Several studies have shown that diverse components of the bone marrow (BM) microenvironment play a central role in the progression, pathophysiology, and drug resistance in multiple myeloma (MM). In ...particular, the dynamic interaction between BM mesenchymal stem cells (BM-MSC) and MM cells has shown great relevance. Here we showed that inhibiting both PKC and NF-κB signalling pathways in BM-MSC reduced cell survival in the MM cell line H929 and increased its susceptibility to the proteasome inhibitor bortezomib. PKC-mediated cell survival inhibition and bortezomib susceptibility induction were better performed by the chimeric peptide HKPS than by the classical enzastaurin inhibitor, probably due to its greatest ability to inhibit cell adhesion and its increased capability to counteract the NF-κB-related signalling molecules increased by the co-cultivation of BM-MSC with H929 cells. Thus, inhibiting two coupled signalling molecules in BM-MSC was more effective in blocking the supportive cues emerging from the mesenchymal stroma. Considering that H929 cells were also directly susceptible to PKC and NF-κB inhibition, we showed that treatment of co-cultures with the HKPS peptide and BAY11-7082, followed by bortezomib, increased H929 cell death. Therefore, targeting simultaneously connected signalling elements of BM-MSC responsible for MM cells support with compounds that also have anti-MM activity can be an improved treatment strategy.
We study numerically and analytically isolated interacting quantum systems that are taken out of equilibrium instantaneously (quenched). The probability of finding the initial state in time, the ...so-called fidelity, decays fastest for systems described by full random matrices, where simultaneous many-body interactions are implied. In the realm of realistic systems with two-body interactions, the dynamics is slower and depends on the interplay between the initial state and the Hamiltonian characterizing the system. The fastest fidelity decay in this case is Gaussian and can persist until saturation. A simple general picture, in which the fidelity plays a central role, is also achieved for the short-time dynamics of few-body observables. It holds for initial states that are eigenstates of the observables. We also discuss the need to reassess analytical expressions that were previously proposed to describe the evolution of the Shannon entropy. Our analyses are mainly developed for initial states that can be prepared in experiments with cold atoms in optical lattices.
More than 3 million infections were attributed to Chikungunya virus (CHIKV) in the 2014-2016 outbreak in Mexico, Central and South America, with over 500 deaths directly or indirectly related to this ...viral disease. CHIKV outbreaks are recurrent and no vaccine nor approved therapeutics exist to prevent or treat CHIKV infection. Reliable and robust diagnostic methods are thus critical to control future CHIKV outbreaks. Direct CHIKV detection in serum samples via highly specific and high affinity anti-CHIKV antibodies has shown to be an early and effective clinical diagnosis.
To isolate highly specific and high affinity anti-CHIKV, Chikungunya virions were isolated from serum of a patient in Veracruz, México. After purification and characterization via electron microscopy, SDS-PAGE and binding to well-characterized anti-CHIKV antibodies, UV-inactivated particles were utilized as selector in a solid-phase panning in combination with ALTHEA Gold Libraries™, as source of antibodies. The screening was based on ELISA and Next-Generation Sequencing.
The CHIKV isolate showed the typical morphology of the virus. Protein bands in the SDS-PAGE were consistent with the size of CHIKV capsid proteins. UV-inactivated CHIKV particles bound tightly the control antibodies. The lead antibodies here obtained, on the other hand, showed high expression yield, > 95% monomeric content after a single-step Protein A purification, and importantly, had a thermal stability above 75 °C. Most of the antibodies recognized linear epitopes on E2, including the highest affinity antibody called C7. A sandwich ELISA implemented with C7 and a potent neutralizing antibody isolated elsewhere, also specific for E2 but recognizing a discontinuous epitope, showed a dynamic range of 0.2-40.0 mg/mL of UV-inactivated CHIKV purified preparation. The number of CHIKV particles estimated based on the concentration of E2 in the extract suggested that the assay could detect clinically meaningful amounts of CHIKV in serum.
The newly discovered antibodies offer valuable tools for characterization of CHIKV isolates. Therefore, the strategy here followed using whole viral particles and ALTHEA Gold Libraries
could expedite the discovery and development of antibodies for detection and control of emergent and quickly spreading viral outbreaks.
BACKGROUND: Early intervention with nutritional support has been found to stop weight loss in older people malnourished or at risk of malnutrition. Enriched food could be a more attractive ...alternative to improve meals, than conventional oral nutritional supplements. AIMS: To determine the effectiveness of food-based fortification to prevent risk of malnutrition in elderly patients in community or institutionalized elderly patients. METHODS: A systematic review was conducted of randomized controlled trials, quasi-experimental, and interrupted time series including a longitudinal analysis. PARTICIPANTS: Elderly patients who are institutionalized, hospitalized or community-dwelling, with a minimum average age of 65 years. All type of patient groups, with the exception of people in critical care, or those who were recovering from cancer treatment, were included. INTERVENTION: Studies had to compare food-based fortification against alternatives. Studies that used oral nutritional supplementation such as commercial sip feeds, vitamin or mineral supplements were excluded. The search was conducted in Cochrane, CINAHL, PubMed, EMBASE, LILACS, and Cuiden. An independent peer review was carried out. RESULTS: From 1011 studies obtained, 7 were included for the systematic review, with 588 participants. It was possible to perform meta-analysis of four studies that provided results on caloric and protein intake. Food-based fortification yielded positive results in the total amount of ingested calories and protein. Nevertheless, due to the small number of participants and the poor quality of some studies, further high quality studies are required to provide reliable evidence. IMPLICATIONS FOR PRACTICE: Despite the limited evidence, due to their simplicity, low cost, and positive results in protein and calories intake, simple dietary interventions based on the food-based fortification or densification with protein or energy of the standard diet could be considered in patients at risk of malnutrition.
The degradation and detoxification towards the duckweed Lemna minor of 4-nitrophenol (4NP) was studied by means of bench-scale constructed wetlands (CWs), TiO2-photocatalysis and Fenton + photoFenton ...reactions. The main goal of this work was to compare the three treatment techniques to evaluate their possible combination for the efficient, low cost treatment of 4NP effluents. In CWs, adsorption on the substrate of 4NP was found to achieve 34–45%. Low concentrations (up to 100 ppm) of 4NP were successfully treated by CWs in 8–12 h. The microbial degradation of 4NP started after a lag phase which was longer with higher initial concentrations of the pollutant. The greatest degradation rate was found to occur at initial concentrations of 4NP between 60 and 90 ppm. Solar TiO2-photocatalysis was faster than the CWs. The greatest removals in terms of mass of 4NP removed after 6 h of irradiation were found to occur at 4NP concentrations of about 200 ppm. Fenton reaction provided complete 4NP degradation up to 500 ppm in only 30 min but TOC was removed by only about 40%. The resulting toxicities were below 20% for initial 4NP concentrations below 300 ppm. It was the Fenton + photoFenton combination (180 min in total) that provided TOC reductions up to 80% and negative L. minor growth inhibition for almost all the 4NP concentrations tested. The combination of solar TiO2-photocatalysis (6 h) with CWs (16 h) was able to completely treat and detoxify 4NP effluents with concentrations as high as 200 ppm of the organic.
► We studied the treatment 4NP by CWs and advanced oxidation technologies. ► In CWs biodegradation and adsorption were the main removal pathways. ► The 4NP removal order was: CWs < TiO2-photocatalysis < Fenton–photoFenton. ► The combination of CWs with photocatalysis is proposed as a convenient treatment.
It is thought that Paleo-Inuit were the first people that settled the American Arctic about 5000 BP (before the present) from a migration that crossed Beringia from Northeast Asia. It is theorized ...that this group initially migrated to the North Slopes of Alaska and subsequently expanded eastward, eventually reaching Greenland. A second circumpolar dispersal of Neo-Inuit from the North Slopes associated with the Thule-Inuk culture has been postulated to have extended eastward around 800 BP, totally replacing the original Paleo-Inuit without admixing. Although generally accepted, this migration scenario is incompatible with previously reported indications of east to west gene flow across the American Arctic. Here we report on the Y-chromosome haplogroup and Y-STR diversity of the four circumpolar populations of the Tuva Republic (N = 24), Northeast Siberia (N = 9), Bethel, Alaska (N = 40), and Barrow, Alaska (N = 31). Four haplogroup lineages (Q-NWT01, Q-M3, Q-M346, and Q-M120) were detected, Q-NWT01 and Q-M3 being the most abundant at 11.11 and 66.67% in Northeast Siberia, 32.50 and 65.00% in Bethel, and 67.74 and 32.26% in Barrow, respectively. The same samples genotyped for Y-chromosome SNPs were typed for 17 Y-STYR loci using the AmpFlSTR Yfiler system. Age estimates and diversity values for the Q-NWT01 and Q-M3 mutations suggest extensive movement of male individuals along the entire longitudinal stretch of the American circumpolar region. Throughout the entire region, Q-M3 exhibits a west to east decreasing gradient in age and diversity while Q-NWT01 indicates the opposite with older TMRCA and higher diversity values running from east to west with the most recent estimates in Canada and Alaska. The high age and diversity values in Greenland are congruent with an origin of the Q-NWT01 mutation in the east of the circumpolar range about 2000-3000 ya. This scenario is incompatible with a complete biological replacement starting about 700 BP of Paleo-Inuit like the Dorset by the Thule-Inuit (Neo-Inuit), as is currently thought, and more parsimonious with gene flow carrying the NWT01 mutation from a pre-Thule population to the ancestors of the present-day Inuit.
Nowadays society is demanding more and more smart healthcare services that allow monitoring patient status in a non-invasive way, anywhere and anytime. Thus, healthcare applications are currently ...facing important challenges guided by the u-health (ubiquitous health) and p-health (pervasive health) paradigms. New emerging technologies can be combined with other widely deployed ones to develop such next-generation healthcare systems. The main objective of this paper is to review and provide more details on the work presented in "LOBIN: E-Textile and Wireless-Sensor-Network-Based Platform for Healthcare Monitoring in Future Hospital Environments", published in the IEEE Transactions on Information Technology in Biomedicine, as well as to extend and update the comparison with other similar systems. As a result, the paper discusses the main advantages and disadvantages of using different architectures and communications technologies to develop wearable systems for pervasive healthcare applications.
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•InP-In2O3 QDs are synthesized by a single-step chemical method without injection of hot precursors.•HR-TEM images show the synthesis of InP and In2O3 QDs.•The InP and In2O3 QDs size ...increases with the P(TMS)3 concentration.•PL spectra reveal emission bands attributed to InP and In2O3 QDs.•XPS confirms the formation of InP, In2O3 and amorphous InPOx.
InP-In2O3 colloidal quantum dots (QDs) synthesized by a single-step chemical method without injection of hot precursors (one-pot) were investigated. Specifically, the effect of the tris(trimethylsilyl)phosphine, P(TMS)3, precursor concentration on the QDs properties was studied to effectively control the size and shape of the samples with a minimum size dispersion. The effect of the P(TMS)3 precursor concentration on the optical, structural, chemical surface, and electronic properties of InP-In2O3 QDs is discussed. The absorption spectra of InP-In2O3 colloids, obtained by both UV–Vis spectrophotometry and photoacoustic spectroscopy, showed a red-shift in the high-energy regime as the concentration of the P(TMS)3 increased. In addition, these results were used to determine the band-gap energy of the InP-In2O3 nanoparticles, which changed between 2.0 and 2.9 eV. This was confirmed by Photoluminescence spectroscopy, where a broad-band emission displayed from 2.0 to 2.9 eV is associated with the excitonic transition of the InP and In2O3 QDs. In2O3 and InP QDs with diameters ranging approximately from 8 to 10 nm and 6 to 9 nm were respectively found by HR-TEM. The formation of the InP and In2O3 phases was confirmed by X-ray Photoelectron Spectroscopy.
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