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The rate constants of the hydroxyl radical reactions (kOH) with organic micropollutants (OMPs) in aqueous medium are important in designing the advanced oxidation processes (AOPs) for their removal. In this study, a quantitative structure-property relationship (QSPR) model for the prediction of kOH of diverse and emerging OMPs was developed in accordance with the OECD guidelines. A large experimental data set (n = 995) comprised of compounds with kOH values ranging from 7.9 × 105 to 6.8 × 1010 M-1 s-1 was considered and several molecular descriptors were calculated. As a result, five descriptors were found to be important in predicting the kOH values which related to the electronegativity, topological polar surface area, double bonds, average molecular weight, and halogen atoms in the molecule. The optimal model was validated internally and externally and several statistical stringent parameters were derived. High values of the coefficient of determination (R2) and small root mean squared error (RMSE) in the training (0.954; 0.17) and validation (0.925; 0.14) sets indicated high generalization and predictivity of the developed model. Other statistical parameters derived from the training and validation data also supported the robustness of the model. The proposed model outperformed the earlier QSARs reported for kOH prediction. Overall, the developed QSPR model provides a valuable tool for an initial assessment of the susceptibility of organic micropollutants to AOPs.
Research in recent years has largely explored the immunomodulatory effects of mesenchymal stem cells (MSCs) and their secretory products, called "secretome," in the treatment of neuroinflammatory diseases. Here, we examined whether such immunosuppressive effects might be elicited due to inflammasome inactivation. To this end, we treated experimental autoimmune encephalomyelitis (EAE) mice model of multiple sclerosis (MS) with the conditioned medium or purified exosomes/microvesicles (EMVs) obtained from relapsing-remitting-MS patients human periodontal ligament stem cells (hPDLSCs) and investigated the regulation of NALP3 inflammasome. We noticed enhanced expression of NALP3, Cleaved Caspase 1, interleukin (IL)-1β, and IL-18 in EAE mouse spinal cord. Conversely, hPDLSCs-conditioned medium and EMVs significantly blocked NALP3 inflammasome activation and provided protection from EAE. Reduction in NALP3, Cleaved Caspase 1, IL-1β, and IL-18 level was noticed in conditioned medium and EMVs-treated EAE mice. Pro-inflammatory Toll-like receptor (TLR)-4 and nuclear factor (NF)-κB were elevated in EAE, while hPDLSCs-conditioned medium and EMVs treatment reduced their expression and increased IκB-α expression. Characterization of hPDLSCs-conditioned medium showed substantial level of anti-inflammatory IL-10, transforming growth factor (TGF)-β, and stromal cell-derived factor 1α (SDF-1α). We propose that the immunosuppressive role of hPDLSCs-derived conditioned medium and EMVs in EAE mice may partly attribute to the presence of soluble immunomodulatory factors, NALP3 inflammasome inactivation, and NF-κB reduction.
Evidence suggests that urban regeneration programs can stimulate leisure-time walking (LTW) in deprived areas. However, underlying pathways remain unclear. This study explored how urban regeneration might stimulate LTW among adults in deprived areas. We conducted a realist review, a theory-driven approach to evidence synthesis that focuses on mechanisms. We searched three electronic databases for peer-reviewed literature that describes how the neighborhood environment or urban regeneration influences LTW among adults in deprived areas. Evidence from 13 qualitative studies was synthesized. All studies indicated that safety problems and poor physical neighborhood design make adults fearful of walking. Seven studies indicated that poor aesthetics makes walking less relaxing and stress releasing. Seven studies indicated that poor infrastructure makes it inconvenient for adults to walk. A limited number of studies indicated that a lack of LTW facilities creates a shortage of settings for walking and that low levels of social capital constrain social support for walking and social interaction while walking. Evidence from this study suggests that urban regeneration might stimulate LTW among adults in deprived areas by creating a neighborhood that is less frightening, more relaxing, and more convenient to walk in.
High-throughput sequence (HTS) data exhibit position-specific nucleotide biases that obscure the intended signal and reduce the effectiveness of these data for downstream analyses. These biases are particularly evident in HTS assays for identifying regulatory regions in DNA (DNase-seq, ChIP-seq, FAIRE-seq, ATAC-seq). Biases may result from many experiment-specific factors, including selectivity of DNA restriction enzymes and fragmentation method, as well as sequencing technology-specific factors, such as choice of adapters/primers and sample amplification methods.
Although starch consists of large macromolecules composed of glucose units linked by α-1,4-glycosidic linkages with α-1,6-glycosidic branchpoints, variation in starch structural and functional properties is found both within and between species. Interest in starch genetics is based on the importance of starch in food and industrial processes, with the potential of genetics to provide novel starches. The starch metabolic pathway is complex but has been characterized in diverse plant species, including pea.
Hepatic iron overload has been implicated in many liver diseases; however, whether it is involved in clonorchiasis remains unknown. The purpose of this study is to investigate whether Clonorchis sinensis (C. sinensis) infection causes hepatic iron overload, analyze the relationship between the iron overload and associated cell apoptosis, so as to determine the role of excess iron plays in C. sinensis-induced liver injury.
Bull fertility is the degree of sperm's ability to fertilize and activate the egg and support embryo development, and this is critical for herd reproductive performance. We used the bull as a unique model organism for the study of male fertility because cattle genetics and physiology is similar to those of other mammals including humans. Moreover, reliable fertility data along with well-established in vitro systems are available for bovine. The objective of this original study was to ascertain evolutionary diversification and expression dynamics of Testis Specific Histone 2B (TH2B) in sperm from Holstein bulls with different fertility scores.
Nano- and microscale copper oxide particles (CuO NP, CuO MP) are applied for manifold purposes, enhancing exposure and thus the potential risk of adverse health effects. Based on the pronounced in vitro cytotoxicity of CuO NP, systematic investigations on the mode of action are required. Therefore, the impact of CuO NP, CuO MP and CuCl2 on the DNA damage response on transcriptional level was investigated by quantitative gene expression profiling via high-throughput RT-qPCR. Cytotoxicity, copper uptake and the impact on the oxidative stress response, cell cycle regulation and apoptosis were further analysed on the functional level.
Malaria research is greatly dependent on and has drastically advanced with the possibility of genetically modifying Plasmodium parasites. The commonly used transfection protocol by Janse and colleagues utilizes blood stage-derived Plasmodium berghei schizonts that have been purified from a blood culture by density gradient centrifugation. Naturally, this transfection protocol depends on the availability of suitably infected mice, constituting a time-based variable. In this study, the potential of transfecting liver stage-derived merozoites was explored. In cell culture, upon merozoite development, infected cells detach from the neighbouring cells and can be easily harvested from the cell culture supernatant. This protocol offers robust experimental timing and temporal flexibility.
Schistosoma haematobium is the causative agent of human urogenital schistosomiasis affecting ~112 million people in Africa and the Middle East. The parasite is transmitted by snails of the genus Bulinus, which also transmit other closely related human and animal schistosomes. The accurate discrimination of S. haematobium from species infecting animals will aid effective control and elimination programs. Previously we have shown the utility of different repetitive nuclear DNA sequences (DraI, sh73bp, and sh77bp) for the identification of S. haematobium-group species and inter-repeat sequences for discriminating S. haematobium from S. bovis.
Anaplasma phagocytophilum is a zoonotic tick-borne pathogen responsible for granulocytic anaplasmosis, a mild to a severe febrile disease that affects man and several animal species, including cows and horses. In Europe, I. ricinus is the only proven vector for this pathogen, but studies suggest that other tick genera and species could be involved in its transmission. Our objective was to assess the presence and genetic diversity of A. phagocytophilum in domestic animals and different tick species from the Camargue region, located in the south of France.
Clinicians are inaccurate at predicting survival. The 'Surprise Question' (SQ) is a screening tool that aims to identify people nearing the end of life. Potentially, its routine use could help identify patients who might benefit from palliative care services. The objective was to assess the accuracy of the SQ by time scale, clinician, and speciality.
This study examined whether the densities of stem- and enteroendocrine cell progenitors are abnormal in the ileum of patients with irritable bowel syndrome (IBS), and whether any abnormalities in ileal enteroendocrine cells are correlated with abnormalities in stem cells and enteroendocrine cell progenitors.
Multivariate pattern analysis (MVPA) methods are now widely used in life-science research. They have great potential but their complexity also bears unexpected pitfalls. In this paper, we explore the possibilities that arise from the high sensitivity of MVPA for stimulus-related differences, which may confound estimations of class differences during decoding of cognitive concepts. We propose a method that takes advantage of concept-unrelated grouping factors, uses blocked permutation tests, and gradually manipulates the proportion of concept-related information in data while the stimulus-related, concept-irrelevant factors are held constant. This results in a concept-response curve, which shows the relative contribution of these two components, i.e. how much of the decoding performance is specific to higher-order category processing and to lower order stimulus processing. It also allows separating stimulus-related from concept-related neuronal processing, which cannot be achieved experimentally. We applied our method to three different EEG data sets with different levels of stimulus-related confound to decode concepts of digits vs. letters, faces vs. houses, and animals vs. fruits based on event-related potentials at the single trial level. We show that exemplar-specific differences between stimuli can drive classification accuracy to above chance levels even in the absence of conceptual information. By looking into time-resolved windows of brain activity, concept-response curves can help characterize the time-course of lower-level and higher-level neural information processing and detect the corresponding temporal and spatial signatures of the corresponding cognitive processes. In particular, our results show that perceptual information is decoded earlier in time than conceptual information specific to processing digits and letters. In addition, compared to the stimulus-level predictive sites, concept-related topographies are spread more widely and, at later time points, reach the frontal cortex. Thus, our proposed method yields insights into cognitive processing as well as corresponding brain responses.
In 2009, Monfils and colleagues proposed a behavioral procedure that was said to result in a permanent attenuation of a previously established fear memory, thereby precluding a possible return of fear after extinction (Monfils, Cowansage, Klann, & LeDoux, 2009). By presenting a single retrieval trial one hour before standard extinction training, they found an enduring reduction of fear. The retrieval-extinction procedure holds great clinical potential, particularly for anxiety patients, but the findings are not undisputed, and several conceptual replications have failed to reproduce the effect. These failures have largely been attributed to small procedural differences. This preregistered study is the first endeavor to exactly replicate three key experiments of the original report by Monfils et al. (2009), thereby gauging the robustness of their seminal findings. Despite adhering to the original procedures as closely as possible, we did not find any evidence for reduced return of fear with the retrieval-extinction procedure relative to regular extinction training, as assessed through spontaneous recovery, reinstatement and renewal. Behavior of animals in the control condition (extinction only) was comparable to that in the original studies and provided an adequate baseline to reveal differences with the retrieval-extinction condition. Our null findings indicate that the effect sizes in the original paper may have been inflated and question the legitimacy of previously proposed moderators of the retrieval-extinction effect. We argue that direct experimental evaluation of purported moderators of the retrieval-extinction effect will be key to shed more light on its nature and prerequisites.
The adoption of evidence-based practice (EBP) is promoted because it is widely recognized for improving the quality and safety of health care for patients, and reducing avoidable costs. Providers of primary care face numerous challenges to ensuring the effectiveness of their daily practices. Primary health care is defined as: the entry level into a health care services system, providing a first point of contact for all new needs and problems; patient-focused (not disease-oriented) care over time; care for all but the most uncommon or unusual conditions; and coordination or integration of care, regardless of where or by whom that care is delivered. Primary health care is the principal means by which to approach the main goal of any health care services system: optimization of health status.
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