Ryedahlgaard9689
Direct quantification of pathogens in unprocessed complex samples remain challenging due to the severe inhibition of nucleic acid amplification. In this work, we report a nanoporous polyethylene glycol hydrogel with self-cleaning capacity for direct amplification of nucleic acid in complex matrices (human whole blood, animal blood, milky tea, humic acid, and surfactants) without any sample pretreatment or DNA extraction. During isothermal amplification inside the hydrogel, the inhibitors in the assay will be adsorbed and removed by the surrounding nanostructured polymers, and nucleic acid amplification was proceeding successfully, resulting in a series of bright dots for single bacteria counting. Thus, the loop-mediated isothermal amplifications (LAMP) performed inside hydrogel demonstrated a high level of resistance to inhibition in various complex matrices. The underlying anti-inhibition mechanism was also investigated. Digital quantification of Escherichia coli, Salmonella typhi and Listeria monocytogenes in whole blood were achieved within 20 min, with wide dynamic range, high specificity and low detection limit down to single bacterium. Visual counting via naked eye was also successfully established with the help of a conventional LED flashlight. We believe the developed hydrogel nanofluidic system has an enormous potential for on-site direct analysis of complex, crude, and unprocessed samples in clinical, food, agricultural, and environmental fields.Combinatorial therapies based on the simultaneous administration of multiple drugs can lead to synergistic effects, increasing the efficacy of the cancer therapy. However, it is crucial to develop new delivery systems that can increase the drugs' therapeutic selectivity and efficacy. Gold core silica shell (AuMSS) nanoparticles present physicochemical properties that allow their simultaneous application as drug delivery and imaging agents. Herein, poly(ethylene glycol) was modified with 4-methoxybenzamide and 3-(triethoxysilyl)propyl isocyanate (TPANIS) to create a novel surface functionalization capable of improving the colloidal stability and specificity of AuMSS nanospheres towards cancer cells. Moreover, a dual drug combination based on Doxorubicin (DOX) and Acridine orange (AO) was characterized and administered using the AuMSS-TPANIS nanospheres. The obtained results show that the DOXAO drug combination can mediate a synergistic therapeutic effect in both HeLa and MCF-7 cells, particularly at the 21, 11, and 12 ratios. Additionally, the TPANIS functionalization increased the AuMSS nanospheres colloidal stability and selectivity towards MCF-7 cancer cells (overexpressing sigma receptors). Such also resulted in an enhanced cytotoxic effect against MCF-7 cells when administering the DOXAO drug combination with the AuMSS-TPANIS nanospheres. Overall, the obtained results confirm the therapeutic potential of the DOXAO drug combination as well as the targeting capacity of AuMSS-TPANIS, supporting its application in the cancer-targeted combinatorial chemotherapy.
Emergency handover of critical patients is used to describe the moment of union between prehospital and hospital health team. However, the literature shows several definitions leading to great heterogeneity.
To study the emergency handover of critical patients between two critical-emergency care wards performed by emergency nurses worldwide and to identify the features of these processes.
We conducted an integrative review in eleven databases published from 2010 to 2019. Quality criteria and PRISMA checklist were applied. The protocol is registered with PROSPERO (CRD42020182335).
A total of 22 studies included and the following factors were identified variability vs standardization, identification, professionals' behavior, localization, environmental factors, patient participation, clinical records, education/training, responsability, and communication.
The actual emergency handover occurs under conditions quite contrary to those recommended by experts so that it is neither safe nor effective, leading a serious problem for patient safety and quality care.
The actual emergency handover occurs under conditions quite contrary to those recommended by experts so that it is neither safe nor effective, leading a serious problem for patient safety and quality care.Natural Killer (NK) cells are components of innate immune surveillance against transformed cells. NK cell immunotherapy has attracted attention as a promising strategy for cancer treatment, whose antitumor effects, however, require further improvement. The use of small molecules with immunomodulatory potentials and selective tumor-killing possesses the potential to complement immunotherapy. This study demonstrated that Piperlongumine (PL), a natural alkaloid obtained from long pepper fruit, alone has antitumor and anti-proliferative potential on all the tested tumors in vitro. PL pretreatment of tumor cells also potentiates their susceptibility to NK cell cytolysis at the doses where NK cell functions were preserved. Importantly, PL suppresses both NK -sensitive MHC-I -deficient and MHC-I -sufficient tumor growth in vivo. Mechanistically, PL induces misfolded proteins, impedes autophagy, increases ROS and tumor conjugation with NK cells. Furthermore, PL enhances the expression of NK cell-activating receptors on NK cells and its ligands on tumor cells, possibly leading to increased susceptibility to NK cell killing. Selleckchem ITF2357 Our findings showed the antitumor and immunomodulatory potential of PL, which could be explored to complement NK cell immunotherapy for cancer treatment.
The Symbol Digit Modalities Test (SDMT) is the most sensitive metric of neurocognitive function in multiple sclerosis (MS), and is consistently interpreted as a measure of information processing speed (IPS).
To evaluate the cognitive psychometric profile captured by the SDMT to identify whether different cognitive processes independently underlie performance.
Three samples of MS patients (total n=661; 185 research patients at MS center; 370 clinical patients at MS center; 106 persons with MS from the community) completed objective assessments of neuropsychological function across cognitive domains. Exploratory factor analysis (EFA) was used to derive latent cognitive factor scores, and operationalize cognitive domain composite scores, to understand the unique, shared and redundant contribution of different cognitive domains to SDMT performance using hierarchical multiple regression and commonality analysis.
Across three independent samples we provide converging strong evidence that the cognitive domains of Memory, IPS and Rapid Automatized Naming (lexical access speed) jointly and uniquely contribute to SDMT performance.