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This study investigates the potential of applying water to the wheel-rail contact to reduce squealing noise. For this purpose, a twin-disc device with a single tram wheel and real wheel suspension stiffnesses was developed. Three types of tests were performed. During the tests, adhesion coefficient, sound pressure level and wheel axial vibration were measured. The tests under dry conditions were carried out to describe the frequency spectrum of wheel vibration and to establish reference values for further measurements. The tests under wet conditions were carried out to investigate the ability of water to reduce adhesion and noise. Finally, tests with varying amounts of water in contact were carried out because of the low adhesion risk. The experimental results showed that the twin-disc device was able to reproduce both the adhesion and noise properties of the contact. Tests with different amounts of water showed that the application of water can be a promising way to reduce squealing noise from wheel-rail contact.

Alzheimers disease (AD) is a chronic neurodegenerative disorder characterized by memory loss and progressive cognitive impairments. In mouse models of AD pathology, studies have found neuronal and synaptic deficits in hippocampus, but less is known about changes in medial entorhinal cortex (MEC), which is the primary spatial input to the hippocampus and an early site of AD pathology. Here, we measured neuronal intrinsic excitability and synaptic activity in MEC layer II (MECII) stellate cells, MECII pyramidal cells, and MEC layer III (MECIII) excitatory neurons at 3 and 10 months of age in the 3xTg mouse model of AD pathology, using male and female mice. At 3 months of age, before the onset of memory impairments, we found early hyperexcitability in intrinsic properties of MECII stellate and pyramidal cells, but this was balanced by a relative reduction in synaptic excitation (E) compared with inhibition (I; E/I ratio), suggesting intact homeostatic mechanisms regulating MECII activity. Conversely, MECIII neurons had reduced intrinsic excitability at this early time point with no change in synaptic E/I ratio. By 10 months of age, after the onset of memory deficits, neuronal excitability of MECII pyramidal cells and MECIII excitatory neurons was largely normalized in 3xTg mice. However, MECII stellate cells remained hyperexcitable, and this was further exacerbated by an increased synaptic E/I ratio. This observed combination of increased intrinsic and synaptic hyperexcitability suggests a breakdown in homeostatic mechanisms specifically in MECII stellate cells at this postsymptomatic time point, which may contribute to the emergence of memory deficits in AD.SIGNIFICANCE STATEMENT AD causes cognitive deficits, but the specific neural circuits that are damaged to drive changes in memory remain unknown. Using a mouse model of AD pathology that expresses both amyloid and tau transgenes, we found that neurons in the MEC have altered excitability. Before the onset of memory impairments, neurons in layer 2 of MEC had increased intrinsic excitability, but this was balanced by reduced inputs onto the cell. However, after the onset of memory impairments, stellate cells in MEC became further hyperexcitable, with increased excitability exacerbated by increased synaptic inputs. Thus, it appears that MEC stellate cells are uniquely disrupted during the progression of memory deficits and may contribute to cognitive deficits in AD.

We developed and tested a complete measurement system to quantify CO2 and CH4 emissions at the scale of an industrial site based on the innovative sensor Airborne Ultra-light Spectrometer for Environmental Application (AUSEA), operated on board uncrewed aircraft vehicles (UAVs). The AUSEA sensor is a new light-weight (1.4 kg) open-path laser absorption spectrometer simultaneously recording in situ CO2 and CH4 concentrations at high frequency (24 Hz in this study) with precisions of 10 ppb for CH4 and 1 ppm for CO2 (when averaged at 1 Hz). It is suitable for industrial operation at a short distance from the sources (sensitivity up to 1000 ppm for CO2 and 200 ppm for CH4). Greenhouse gas concentrations monitored by this sensor throughout a plume cross section downwind of a source drive a simple mass balance model to quantify emissions from this source. This study presents applications of this method to different pragmatic cases representative of real-world conditions for oil and gas facilities. Two offshore oil and gas platforms were monitored for which our emissions estimates were coherent with mass balance and combustion calculations from the platforms. Our method has also been compared to various measurement systems (gas lidar, multispectral camera, infrared camera including concentrations and emissions quantification system, acoustic sensors, ground mobile and fixed cavity ring-down spectrometers) during controlled-release experiments conducted on the TotalEnergies Anomaly Detection Initiatives (TADI) test platform at Lacq, France. It proved suitable to detect leaks with emission fluxes down to 0.01 g s−1, with 24 % of estimated CH4 fluxes within the −20 % to +20 % error range, 80 % of quantifications within the −50 % to +100 % error range and all of our results within the −69 % to +150 % error range. Such precision levels are better ranked than current top-down alternative techniques to quantify CH4 at comparable spatial scales. This method has the potential to be operationally deployed on numerous sites and on a regular basis to evaluate the space- and time-dependent greenhouse gas emissions of oil and gas facilities.

Background: In middle-income countries, costs limit widespred use of left ventricular assist device (LVAD) as a strategy for end-stage heart failure. We aim to describe the experience of a LVAD program in a middle-income country in a hub-and-spoke model. Methods: Patients fulfilling strict inclusion and exclusion criteria were referred from different centers in Brazil for LVAD implantation through a philanthropy program financed via a Brazilian Federal Government tax exemption structure. LVAD implantation was performed in a hub-and-spoke model with a single implanting center. Data were collected retrospectively using hospital records and telephone contact with other centers. Patients who received LVAD implants external to the philanthropic program, either at this or other Brazilian centers, were not included. Results: Between January 1, 2013 and December 31, 2020, 20 adult patients underwent long-term continuous flow LVAD implantation with decentralization of postimplant patient care in regional centers. Patients were referred from 11 centers from 7 states in Brazil and underwent LVAD implantation through a philanthropy program. The median age was 52.5 years and 85% were Interagency Registry for Mechanically Assisted Circulatory Support profile 3 patients. Two patients had Chagas cardiomyopathy. The overall survival censored for competing risks at 1 and 2 years were 90% and 84%, respectively. Three patients (15%) underwent heart transplantation in the first 2 years after LVAD implantation. Twelve patients returned to their original centers and were followed remotely. Conclusions: This study presents a successful LVAD implantation program in a hub-and-spoke model in Brazil. Centralization of LVAD implantation with decentralization of postimplant patient care in regional centers is feasible and safe, enabling optimal allocation of resources in middle-income countries.

IntroductionThe growing population of heart failure (HF) patients places a burden on the healthcare system. Patient-centered outcomes such as health-related quality of life (HRQoL) and self-care behaviors are key elements of modern HF management programs. Thus, optimized strategies to improve these outcomes are sought.PurposeTo assess the effects of a new model of medical telecare on HRQoL and self-care in patients with HF (the AMULET study).MethodsThe study was prospective, randomized, open-label, and controlled with two parallel groups: telecare and standard care. In the telecare group, HF nurses performed patient clinical assessments with telemedical support by a cardiologist and provided education focused on the prevention of HF exacerbation. In the standard care group, patients were followed according to standard practices in the existing healthcare system. At the baseline and at 12 months, HRQoL was assessed using the Short Form 36 (SF-36) questionnaire and the Minnesota Living with Heart Failure Questionnaire (MLwHF). The level of self-care was assessed with the 12-item standardized European Heart Failure Self-care Behavior Scale (EHFScBS-12).ResultsIn the overall study group, 79% of the subjects were male, the mean age was 67 ± 14 years, and 59% of the subjects were older than 65 years of age. The majority of the subjects (70%) had a left ventricular ejection fraction below 40%. After 12 months, statistically significant increases in physical component of the SF-36 (43.3 vs. 47.4 for telecare vs. 43.4 vs. 46.6 for standard care) and mental component of SF-36 (58.4 vs. 62 for telecare vs. 60.4 vs. 64.2 for standard care) were noted, with no intergroup differences. However, patients receiving telecare showed improvement in specific domains, such as physical functioning, role-physical, bodily pain, vitality, social functioning, role-emotional, and mental health. There was a significant decrease in MLwHF (29 vs. 35.0; lower is better) at follow-up for both groups. Telecare patients had a statistically significant decrease in EHFScBS-12 (lower is better) at 12 months.ConclusionAMULET outpatient telecare, which is based on nurse-led non-invasive assessments supported by specialist teleconsultations, improved the HRQoL and self-care of HF patients after an episode of acute HF.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Introduction Smoking cessation is the best strategy for reducing tobacco-related morbimortality. The goal of this randomized controlled trial was to test whether using the genetically favorable markers to choose a smoking cessation drug treatment (precision medicine) was superior to using the most effective drug (varenicline) in terms of abstinence rates. Additionally, combination therapy was tested when monotherapy failed. Methods This partially blind, single-center study randomized (1:1) 361 participants into two major groups. In the genetic group (n=184), CYP2B6 rs2279343 (genotype AA) participants started treatment with bupropion, and CHRNA4 rs1044396 (genotype CT or TT) participants started treatment with varenicline; when genetic favorable to both, participants started treatment with bupropion, and when favorable to neither, on both drugs. In the control group (n=177), participants started treatment with varenicline, regardless of genetic markers. Drug treatment lasted 12 weeks. Efficacy endpoints were abstinence rates at Weeks 4, and Weeks 8–12, biochemically validated by carbon monoxide in exhaled air. Participants who did not achieve complete abstinence at Week 4, regardless of group, were given the choice to receive combination therapy. Results Abstinence rates were 42.9% (95% CI: 36–64) in the control group versus 30.4% (95% CI: 23–37) in the genetic group at Week 4 (p=0.01); and 74% (95% CI: 67–80) versus 52% (95% CI: 49–64) at Week 12 (p

Abstract Background Most surveillance systems for catheter-related bloodstream infections (CRBSI) and central line-associated bloodstream infections (CLABSI) are based on manual chart review. Our objective was to validate a fully automated algorithm for CRBSI and CLABSI surveillance in intensive care units (ICU). Methods We developed a fully automated algorithm to detect CRBSI, CLABSI and ICU-onset bloodstream infections (ICU-BSI) in patients admitted to the ICU of a tertiary care hospital in Switzerland. The parameters included in the algorithm were based on a recently performed systematic review. Structured data on demographics, administrative data, central vascular catheter and microbiological results (blood cultures and other clinical cultures) obtained from the hospital’s data warehouse were processed by the algorithm. Validation for CRBSI was performed by comparing results with prospective manual BSI surveillance data over a 6-year period. CLABSI were retrospectively assessed over a 2-year period. Results From January 2016 to December 2021, 854 positive blood cultures were identified in 346 ICU patients. The median age was 61.7 years [IQR 50–70]; 205 (24%) positive samples were collected from female patients. The algorithm detected 5 CRBSI, 109 CLABSI and 280 ICU-BSI. The overall CRBSI and CLABSI incidence rates determined by automated surveillance for the period 2016 to 2021 were 0.18/1000 catheter-days (95% CI 0.06–0.41) and 3.86/1000 catheter days (95% CI: 3.17–4.65). The sensitivity, specificity, positive predictive and negative predictive values of the algorithm for CRBSI, were 83% (95% CI 43.7–96.9), 100% (95% CI 99.5–100), 100% (95% CI 56.5–100), and 99.9% (95% CI 99.2–100), respectively. One CRBSI was misclassified as an ICU-BSI by the algorithm because the same bacterium was identified in the blood culture and in a lower respiratory tract specimen. Manual review of CLABSI from January 2020 to December 2021 (n = 51) did not identify any errors in the algorithm. Conclusions A fully automated algorithm for CRBSI and CLABSI detection in critically-ill patients using only structured data provided valid results. The next step will be to assess the feasibility and external validity of implementing it in several hospitals with different electronic health record systems.

Abstract Objective Current treatments for Friedreich's ataxia, a neurodegenerative disorder characterized by decreased intramitochondrial frataxin, do not address low frataxin concentrations. Nomlabofusp (previously CTI‐1601) is a frataxin replacement therapy with a unique mechanism of action that directly addresses this underlying frataxin deficiency. Phase 1 studies assessed the safety, pharmacokinetic, and pharmacodynamic profiles of subcutaneously administered nomlabofusp in adults with Friedreich's ataxia. Methods Patients were enrolled in two Phase 1, double‐blind, placebo‐controlled studies. The single ascending‐dose (SAD) study (NCT04176991) evaluated single doses of nomlabofusp (25, 50, 75, or 100 mg) or placebo. The multiple ascending‐dose (MAD) study (NCT04519567) evaluated nomlabofusp (25 mg daily for 4 days then every third day, 50 mg daily for 7 days then every 2 days, or 100 mg daily) or placebo for 13 days. Results Patients aged 19–69 years were enrolled (SAD, N = 28; MAD, N = 27). Nomlabofusp was generally well tolerated through 13 days. Most adverse events were mild and resolved quickly. No serious adverse events or deaths were reported. Peak nomlabofusp plasma concentrations occurred 15 min after subcutaneous administration. Nomlabofusp plasma exposures increased with increasing doses and daily administration and decreased with reduced dosing frequency. Increased frataxin concentrations were observed in buccal cells, skin, and platelets with higher and more frequent nomlabofusp administration. Interpretation Results from this study support a favorable safety profile for nomlabofusp. Subcutaneous nomlabofusp injections were quickly absorbed; higher doses and daily administration resulted in increased tissue frataxin concentrations. Future studies will evaluate longer‐term safety and possible efficacy of nomlabofusp.

In his 2013 article, Professor George Aulisio introduced the Weinberg Memorial Library’s Heritage Hunt, an interactive scavenger hunt designed to introduce first-year students to the library. Ten years later, the Heritage Hunt program still plays a critical role in library orientation at the University of Scranton. In this article, the authors discuss changes made in collaboration with multiple library departments to transform and ultimately improve the Heritage Hunt. The article will describe the adaptations made to the orientation program as it has evolved and will also share insights into how to expand the program to broaden its reach to students beyond their first year.

Abstract The 5th edition of the Global Ministerial Summit on Patient Safety was held in Montreux, Switzerland, in February 2023, delayed by three years due to the COVID-19 pandemic. The overarching theme of the summit was “Less Harm, Better Care – from Resolution to Implementation”, focusing on the challenges of implementation of infection prevention and control (IPC) strategies as well as antimicrobial stewardship programs (ASP) around the world. IPC strategies and ASP are of increasing importance due to the substantial burden of healthcare-associated infections and antimicrobial resistance threatening patient safety. Here, we summarize countries’ and regional experiences and activities related to the implementation of IPC strategies and ASP shared at the meeting. Full implementation of effective programs remains a major challenge in all settings due to limited support by political and healthcare leaders, and human and financial constraints. In addition, the COVID-19 pandemic challenged already well-established programs. By enforcing sustained implementation by dedicated, cross-disciplinary healthcare personnel with a broad skill set, a reduction in healthcare-associated infections and multidrug-resistant pathogens can be achieved, leading ultimately to improved patient safety.

Automation and digitalization in various industries towards the Industry 4.0/5.0 paradigms are rapidly progressing thanks to the use of sensors, Industrial Internet of Things (IIoT), and advanced fifth generation (5G) and sixth generation (6G) mobile networks supported by simulation and automation of processes using artificial intelligence (AI) and machine learning (ML). Ensuring the continuity of operations under different conditions is becoming a key factor. One of the most frequently requested solutions is currently predictive maintenance, i.e., the simulation and automation of maintenance processes based on ML. This article aims to extract the main trends in the area of ML-based predictive maintenance present in studies and publications, critically evaluate and compare them, and define priorities for their research and development based on our own experience and a literature review. We provide examples of how BCI-controlled predictive maintenance due to brain–computer interfaces (BCIs) play a transformative role in AI-based predictive maintenance, enabling direct human interaction with complex systems.

The extracellular RNA communication consortium (ERCC) is an NIH-funded program aiming to promote the development of new technologies, resources, and knowledge about exRNAs and their carriers. After Phase 1 (2013-2018), Phase 2 of the program (ERCC2, 2019-2023) aims to fill critical gaps in knowledge and technology to enable rigorous and reproducible methods for separation and characterization of both bulk populations of exRNA carriers and single EVs. ERCC2 investigators are also developing new bioinformatic pipelines to promote data integration through the exRNA atlas database. ERCC2 has established several Working Groups (Resource Sharing, Reagent Development, Data Analysis and Coordination, Technology Development, nomenclature, and Scientific Outreach) to promote collaboration between ERCC2 members and the broader scientific community. We expect that ERCC2's current and future achievements will significantly improve our understanding of exRNA biology and the development of accurate and efficient exRNA-based diagnostic, prognostic, and theranostic biomarker assays.

Resumo Fundamento: Pacientes submetidos à cirurgia cardíaca podem estar expostos à hipoperfusão tecidual e metabolismo anaeróbico. Objetivo: Verificar se os biomarcadores de hipoperfusão tecidual têm valor preditivo para permanência prolongada na Unidade de Terapia Intensiva (UTI) em pacientes com disfunção ventricular esquerda submetidos à cirurgia de bypass da artéria coronária. Métodos: Após aprovação pelo comitê de ética institucional e assinatura do termo de consentimento, 87 pacientes com disfunção ventricular esquerda (fração de ejeção

IntroductionBCL-2 family proteins are important for tumour cell survival and drug resistance in multiple myeloma (MM). Although proteasome inhibitors are effective anti-myeloma drugs, some patients are resistant and almost all eventually relapse. We examined the function of BCL-2 family proteins in stromal-mediated resistance to carfilzomib-induced cytotoxicity in MM cells.MethodsCo-cultures employing HS5 stromal cells were used to model the interaction with stroma. MM cells were exposed to CFZ in a 1-hour pulse method. The expression of BCL-2 family proteins was assessed by flow cytometry and WB. Pro-survival proteins: MCL-1, BCL-2 and BCL-XL were inhibited using S63845, ABT-199 and A-1331852 respectively. Changes in BIM binding partners were examined by immunoprecipitation and WB.ResultsCFZ induced dose-dependent cell death of MM cells, primarily mediated by apoptosis. Culture of MM cells on HS-5 stromal cells resulted in reduced cytotoxicity to CFZ in a cell contact-dependent manner, upregulated expression of MCL-1 and increased dependency on BCL-XL. Inhibiting BCL-XL or MCL-1 with BH-3 mimetics abrogated stromal-mediated protection only at high doses, which may not be achievable in vivo. However, combining BH-3 mimetics at sub-therapeutic doses, which alone were without effect, significantly enhanced CFZ-mediated cytotoxicity even in the presence of stroma. Furthermore, MCL-1 inhibition led to enhanced binding between BCL-XL and BIM, while blocking BCL-XL increased MCL-1/BIM complex formation, indicating the cooperative role of these proteins.ConclusionStromal interactions alter the dependence on BCL-2 family members, providing a rationale for dual inhibition to abrogate the protective effect of stroma and restore sensitivity to CFZ.

The article is dedicated to measuring the thickness of step height standards using the author’s version of the variable wavelength interferometer (VAWI) in the reflected-light mode, where the interference pattern is created by the combination of two Wollaston prisms. The element of novelty consists in replacing the traditional search for the coincidence of fringes in the object and background with a continuous measurement of their periods and phases relative to the zero-order fringe. The resulting system of sinusoids is then analyzed using two methods: the classical one and the second utilizing the criterion of uniform thickness. The theory is followed by simulation and experimental parts, providing insight to the metrological potential of the VAWI technology.

Oleacein, a bioactive compound of olive oil and olive mill wastewater, has one of the strongest antioxidant activities among olive phenolics. However, few reports explore the in vivo antioxidant activity of oleacein, with no clear identification of the biological pathway involved. Earlier studies have demonstrated a link between stress resistance, such as oxidative stress, and longevity. This study presents the effects of oleacein on Caenorhabditis elegans mean lifespan and stress resistance. A significant lifespan extension was observed with an increase of 20% mean lifespan at 5 µg/mL with a hormetic-like dose-dependent effect. DAF-16 and SIR-2.1 were involved in the effects of oleacein on the longevity of C. elegans, while the DAF-2 receptor was not involved. This study also shows the capacity of oleacein to significantly enhance C. elegans resistance to oxidative and thermal stress and allows a better understanding of the positive effects of olive phenolics on health.

Galanin, one of the most inducible neuropeptides, is widely present in developing brains, and its expression is altered by pathologic events (e.g., epilepsy, ischemia, and axotomy). The roles of galanin in brain development under both normal and pathologic conditions have been hypothesized, but the question of how galanin is involved in fetal and early postnatal brain development remains largely unanswered. In this study, using granule cell migration in the cerebellum of early postnatal mice (both sexes) as a model system, we examined the role of galanin in neuronal cell migration during normal development and after brain injury. Here we show that, during normal development, endogenous galanin participates in accelerating granule cell migration via altering the Ca2+ and cAMP signaling pathways. Upon brain injury induced by the application of cold insults, galanin levels decrease at the lesion sites, but increase in the surroundings of lesion sites. Granule cells exhibit the following corresponding changes in migration: (1) slowing down migration at the lesion sites; and (2) accelerating migration in the surroundings of lesion sites. Experimental manipulations of galanin signaling reduce the lesion site-specific changes in granule cell migration, indicating that galanin plays a role in such deficits in neuronal cell migration. The present study suggests that manipulating galanin signaling may be a potential therapeutic target for acutely injured brains during development.SIGNIFICANCE STATEMENT Deficits in neuronal cell migration caused by brain injury result in abnormal development of cortical layers, but the underlying mechanisms remain to be determined. Here, we report that on brain injury, endogenous levels of galanin, a neuropeptide, are altered in a lesion site-specific manner, decreasing at the lesion sites but increasing in the surroundings of lesion sites. The changes in galanin levels positively correlate with the migration rate of immature neurons. Manipulations of galanin signaling ameliorate the effects of injury on neuronal migration and cortical layer development. These results shed a light on galanin as a potential therapeutic target for acutely injured brains during development.

The primary purpose of this study was to adapt selected accuracy and precision tests in table tennis to the specific skills of elite table tennis players with impairment. The study included a sample of 23 Para table tennis players with an average age of 31.8 ± 12.22 years (including 30.4% females) who belonged to the senior Polish Para table tennis team. A battery of six tests evaluating stroke accuracy and serve precision was assessed. The analysis of the reliability of these tests confirmed the legitimacy of using this battery of accuracy and precision tests to assess the skills of Para table tennis players in all three integrated sport classes: players in wheelchairs, in a standing position, and with intellectual impairment. Analysis of the data obtained from the tests could provide coaches with relevant information regarding elite Para table tennis players' level of performance and examine selected accuracy and precision elements of their individual technique. [ABSTRACT FROM AUTHOR]

Vaccination through the upper respiratory tract is a promising strategy, and particulate antigens, such as antigens associated with nanoparticles, triggered a stronger immune response than the sole antigens. Cationic maltodextrin-based nanoparticles loaded with phosphatidylglycerol (NPPG) are efficient for intranasal vaccination but non-specific to trigger immune cells. Here we focused on phosphatidylserine (PS) receptors, specifically expressed by immune cells including macrophages, to improve nanoparticle targeting through an efferocytosis-like mechanism. Consequently, the lipids associated with NPPG have been substituted by PS to generate cationic maltodextrin-based nanoparticles with dipalmitoyl-phosphatidylserine (NPPS). Both NPPS and NPPG exhibited similar physical characteristics and intracellular distribution in THP-1 macrophages. NPPS cell entry was faster and higher (two times more) than NPPG. Surprisingly, competition of PS receptors with phospho-L-serine did not alter NPPS cell entry and annexin V did not preferentially interact with NPPS. Although the protein association is similar, NPPS delivered more proteins than NPPG in cells. On the contrary, the proportion of mobile nanoparticles (50%), the movement speed of nanoparticles (3 µm/5 min), and protein degradation kinetics in THP-1 were not affected by lipid substitution. Together, the results indicate that NPPS enter cells and deliver protein better than NPPG, suggesting that modification of the lipids of cationic maltodextrin-based nanoparticles may be a useful strategy to enhance nanoparticle efficacy for mucosal vaccination.

Abstract Background As a COVID-19 risk mitigation measure, Australia closed its international borders for two years with significant socioeconomic disruption including impacting approximately 30% of the Australian population who are migrants. Migrant populations during the peripartum often rely on overseas relatives visiting for social support. High quality social support is known to lead to improved health outcomes with disruption to support a recognised health risk. Aim To explore women’s experience of peripartum social support during the COVID-19 pandemic in a high migrant population. To quantify type and frequency of support to identify characteristics of vulnerable perinatal populations for future pandemic preparedness. Methods A mixed methods study with semi-structured interviews and a quantitative survey was conducted from October 2020 to April 2021. A thematic approach was used for analysis. Results There were 24 participants interviewed both antenatally and postnatally (22 antenatal; 18 postnatal). Fourteen women were migrants and 10 Australian born. Main themes included; ‘Significant disruption and loss of peripartum support during the COVID-19 pandemic and ongoing impact for migrant women’; ‘Husbands/partners filling the support gap’ and ‘Holding on by a virtual thread’. Half of the participants felt unsupported antenatally. For Australian born women, this dissipated postnatally, but migrants continued to feel unsupported. Migrant women discussed partners stepped into traditional roles and duties of absent mothers and mothers-in-law who were only available virtually. Conclusion This study identified disrupted social support for migrant women during the pandemic, providing further evidence that the pandemic has disproportionately impacted migrant populations. However, the benefits identified in this study included high use of virtual support, which could be leveraged for improving clinical care in the present and in future pandemics. The COVID-19 pandemic impacted most women’s peripartum social support with migrant families having ongoing disruption. Gains in the pandemic included greater gender equity for domestic work as husbands/partners increased their contribution to domestic work and childcare.

IntroductionPhaeodactylum tricornutum is a model species frequently used to study lipid metabolism in diatoms. When exposed to a nutrient limitation or starvation, diatoms are known to accumulate neutral lipids in cytoplasmic lipid droplets (LDs). Those lipids are produced partly de novo and partly from the recycle of plastid membrane lipids. Under a nitrogen resupply, the accumulated lipids are catabolized, a phenomenon about which only a few data are available. Various strains of P. tricornutum have been isolated around the world that may differ in lipid accumulation patterns.MethodsTo get further information on this topic, two genetically distant ecotypes of P. tricornutum (Pt1 and Pt4) have been cultivated under nitrogen deprivation during 11 days followed by a resupply period of 3 days. The importance of cytoplasmic LDs relative to the plastid was assessed by a combination of confocal laser scanning microscopy and cell volume estimation using bright field microscopy pictures.Results and discussionWe observed that in addition to a basal population of small LDs (0.005 μm3 to 0.7 μm3) present in both strains all along the experiment, Pt4 cells immediately produced two large LDs (up to 12 μm3 after 11 days) while Pt1 cells progressively produced a higher number of smaller LDs (up to 7 μm3 after 11 days). In this work we showed that, in addition to intracellular available space, lipid accumulation may be limited by the pre-starvation size of the plastid as a source of membrane lipids to be recycled. After resupplying nitrogen and for both ecotypes, a fragmentation of the largest LDs was observed as well as a possible migration of LDs to the vacuoles that would suggest an autophagic degradation. Altogether, our results deepen the understanding of LDs dynamics and open research avenues for a better knowledge of lipid degradation in diatoms.

Given the increasing interest in their use as disease biomarkers, the establishment of reproducible, accurate, sensitive, and specific platforms for microRNA (miRNA) quantification in biofluids is of high priority. We compare four platforms for these characteristics: small RNA sequencing (RNA-seq), FirePlex, EdgeSeq, and nCounter. For a pool of synthetic miRNAs, coefficients of variation for technical replicates are lower for EdgeSeq (6.9%) and RNA-seq (8.2%) than for FirePlex (22.4%); nCounter replicates are not performed. Receiver operating characteristic analysis for distinguishing present versus absent miRNAs shows small RNA-seq (area under curve 0.99) is superior to EdgeSeq (0.97), nCounter (0.94), and FirePlex (0.81). Expected differences in expression of placenta-associated miRNAs in plasma from pregnant and non-pregnant women are observed with RNA-seq and EdgeSeq, but not FirePlex or nCounter. These results indicate that differences in performance among miRNA profiling platforms impact ability to detect biological differences among samples and thus their relative utility for research and clinical use.

Introduction It is known that regular physical activity (PA) brings many health benefits. However, during the COVID-19 (coronavirus disease 19) pandemic the lifestyle, everyday work, social behavior, quality of life, ways and forms of spending free time changed. The aim of the study was to assess the impact of the COVID-19 pandemic on the level of PA in menopausal women. Material and methods The study material consisted of 126 women before the onset of the pandemic and 114 women during the COVID-19 pandemic. The research was carried out in the area of Silesia. The research tool was a short version of the International Physical Activity Questionnaire (IPAQ) and the Menopause Rating Scale (MRS). Results A statistically significant correlation was observed in the case of a difference in the moderate level of PA (627.32 MET-min/week before COVID-19 and 138.6 during COVID-19, p = 0.01) and walking (1952.25 MET-min/week before COVID-19 and 422.63 MET-min/week during COVID-19, p = 0.03). The results showed that the time devoted to moderate PA decreased statistically. The mean days decreased from 2.8 to 0.96 (p = 0.02) and the mean duration of moderate PA decreased from 39.92 to 15.61 minutes (p < 0.001). Conclusions The COVID-19 pandemic significantly affected the level of PA in menopausal women. The respondents exercised much less often and the time devoted to PA was also shortened. The subjects most often chose walking as the form of PA.