429 research outputs found
Accelerated diabetic wound healing by topical application of combination oral antidiabetic agents-loaded nanofibrous scaffolds: An in vitro and in vivo evaluation study
The combination of oral antidiabetic drugs, pioglitazone, metformin, and glibenclamide, which also
exhibit the strongest anti-inflammatory action among oral antidiabetic drugs, were loaded into
chitosan/gelatin/polycaprolactone (PCL) by electrospinning and polyvinyl pyrrolidone (PVP)/PCL
composite nanofibrous scaffolds by pressurized gyration to compare the diabetic wound healing
effect. The combination therapies significantly accelerated diabetic wound healing in type-1
diabetic rats and organized densely packed collagen fibers in the dermis, it also showed better
regeneration of the dermis and epidermis than single drug-loaded scaffolds with less inflammatory
cell infiltration and edema. The formation of the hair follicles started in 14 days only in the
combination therapy and lower proinflammatory cytokine levels were observed compared to single
drug-loaded treatment groups. The combination therapy increased the wettability and hydrophilicity
of scaffolds, demonstrated sustained drug release over 14 days, has high tensile strength and
suitable cytocompatibility on L929 (mouse fibroblast) cell and created a suitable area for the
proliferation of fibroblast cells. Consequently, the application of metformin and pioglitazone-loaded
chitosan/gelatin/PCL nanofibrous scaffolds to a diabetic wound area offer high bioavailability,
fewer systemic side effects, and reduced frequency of dosage and amount of drug
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Optimization of Cryoprotectant Loading into Murine and Human Oocytes
Loading of cryoprotectants into oocytes is an important step of the cryopreservation process, in
which the cells are exposed to potentially damaging osmotic stresses and chemical toxicity.
Thus, we investigated the use of physics-based mathematical optimization to guide design of
cryoprotectant loading methods for mouse and human oocytes. We first examined loading of
1.5 M dimethylsulfoxide (Me₂SO) into mouse oocytes at 23°C. Conventional one-step loading
resulted in rates of fertilization (34%) and embryonic development (60%) that were significantly
lower than those of untreated controls (95% and 94%, respectively). In contrast, the
mathematically optimized two-step method yielded much higher rates of fertilization (85%) and
development (87%). To examine the causes for oocyte damage, we performed experiments to
separate the effects of cell shrinkage and Meâ‚‚SO exposure time, revealing that neither
shrinkage nor Meâ‚‚SO exposure single-handedly impairs the fertilization and development rates.
Thus, damage during one-step Meâ‚‚SO addition appears to result from interactions between the
effects of Meâ‚‚SO toxicity and osmotic stress. We also investigated Meâ‚‚SO loading into mouse
oocytes at 30°C. At this temperature, fertilization rates were again lower after one-step loading
(8%) in comparison to mathematically optimized two-step loading (86%) and untreated controls
(96%). Furthermore, our computer algorithm generated an effective strategy for reducing
Meâ‚‚SO exposure time, using hypotonic diluents for cryoprotectant solutions. With this
technique, 1.5 M Meâ‚‚SO was successfully loaded in only 2.5 min, with 92% fertilizability. Based
on these promising results, we propose new methods to load cryoprotectants into human
oocytes, designed using our mathematical optimization approach.Keywords: Propane-1,2-diol,
Freezing,
Propylene glycol,
DMSO,
Vitrification,
Cryopreservation,
Mouse,
Cryoprotectant,
Dimethyl sulfoxide,
Simplex optimization,
Oocyte,
Human,
Meâ‚‚S
Systematic study of trace radioactive impurities in candidate construction materials for EXO-200
The Enriched Xenon Observatory (EXO) will search for double beta decays of
136Xe. We report the results of a systematic study of trace concentrations of
radioactive impurities in a wide range of raw materials and finished parts
considered for use in the construction of EXO-200, the first stage of the EXO
experimental program. Analysis techniques employed, and described here, include
direct gamma counting, alpha counting, neutron activation analysis, and
high-sensitivity mass spectrometry.Comment: 32 pages, 6 figures. Expanded introduction, added missing table
entry. Accepted for publication in Nucl. Instrum. Meth.
Effect of severe versus moderate energy restriction on physical activity among postmenopausal female adults with obesity: a pre-specified secondary analysis of the TEMPO Diet randomized controlled Trial
BackgroundAn under-explored strategy for increasing physical activity is the dietary treatment of obesity, but empirical evidence is lacking.ObjectivesTo compare the effects of weight loss via severe versus moderate energy restriction on physical activity over 36 months.Methods101 postmenopausal female adults (45–65 years, 30–40 kg/m2, ResultsCompared to the moderate group, the severe group exhibited greater mean levels of: total volume of physical activity; duration of moderate-to-vigorous-intensity physical activity (MVPA); duration of light-intensity physical activity; and step counts, as well as lower mean duration of sedentary time. All these differences (except step counts) were apparent at 6 months (e.g., 1006 [95% confidence interval 564, 1449] MET-minutes per week for total volume of physical activity), and some were also apparent at 4 and/or 12 months. There were no differences between groups in the two other outcomes investigated (self-efficacy to regulate exercise; and proportion of participants meeting the World Health Organization's 2020 Physical Activity Guidelines for MVPA). When the analyses were adjusted for weight at each time point, the differences between groups were either attenuated or abolished.ConclusionsAmong female adults with obesity, including a dietary component to reduce excess body weight—notably one involving severe energy restriction—could potentially enhance the effectiveness of physical activity interventions
A Large Hadron Electron Collider at CERN
This document provides a brief overview of the recently published report on
the design of the Large Hadron Electron Collider (LHeC), which comprises its
physics programme, accelerator physics, technology and main detector concepts.
The LHeC exploits and develops challenging, though principally existing,
accelerator and detector technologies. This summary is complemented by brief
illustrations of some of the highlights of the physics programme, which relies
on a vastly extended kinematic range, luminosity and unprecedented precision in
deep inelastic scattering. Illustrations are provided regarding high precision
QCD, new physics (Higgs, SUSY) and electron-ion physics. The LHeC is designed
to run synchronously with the LHC in the twenties and to achieve an integrated
luminosity of O(100) fb. It will become the cleanest high resolution
microscope of mankind and will substantially extend as well as complement the
investigation of the physics of the TeV energy scale, which has been enabled by
the LHC
Exposure to Perchlorate in Lactating Women and Its Associations With Newborn Thyroid Stimulating Hormone
Background: Perchlorate, thiocyanate, and nitrate can block iodide transport at the sodium iodide symporter (NIS) and this can subsequently lead to decreased thyroid hormone production and hypothyroidism. NIS inhibitor exposure has been shown to reduce iodide uptake and thyroid hormone levels; therefore we hypothesized that maternal NIS inhibitor exposure will influence both maternal and newborn thyroid function.Methods: Spot urine samples were collected from 185 lactating mothers and evaluated for perchlorate, thiocyanate, and nitrate concentrations. Blood and colostrum samples were collected from the same participants in the first 48 h after delivery. Thyroid hormones and thyroid-related antibodies (TSH, fT3, fT4, anti-TPO, anti-Tg) were analyzed in maternal blood and perchlorate was analyzed in colostrum. Also, spot blood samples were collected from newborns (n = 185) between 48 and 72 postpartum hours for TSH measurement. Correlation analysis was performed to assess the effect of NIS inhibitors on thyroid hormone levels of lactating mothers and their newborns in their first 48 postpartum hours.Results: The medians of maternal urinary perchlorate (4.00 μg/g creatinine), maternal urinary thiocyanate (403 μg/g creatinine), and maternal urinary nitrate (49,117 μg/g creatinine) were determined. Higher concentrations of all three urinary NIS inhibitors (μg/g creatinine) at their 75th percentile levels were significantly correlated with newborn TSH (r = 0.21, p < 0.001). Median colostrum perchlorate level concentration of all 185 participants was 2.30 μg/L. Colostrum perchlorate was not significantly correlated with newborn TSH (p > 0.05); however, there was a significant correlation between colostrum perchlorate level and maternal TSH (r = 0.21, p < 0.01). Similarly, there was a significant positive association between colostrum perchlorate and maternal urinary creatinine adjusted perchlorate (r = 0.32, p < 0.001).Conclusion: NIS inhibitors are ubiquitous in lactating women in Turkey and are associated with increased TSH levels in newborns, thus signifying for the first time that co-exposure to maternal NIS inhibitors can have a negative effect on the newborn thyroid function
E2F-1 Directly Regulates Thrombospondin 1 Expression
Thrombospondin 1 (TSP1) has been shown to play a critical role in inhibiting angiogenesis, resulting in inhibition of tumor growth and metastases. To figure out TSP1's regulators will lead to reveal its biological function mechanistically. In this study, we show that E2F-1 could activate the transcription of TSP1 by both promoter assays and Northern blot. Analysis of various TSP1 promoter mutant constructs showed that a sequence located −144/−137 up-stream of the transcriptional initiation site, related to the consensus E2F-responsive sequence, is necessary for the activation. In consistence with up-regulation of TSP-1 activity by over-expression of E2F-1, the knockdown of endogenous E2F-1 inhibited TSP-1 promoter activity significantly, implying that E2F-1 mediated regulation of TSP-1 is relevant in vivo. In addition, E2F-1 could also directly bind to the TSP1 promoter region covering −144/−137 region as revealed by ChIP assays. Furthermore, the E2F-1-induced activation of TSP1 gene transcription is suppressed by pRB1 in a dose-dependent manner. Taken together, the results demonstrate that TSP1 is a novel target for E2F1, which might imply that E2F-1 can affect angiogenesis by modulating TSP1 expression
Skin Cancer:Epidemiology, Disease Burden, Pathophysiology, Diagnosis, and Therapeutic Approaches
Skin cancer, including both melanoma and non-melanoma, is the most common type of malignancy in the Caucasian population. Firstly, we review the evidence for the observed increase in the incidence of skin cancer over recent decades, and investigate whether this is a true increase or an artefact of greater screening and over-diagnosis. Prevention strategies are also discussed. Secondly, we discuss the complexities and challenges encountered when diagnosing and developing treatment strategies for skin cancer. Key case studies are presented that highlight the practic challenges of choosing the most appropriate treatment for patients with skin cancer. Thirdly, we consider the potential risks and benefits of increased sun exposure. However, this is discussed in terms of the possibility that the avoidance of sun exposure in order to reduce the risk of skin cancer may be less important than the reduction in all-cause mortality as a result of the potential benefits of increased exposure to the sun. Finally, we consider common questions on human papillomavirus infection
Dry Needling for Spine Related Disorders: a Scoping Review
Introduction/Background: The depth and breadth of research on dry needling (DN) has not been evaluated specifically for symptomatic spine related disorders (SRD) from myofascial trigger points (TrP), disc, nerve and articular structures not due to serious pathologies. Current literature appears to support DN for treatment of TrP. Goals of this review include identifying research published on DN treatment for SRD, sites of treatment and outcomes studied. Methods: A scoping review was conducted following Levac et al.’s five part methodological framework to determine the current state of the literature regarding DN for patients with SRD. Results: Initial and secondary search strategies yielded 55 studies in the cervical (C) region (71.43%) and 22 in the thoracolumbar-pelvic (TLP) region (28.57%). Most were randomized controlled trials (60% in C, 45.45% in TLP) and clinical trials (18.18% in C, 22.78% in TLP). The most commonly treated condition was TrP for both the C and TLP regions. In the C region, DN was provided to 23 different muscles, with the trapezius as treatment site in 41.88% of studies. DN was applied to 31 different structures in the TLP region. In the C region, there was one treatment session in 23 studies (41.82%) and 2–6 treatments in 25 (45.45%%). For the TLP region, one DN treatment was provided in 8 of the 22 total studies (36.36%) and 2–6 in 9 (40.9%). The majority of experimental designs had DN as the sole intervention. For both C and TLP regions, visual analogue scale, pressure pain threshold and range of motion were the most common outcomes. Conclusion: For SRD, DN was primarily applied to myofascial structures for pain or TrP diagnoses. Many outcomes were improved regardless of diagnosis or treatment parameters. Most studies applied just one treatment which may not reflect common clinical practice. Further research is warranted to determine optimal treatment duration and frequency. Most studies looked at DN as the sole intervention. It is unclear whether DN alone or in addition to other treatment procedures would provide superior outcomes. Functional outcome tools best suited to tracking the outcomes of DN for SRD should be explored.https://doi.org/10.1186/s12998-020-00310-
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