Summary
Microglia are a proliferative population of resident brain macrophages that under physiological conditions self‐renew independent of hematopoiesis. Microglia are innate immune cells actively ...surveying the brain and are the earliest responders to injury. During aging, microglia elicit an enhanced innate immune response also referred to as ‘priming’. To date, it remains unknown whether telomere shortening affects the proliferative capacity and induces priming of microglia. We addressed this issue using early (first‐generation G1 mTerc−/−)‐ and late‐generation (third‐generation G3 and G4 mTerc−/−) telomerase‐deficient mice, which carry a homozygous deletion for the telomerase RNA component gene (mTerc). Late‐generation mTerc−/− microglia show telomere shortening and decreased proliferation efficiency. Under physiological conditions, gene expression and functionality of G3 mTerc−/− microglia are comparable with microglia derived from G1 mTerc−/− mice despite changes in morphology. However, after intraperitoneal injection of bacterial lipopolysaccharide (LPS), G3 mTerc−/− microglia mice show an enhanced pro‐inflammatory response. Nevertheless, this enhanced inflammatory response was not accompanied by an increased expression of genes known to be associated with age‐associated microglia priming. The increased inflammatory response in microglia correlates closely with increased peripheral inflammation, a loss of blood–brain barrier integrity, and infiltration of immune cells in the brain parenchyma in this mouse model of telomere shortening.
In the present work, superparamagnetic adsorbents based on 3-aminopropyltrimethoxy silane (APTMS)-coated maghemite (γFe2O3@SiO2–NH2) and cobalt ferrite (CoFe2O4@SiO2–NH2) nanoparticles were prepared ...and characterized using transmission-electron microscopy (TEM/HRTEM/EDXS), Fourier-transform infrared spectroscopy (FTIR), specific surface-area measurements (BET), zeta potential (ζ) measurements, thermogravimetric analysis (TGA), and magnetometry (VSM). The adsorption of Dy3+, Tb3+, and Hg2+ ions onto adsorbent surfaces in model salt solutions was tested. The adsorption was evaluated in terms of adsorption efficiency (%), adsorption capacity (mg/g), and desorption efficiency (%) based on the results of inductively coupled plasma optical emission spectrometry (ICP-OES). Both adsorbents, γFe2O3@SiO2–NH2 and CoFe2O4@SiO2–NH2, showed high adsorption efficiency toward Dy3+, Tb3+, and Hg2+ ions, ranging from 83% to 98%, while the adsorption capacity reached the following values of Dy3+, Tb3+, and Hg2+, in descending order: Tb (4.7 mg/g) > Dy (4.0 mg/g) > Hg (2.1 mg/g) for γFe2O3@SiO2–NH2; and Tb (6.2 mg/g) > Dy (4.7 mg/g) > Hg (1.2 mg/g) for CoFe2O4@SiO2–NH2. The results of the desorption with 100% of the desorbed Dy3+, Tb3+, and Hg2+ ions in an acidic medium indicated the reusability of both adsorbents. A cytotoxicity assessment of the adsorbents on human-skeletal-muscle derived cells (SKMDCs), human fibroblasts, murine macrophage cells (RAW264.7), and human-umbilical-vein endothelial cells (HUVECs) was conducted. The survival, mortality, and hatching percentages of zebrafish embryos were monitored. All the nanoparticles showed no toxicity in the zebrafish embryos until 96 hpf, even at a high concentration of 500 mg/L.
The global catastrophe known as COVID-19 has shattered the world’s socioeconomic structure. Effective and affordable diagnosis techniques are crucial for better COVID-19 therapy and the eradication ...of bogus cases. Due to the daily upsurge in cases, hospitals only have a small supply of COVID-19 test kits. The study describes a deep Convolutional Neural Network (CNN) design for categorizing chest x-ray images in the diagnosis of COVID-19. The lack of a substantial, high-quality chest x-ray picture collection made efficient and exact CNN categorization problematic. The dataset has been pre-processed using an image enhancement strategy to provide an effective training dataset for the proposed CNN model to achieve performance. The proposed model achieves 99.73% of accuracy, 98.95% of specificity, 99.47% of precision, 99.62% of sensitivity, and 98.71% of F1 score. A comparative study between the proposed model and numerous CNN-based COVID-19 detection algorithms is carried out to demonstrate that it outperforms other models. When evaluated on a separate dataset, the suggested model excelled over all other models, generally and explicitly.
Purpose
There is a large body of evidence supporting the efficacy of low-level laser therapy (LLLT), more recently termed photobiomodulation (PBM) for the management of oral mucositis (OM) in ...patients undergoing radiotherapy for head and neck cancer (HNC). Recent advances in PBM technology, together with a better understanding of mechanisms involved and dosimetric parameters may lead to the management of a broader range of complications associated with HNC treatment. This could enhance patient adherence to cancer therapy, and improve quality of life and treatment outcomes. The mechanisms of action, dosimetric, and safety considerations for PBM have been reviewed in part 1. Part 2 discusses the head and neck treatment side effects for which PBM may prove to be effective. In addition, PBM parameters for each of these complications are suggested and future research directions are discussed.
Methods
Narrative review and presentation of PBM parameters are based on current evidence and expert opinion.
Results
PBM may have potential applications in the management of a broad range of side effects of (chemo)radiation therapy (CRT) in patients being treated for HNC. For OM management, optimal PBM parameters identified were as follows:
wavelength
, typically between 633 and 685 nm or 780–830 nm;
energy density
, laser or light-emitting diode (LED) output between 10 and 150 mW;
dose
, 2–3 J (J/cm
2
), and no more than 6 J/cm
2
on the tissue surface treated;
treatment schedule
, two to three times a week up to daily;
emission type
, pulsed (<100 Hz); and
route of delivery
, intraorally and/or transcutaneously. To facilitate further studies, we propose potentially effective PBM parameters for prophylactic and therapeutic use in supportive care for dermatitis, dysphagia, dry mouth, dysgeusia, trismus, necrosis, lymphedema, and voice/speech alterations.
Conclusion
PBM may have a role in supportive care for a broad range of complications associated with the treatment of HNC with CRT. The suggested PBM irradiation and dosimetric parameters, which are potentially effective for these complications, are intended to provide guidance for well-designed future studies. It is imperative that such studies include elucidating the effects of PBM on oncology treatment outcomes.
We present the final data release of the APEX low-redshift legacy survey for molecular gas (ALLSMOG), comprising CO(2–1) emission line observations of 88 nearby, low-mass (108.5<M∗ M⊙ < 1010) ...star-forming galaxies carried out with the 230 GHz APEX-1 receiver on the APEX telescope. The main goal of ALLSMOG is to probe the molecular gas content of more typical and lower stellar mass galaxies than have been studied by previous CO surveys. We also present IRAM 30 m observations of the CO(1–0) and CO(2–1) emission lines in nine galaxies aimed at increasing the M∗< 109M⊙ sample size. In this paper we describe the observations, data reduction and analysis methods and we present the final CO spectra together with archival Hi 21 cm line observations for the entire sample of 97 galaxies. At the sensitivity limit of ALLSMOG, we register a total CO detection rate of 47%. Galaxies with higher M∗, SFR, nebular extinction (AV), gas-phase metallicity (O/H), and Hi gas mass have systematically higher CO detection rates. In particular, the parameter according to which CO detections and non-detections show the strongest statistical differences is the gas-phase metallicity, for any of the five metallicity calibrations examined in this work. We investigate scaling relations between the CO(1–0) line luminosity (L'CO(1-0)) and galaxy-averaged properties using ALLSMOG and a sub-sample of COLD GASS for a total of 185 sources that probe the local main sequence (MS) of star-forming galaxies and its ± 0.3 dex intrinsic scatter from M∗ = 108.5M⊙ to M∗ = 1011M⊙. L'CO(1-0) is most strongly correlated with the SFR, but the correlation with M∗ is closer to linear and almost comparably tight. The relation between L'CO(1-0) and metallicity is the steepest one, although deeper CO observations of galaxies with AV< 0.5 mag may reveal an as much steep correlation with AV. Our results suggest that star-forming galaxies across more than two orders of magnitude in M∗ obey similar scaling relations between CO luminosity and the galaxy properties examined in this work. Besides SFR, the CO luminosity is likely most fundamentally linked to M∗, although we note that stellar mass alone cannot explain all of the variation in CO emission observed as a function of O/H and MHI.
Identification of a biomarker that predicts response to inhaled corticosteroids (ICS) would help evaluate the risk/benefit profile of ICS in chronic obstructive pulmonary disease (COPD) and guide ...treatment.The ISOLDE study randomised 751 patients (mean post-bronchodilator forced expiratory volume in 1 s (FEV1) 1.4 L: 50% predicted normal) to fluticasone propionate 500 μg twice daily or placebo for 3 years, finding no difference in FEV1 rate of decline between treatments (p=0.16) and a significant reduction in median exacerbation rate with fluticasone propionate versus placebo (p=0.026). We re-analysed ISOLDE results by baseline blood eosinophil count to investigate whether eosinophil level predicts ICS benefit.Patients with eosinophils <2% (n=456) had a similar rate of post-bronchodilator FEV1 decline with fluticasone propionate as placebo (-2.9 mL·year(-1); p=0.688). With eosinophils ≥2% (n=214), the rate of decline decreased by 33.9 mL·year(-1) with fluticasone propionate versus placebo (p=0.003). Exacerbation rate reduction on ICS for fluticasone propionate versus placebo was higher in the eosinophil <2% group compared with the ≥2% group; time-to-first moderate/severe exacerbation was not different between treatments in either group.A baseline blood eosinophil count of ≥2% identifies a group of COPD patients with slower rates of decline in FEV1 when treated with ICS: prospective testing of this hypothesis is now warranted.
After a median follow-up of 4.7 years, there were 1.6 more deaths per 1000 person-years among healthy older adults who were randomly assigned to receive aspirin than among those who received placebo. ...Cancer-related death accounted for much of the excess mortality.
BACKGROUND:Reducing intraocular pressure (IOP) in primary open-angle glaucoma (POAG) is currently the only approach to prevent further optic nerve head damage. However, other mechanisms such as ...ischemia, oxidative stress, glutamate excitotoxicity, neurotrophin loss, inflammation/glial activation, and vascular dysregulation are not addressed. Because stress is a key risk factor affecting these mechanisms, we evaluated whether mindfulness-based stress reduction can lower IOP and normalize typical stress biomarkers.
MATERIALS AND METHODS:In a prospective, randomized trial 90 POAG patients (180 eyes; age above 45 y) were assigned to a waitlist control or mindfulness meditation group which practiced daily for 21 days. We measured IOP (primary endpoint), quality of life (QOL), stress-related serum biomarkers cortisol, β-endorphins, IL6, TNF-α, brain-derived neurotrophic factor (BDNF), reactive oxygen species (ROS), total antioxidant capacity (TAC), and whole genome expression.
RESULTS:Between-group comparisons revealed significantly lowered IOP in meditators (OD18.8 to 12.7, OS 19.0 to 13.1 mm Hg) which correlated with significantly lowered stress-biomarker levels including cortisol (497.3 to 392.3 ng/mL), IL6 (2.8 to 1.5 ng/mL), TNF-α (57.1 to 45.4 pg/mL), ROS (1625 to 987 RLU/min/104 neutrophils), and elevated β-endorphins (38.4 to 52.7 pg/mL), BDNF (56.1 to 83.9 ng/mL), and TAC (5.9 to 9.3) (all P<0.001). These changes correlated well with gene expression profiling. Meditators improved in QOL (P<0.05).
CONCLUSIONS:A short course of mindfulness-based stress reduction by meditation in POAG, reduces IOP, improves QOL, normalizes stress biomarkers, and positively modifies gene expression. Mindfulness meditation can be recommended as adjunctive therapy for POAG.
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