5,312 research outputs found

    Optimization of CO2 production rate for firefighting robot applications using response surface methodology

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    A carbon dioxide gas-powered pneumatic actuation has been proposed as a suitable power source for an autonomous firefighting robot (CAFFR), which is designed to operate in an indoor fire environment in our earlier study. Considering the consumption rate of the pneumatic motor, the gas-powered actuation that is based on the theory of phase change material requires optimal determination of not only the sublimation rate of carbon dioxide but also the sizing of dry ice granules. Previous studies that have used the same theory are limited to generating a high volume of carbon dioxide without reference to neither the production rate of the gas nor the size of the granules of the dry ice. However, such consideration remains a design requirement for efficient driving of a carbon dioxide-powered firefighting robot. This paper investigates the effects of influencing design parameters on the sublimation rate of dry ice for powering a pneumatic motor. The optimal settings of these parameters that maximize the sublimation rate at the minimal time and dry ice mass are presented. In the experimental design and analysis, we employed full-factorial design and response surface methodology to fit an acceptable model for the relationship between the design factors and the response variables. Predictive models of the sublimation rate were examined via ANOVA, and the suitability of the linear model is confirmed. Further, an optimal sublimation rate value of 0.1025 g/s is obtained at a temperature of 80°C, the mass of 16.1683 g, and sublimation time of 159.375 s

    Antiglycation and Hypolipidemic Effects of Polyphenols from Zingiber officinale Roscoe (Zingiberaceae) in Streptozotocin-Induced Diabetic Rats

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    Purpose: To evaluate the antiglycation and hypolipidemic potential of polyphenols from Zingiber officinale in streptozotocin-induced diabetic rats.Methods: Diabetes was induced in male Wistar rats by single intraperitoneal injection of 50 mg/kg body weight (bw) of streptozotocin. This was followed by oral administration of 500 mg/kg each of free and bound polyphenol extracts of Z. officinale to the rats daily for 42 days. Distilled water and glibenclamide (5 mg/kg) were used as normal and positive controls, respectively.Results: Significant increases (p < 0.05) in blood glucose level (369.26 mg/dL), serum advanced glycation end-products (AGEs) (6.80 μg/mL), lipid profile and atherogenic indices, with decrease in high density lipoprotein cholesterol (HDL-C) (15.55 mg/dL) were observed in diabetic rats compared to control. Free polyphenol extracts of Z. officinale significantly reduced (p < 0.05) blood glucose (147.96 mg/dL), serum AGEs (1.98 μg/mL), lipid profile and atherogenic indices while it significantly increased HDL-C (23.28 mg/dL). However, bound polyphenol extract did not cause any significant change in the lipid profile of the diabetic rats except for LDL-C.Conclusion: This study indicates that free and bound polyphenols from Z. officinale can ameliorate diabetes as well as its complications, and its effect is comparable to that of the standard drug, glibenclamide.Keywords: Zingiber officinale, Diabetes, Lipid profile, Atherogenic index, Polyphenol, Glycation, Streptozotoci

    miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development

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    MicroRNAs play a crucial role in the regulation of cell growth and differentiation. Mice with genetic deletion of miR-375 exhibit impaired glycemic control due to decreased β-cell and increased α-cell mass and function. The relative importance of these processes for the overall phenotype of miR-375KO mice is unknown. Here, we show that mice overexpressing miR-375 exhibit normal β-cell mass and function. Selective re-expression of miR-375 in β-cells of miR-375KO mice normalizes both, α- and β-cell phenotypes as well as glucose metabolism. Using this model, we also analyzed the contribution of β-cells to the total plasma miR-375 levels. Only a small proportion (≈1 %) of circulating miR-375 originates from β-cells. Furthermore, acute and profound β-cell destruction is sufficient to detect elevations of miR-375 levels in the blood. These findings are supported by higher miR-375 levels in the circulation of type 1 diabetes (T1D) subjects but not mature onset diabetes of the young (MODY) and type 2 diabetes (T2D) patients. Together, our data support an essential role for miR-375 in the maintenance of β-cell mass and provide in vivo evidence for release of miRNAs from pancreatic β-cells. The small contribution of β-cells to total plasma miR-375 levels make this miRNA an unlikely biomarker for β-cell function but suggests a utility for the detection of acute β-cell death for autoimmune diabetes

    Development and Evaluation of Orally Disintegrating Tablets of Montelukast Sodium by Direct Compression Method

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    Purpose: To design an orally disintegrating montelukast sodium tablet (ODT) that disintegrates in the oral cavity leaving an easy-to-swallow residue especially for pediatric and elderly patients who have difficulty swallowing tablets.Methods: Two different formulations of montelukast sodium (5 mg) orally disintegrating tablets were designed and manufactured by direct compression method, using microcrystalline (Avicel PH-102), mannitol, sodium bicarbonate, crospovidone and magnesium stearate as key excipients, and with cherry flavor and aspartame as flavor and sweetener, respectively. These formulations were then evaluated using pharmacopoeial and non-pharmacopoeial physical and chemical tests. Dissolution and assay tests were performed using USP apparatus II and ultraviolet (UV) spectrophotometry, respectively. Formulations with better results were further subjected for optimization study using central composite design method.Results: The results of prototype formulation batch (Trial-02) and the finest optimization formulation batch (FOB-01) reflected the successful development of new formulation of orally disintegrating montelukast sodium 5 mg tablet by direct compression technique. The value of similarity factor (f2 > 50), indicating that both formulations have similar drug release profiles. The formulations were further evaluated for three and six months under accelerated conditions to ascertain their stability.Conclusion: The results obtained demonstrate the suitability of the formulation as an ODT for convenient delivery of montelukast sodium for asthmatic patients. However, clinical studies are required to confirm this.Keywords: Orally disintegrating tablets, Asthma, Disintegration, Dissolution, Montelukast sodiu

    Accelerated Pulsed High-Fluence Corneal Cross-Linking for Progressive Keratoconus

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    PURPOSE: To report on 2-year results of accelerated corneal collagen cross-linking (CXL) in progressive ectasia using the Avedro KXL system. DESIGN: Prospective interventional case series. METHODS: A total of 870 patients (1,192 eyes) attending Moorfields Eye Hospital after CXL were included. All patients undergoing CXL had progressive keratoconus. Corneas with a minimum stromal thickness <375 μm were excluded. Riboflavin 0.1% soak duration was 10 minutes. High-fluence pulsed UVA was delivered at 30 mW/cm2 for 4 minutes, with a 1.5-second on/off cycle (total energy 7.2 J/cm2). Subjective refractive, corneal tomography, and specular microscopy were performed at baseline, 6, 12, and 24 months postoperatively. The primary outcome measure was a change in maximum keratometry (Kmax) at 24 months. RESULTS: Twelve- and 24-month follow-up data were available on 543 and 213 patients, respectively (mean age 25.4 ± 6.6 years). In mild cones (Kmax < 55 diopter [D]), mean keratometry remained unchanged at 24 months. In more advanced disease, we observed modest corneal flattening compared to baseline (Kmax 63.2 ± 6.5 D vs 61.9 ± 8.1 D, P = .02), but no significant changes in central keratometry (K1 or K2). Keratometric stabilization was confirmed in 98.3% of eyes. Mean CDVA, manifest refraction and endothelial cell density did not change. Overall, 2.7% of eyes lost more than 2 lines of CDVA. CONCLUSION: Accelerated pulsed CXL is a safe, effective, and refractively neutral intervention (at 2 years) to halt disease progression in keratoconus

    Menhaden fish oil attenuates postpartum depression in rat model via inhibition of NLRP3-inflammasome driven inflammatory pathway.

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    Background and aimPostpartum depression (PPD) is a familiar problem which is associated with about 10–20% of women after child delivery. Fish oil (FO) has a therapeutic potentials to many diseases including mood disorders. However, there is paucity of data on the effects of FO supplementation on PPD rat model. Hence, this study aimed at investigating the potentials of FO in ameliorating depressive-like behaviors in PPD rat by evaluating the involvement of NLRP3-inflammasome.Experimental procedureThirty six virgin adult female rats (n = 6) were randomly divided into six groups; Group 1–3 were normal control (NC), Sham (SHAM) and ovariectomized group (OVX) respectively whereas group 4–6 were PPD rats forced-fed once daily with distilled water (PPD), fish oil (PPD + FO; 9 g/kg) and Fluoxetine (PPD + FLX; 15 mg/kg) respectively from postpartum day 1 and continued for 10 consecutive days. Rats behaviors were evaluated on postpartum day 10 through open field test (OFT) and forced swimming test (FST), followed by biochemical analysis of NLRP3 inflammasome proteins pathway in their brain and determination of neutrophil to lymphocyte ratio (NLR).ResultsPPD-induced rats exhibited high immobility and low swimming time in FST with increased inflammatory status; NLR, IL-1β and NFкB/NLRP3/caspase-1 activity in their hippocampus. However, administration of FO or fluoxetine reversed the aforementioned abnormalities.ConclusionIn conclusion, 10 days supplementation with FO ameliorated the depressive-like behaviors in PPD rats by targeting the NFкB/NLRP3/caspase-1/IL-1β activity. This has shed light on the potential of NLRP3 as a therapeutic target in treatment of PPD in rats

    The effect of transmucosal 0.2mg/kg Midazolam premedication on dental anxiety, anaesthetic induction and psychological morbidity in children undergoing general anaesthesia for tooth extraction

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    &lt;b&gt;Background:&lt;/b&gt; The project aims were to evaluate the benefit of transmucosal Midazolam 0.2mg/kg pre-medication on anxiety, induction behaviour and psychological morbidity in children undergoing general anaesthesia (GA) extractions. &lt;b&gt;Method:&lt;/b&gt; 179 children aged 5-10 years (mean 6.53 years) participated in this randomised, double blind, placebo controlled trial. Ninety children had Midazolam placed in the buccal pouch. Dental anxiety was recorded pre operatively and 48 hours later using a child reported MCDAS-FIS scale. Behaviour at anaesthetic induction was recorded and psychological morbidity was scored by the parent using the Rutter Scale pre-operatively and again one-week later. Subsequent dental attendance was recorded at one, three and six months after GA. &lt;b&gt;Results:&lt;/b&gt; Whilst levels of mental anxiety did not reduce overall, the most anxious patients demonstrated a reduction in anxiety after receiving midazolam premedicationmay (p=0.01). Neither induction behaviour nor psychological morbidity improved. Irrespective of group, parents reported less hyperactive (p= 0.002) and more prosocial behaviour (p=0.002) after the procedure:;, older children improved most (p=0.048), Post GA Dental attendance was poor and unrelated to after the procedure and unaffected by premedication. &lt;b&gt;Conclusion:&lt;/b&gt; 0.2mg/kg buccal Midazolam provided some evidence for reducing anxiety in the most dentally anxious patients. However, induction behaviour, psychological morbidity and subsequent dental attendance were not found to alter between the premedication groups

    Comparison of macrocyclic and acyclic chelators for gallium-68 radiolabelling

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    Gallium-68 (68Ga) is a positron-emitting isotope used for clinical PET imaging of peptide receptor expression. 68Ga radiopharmaceuticals used in molecular PET imaging consist of disease-targeting biomolecules tethered to chelators that complex 68Ga3+. Ideally, the chelator will rapidly, quantitatively and stably coordinate 68Ga3+ at room temperature, near neutral pH and low chelator concentration, allowing for simple routine radiopharmaceutical formulation. Identification of chelators that fulfil these requirements will facilitate development of kit-based 68Ga radiopharmaceuticals. Herein the reaction of a range of widely used macrocyclic and acyclic chelators with 68Ga3+ is reported. Radiochemical yields have been measured under conditions of varying chelator concentrations, pH (3.5 and 6.5) and temperature (25 and 90 °C). These chelators are: 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7-triazacyclononane macrocycles substituted with phosphonic (NOTP) and phosphinic (TRAP) groups at the amine, bis(2-hydroxybenzyl)ethylenediaminediacetic acid (HBED), a tris(hydroxypyridinone) containing three 1,6-dimethyl-3-hydroxypyridin-4-one groups (THP) and the hexadentate tris(hydroxamate) siderophore desferrioxamine-B (DFO). Competition studies have also been undertaken to assess relative complexation efficiencies of each chelator for 68Ga3+ under different pH and temperature conditions. Performing radiolabelling reactions at pH 6.5, 25 °C and 5–50 μM chelator concentration resulted in near quantitative radiochemical yields for all chelators, except DOTA. Radiochemical yields either decreased or were not substantially improved when the reactions were undertaken at lower pH or at higher temperature, except in the case of DOTA. THP and DFO were the most effective 68Ga3+ chelators at near-neutral pH and 25 °C, rapidly providing near-quantitative radiochemical yields at very low chelator concentrations. NOTP and HBED were only slightly less effective under these conditions. In competition studies with all other chelators, THP demonstrated highest reactivity for 68Ga3+ complexation under all conditions. These data point to THP possessing ideal properties for rapid, one-step kit-based syntheses of 68Ga-biomolecules for molecular PET imaging. LC-MS and 1H, 13C{1H} and 71Ga NMR studies of HBED complexes of Ga3+ showed that under the analytical conditions employed in this study, multiple HBED-bound Ga complexes exist. X-ray diffraction data indicated that crystals isolated from these solutions contained octahedral [Ga(HBED)(H2O)], with HBED coordinated in a pentadentate N2O3 mode, with only one phenolic group coordinated to Ga3+, and the remaining coordination site occupied by a water molecule

    Ecological and methodological drivers of species' distribution and phenology responses to climate change

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    Climate change is shifting species’ distribution and phenology. Ecological traits, such as mobility or reproductive mode, explain variation in observed rates of shift for some taxa. However, estimates of relationships between traits and climate responses could be influenced by how responses are measured. We compiled a global data set of 651 published marine species’ responses to climate change, from 47 papers on distribution shifts and 32 papers on phenology change. We assessed the relative importance of two classes of predictors of the rate of change, ecological traits of the responding taxa and methodological approaches for quantifying biological responses. Methodological differences explained 22% of the variation in range shifts, more than the 7.8% of the variation explained by ecological traits. For phenology change, methodological approaches accounted for 4% of the variation in measurements, whereas 8% of the variation was explained by ecological traits. Our ability to predict responses from traits was hindered by poor representation of species from the tropics, where temperature isotherms are moving most rapidly. Thus, the mean rate of distribution change may be underestimated by this and other global syntheses. Our analyses indicate that methodological approaches should be explicitly considered when designing, analysing and comparing results among studies. To improve climate impact studies, we recommend that (1) reanalyses of existing time series state how the existing data sets may limit the inferences about possible climate responses; (2) qualitative comparisons of species’ responses across different studies be limited to studies with similar methodological approaches; (3) meta-analyses of climate responses include methodological attributes as covariates; and (4) that new time series be designed to include the detection of early warnings of change or ecologically relevant change. Greater consideration of methodological attributes will improve the accuracy of analyses that seek to quantify the role of climate change in species’ distribution and phenology changes

    Risk factors for exacerbations and pneumonia in patients with chronic obstructive pulmonary disease: a pooled analysis.

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    BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) are at risk of exacerbations and pneumonia; how the risk factors interact is unclear. METHODS: This post-hoc, pooled analysis included studies of COPD patients treated with inhaled corticosteroid (ICS)/long-acting β2 agonist (LABA) combinations and comparator arms of ICS, LABA, and/or placebo. Backward elimination via Cox's proportional hazards regression modelling evaluated which combination of risk factors best predicts time to first (a) pneumonia, and (b) moderate/severe COPD exacerbation. RESULTS: Five studies contributed: NCT01009463, NCT01017952, NCT00144911, NCT00115492, and NCT00268216. Low body mass index (BMI), exacerbation history, worsening lung function (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage), and ICS treatment were identified as factors increasing pneumonia risk. BMI was the only pneumonia risk factor influenced by ICS treatment, with ICS further increasing risk for those with BMI <25 kg/m2. The modelled probability of pneumonia varied between 3 and 12% during the first year. Higher exacerbation risk was associated with a history of exacerbations, poorer lung function (GOLD stage), female sex and absence of ICS treatment. The influence of the other exacerbation risk factors was not modified by ICS treatment. Modelled probabilities of an exacerbation varied between 31 and 82% during the first year. CONCLUSIONS: The probability of an exacerbation was considerably higher than for pneumonia. ICS reduced exacerbations but did not influence the effect of risks associated with prior exacerbation history, GOLD stage, or female sex. The only identified risk factor for ICS-induced pneumonia was BMI <25 kg/m2. Analyses of this type may help the development of COPD risk equations
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