Investigating the mechanism of acoustically activated uptake of drugs from Pluronic micelles

BACKGROUND: This paper examines the mechanism of ultrasonic enhanced drug delivery from Pluronic micelles. In previous publications by our group, fluorescently labeled Pluronic was shown to penetrate HL-60 cells with and without the action of ultrasound, while drug uptake was increased with the application of ultrasound. METHODS: In this study, the amount of uptake of two fluorescent probes, Lysosensor Green (a pH-sensitive probe) and Cell Tracker Orange CMTMR (a pH-independent probe), was measured in HL-60 and HeLa cells. RESULTS: The results of our experiments show that the increase in drug accumulation in the cells as a result of ultrasonication is not due to an increase in endocytosis due to ultrasonication. CONCLUSIONS: We hypothesize that sonoporation plays an important role in the acoustically activated drug delivery of chemotherapy drugs delivered from Pluronic micelles

Control of Recoil Losses in Nanomechanical SiN Membrane Resonators

In the context of a recoil damping analysis, we have designed and produced a membrane resonator equipped with a specific on-chip structure working as a "loss shield" for a circular membrane. In this device the vibrations of the membrane, with a quality factor of $10^7$, reach the limit set by the intrinsic dissipation in silicon nitride, for all the modes and regardless of the modal shape, also at low frequency. Guided by our theoretical model of the loss shield, we describe the design rationale of the device, which can be used as effective replacement of commercial membrane resonators in advanced optomechanical setups, also at cryogenic temperatures

Systematic assessment of wastewater resource circularity and sustainable value creation

Data availability: Data will be made available on request.Supplementary materials are avalable online at: https://www.sciencedirect.com/science/article/pii/S0043135424000411#sec0032 .Copyright © 2024 The Authors. The circular use of wastewater has attracted significant attention in recent years. However, there is a lack of universal definitions and measurement tools that are required to achieve the circular economy's full potential. Therefore, a methodology was developed using three indicator typologies, namely resource flow, circular action, and sustainability indicators, to facilitate a robust and holistic circularity assessment. The method uses value propositions to integrate the assessment of intrinsic circularity performance with consequential circularity impacts, by quantifying sustainable value creation (using techniques such as life cycle assessment or cost-benefit analysis). Assessment method capabilities were exhibited by applying the defined steps to a wastewater treatment plant, comparing conventional and novel photobioreactor technologies. The resource flow indicator taxonomy results highlight improved outflow circularity, renewable energy usage, and economic efficiency of the novel system. Action indicators revealed that the photobioreactor technology was successful at achieving its defined circular goals. Lastly, sustainability indicators quantified a reduction of carbon footprint by two thirds and eutrophication by 41%, a M€ 0.5 per year increase of economic value, and that disability adjusted life year impacts are 58% lower. This supports that improving wastewater system circularity using photobioreactor technology results in environmental, economic, and social value for stakeholders.Horizon 2020 research and innovation programme DEEP PURPLE. The H2020 DEEP PURPLE project has received funding from the Bio-based Industries Joint Undertaking (JU) under the European Union's Horizon 2020 research and innovation programme under grant agreement No 837998. The JU receives support from the European Union's Horizon 2020 research and innovation programme and the Bio-based Industries Consortium

Silicon Nitride MOMS Oscillator for Room Temperature Quantum Optomechanics

IEEE Optomechanical SiN nano-oscillators in high-finesse Fabry-Perot cavities can be used to investigate the interaction between mechanical and optical degree of freedom for ultra-sensitive metrology and fundamental quantum mechanical studies. In this paper, we present a nano-oscillator made of a high-stress round-shaped SiN membrane with an integrated on-chip 3-D acoustic shield properly designed to reduce mechanical losses. This oscillator works in the range of 200 kHz to 5 MHz and features a mechanical quality factor of Q ≃10⁷ and a Q-frequency product in excess of 6.2 x 10¹² Hz at room temperature, fulfilling the minimum requirement for quantum ground-state cooling of the oscillator in an optomechanical cavity. The device is obtained by MEMS deep reactive-ion etching (DRIE) bulk micromachining with a two-side silicon processing on a silicon-on-insulator wafer. The microfabrication process is quite flexible such that additional layers could be deposited over the SiN membrane before the DRIE steps, if required for a sensing application. Therefore, such oscillator is a promising candidate for quantum sensing applications in the context of the emerging field of quantum technologies

Practical and clinical utility of non-invasive vagus nerve stimulation (nVNS) for the acute treatment of migraine. A post hoc analysis of the randomized, sham-controlled, double-blind PRESTO trial

Background: The PRESTO study of non-invasive vagus nerve stimulation (nVNS; gammaCore®) featured key primary and secondary end points recommended by the International Headache Society to provide Class I evidence that for patients with an episodic migraine, nVNS significantly increases the probability of having mild pain or being pain-free 2 h post stimulation. Here, we examined additional data from PRESTO to provide further insights into the practical utility of nVNS by evaluating its ability to consistently deliver clinically meaningful improvements in pain intensity while reducing the need for rescue medication. Methods: Patients recorded pain intensity for treated migraine attacks on a 4-point scale. Data were examined to compare nVNS and sham with regard to the percentage of patients who benefited by at least 1 point in pain intensity. We also assessed the percentage of attacks that required rescue medication and pain-free rates stratified by pain intensity at treatment initiation. Results: A significantly higher percentage of patients who used acute nVNS treatment (n = 120) vs sham (n = 123) reported a ≥ 1-point decrease in pain intensity at 30 min (nVNS, 32.2%; sham, 18.5%; P = 0.020), 60 min (nVNS, 38.8%; sham, 24.0%; P = 0.017), and 120 min (nVNS, 46.8%; sham, 26.2%; P = 0.002) after the first attack. Similar significant results were seen when assessing the benefit in all attacks. The proportion of patients who did not require rescue medication was significantly higher with nVNS than with sham for the first attack (nVNS, 59.3%; sham, 41.9%; P = 0.013) and all attacks (nVNS, 52.3%; sham, 37.3%; P = 0.008). When initial pain intensity was mild, the percentage of patients with no pain after treatment was significantly higher with nVNS than with sham at 60 min (all attacks: nVNS, 37.0%; sham, 21.2%; P = 0.025) and 120 min (first attack: nVNS, 50.0%; sham, 25.0%; P = 0.018; all attacks: nVNS, 46.7%; sham, 30.1%; P = 0.037). Conclusions: This post hoc analysis demonstrated that acute nVNS treatment quickly and consistently reduced pain intensity while decreasing rescue medication use. These clinical benefits provide guidance in the optimal use of nVNS in everyday practice, which can potentially reduce use of acute pharmacologic medications and their associated adverse events. Trial registration: ClinicalTrials.gov identifier: NCT02686034

Welcoming low testosterone as a cardiovascular risk factor

Male hypogonadism now has a new spectrum of complications. They are mainly cardiometabolic in nature. Low serum testosterone levels are a risk factor for diabetes, metabolic syndrome, inflammation and dyslipidemia. These metabolic and inflammatory complications are not without consequences. Recent studies have shown low serum testosterone levels to be an independent risk factor of cardiovascular and all-cause mortality. It is time to welcome low serum testosterone levels as a cardiovascular risk factor

Evaluation of a joint Bioinformatics and Medical Informatics international course in Peru

Background: New technologies that emerge at the interface of computational and biomedical science could drive new advances in global health, therefore more training in technology is needed among health care workers. To assess the potential for informatics training using an approach designed to foster interaction at this interface, the University of Washington and the Universidad Peruana Cayetano Heredia developed and assessed a one-week course that included a new Bioinformatics (BIO) track along with an established Medical/Public Health Informatics track (MI) for participants in Peru. Methods: We assessed the background of the participants, and measured the knowledge gained by track-specific (MI or BIO) 30-minute pre- and post-tests. Participants' attitudes were evaluated both by daily evaluations and by an end-course evaluation. Results: Forty-three participants enrolled in the course - 20 in the MI track and 23 in the BIO track. Of 20 questions, the mean % score for the MI track increased from 49.7 pre-test (standard deviation or SD = 17.0) to 59.7 (SD = 15.2) for the post-test (P = 0.002, n = 18). The BIO track mean score increased from 33.6 pre-test to 51.2 post-test (P less than 0.001, n = 21). Most comments (76%) about any aspect of the course were positive. The main perceived strength of the course was the quality of the speakers, and the main perceived weakness was the short duration of the course. Overall, the course acceptability was very good to excellent with a rating of 4.1 (scale 1-5), and the usefulness of the course was rated as very good. Most participants (62.9%) expressed a positive opinion about having had the BIO and MI tracks come together for some of the lectures. Conclusion: Pre- and post-test results and the positive evaluations by the participants indicate that this first joint Bioinformatics and Medical/Public Health Informatics (MI and BIO) course was a success.The University of Washington AMAUTA Global Training in Health Informatics, a Fogarty International Center/NIH funded grant (5D43TW007551), and the AMAUTA Research Practica Program, a Puget Sound Partners for Global Health-funded grant

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

Molecular measurement of BCR-ABL transcript variations in chronic myeloid leukemia patients in cytogenetic remission

<p>Abstract</p> <p>Background</p> <p>The monitoring of <it>BCR-ABL </it>transcript levels by real-time quantitative polymerase chain reaction (RT-qPCR) has become important to assess minimal residual disease (MRD) and standard of care in the treatment of chronic myeloid leukemia (CML). In this study, we performed a prospective, sequential analysis using RT-qPCR monitoring of <it>BCR-ABL </it>gene rearrangements in blood samples from 91 CML patients in chronic phase (CP) who achieved complete cytogenetic remission (CCyR) and major molecular remission (MMR) throughout imatinib treatment.</p> <p>Methods</p> <p>The absolute level of <it>BCR-ABL </it>transcript from peripheral blood was serially measured every 4 to 12 weeks by RT-qPCR. Only level variations > 0.5%, according to the international scale, was considered positive. Sequential cytogenetic analysis was also performed in bone marrow samples from all patients using standard protocols.</p> <p>Results</p> <p>Based on sequential analysis of <it>BCR-ABL </it>transcripts, the 91 patients were divided into three categories: (A) 57 (62.6%) had no variation on sequential analysis; (B) 30 (32.9%) had a single positive variation result obtained in a single sample; and (C) 4 (4.39%) had variations of <it>BCR-ABL </it>transcripts in at least two consecutive samples. Of the 34 patients who had elevated levels of transcripts (group B and C), 19 (55.8%) had a < 1% of <it>BCR-ABL/BCR </it>ratio, 13 (38.2%) patients had a 1% to 10% increase and 2 patients had a >10% increase of RT-qPCR. The last two patients had lost a CCyR, and none of them showed mutations in the <it>ABL </it>gene. Transient cytogenetic alterations in Ph-negative cells were observed in five (5.5%) patients, and none of whom lost CCyR.</p> <p>Conclusions</p> <p>Despite an increase levels of <it>BCR-ABL/BCR </it>ratio variations by RT-qPCR, the majority of CML patients with MMR remained in CCyR. Thus, such single variations should neither be considered predictive of subsequent failure and nor an indication for altering imatinib dose or switching to second generation therapy. Changing of imatinib on the basis of <it>BCR-ABL/BCR</it>% sustained increase and mutational studies is a prudent approach for preserving other therapeutic options in imatinib-resistant patients.</p