[Creation and Study of Triterpenoid Nanoparticles and Amphiphilic meso-Arylporphyrins].

This work is devoted to the study of nanoparticles based on amphiphilic meso-arylporphyrins and spherical amorphous nanoparticles (SANp), consisting of birch bark triterpenoids mixture. Nanoparticles were investigated by electron microscopy, dynamic light scattering, UV spectroscopy and fluorimetry. It was shown the efficiency of the inclusion of porphyrin sensitizer to the nanoparticles and the use of these nanoparticles as drug delivery system.

Creation and study of triterpenoid nanoparticles and radioprotective substance genistein.

This work is devoted to the study and obtaining of new radioprotective agents based on natural flavonoid genistein and spherical amorphous nanoparticles (SANPs) produced from a mixture of birch bark triterpenoids. The physicochemical characteristics of the nanoparticles were studied by electron microscopy, dynamic light scattering, and UV-VIS spectroscopy. The radioprotective efficacy of the nanodrug in vivo and the possibility of its use as a radioprotective agent was shown.

Control of metamorphic buffer structure and device performance of In(x)Ga(1-x)As epitaxial layers fabricated by metal organic chemical vapor deposition.

Using a step-graded (SG) buffer structure via metal-organic chemical vapor deposition, we demonstrate a high suitability of In0.5Ga0.5As epitaxial layers on a GaAs substrate for electronic device application. Taking advantage of the technique's precise control, we were able to increase the number of SG layers to achieve a fairly low dislocation density (∼10(6) cm(-2)), while keeping each individual SG layer slightly exceeding the critical thickness (∼80 nm) for strain relaxation. This met the demanded but contradictory requirements, and even offered excellent scalability by lowering the whole buffer structure down to 2.3 µm. This scalability overwhelmingly excels the forefront studies. The effects of the SG misfit strain on the crystal quality and surface morphology of In0.5Ga0.5As epitaxial layers were carefully investigated, and were correlated to threading dislocation (TD) blocking mechanisms. From microstructural analyses, TDs can be blocked effectively through self-annihilation reactions, or hindered randomly by misfit dislocation mechanisms. Growth conditions for avoiding phase separation were also explored and identified. The buffer-improved, high-quality In0.5Ga0.5As epitaxial layers enabled a high-performance, metal-oxide-semiconductor capacitor on a GaAs substrate. The devices displayed remarkable capacitance-voltage responses with small frequency dispersion. A promising interface trap density of 3 × 10(12) eV(-1) cm(-2) in a conductance test was also obtained. These electrical performances are competitive to those using lattice-coherent but pricey InGaAs/InP systems.

Plastic does not simply flow into the sea: River transport dynamics affected by tides and floating plants.

Plastic pollution is ubiquitous in aquatic environments worldwide. Rivers connect terrestrial and marine ecosystems, playing a key role in the transport of land-based plastic waste towards the sea. Emerging research suggests that in estuaries and tidal rivers, tidal dynamics play a significant role in plastic transport and retention dynamics. To date, observations in these systems have been limited, and plastic transport dynamics during single tidal cycles remain poorly understood. Here, we investigated plastic transport, trapping, and re-mobilization of macroplastics (> 0.5 cm) in the Saigon River, focusing on short-term dynamics of individual tidal cycles. We used GPS trackers, released at different stages of the tidal cycle (ebb, flood, neap, spring). Plastic items demonstrated dynamic and intermittent transport behavior. Items spent almost half of the time (49%) temporarily stopped, mainly due to their entrapment in vegetation, infrastructure, or deposition on riverbanks. Items were almost always re-mobilized within 10 h (85%), leading to successive phases of stopping and transport. Tidal dynamics also resulted in bidirectional transport of plastic items, with median daily total transport distance within the 40 km study reach (8.9 km day-1) over four times larger than the median daily net distance (2.0 km day-1). The median retention time of plastic items within the reach was 21 days (mean = 202 days). In total, 81% of the retrieved items were trapped within water hyacinths, emphasizing the important role of floating vegetation on river plastic transport dynamics. With this paper, we aim to provide data-driven insights into macroplastic transport and retention dynamics in a tropical tidal river. These are crucial in the design of effective intervention and monitoring strategies, and estimating net plastic emission from rivers into the sea.

Effectiveness of an enhanced antibiotic stewardship programme among paediatric patients in a tertiary hospital in Vietnam.

BACKGROUND: In 2016, the Vietnamese Ministry of Health promoted development of antimicrobial stewardship for hospitals. AIM: To evaluate the effectiveness and safety of the enhanced antibiotic stewardship programme (ASP) compared to the original ASP among paediatric patients at a tertiary hospital for infectious diseases in Vietnam. METHODS: An interrupted time-series analysis was conducted to examine antibiotic use in paediatric patients aged 0-17 years admitted to the Hospital for Tropical Diseases in Ho Chi Minh City from April 2016 to March 2020. Outcomes measured were defined daily doses (DDDs) per 1000 patient-days; antibiotic days of therapy (DOT) per 1000 patient-days; percentage of antibiotic use by the World Health Organization Access, Watch, and Reserve (AWaRe) system; Access-to-Watch ratio; and worse clinical outcomes at discharge. FINDINGS: Of 60,172 admissions during the study period, 28,019 received at least one antibiotic (46.6%) during hospital stay. The Watch antibiotics were the most frequently prescribed (78.1% of total antibiotic courses). The enhanced ASP did not improve antibiotic prescribing by DDDs per 1000 patient-days (risk ratio: 1.05; 95% confidence interval: 0.94-1.17) and DOT per 1000 patient-days (1.11; 0.99-1.25) compared to the original ASP. However, the percentage of Access antibiotics prescribed, and the Access-to-Watch ratio increased after the enhanced ASP (1.73; 1.38-2.17). There was no significant difference in worse clinical outcomes at discharge between the original and enhanced ASP (1.25; 0.78-2.00). CONCLUSION: The enhanced ASP had modest impact on antibiotic consumption in the paediatric population despite the improvement of Access antibiotic use and the Access-to-Watch ratio.

Effects of automated prompts for logging symptom and exercise data on mobile devices in patients with chronic obstructive pulmonary disease.

Traditional approaches to patient-reported outcomes diaries have been largely paper based. However, paper-based approaches have inherent inefficiencies such as an inability to communicate the entries in real time to the healthcare team, issues related to transport and mobility, and no tailored output related to what is entered. Traditional paper-based approaches also lack the ability to prompt users at regular intervals to record data. This lack of prompting may lead to delays in entering symptoms and exercises (diary hoarding). Electronic mobile devices have addressed some of these limitations. However, until recently these electronic devices have not been able to deliver the data in real time, thus limiting the ability of the care team to interact and respond. With the emergence of wireless mobile devices, which provide real-time linkages between the patient and the researchers, these limitations are largely eliminated. Yet, it is unclear (whether diary hoarding still occurs and) whether prompts are effective in reducing hoarding over the course of many months. The purpose of this analysis was to conduct a summative evaluation of 7474 automated prompts sent to participants with chronic obstructive pulmonary disease (n = 19). These participants were provided with mobile devices for logging exercise and symptom data over a 6-month period as part of a clinical trial. We found a marginal association between length in the study and delay in submission of exercise and symptom data in response to electronic prompts. Factors associated with delayed response to the prompts included older age, limited computer skills, and reports of no exercise. We recommend that future investigators who are using mobile devices in their research pay careful attention to usability issues as well as strategies that might keep patients engaged and motivated.

Effects of automated prompts for logging symptom and exercise data on mobile devices in patients with chronic obstructive pulmonary disease.

Traditional approaches to patient-reported outcomes diaries have been largely paper based. However, paper-based approaches have inherent inefficiencies such as an inability to communicate the entries in real time to the healthcare team, issues related to transport and mobility, and no tailored output related to what is entered. Traditional paper-based approaches also lack the ability to prompt users at regular intervals to record data. This lack of prompting may lead to delays in entering symptoms and exercises (diary hoarding). Electronic mobile devices have addressed some of these limitations. However, until recently these electronic devices have not been able to deliver the data in real time, thus limiting the ability of the care team to interact and respond. With the emergence of wireless mobile devices, which provide real-time linkages between the patient and the researchers, these limitations are largely eliminated. Yet, it is unclear (whether diary hoarding still occurs and) whether prompts are effective in reducing hoarding over the course of many months. The purpose of this analysis was to conduct a summative evaluation of 7474 automated prompts sent to participants with chronic obstructive pulmonary disease (n = 19). These participants were provided with mobile devices for logging exercise and symptom data over a 6-month period as part of a clinical trial. We found a marginal association between length in the study and delay in submission of exercise and symptom data in response to electronic prompts. Factors associated with delayed response to the prompts included older age, limited computer skills, and reports of no exercise. We recommend that future investigators who are using mobile devices in their research pay careful attention to usability issues as well as strategies that might keep patients engaged and motivated.

Cardiovascular changes in calcium-deficient chick embryos.

We have developed an experimental system involving calcium-deficient chick embryos to examine the relationship between calcium homeostasis and cardiovascular activities. We have found that the calcium-deficient embryos, when compared with control animals, exhibit tachycardia and are significantly hypertensive. The effects are unlikely to be due to gross cardiac malformations or hypertrophy. The hypertensive condition appears to be a specific result of the systemic calcium deficiency since calcium supplementation to these embryos significantly restores the functions to normality.

Antimicrobial stewardship in care homes: outcomes of importance to stakeholders.

BACKGROUND: Heterogeneity of outcomes measured in trials to improve antimicrobial stewardship (AMS) in care homes has compromised quality of evidence. A core outcome set (COS) is needed to facilitate interpretation and synthesis of evidence in this area. AIM: To determine outcomes deemed important by relevant stakeholders for interventions aimed at improving AMS in care homes, and to produce a refined list of outcomes that could be considered for use in future research. METHODS: Semi-structured face-to-face or telephone interviews were conducted with key stakeholders. Outcomes reported in previous randomized controlled trials (RCTs) of AMS in care homes were included in a topic guide for interviews. Content analysis was undertaken to identify potential outcomes suggested by participants, followed by further review. FINDINGS: Twenty-seven outcomes reported in RCTs were refined into a list of 12 overarching outcomes. Interviews with participants (six researchers, 31 healthcare professionals, and four family members of care home residents) identified 40 additional outcomes that were important to them. From these 52 outcomes, the total number of antimicrobials, the appropriateness of antimicrobial prescribing and adherence to guidelines were highlighted by most participants. After reviewing all 52 outcomes, a refined list of 14 outcomes potentially feasible for use in AMS trials in care homes was generated. CONCLUSION: s: A number of potential outcomes for AMS in care homes, some of which had not been reported in previous studies, were identified. The refined list of 14 outcomes will be used in a future study to agree a COS for care home AMS trials.

From radiometry to chronology of a marine sediment core: A 210Pb dating interlaboratory comparison exercise organised by the IAEA.

Laboratories from 14 countries (with different levels of expertise in radionuclide measurements and 210Pb dating) participated in an interlaboratory comparison exercise (ILC) related to the application of 210Pb sediment dating technique within the framework of the IAEA Coordinated Research Project. The laboratories were provided with samples from a composite sediment core and were required to provide massic activities of several radionuclides and an age versus depth model from the obtained results, using the most suitable 210Pb dating model. Massic concentrations of Zn and Cu were also determined to be used for chronology validation. The ILC results indicated good analytical performances while the dating results didn't demonstrate the same degree of competence in part due to the different experience in dating of the participant laboratories. The ILC exercise enabled evaluation of the difficulties faced by laboratories implementing 210Pb dating methods and identified some limitations in providing reliable chronologies.

Observation of giant positive magnetoresistance in a Cooper pair insulator.

Ultrathin amorphous Bi films, patterned with a nanohoneycomb array of holes, can exhibit an insulating phase with transport dominated by the incoherent motion of Cooper pairs (CP) of electrons between localized states. Here, we show that the magnetoresistance (MR) of this Cooper pair insulator (CPI) phase is positive and grows exponentially with decreasing temperature T, for T well below the pair formation temperature. It peaks at a field estimated to be sufficient to break the pairs and then decreases monotonically into a regime in which the film resistance assumes the T dependence appropriate for weakly localized single electron transport. We discuss how these results support proposals that the large MR peaks in other unpatterned, ultrathin film systems disclose a CPI phase and provide new insight into the CP localization.

Long-term impaired neutrophil migration in mice overexpressing human interleukin-8.

The proinflammatory chemokine interleukin-8 (IL-8/NAP-1) has been implicated in recruiting neutrophils to sites of acute and chronic tissue inflammation. In transgenic mice, elevated serum IL-8 levels ranging from 1 to 118 ng/ml were correlated with proportional increases in circulating neutrophils and proportional decreases in L-selectin expression on the surface of blood neutrophils. No change in the expression of the beta 2-integrins Mac-1 and LFA-1 was apparent on peripheral blood neutrophils of the IL-8 transgenic mice. Additionally, L-selectin expression on bone marrow neutrophils and neutrophil precursors was normal in all transgenic lines. IL-8 transgenic mice demonstrated an accumulation of neutrophils in the microcirculation of the lung, liver and spleen. Moreover, there was no evidence of neutrophil extravasation, plasma exudation or tissue damage in any IL-8 transgenic mice. Neutrophil migration into the inflamed peritoneal cavity was severely inhibited in IL-8 transgenic mice, but not in nontransgenic littermates. The IL-8 transgenic mice should serve as useful models for studying the putative role of neutrophils in mediating tissue damage in models of inflammation, such as hepatic ischemia and reperfusion injury, cecal puncture and ligation, and glomerulonephritis.

The zinc finger transcription factor Egr-1 potentiates macrophage differentiation of hematopoietic cells.

Previously we have shown that the zinc finger transcription factor Egr-1 is essential for and restricts differentiation of hematopoietic cells along the macrophage lineage, raising the possibility that Egr-1 actually plays a deterministic role in governing the development of hematopoietic precursor cells along the monocytic lineage. To test this hypothesis, we have taken advantage of interleukin-3-dependent 32Dcl3 hematopoietic precursor cells which, in addition to undergoing granulocytic differentiation in response to granulocyte colony-stimulating factor, were found to be induced for limited proliferation, but not differentiation, by granulocyte-macrophage colony-stimulating factor. It was shown that ectopic expression of Egr-1 blocked granulocyte colony-stimulating factor-induced terminal granulocytic differentiation, consistent with previous findings. In addition, ectopic expression of Egr-1 endowed 32Dcl3 cells with ability to be induced by granulocyte-macrophage colony-stimulating factor for terminal differentiation exclusively along the macrophage lineage. Thus, evidence that Egr-1 potentiates terminal macrophage differentiation has been obtained, suggesting that Egr-1 plays a deterministic role in governing the development of hematopoietic cells along the macrophage lineage.

Programmable Microfluidic Synthesis of Over One Thousand Uniquely Identifiable Spectral Codes.

Encoded microparticles have become a powerful tool for a wide array of applications, including high-throughput sample tracking and massively parallel biological multiplexing. Spectral encoding, where particles are encoded with distinct luminescence spectra, provides a particularly appealing encoding strategy because of the ease of reading codes and assay flexibility. To date, spectral encoding has been limited in the number of codes that can be accurately resolved. Here, we demonstrate an automated 5-dimensional spectral encoding scheme using lanthanide nanophosphors that is capable of producing isotropic spherical microparticles with up to 1,100 unique codes, which we term MRBLEs (Microspheres with Ratiometric Barcode Lanthanide Encoding). We further develop a quantitative framework for evaluating global ability to distinguish codes and demonstrate that for six different sets of MRBLEs ranging from 106 to 1,101 codes in size, > 98% of MRBLEs can be assigned to a code with 99.99% confidence. These > 1,000 code sets represent the largest spectral code libraries built to date. We expect that these MRBLEs will enable a wide variety of novel multiplexed assays.

Driving a Superconductor to Insulator Transition with Random Gauge Fields.

Typically the disorder that alters the interference of particle waves to produce Anderson localization is potential scattering from randomly placed impurities. Here we show that disorder in the form of random gauge fields that act directly on particle phases can also drive localization. We present evidence of a superfluid bose glass to insulator transition at a critical level of this gauge field disorder in a nano-patterned array of amorphous Bi islands. This transition shows signs of metallic transport near the critical point characterized by a resistance , indicative of a quantum phase transition. The critical disorder depends on interisland coupling in agreement with recent Quantum Monte Carlo simulations. We discuss how this disorder tuned SIT differs from the common frustration tuned SIT that also occurs in magnetic fields. Its discovery enables new high fidelity comparisons between theoretical and experimental studies of disorder effects on quantum critical systems.

Blocking c-Myc and Max expression inhibits proliferation and induces differentiation of normal and leukemic myeloid cells.

Given the central role c-Myc plays in growth control, differentiation and apoptosis, understanding how c-Myc functions will increase our understanding about normal cell development, and how alterations in these processes can lead to malignancy. C-Myc is a negative regulator of terminal myeloid differentiation; therefore, it was of interest to determine what effect blocking c-Myc expression would have on proliferation and differentiation. In this work we showed that blocking expression of either c-Myc or Max, its molecular partner, in myeloblastic leukemia M1 cells activated the differentiation program in the absence of an exogenous source of differentiation inducer; the cells assumed an intermediate stage myeloid morphology. Moreover, when both c-Myc and Max expression was concommitantly blocked, many of the cells underwent terminal differentiation. Finally, extending these studies to myeloblast enriched normal bone marrow (BM) cell has shown that blocking expression of either c-Myc or Max accelerated GM-CSF-induced differentiation along both the granulocytic and monocytic lineages. Thus, it can be concluded that blocking either c-Myc or Max expression in myeloid cells at specific stages of development activates and accelerates the terminal differentiation program.

Expression of keratinocyte growth factor in embryonic liver of transgenic mice causes changes in epithelial growth and differentiation resulting in polycystic kidneys and other organ malformations.

Expression of human keratinocyte growth factor (KGF/FGF-7) was directed to hepatocytes during the later period of mouse gestation using a human apolipoprotein E (ApoE) gene promoter and its associated liver-specific enhancer. Human KGF was detectable in liver extracts and serum prepared from e17.5-e19.5 embryos, concomitant with the appearance of morphological abnormalities in several organs which express KGF receptor. The most striking phenotypic aberration in the ApoE-hKGF transgenic embryos was marked hyperplasia and cystic dilation of the cortical and medullary kidney collecting duct system, a phenotype resembling infantile polycystic kidney disease in humans. Transgenic embryos had enlarged livers, with prominent biliary epithelial hyperplasia, and also exhibited enhanced bronchiolar epithelial and type II pneumocyte proliferation. There was variable hyperplasia of intestinal epithelia, and urothelium of the urinary bladder and ureters. When compared to age-matched littermate controls, marked epidermal papillomatous acanthosis and hyperkeratosis in the skin, with a notable decrease in the number of developing hair follicles was seen in transgenic embryos. The pancreas exhibited significant ductal hyperplasia, with an increase in the number of ductal epithelial cells staining positive for insulin expression. High systemic levels of KGF during the latter stages of embryogenesis causes abnormalities in epithelial growth and differentiation within multiple organ systems and results in perinatal lethality. Correct temporal and spatial expression of KGF during the latter stages of organ development is likely to play a critical role in mesenchymal-epithelial signaling required for normal embryonic growth and development.

Reduced turn-around time for Mycobacterium tuberculosis drug susceptibility testing with a proportional agar microplate assay.

Multidrug-resistant tuberculosis is a major issue worldwide; however, accessibility to drug susceptibility testing (DST) is still limited in developing countries, owing to high costs and complexity. We developed a proportion method on 12-well microplates for DST. The assay reduced the time to results to <12 days and <10 days when bacterial growth was checked with the naked eye or a microscope, respectively. Comparison with the Canetti-Grosset method showed that the results of the two assays almost overlapped (kappa index 0.98 (95% CI 0.91-1.00) for isoniazid, rifampicin, streptomycin; and kappa index 0.92 (95% CI 0.85-0.99) for ethambutol). The sequencing of genes involved in drug resistance showed similar level of phenotype-genotype agreement between techniques. Finally, measurement of the MICs of rifampicin and ethambutol suggests that the currently used critical ethambutol concentration should be revised, and that the current molecular drug susceptibility tests for rifampicin need to be re-evaluated, as in vitro rifampicin-sensitive isolates could harbour drug resistance-associated mutation(s).

Interfacial Engineering of Semiconductor-Superconductor Junctions for High Performance Micro-Coolers.

The control of electronic and thermal transport through material interfaces is crucial for numerous micro and nanoelectronics applications and quantum devices. Here we report on the engineering of the electro-thermal properties of semiconductor-superconductor (Sm-S) electronic cooler junctions by a nanoscale insulating tunnel barrier introduced between the Sm and S electrodes. Unexpectedly, such an interface barrier does not increase the junction resistance but strongly reduces the detrimental sub-gap leakage current. These features are key to achieving high cooling power tunnel junction refrigerators, and we demonstrate unparalleled performance in silicon-based Sm-S electron cooler devices with orders of magnitudes improvement in the cooling power in comparison to previous works. By adapting the junctions in strain-engineered silicon coolers we also demonstrate efficient electron temperature reduction from 300 mK to below 100 mK. Investigations on junctions with different interface quality indicate that the previously unexplained sub-gap leakage current is strongly influenced by the Sm-S interface states. These states often dictate the junction electrical resistance through the well-known Fermi level pinning effect and, therefore, superconductivity could be generally used to probe and optimize metal-semiconductor contact behaviour.

Comparative distribution of messenger RNAs encoding glutamic acid decarboxylases (Mr 65,000 and Mr 67,000) in the basal ganglia of the rat.

Glutamic acid decarboxylase, the enzyme required for GABA synthesis, exists as distinct isoforms, which have recently been found to be encoded by different genes. The relative expression of messenger RNAs encoding two isoforms of glutamic acid decarboxylase (Mr 67,000 and Mr 65,000) was measured at the single-cell level in neurons of the rat basal ganglia with in situ hybridization histochemistry. Both messenger RNAs were expressed in neurons of the striatum, pallidum, and substantia nigra pars reticulata, but marked differences in the relative level of labelling were observed with the two probes. In striatum, efferent neurons were more densely labelled for the messenger RNA encoding glutamic acid decarboxylase (Mr 65,000) than for the messenger RNA encoding glutamic acid decarboxylase (Mr 67,000), whereas the reverse was observed for GABA-ergic interneurons. Neurons of the entopeduncular nucleus were much more densely labelled for messenger RNA encoding glutamic acid decarboxylase (Mr 65,000) than for messenger RNA encoding glutamic acid decarboxylase (Mr 67,000). In addition, labelling for messenger RNA encoding glutamic acid decarboxylase (Mr 65,000) was higher in the entopeduncular nucleus (internal pallidum) than in the globus pallidus (external pallidum), a structure which expressed similar levels of both mRNAs. In contrast to neurons of the internal pallidum, efferent neurons of the substantia nigra pars reticulata expressed slightly more messenger RNA encoding glutamic acid decarboxylase (Mr 67,000) than that encoding the other isoform of the enzyme. The results suggest a differential expression of the messenger RNAs encoding the two isoforms of glutamic acid decarboxylase in subpopulations of basal ganglia neurons in rats.