used to link the two scales. The averaging theorems are revisited and generalized to account for surfaces. In the absence of surface energy this generalized framework reduces to classical homogenization. The influence of the length scale is elucidated via a series of numerical examples performed using the finite element method. The numerical results are compared against the analytical ones at small strains for tetragonal and hexagonal microstructures. Furthermore, numerical results at small strains are compared with those at finite strains for both microstructures. Finally, it is shown that there exists an upper bound for the material response of nano-porous media. This finding surprisingly restricts the notion of “smaller is stronger”.ERC Advanced Grant MOCOPOLY, National Research Foundation of South Africa, Samsung Electronics

Perceived manageability of debt and mental health during the COVID-19 pandemic: A UK population analysis

Objectives: This study examined the association between perceived manageability of debt and risk of depression, anxiety, and mental health help-seeking among a nationally representative sample of adults living in the United Kingdom (UK). Methods: Data was derived from the COVID-19 Psychological Research Consortium (C19PRC) Study Wave 6 (August/September 2021) which examined the psychological, social, and economic effects of the COVID-19 pandemic on the UK adult population. Bivariate and logistic regression analyses were conducted to determine the association between different levels of perceived debt manageability (i.e., “easily manageable”, “some problems”, “quite serious problems”, “very serious problems”, “cannot manage at all”) and mental health related outcomes. Results: Almost a quarter of the sample (24%, n = 494) reported debt management problems, and debt manageability associated with higher levels of anxiety, depression, and mental health help-seeking. After adjusting for demographic variables (e.g. income, receipt of benefits), logistic regression analysis demonstrated a dose-response association between increasing levels of debt manageability problems and mental health outcomes. Specifically, adjusted odds ratios for anxiety ranged from 2.28 (‘some problems’) to 11.18 (‘very serious problems’), for depression ranged from 2.80 (‘some problems’) to 16.21 (‘cannot manage at all’), and for mental health help-seeking ranged from 1.69 (‘some problems’) to 3.18 (‘quite serious problems’, ‘very serious problems’). Conclusion: This study highlights that debt manageability problems represent a robust predictor of depression, anxiety, and mental-health help seeking

Intentional left subclavian artery coverage during thoracic endovascular aortic repair for traumatic aortic injury

BackgroundThoracic endovascular aortic repair (TEVAR) is widely used for treatment of traumatic aortic injury (TAI). Stent graft coverage of the left subclavian artery (LSA) may be required in up to 40% of patients. We evaluated the long-term effects of intentional LSA coverage (LSAC) on symptoms and return to normal activity in TAI patients compared with a similarly treated group whose LSA was uncovered (LSAU).MethodsPatients were identified from a prospective institutional trauma registry between September 2005 and July 2012. TAI was confirmed using computed tomography angiography. The electronic medical records, angiograms, and computed tomography angiograms were reviewed in a retrospective fashion. In-person or telephone interviews were conducted using the SF-12v2 (Quality Metrics, Lincoln, RI) to assess quality of life. An additional questionnaire was used to assess specific LSA symptoms and the ability to return to normal activities. Data were analyzed by Spearman rank correlation and multiple linear and logistic regression analysis with appropriate transformations using SAS software (SAS Institute, Cary, NC).ResultsDuring the study period, 82 patients (57 men; mean age 40.5 ± 20 years, mean Injury Severity Score, 34 ± 10.0) underwent TEVAR for treatment of TAI. Among them, LSAC was used in 32 (39.5%) and LSAU in 50. A group of the LSAU patients (n = 22) served as matched controls in the analysis. We found no statistically significant difference in SF-12v2 physical health scores (ρ = −0.08; P = .62) between LSAC and LSAU patients. LSAC patients had slightly better mental health scores (ρ = 0.62; P = .037) than LSAU patients. LSAC patients did not have an increased likelihood of experiencing pain (ρ = −0.0056; P = .97), numbness (ρ = −0.12; P = .45), paresthesia (ρ = −0.11; P = .48), fatigue (ρ = −0.066; P = .69), or cramping (ρ = −0.12; P = .45). We found no difference between groups in the ability to return to activities. The mean follow-up time was 3.35 years. Six LSAC patients (19%) died during the follow-up period of unrelated causes.ConclusionsIntentional LSAC during TEVAR for TAI appears safe, without compromising mental or physical health outcomes. Furthermore, LSAC does not increase the long-term risk of upper extremity symptoms or impairment of normal activities

Systemic RALA/iNOS nanoparticles; a potent gene therapy for metastatic breast cancer coupled as a biomarker of treatment

This study aimed to determine the therapeutic benefit of a nanoparticular formulation for the delivery of inducible nitric oxide synthase (iNOS) gene therapy in a model of breast cancer metastasis. Nanoparticles comprising a cationic peptide vector, RALA, and plasmid DNA were formulated and characterized using a range of physiochemical analyses. Nanoparticles complexed using iNOS plasmids and RALA approximated 60 nm in diameter with a charge of 25 mV. A vector neutralization assay, performed to determine the immunogenicity of nanoparticles in immunocompetent C57BL/6 mice, revealed that no vector neutralization was evident. Nanoparticles harboring iNOS plasmids (constitutively active cytomegalovirus [CMV]-driven or transcriptionally regulated human osteocalcin [hOC]-driven) evoked iNOS protein expression and nitrite accumulation and impaired clonogenicity in the highly aggressive MDA-MB-231 human breast cancer model. Micrometastases of MDA-MB-231-luc-D3H1 cells were established in female BALB/c SCID mice by intracardiac delivery. Nanoparticulate RALA/CMV-iNOS or RALA/hOC-iNOS increased median survival in mice bearing micrometastases by 27% compared with controls and also provoked elevated blood nitrite levels. Additionally, iNOS gene therapy sensitized MDA-MB-231-luc-D3H1 tumors to docetaxel treatment. Studies demonstrated that systemically delivered RALA-iNOS nanoparticles have therapeutic potential for the treatment of metastatic breast cancer. Furthermore, detection of nitrite levels in the blood serves as a reliable biomarker of treatment. Keywords: nonviral gene therapy, nitric oxide, nanoparticle, breast cancer, metastasi

Expanded access to cancer treatments from conversion to neutropenia prophylaxis with biosimilar filgrastim-sndz

Aim: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis. Methods: Simulation study using cost data for the USA under consideration of several prophylaxis patterns. Results: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz). Conclusion: The combination of biosimilar savings and expanded access increases the value of cancer care as the same supportive care is provided at lower cost, additional cancer care is enabled at no additional cost, and more patients will have access to cancer care.Sandoz Inc., Princeton, NJ, USAOpen access article.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]