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Vitamin supplements and natural treatments with regard to COVID-19: A systematic review of randomized control tests.
Large amounts of high quality biophysical data are needed to improve current biological effects models but such data are lacking and difficult to obtain. The present study aimed to more efficiently measure the spatial distribution of relative biological effectiveness (RBE) of charged particle beams using a novel high-accuracy and high-throughput experimental platform. Clonogenic survival was selected as the biological endpoint for two lung cancer cell lines, H460 and H1437, irradiated with protons, carbon, and helium ions. Ion-specific multi-step microplate holders were fabricated such that each column of a 96-well microplate is spatially situated at a different location along a particle beam path. Dose, dose-averaged linear energy transfer (LETd), and dose-mean lineal energy (yd) were calculated using an experimentally validated Geant4-based Monte Carlo system. Cells were irradiated at the Heidelberg Ion Beam Therapy Center (HIT). The experimental results showed that the clonogenic survival curves of all tested ions were yd-dependent. Both helium and carbon ions achieved maximum RBEs within specific yd ranges before biological efficacy declined, indicating an overkill effect. For protons, no overkill was observed, but RBE increased distal to the Bragg peak. Measured RBE profiles strongly depend on the physical characteristics such as yd and are ion specific.The quality of cat care practices depends in part on the type of management applied, which either positively or negatively impacts cat welfare. This study investigated whether the type of cat management (indoor vs. outdoor) was related to other cat care practices adopted by cat owners, associated with the quality of human-cat relationships and cat welfare. check details An online survey was distributed via social networks. Descriptive statistics, categorical Principal Component Analysis, Fisher's Exact test and Chi-square test in contingency table were applied. A total of 16,302 cat owners returned the survey. Most Brazilian owners reported indoor management of their cats; this was related to owners living in apartments, more frequent use of cat care practices, and more interactions with their pets. Outdoor management was related to cats living in houses or farms, sleeping outdoors or around the neighborhood, and owners had fewer interaction with their pets. In conclusion, owners practicing indoor management seemed to be closer to their cats than owners reporting outdoor management. However, obesity and owner-reported behavioral problems were associated with indoor management.The efficacy of paclitaxel (PTX) is limited due to its poor solubility, poor bioavailability, and acquired drug resistance mechanisms. Designing paclitaxel prodrugs can improve its anticancer activity and enable formulation of nanoparticles. Overall, the aim of this work is to improve the potency of paclitaxel with prodrug synthesis, nanoparticle formation, and synergistic formulation with lapatinib. Specifically, we improve potency of paclitaxel by conjugating it to α-tocopherol (vitamin E) to produce a hydrophobic prodrug (Pro); this increase in potency is indicated by the 8-fold decrease in half maximal inhibitory concentration (IC50) concentration in ovarian cancer cell line, OVCA-432, used as a model system. The efficacy of the paclitaxel prodrug was further enhanced by encapsulation into pH-labile nanoparticles using Flash NanoPrecipitation (FNP), a rapid, polymer directed self-assembly method. There was an 1100-fold decrease in IC50 concentration upon formulating the prodrug into nanoparticles. Notably, the prodrug formulations were 5-fold more potent than paclitaxel nanoparticles. Finally, the cytotoxic effects were further enhanced by co-encapsulating the prodrug with lapatinib (LAP). Formulating the drug combination resulted in synergistic interactions as indicated by the combination index (CI) of 0.51. Overall, these results demonstrate this prodrug combined with nanoparticle formulation and combination therapy is a promising approach for enhancing paclitaxel potency.Modern medicine relies upon antibiotics, but we have arrived to the point where our inability to come up with new effective molecules against resistant pathogens, together with the declining private investment, is resulting in the number of untreatable infections increasing worldwide at worrying pace. Among other pathogens, widely recognized institutions have indicated Gram-negative bacteria as particularly challenging, due to the presence of the outer membrane. The very first step in the action of every antibiotic or adjuvant is the permeation through this membrane, with small hydrophilic drugs usually crossing through protein channels. Thus, a detailed understanding of their properties at a molecular level is crucial. By making use of Molecular Dynamics simulations, we compared the two main porins of four members of the Enterobacteriaceae family, and, in this paper, we show their shared geometrical and electrostatic characteristics. Then, we used metadynamics simulations to reconstruct the free energy for permeation of selected diazobicyclooctans through OmpF. We demonstrate how porins features are coupled to those of the translocating species, modulating their passive permeation. In particular, we show that the minimal projection area of a molecule is a better descriptor than its molecular mass or the volume. Together with the magnitude and orientation of the electric dipole moment, these are the crucial parameters to gain an efficient compensation between the entropic and enthalpic contributions to the free energy barrier required for permeation. Our results confirm the possibility to predict the permeability of molecules through porins by using a few molecular parameters and bolster the general model according to which the free energy increase is mostly due to the decrease of conformational entropy, and this can be compensated by a favorable alignment of the electric dipole with respect to the channel intrinsic electric field.In power inspection tasks, the insulator and spacer are important inspection objects. UAV (unmanned aerial vehicle) power inspection is becoming more and more popular. However, due to the limited computing resources carried by a UAV, a lighter model with small model size, high detection accuracy, and fast detection speed is needed to achieve online detection. In order to realize the online detection of power inspection objects, we propose an improved SSD (single shot multibox detector) insulator and spacer detection algorithm using the power inspection images collected by a UAV. In the proposed algorithm, the lightweight network MnasNet is used as the feature extraction network to generate feature maps. Then, two multiscale feature fusion methods are used to fuse multiple feature maps. Lastly, a power inspection object dataset containing insulators and spacers based on aerial images is built, and the performance of the proposed algorithm is tested on real aerial images and videos. Experimental results show that the proposed algorithm can efficiently detect insulators and spacers. Compared with existing algorithms, the proposed algorithm has the advantages of small model size and fast detection speed. The detection accuracy can achieve 93.8%. The detection time of a single image on TX2 (NVIDIA Jetson TX2) is 154 ms and the capture rate on TX2 is 8.27 fps, which allows realizing online detection.Membranes are widely used for liquid separations such as removing solute components from solvents or liquid/liquid separations. Due to negligible vapor pressure, adjustable physical properties, and thermal stability, the application of ionic liquids (ILs) has been extended to fabricating a myriad of membranes for liquid separations. A comprehensive overview of the recent developments in ILs in fabricating membranes for liquid separations is highlighted in this review article. Four major functions of ILs are discussed in detail, including their usage as (i) raw membrane materials, (ii) physical additives, (iii) chemical modifiers, and (iv) solvents. Meanwhile, the applications of IL assisted membranes are discussed, highlighting the issues, challenges, and future perspectives of these IL assisted membranes in liquid separations.Previously, we characterized qualitative imaging-based subtypes of pancreatic ductal adenocarcinoma (PDAC) on computed tomography (CT) scans. Conspicuous (high delta) PDAC tumors are more likely to have aggressive biology and poorer clinical outcomes compared to inconspicuous (low delta) tumors. Here, we developed a quantitative classification of this imaging-based subtype (quantitative delta; q-delta). Retrospectively, baseline pancreatic protocol CT scans of three cohorts (cohort#1 = 101, cohort#2 = 90 and cohort#3 = 16 [external validation]) of patients with PDAC were qualitatively classified into high and low delta. We used a voxel-based method to volumetrically quantify tumor enhancement while referencing normal-pancreatic-parenchyma and used machine learning-based analysis to build a predictive model. In addition, we quantified the stromal content using hematoxylin- and eosin-stained treatment-naïve PDAC sections. Analyses revealed that PDAC quantitative enhancement values are predictive of the qualitative delta scoring and were used to build a classification model (q-delta). Compared to high q-delta, low q-delta tumors were associated with improved outcomes, and the q-delta class was an independent prognostic factor for survival. In addition, low q-delta tumors had higher stromal content and lower cellularity compared to high q-delta tumors. Our results suggest that q-delta classification provides a clinically and biologically relevant tool that may be integrated into ongoing and future clinical trials.The aim of this study was to determine the association between high-density mineralized protrusions (HDMPs) and central osteophytes (COs), and describe the varying appearance of these lesions using advanced clinical imaging and a novel histological protocol. Seventeen consecutive patients with clinically advanced knee osteoarthritis undergoing knee arthroplasty were included. Surgical tissues containing the osteochondral region were investigated using computed tomography (CT); a subset was evaluated using confocal microscopy with fluorescence. Tissues from seven subjects (41.2%) contained HDMPs, and tissues from seven subjects (41.2%) contained COs. A significant association between HDMPs and COs was present (p = 0.003), with 6 subjects (35.2%) demonstrating both lesions. In total, 30 HDMPs were found, most commonly at the posterior medial femoral condyle (13/30, 43%), and 19 COs were found, most commonly at the trochlea (5/19, 26.3%). The HDMPs had high vascularity at their bases in cartilaginous areas (14/20, 70%), while the surrounding areas had elevated levels of long vascular channels penetrating beyond the zone of calcified cartilage (p = 0.012) compared to HDMP-free areas. Both COs and HDMPs had noticeable bone-resorbing osteoclasts amassing at the osteochondral junction and in vascular channels entering cartilage. In conclusion, HDMPs and COs are associated lesions in patients with advanced knee osteoarthritis, sharing similar histologic features, including increased vascularization and metabolic bone activity at the osteochondral junction. Future studies are needed to determine the relationship of these lesions with osteoarthritis progression and symptomatology.
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