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Background: Evidence from the science of learning suggests that playful learning pedagogical approaches exist along a spectrum and can support student learning. Leveraging active engagement, iterative, socially interactive, meaningful, and joyful interactions with content also supports student learning. Translating these concepts into guidance and support for teachers is lacking., Method: We introduce a tool designed to support teachers in implementing across the facilitation spectrum and leverage the characteristics that help children learn. Across three international contexts, we engaged with 1207 teachers and the tool was used 4911 times., Results: Student age, the intended learning goal, and context influenced teachers' use of the tool, suggesting that contextualization is critical, even when basing programs on evidence-based, universal principles given by the science of learning., Conclusion: Science of learning research must be effectively translated but we must use evidence from teachers and real-life classrooms to inform those studying the science of learning., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Funding for the project was provided by the Lego Foundation. The Lego Foundation provided feedback on study design, but was not involved in the collection, analysis, and interpretation of the data, nor were they involved with the writing of the manuscript or the decision to submit the manuscript for publication. The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2024. Published by Elsevier GmbH.)

Frontal ring-opening metathesis polymerization (FROMP) presents an energy-efficient approach to produce high-performance polymers, typically utilizing norbornene derivatives from Diels-Alder reactions. This study broadens the monomer repertoire for FROMP, incorporating the cycloaddition product of biosourced furan compounds and benzyne, namely 1,4-dihydro-1,4-epoxynaphthalene (HEN) derivatives. A computational screening of Diels-Alder products is conducted, selecting products with resistance to retro-Diels-Alder but also sufficient ring strain to facilitate FROMP. The experiments reveal that varying substituents both modulate the FROMP kinetics and enable the creation of thermoplastic materials characterized by different thermomechanical properties. Moreover, HEN-based crosslinkers are designed to enhance the resulting thermomechanical properties at high temperatures (>200 °C). The versatility of such materials is demonstrated through direct ink writing (DIW) to rapidly produce 3D structures without the need for printed supports. This research significantly extends the range of monomers suitable for FROMP, furthering efficient production of high-performance polymeric materials., (© 2024 The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)

Complex oxides offer rich magnetic and electronic behavior intimately tied to the composition and arrangement of cations within the structure. Rare earth iron garnet films exhibit an anisotropy along the growth direction which has long been theorized to originate from the ordering of different cations on the same crystallographic site. Here, we directly demonstrate the three-dimensional ordering of rare earth ions in pulsed laser deposited (Eu x Tm 1-x ) 3 Fe 5 O 12 garnet thin films using both atomically-resolved elemental mapping to visualize cation ordering and X-ray diffraction to detect the resulting order superlattice reflection. We quantify the resulting ordering-induced 'magnetotaxial' anisotropy as a function of Eu:Tm ratio using transport measurements, showing an overwhelmingly dominant contribution from magnetotaxial anisotropy that reaches 30 kJ m -3 for garnets with x = 0.5. Control of cation ordering on inequivalent sites provides a strategy to control matter on the atomic level and to engineer the magnetic properties of complex oxides., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Background: Arthropods vector a multitude of human disease-causing organisms, and their geographic ranges are shifting rapidly in response to changing climatic conditions. This is, in turn, altering the landscape of disease risk for human populations that are brought into novel contact with the vectors and the diseases they carry. Sand flies in the genera Lutzomyia and Pintomyia are vectors of serious disease-causing agents such as Leishmania (the etiological agent of leishmaniasis) and may be expanding their range in the face of climate change. Understanding the climatic conditions that vector species both tolerate physiologically and prefer behaviorally is critical to predicting the direction and magnitude of range expansions and the resulting impacts on human health. Temperature and humidity are key factors that determine the geographic extent of many arthropods, including vector species., Methods: We characterized the habitat of two species of sand flies, Lutzomyia longipalpis and Pintomyia evansi. Additionally, we studied two behavioral factors of thermal fitness-thermal and humidity preference in two species of sand flies alongside a key aspect of physiological tolerance-desiccation resistance., Results: We found that Lu. longipalpis is found at cooler and drier conditions than Pi. evansi. Our results also show significant interspecific differences in both behavioral traits, with Pi. evansi preferring warmer, more humid conditions than Lu. longipalpis. Finally, we found that Lu. longipalpis shows greater tolerance to extreme low humidity, and that this is especially pronounced in males of the species., Conclusions: Taken together, our results suggest that temperature and humidity conditions are key aspects of the climatic niche of Lutzomyia and Pintomyia sand flies and underscore the value of integrative studies of climatic tolerance and preference in vector biology., (© 2024. The Author(s).)

Electrospun polymer nanofibers, due to high surface area-to-volume ratio, high porosity, good mechanical strength, and ease of functionalization, appear as promising multifunctional materials for biomedical applications. Thanks to their unidirectional structure, imitating the extracellular matrix (ECM), they can be used as scaffolds for cell adhesion and proliferation. In addition, the incorporation of active groups inside nanofiber can give properties for bactericides. The proposed nanomats incorporate nanoparticles templated within the electrospun nanofibers that prevent infections and stimulate tissue regeneration. The generated hybrid electrospun nanofibers are composed of a copolymer of L-lactide-block-ε-caprolactone (PL-b-CL), 70:30, blended with homopolymer polyvinylpyrrolidone (PVP) and gold (Au) nanoparticles. A low cytotoxicity and slightly increased immunoreactivity, stimulated by the nanomat, are observed. Moreover, the decoration of the hybrid nanomat with dendronized silver nanoparticles (Dend-Ag) improves their antibacterial activity against antibiotic-resistant Pseudomonas aeruginosa. The use of Dend-Ag for decorating offers several functional effects; namely, it enhances the antibacterial properties of the produced nanomats and induces a significant increase within macrophages' cytotoxicity. The unidirectional nanostructures of the generated hybrid nanomats demonstrate unique collective physio-chemical and biological properties suitable for a wide range of biomedical applications. Here, the antibacterial properties facilitate an optimal environment, contributing to accelerated wound healing., (© 2024 Wiley‐VCH GmbH.)

Two case studies of parenting programs for parents of children 0 to 36 months of age, developed and implemented by Save the Children/Ministry of Health/Khesar Gyalpo University in Bhutan and UNICEF Zambia, were conducted by an independent research group. The focus was on how program delivery and scale-up were revised on the basis of feedback from implementation research. Feedback on workforce delivery quality was based on observations of deliveries using a monitoring form, as well as survey and interview data collected from the workforce. In-depth interviews with the resource team during the fourth year of implementation revealed how the feedback was used to address horizontal and vertical scaling. Delivery quality was improved in some cases by revising the delivery manual, offering refresher courses, and instituting regular monitoring. Scaling challenges in Zambia included slow progress with regard to reaching families in the two districts, which they addressed by trialing group sessions, and stemming workforce attrition. The challenges in Bhutan were low attendance and reducing the workload of providers. Vertical scaling challenges for both countries concerned maintaining demand through continuous advocacy at community and government levels to sustain financing and to show effectiveness in outcomes.

Background: Spodoptera frugiperda (FAW) is a pest that poses a significant threat to corn production worldwide, causing millions of dollars in losses. The species has evolved into two strains (corn and rice) that differ in their genetics, reproductive isolation, and resistance to insecticides and Bacillus thuringiensis endotoxins. The microbiota plays an important role in insects' physiology, nutrient acquisition, and response to chemical and biological controls. Several studies have been carried out on FAW microbiota from larvae guts using laboratory or field samples and a couple of studies have analyzed the corn strain microbiota across its life cycle. This investigation reveals the first comparison between corn strain (CS) and rice strain (RS) of FAW during different developmental insect stages and, more importantly, endosymbiont detection in both strains, highlighting the importance of studying both FAW populations and samples from different stages., Methods: The composition of microbiota during the life cycle of the FAW corn and rice strains was analyzed through high-throughput sequencing of the bacterial 16S rRNA gene using the MiSeq system. Additionally, culture-dependent techniques were used to isolate gut bacteria and the Transcribed Internal Spacer-ITS, 16S rRNA, and gyr B genes were examined to enhance bacterial identification., Results: Richness, diversity, and bacterial composition changed significantly across the life cycle of FAW. Most diversity was observed in eggs and males. Differences in gut microbiota diversity between CS and RS were minor. However, Leuconostoc , A2, Klebsiella , Lachnoclostridium , Spiroplasma , and Mucispirilum were mainly associated with RS and Colidextribacter , Pelomonas , Weissella , and Arsenophonus to CS, suggesting that FAW strains differ in several genera according to the host plant. Firmicutes and Proteobacteria were the dominant phyla during FAW metamorphosis. Illeobacterium, Ralstonia , and Burkholderia exhibited similar abundancies in both strains. Enterococcus was identified as a conserved taxon across the entire FAW life cycle. Microbiota core communities mainly consisted of Enterococcus and Illeobacterium . A positive correlation was found between Spiroplasma with RS (sampled from eggs, larvae, pupae, and adults) and Arsenophonus (sampled from eggs, larvae, and adults) with CS. Enterococcus mundtii was predominant in all developmental stages. Previous studies have suggested its importance in FAW response to B. thuringensis . Our results are relevant for the characterization of FAW corn and rice strains microbiota to develop new strategies for their control. Detection of Arsenophonus in CS and Spiroplasma in RS are promising for the improvement of this pest management, as these bacteria induce male killing and larvae fitness reduction in other Lepidoptera species., Competing Interests: The authors declare that they have no competing interests., (© 2024 Marulanda-Moreno et al.)

We report the one-pot synthesis of a chabazite (CHA)/erionite (ERI)-type zeolite intergrowth structure characterized by adjustable extents of intergrowth enrichment and Si/Al molar ratios. This method utilizes readily synthesizable 6-azaspiro[5.6]dodecan-6-ium as the exclusive organic structure-directing agent (OSDA) within a potassium-dominant environment. High-throughput simulations were used to accurately determine the templating energy and molecular shape, facilitating the selection of an optimally biselective OSDA from among thousands of prospective candidates. The coexistence of the crystal phases, forming a distinct structure comprising disk-like CHA regions bridged by ERI-rich pillars, was corroborated via rigorous powder X-ray diffraction and integrated differential-phase contrast scanning transmission electron microscopy (iDPC S/TEM) analyses. iDPC S/TEM imaging further revealed the presence of single offretite layers dispersed within the ERI phase. The ratio of crystal phases between CHA and ERI in this type of intergrowth could be varied systematically by changing both the OSDA/Si and K/Si ratios. Two intergrown zeolite samples with different Si/Al molar ratios were tested for the selective catalytic reduction (SCR) of NO x with NH 3 , showing competitive catalytic performance and hydrothermal stability compared to that of the industry-standard commercial NH 3 -SCR catalyst, Cu-SSZ-13, prevalent in automotive applications. Collectively, this work underscores the potential of our approach for the synthesis and optimization of adjustable intergrown zeolite structures, offering competitive alternatives for key industrial processes.

This paper evaluates the effectiveness and safety of XEN63 stent, either standalone or in combination with phacoemulsification, in patients with primary open-angle glaucoma (POAG). Eighty eyes from 80 patients with medically uncontrolled POAG were assigned to undergo XEN63 implant. The primary outcome was the surgical success, defined as an intraocular pressure (IOP) lowering from preoperative values ≥ 20% and an IOP absolute value between 6 and 18 mmHg, with or without antiglaucoma medications. Forty-three (53.7%) eyes underwent XEN63-standalone and 37(46.2%) eyes a XEN63 + Phacoemulsification procedure. Success rate was 68.8% (55/80) eyes in the overall study sample, 69.8% (30/43) eyes in the XEN63-standalone group; and 67.6% (25/37) eyes in the XEN63 + Phaco group (p = 0.6133). Preoperative IOP was significantly lowered from 22.1 ± 4.9 mmHg and 19.8 ± 3.7 mmHg to 14.7 ± 5.3 mmHg and 13.8 ± 3.4 mmHg in the XEN63-standalone and XEN63 + Phaco groups, respectively (p < 0.0001 each, respectively); without significant differences between them at any of the time-points measured. Preoperative number of ocular-hypotensive drugs was significantly reduced from 2.3 ± 0.8 to 0.3 ± 0.7 drugs, from 2.5 ± 0.7 to 0.3 ± 0.7 drugs; and from 2.0 ± 0.8 to 0.3 ± 0.7 drugs, in the overall, XEN63-standalone, and XEN63 + Phaco groups, respectively. Regarding safety, 3(42.5%) eyes had transient hypotony at some point during the study, although only in one (1.2%) eye was clinically significant. Four (5.0%) eyes underwent a needling, 4 (5.0%) eyes underwent surgical-bleb-revision, 1 (1.2%) eye required a device replacement and 1 (1.2%) eye a device removal due to maculopathy. XEN63, either alone or in combination with phacoemulsification, significantly lowered IOP and reduced the number of ocular hypotensive medications. The rate of ocular hypotony was relatively high, although it was clinically relevant only in one eye., (© 2024. The Author(s).)

Introduction: Respiratory syncytial virus (RSV) causes an acute respiratory illness similar to influenza, although there are few data comparing both of them in adults. The existence of clinical differences between these two infections could have implications for their management., Materials and Methods: Retrospective observational cohort study including 63 adults with positive PCR for RSV and 221 for influenza during winter 2018-2019. Epidemiological, clinical characteristics and outcomes were contrasted between both groups., Results: Compared to influenza, RSV-positive patients presented a higher association with active neoplasia (OR=2.9; 95% CI: 1.2-6.9), dependence for basic activities of daily living (OR=3.4; 95% CI: 1.4-8.2) and immunosuppression due to chronic glucocorticoid administration (OR=7.6; 95% CI: 1.6-36.1). At diagnosis, fever was less common (OR=0.3; 95% CI: 0.2-0.7), and C-reactive protein level ≥100mg/l was more frequent (OR=2.1; 95% CI: 1.0-4.5). They developed bacterial co-infection by Staphylococcus aureus in a higher proportion (OR=8.3; 95% CI: 1.5-46.9) and presented a greater need for admission to the intensive care unit (OR=5.4; 95% CI: 1.4-19.2)., Conclusion: RSV is an important cause of respiratory illness in adults during the influenza season. It especially affects vulnerable patients with chronic underlying diseases, and has a higher morbidity than influenza. For all these reasons, specific detection, prevention and treatment of RSV is necessary in order to reduce the consumption of health care resources due to RSV disease in adults., (Copyright © 2022 Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Published by Elsevier España, S.L.U. All rights reserved.)

Background/objective: Physical literacy assessment is considered a vital resource to decrease the prevalence of sedentary lifestyles and physical inactivity in children and adolescents worldwide. In Portugal, there is no physical literacy assessment tool for children under 15 years old. The main objective of this study was to carry out a translation and cultural adaptation of the Canadian Physical Literacy Assessment 2 (CAPL-2) into Portuguese, as well as to test its psychometric properties, in children between 8 and 12 years of age., Methods: The questionnaires included in the CAPL-2 were translated using the translation-back-translation method and adapted to their context. The test-retest reliability, internal consistency, and confirmatory factor analysis of the CAPL-2 Portuguese version were analyzed in a sample of 69 and 138 students, respectively, from a school in the Alentejo region (Portugal)., Results: The Portuguese version of the CAPL-2 questionnaires demonstrated high internal consistency (Cronbach's α: 0.713-0.979) and test-retest reliability ranging from moderate to nearly perfect in the motivation and confidence domain and knowledge and comprehension domain (ICC = 0.549-0.932). The results showed a good fit after adjusting for covariation paths (CMIN/DF = 1.382, p  = 0.105, RMSEA = 0.053, CFI = 0.971, TLI = 0.955, NFI = 0.907)., Conclusion: The CAPL-2 version of the questionnaires, translated and adapted to the Portuguese context, demonstrated validity and reliability, making them suitable for assessing physical literacy in children aged 8-12 years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Mendoza-Muñoz, Carlos-Vivas, Castillo-Paredes, Parraca, Raimundo, Alegrete, Pastor-Cisneros and Gomez-Galan.)

Graph neural networks (GNNs) have recently been used to learn the representations of crystal structures through an end-to-end data-driven approach. However, a systematic top-down approach to evaluate and understand the limitations of GNNs in accurately capturing crystal structures has yet to be established. In this study, we introduce an approach using human-designed descriptors as a compendium of human knowledge to investigate the extent to which GNNs can comprehend crystal structures. Our findings reveal that current state-of-the-art GNNs fall short in accurately capturing the periodicity of crystal structures. We analyze this failure by exploring three aspects: local expressive power, long-range information processing, and readout function. To address these identified limitations, we propose a straightforward and general solution: the hybridization of descriptors with GNNs, which directly supplements the missing information to GNNs. The hybridization enhances the predictive accuracy of GNNs for specific material properties, most notably phonon internal energy and heat capacity, which heavily rely on the periodicity of materials.

Cu-exchanged zeolites rely on mobile solvated Cu + cations for their catalytic activity, but the role of the framework composition in transport is not fully understood. Ab initio molecular dynamics simulations can provide quantitative atomistic insight but are too computationally expensive to explore large length and time scales or diverse compositions. We report a machine-learning interatomic potential that accurately reproduces ab initio results and effectively generalizes to allow multinanosecond simulations of large supercells and diverse chemical compositions. Biased and unbiased simulations of [Cu(NH 3 ) 2 ] + mobility show that aluminum pairing in eight-membered rings accelerates local hopping and demonstrate that increased NH 3 concentration enhances long-range diffusion. The probability of finding two [Cu(NH 3 ) 2 ] + complexes in the same cage, which is key for SCR-NOx reaction, increases with Cu content and Al content but does not correlate with the long-range mobility of Cu + . Supporting experimental evidence was obtained from reactivity tests of Cu-CHA catalysts with a controlled chemical composition., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Thermosets present sustainability challenges that could potentially be addressed through the design of deconstructable variants with tunable properties; however, the combinatorial space of possible thermoset molecular building blocks (e.g., monomers, cross-linkers, and additives) and manufacturing conditions is vast, and predictive knowledge for how combinations of these molecular components translate to bulk thermoset properties is lacking. Data science could overcome these problems, but computational methods are difficult to apply to multicomponent, amorphous, statistical copolymer materials for which little data exist. Here, leveraging a data set with 101 examples, we introduce a closed-loop experimental, machine learning (ML), and virtual screening strategy to enable predictions of the glass transition temperature ( T g ) of polydicyclopentadiene (pDCPD) thermosets containing cleavable bifunctional silyl ether (BSE) comonomers and/or cross-linkers with varied compositions and loadings. Molecular features and formulation variables are used as model inputs, and uncertainty is quantified through model ensembling, which together with heavy regularization helps to avoid overfitting and ultimately achieves predictions within <15 °C for thermosets with compositionally diverse BSEs. This work offers a path to predicting the properties of thermosets based on their molecular building blocks, which may accelerate the discovery of promising plastics, rubbers, and composites with improved functionality and controlled deconstructability., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: After coronavirus disease 2019, there has been an increase in patients in the emergency department with mental health conditions. They are usually received by professionals who are not specialized in mental health. This study aimed to describe nursing staff's experiences in the emergency department, in the care they provide to people with mental health problems who often feel stigmatized by society and also in health care settings., Methods: This is a descriptive qualitative study with a phenomenological approach. The participants were nurses from the Spanish Health Service from the emergency department of the Community of Madrid hospitals. Recruitment was performed by convenience sampling snowball sampling until data satruation was met. Data were collected through semistructured interviews conducted during January and February 2022., Results: The exhaustive and detailed analysis of the nurses' interviews made it possible to extract 3 main categories-health care, psychiatric patient, and work environment-with 10 subcategories., Discussion: The main study findings were the need to train emergency nurses to be prepared to care for people who experience mental health concerns including bias education and the need for implementation of standardized protocols. Emergency nurses never doubted their ability to care for people experiencing mental health disorders. Still, they recognized that they needed specialized professionals' support at certain critical moments., (Copyright © 2023 Emergency Nurses Association. Published by Elsevier Inc. All rights reserved.)

Background: Optic nerve head (ONH) interpretation is a glaucoma screening method which may be influenced by criteria variability. Laguna ONhE software is a low-cost and non-invasive method of ONH analysis., Methods: We analysed the results of the Laguna ONhE application, interpreting 552 ONH images from the ACRIMA database, publicly available on the Internet, and compared them with the opinion of five experts. Diagnostic agreement was investigated using Cohen's kappa (κ) with 95% confidence., Results: The kappa concordance index obtained with Laguna ONhE and the majority of the experts' criterion (0.77) was significantly higher compared to that obtained with ACRIMA and the majority of the experts' criterion (0.61). In 44.7% of the cases there was absolute agreement among the 5 experts and the Laguna ONhE program. Removing borderline cases from the analysis yielded increased diagnostic agreement (0.81). The area under the receiver operating characteristic (AUROC) of the Laguna ONhE program (0.953, p < 0.001) was not significantly different than AUROC of the majority of the experts' criterion (0.925, p < 0.001), p = 0.052. Individually obtained expert's AUROCs were significantly lower (0.636 to 0.913; p < 0.01)., Conclusions: Laguna ONhE's agreement with the experts is high, particularly where the diagnosis may be more obvious by the appearance of the ONH.

Two case studies of parenting programs, aiming to improve parenting practices and child development outcomes, and implemented by Save the Children/Ministry of Health/Khesar Gyalpo University in Bhutan and Boston College/University of Rwanda/FXB in Rwanda, respectively called Prescription to Play and Sugira Muryango, were conducted by an independent research and learning group. Implementation research focused on the workforce, a crucial but little-studied element determining the success of programs going to scale. Mixed methods were used to examine their training, workload, challenges, and quality of delivery. Health assistants in Bhutan and volunteers in Rwanda were trained for 10-11 days using demonstrations, role plays, and manuals outlining activities to deliver to groups of parents (Bhutan) or during home visits (Rwanda). Workers' own assessments of their delivery quality, their confidence, and their motivations revealed that duty, confidence, and community respect were strong motivators. According to independent observations, the quality of their delivery was generally good, with an overall mean rating on 10 items of 2.36 (Bhutan) and 2.44 (Rwanda) out of 3. The facilitators of scaling for Bhutan included institutionalizing training and a knowledgeable workforce; the barrier was an overworked workforce. The facilitators of scaling for Rwanda included strong follow-up supervision; the barriers included high attrition among a volunteer workforce.

Solid polymer electrolytes (SPEs) have the potential to improve lithium-ion batteries by enhancing safety and enabling higher energy densities. However, SPEs suffer from significantly lower ionic conductivity than liquid and solid ceramic electrolytes, limiting their adoption in functional batteries. To facilitate more rapid discovery of high ionic conductivity SPEs, we developed a chemistry-informed machine learning model that accurately predicts ionic conductivity of SPEs. The model was trained on SPE ionic conductivity data from hundreds of experimental publications. Our chemistry-informed model encodes the Arrhenius equation, which describes temperature activated processes, into the readout layer of a state-of-the-art message passing neural network and has significantly improved accuracy over models that do not encode temperature dependence. Chemically informed readout layers are compatible with deep learning for other property prediction tasks and are especially useful where limited training data are available. Using the trained model, ionic conductivity values were predicted for several thousand candidate SPE formulations, allowing us to identify promising candidate SPEs. We also generated predictions for several different anions in poly(ethylene oxide) and poly(trimethylene carbonate), demonstrating the utility of our model in identifying descriptors for SPE ionic conductivity., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Expanded helicenes are an emerging class of helical nanocarbons composed of alternating linear and angularly fused rings, which give rise to an internal cavity and a large diameter. The latter is expected to impart exceptional chiroptical properties, but low enantiomerization free energy barriers (Δ G ‡ e ) have largely precluded experimental interrogation of this prediction. Here, we report the syntheses of expanded helicenes containing 15, 19, and 23 rings on the inner helical circuit, using two iterations of an Ir-catalyzed, site-selective [2 + 2 + 2] reaction. This series of compounds displays a linear relationship between the number of rings and Δ G ‡ e . The expanded [23]-helicene, which is 7 rings longer than any known single carbohelicene and among the longest known all-carbon ladder oligomers, exhibits a Δ G ‡ e that is high enough (29.2 ± 0.1 kcal/mol at 100 °C in o -DCB) to halt enantiomerization at ambient temperature. This enabled the isolation of enantiopure samples displaying circular dichroism dissymmetry factors of ±0.056 at 428 nm, which are ≥1.7× larger than values for previously reported classical and expanded helicenes. Computational investigations suggest that this improved performance is the result of both the increased diameter and length of the [23]-helicene, providing guiding design principles for high dissymmetry molecular materials.

In non-anuric patients undergoing peritoneal dialysis (PD), residual kidney function (RKF) is a main contributor to fluid and solute removal and an independent predictor of survival. We investigated if urine volume could be used to estimate renal clearances and removal of urea, creatinine, and phosphorus in PD patients. The observational, cross-sectional study included 93 non-anuric prevalent PD patients undergoing continuous ambulatory PD (CAPD; n = 34) or automated PD (APD; n = 59). Concentrations of urea, creatinine and phosphorus in serum and in 24-h collections of urine volume were measured to calculate weekly residual renal clearance (L/week) and removed solute mass (g/week). Median [interquartile range], 24-h urine output was 560 [330-950] mL and measured GFR (the mean of creatinine and urea clearances) was 3.24 [1.47-5.67] mL/min. For urea, creatinine and phosphorus, residual renal clearance was 20.60 [11.49-35.79], 43.02 [19.13-75.48] and 17.50 [8.34-33.58] L/week, respectively, with no significant differences between CAPD and APD. Urine volume correlated positively with removed solute masses (rho = 0.82, 0.67 and 0.74) and with weekly residual renal clearances (rho = 0.77, 0.62 and 0.72 for urea, creatinine, and phosphorus, respectively, all p < 0.001). Residual renal clearances and urinary mass removal rates for urea, creatinine, and phosphorus correlate strongly with 24-h urine volume suggesting that urine volume could serve as an estimator of typical values of residual solute removal indices in PD patients., (© 2022. The Author(s).)

Biomedical applications of gold nanoparticles (AuNPs) may be limited by their toxicological effects. Although surface-modified AuNPs can induce apoptosis, less is known about whether they can induce other types of cell death. Pyroptosis, an inflammatory type of programmed cell death, can be induced in immune cells, especially macrophages, by bacterial endotoxins. Therefore, in this study, dendronized AuNPs were combined with bacterial lipopolysaccharides (LPSs) as the main stimulators of pro-inflammatory responses to test the induction of pyroptosis in THP-1 myeloid cell line. These AuNPs induced caspase-1 activity (3-4 times more compared to control) and enhanced the release of interleukin (IL)-18 and IL-1β without inducing gasdermin D cleavage and related pore formation. The production of pro-inflammatory cytokines occurred mainly visible during LPS treatment, although their secretion was observed only after administration of dendronized AuNPs (release of IL-1β to supernatant up to 80 pg/mL). These findings suggest that dendronized AuNPs can induce pyroptosis-like inflammatory mechanisms and that these mechanisms are enhanced in the presence of bacterial LPS. The intensity of this effect was dependent on AuNP surface modification. These results shed new light on the cytotoxicity of metal NPs, including immune responses, indicating that surface modifications play crucial roles in their nanotoxicological effects., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Palliative care knowledge is essential in primary healthcare due to the increasing number of patients who require attention in the final stage of their life. Health professionals (physicians and nurses) need to acquire specific knowledge and abilities to provide high-quality palliative care. The development of education programmes in palliative care is necessary. The Palliative Care Knowledge Test (PCKT) is a questionnaire that evaluates the basic knowledge about palliative care, but it has not been adapted into Spanish, and its effectiveness and utility for Spanish culture have not been analysed., Objective: The aim of this study was to report the translation into Spanish and a psychometric analysis of the PCKT., Methods: The questionnaire survey was validated with a group of 561 physicians and nurses. The PCKT Spanish Version (PCKT-SV) was obtained from a process, including translation, back translation and revision by experts and a pilot study. The content validity and reliability of the questionnaire were analysed., Results: The results showed internal consistency and reliability indexes similar to those obtained by the original version of PCKT., Conclusion: The PCKT-SV is a useful instrument for measuring Spanish-speaking physician and nurse knowledge of palliative care, and it is suitable to evaluate the effectiveness of training activities in palliative care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Polymer electrolytes are promising candidates for the next generation lithium-ion battery technology. Large scale screening of polymer electrolytes is hindered by the significant cost of molecular dynamics (MD) simulation in amorphous systems: the amorphous structure of polymers requires multiple, repeated sampling to reduce noise and the slow relaxation requires long simulation time for convergence. Here, we accelerate the screening with a multi-task graph neural network that learns from a large amount of noisy, unconverged, short MD data and a small number of converged, long MD data. We achieve accurate predictions of 4 different converged properties and screen a space of 6247 polymers that is orders of magnitude larger than previous computational studies. Further, we extract several design principles for polymer electrolytes and provide an open dataset for the community. Our approach could be applicable to a broad class of material discovery problems that involve the simulation of complex, amorphous materials., (© 2022. The Author(s).)

Cationic dendrimers are effective carriers for the delivery of siRNA into cells; they can penetrate cell membranes and protect nucleic acids against RNase degradation. Two types of dendrimers (CBD-1 and CBD-2) and their complexes with pro-apoptotic siRNA (Mcl-1 and Bcl-2) were tested on MCF-7 cells cultured as spheroids. Cytotoxicity of dendrimers and dendriplexes was measured using the live-dead test and Annexin V-FITC Apoptosis Detection Kit (flow cytometry). Uptake of dendriplexes was examined using flow cytometry and confocal microscopy. The live-dead test showed that for cells in 3D, CBD-2 is more toxic than CBD-1, contrasting with the data for 2D cultures. Attaching siRNA to a dendrimer molecule did not lead to increased cytotoxic effect in cells, either after 24 or 48 h. Measurements of apoptosis did not show a high increase in the level of the apoptosis marker after 24 h exposure of spheroids to CBD-2 and its dendriplexes. Measurements of the internalization of dendriplexes and microscopy images confirmed that the dendriplexes were transported into cells of the spheroids. Flow cytometry analysis of internalization indicated that CBD-2 transported siRNAs more effectively than CBD-1. Cytotoxic effects were visible after incubation with 3 doses of complexes for CBD-1 and both siRNAs.

Background: Secondary symbionts of insects include a range of bacteria and fungi that perform various functional roles on their hosts, such as fitness, tolerance to heat stress, susceptibility to insecticides and effects on reproduction. These endosymbionts could have the potential to shape microbial communites and high potential to develop strategies for mosquito-borne disease control., Methodology/principal Findings: The relative frequency and molecular phylogeny of Wolbachia, Microsporidia and Cardinium were determined of phlebotomine sand flies and mosquitoes in two regions from Colombia. Illumina Miseq using the 16S rRNA gene as a biomarker was conducted to examine the microbiota. Different percentages of natural infection by Wolbachia, Cardinium, and Microsporidia in phlebotomines and mosquitoes were detected. Phylogenetic analysis of Wolbachia shows putative new strains of Lutzomyia gomezi (wLgom), Brumptomyia hamata (wBrham), and a putative new group associated with Culex nigripalpus (Cnig) from the Andean region, located in Supergroup A and Supergroup B, respectively. The sequences of Microsporidia were obtained of Pi. pia and Cx. nigripalpus, which are located on phylogeny in the IV clade (terrestrial origin). The Cardinium of Tr. triramula and Ps. shannoni were located in group C next to Culicoides sequences while Cardinium of Mi. cayennensis formed two putative new subgroups of Cardinium in group A. In total were obtained 550 bacterial amplicon sequence variants (ASVs) and 189 taxa to the genus level. The microbiota profiles of Sand flies and mosquitoes showed mainly at the phylum level to Proteobacteria (67.6%), Firmicutes (17.9%) and Actinobacteria (7.4%). High percentages of relative abundance for Wolbachia (30%-83%) in Lu. gomezi, Ev. dubitans, Mi. micropyga, Br. hamata, and Cx. nigripalpus were found. ASVs assigned as Microsporidia were found in greater abundance in Pi. pia (23%) and Cx. nigripalpus (11%). An important finding is the detection of Rickettsia in Pi. pia (58,8%) and Bartonella sp. in Cx. nigripalpus., Conclusions/significance: We found that Wolbachia infection significantly decreased the alpha diversity and negatively impacts the number of taxa on sand flies and Culex nigripalpus. The Principal Coordinate Analysis (PCoA) is consistent, which showed statistically significant differences (PERMANOVA, F = 2.4744; R2 = 0.18363; p-value = 0.007) between the microbiota of sand flies and mosquitoes depending on its origin, host and possibly for the abundance of some endosymbionts (Wolbachia, Rickettsia)., Competing Interests: The authors have declared that no competing interests exist.

In this article, we examine whether (and by how much) workers in Canada have been compensated for the 'novel' risks associated with COVID-19. We create a unique dataset from a system that scores occupations in the US O*NET database for COVID-19 exposure. We then combine those COVID exposure scores with Canadian occupational data contained in the Public Use Microdata File of the Labour Force Survey. This allows us to categorize Canadian occupations based on COVID-19 exposure risk. We find a long-tailed distribution of COVID-19 risk scores across occupations, with most jobs at the lower end of the risk spectrum and relatively few occupations accounting for most of the high COVID-19 exposure risk. We find that workers who are already more vulnerable in the labour market (i.e. youth, women and immigrants) are also more likely to be employed in occupations with high COVID-19 exposure risk. When we look at the relationship between high-COVID exposure risks in occupation and wages, we find negative compensating differentials both at the mean (negative 8%) and across the earnings distribution. However, when workers are covered by a union, they enjoy a sizeable hazard pay premium (11.7% on average) as compared to their non-union counterparts. Furthermore, we find that the moderating effects of unionization for workers at high risk of COVID exposure to be largest at the bottom of the earnings distribution (i.e. the 10th percentile of unionized earners receives a 12.3% risk premium for high-COVID exposure, whereas the 90th percentile receives only a 2%)., (© 2021 John Wiley & Sons Ltd.)

The sand fly Lutzomyia (L.) longipalpis has been implicated as the primary vector of Leishmania infantum, the causative agent of visceral leishmaniasis VL. In addition, it has been associated with atypical cutaneous leishmaniasis transmission in the Neotropic and Central America, respectively. The existence of a L. longipalpis complex species has been suggested with important implications for leishmaniasis epidemiology; however, the delimitation of species conforming it remains a topic of controversy. The DNA Barcoding Initiative based on cox1 sequence variation was used to identify the MOTUs in L. longipalpis including previously described L. pseudolongipalpis. The genetic variation was analyzed based on tree and distance methods. Fifty-five haplotypes were obtained from 103 sequences which were assigned to MOTUs, with a clear separation and a high correspondence of individuals to the groups. Maximum likelihood and Bayesian phylogenetic analysis showed eight MOTUs (100% bootstrap) with high genetic divergence (12.6%). Data obtained in the present study suggest that L. longipalpis complex consists of at least 8 lineages that may represent species. It would be desirable perform additional morphological and molecular analysis of L. longipalpis from Colosó (Caribbean ecoregion) considering that specimens from that area were grouped with L. pseudolongipalpis one of the complex species previously described from Venezuela, which has not been registered in Colombia., (Copyright © 2021. Published by Elsevier B.V.)

Water removal which is a key treatment goal of automated peritoneal dialysis (APD) can be assessed cycle-by-cycle using remote patient monitoring (RPM). We analysed ultrafiltration patterns during night APD following a dry day (APD DD ; no daytime fluid exchange) or wet day (APD WD ; daytime exchange). Ultrafiltration for each APD exchange were recorded for 16 days using RPM in 14 patients. The distributed model of fluid and solute transport was applied to simulate APD and to explore the impact of changes in peritoneal tissue hydration on ultrafiltration. We found lower ultrafiltration (mL, median [first quartile, third quartile]) during first and second vs. consecutive exchanges in APD DD (-61 [-148, 27], 170 [78, 228] vs. 213 [126, 275] mL; p < 0.001), but not in APD WD (81 [-8, 176], 81 [-4, 192] vs. 115 [4, 219] mL; NS). Simulations in a virtual patient showed that lower ultrafiltration (by 114 mL) was related to increased peritoneal tissue hydration caused by inflow of 187 mL of water during the first APD DD exchange. The observed phenomenon of lower ultrafiltration during initial exchanges of dialysis fluid in patients undergoing APD DD appears to be due to water inflow into the peritoneal tissue, re-establishing a state of increased hydration typical for peritoneal dialysis., (© 2021. The Author(s).)

Candida albicans is a human pathogen of significant clinical relevance. This pathogen is resistant to different drugs, and most clinical antifungals are not effective against the prevention and treatment of C. albicans infections. As with other microorganisms, it can produce biofilms that serve as a barrier against antifungal agents and other substances, contributing to infection in humans and environmental tolerance of this microorganism. Thus, resistances and biofilm formation make treatment difficult. In addition, the complete eradication of biofilms in implants, catheters and other medical devices, is challenging and necessary to prevent relapses of candidemia. Therefore, it is a priority to find new molecules or combinations of compounds with anti- Candida biofilm activity. Due to the difficulty of treating and removing biofilms, the aim of this study was to evaluate the in vitro ability of different generation of cationic carbosilane dendrons derived from 4-phenylbutyric acid, ArCO 2 G n (SNMe 3 I) m , to eradicate C. albicans biofilms. Here, we assessed the antifungal activity of the second generation dendron ArCO2G 2 (SNMe 3 I) 4 against C. albicans cells and established biofilms since it managed to seriously damage the membrane. In addition, the combinations of the second generation dendron with AgNO 3 or EDTA eradicated the viability of biofilm cells. Alterations were observed by scanning electron microscopy and cytotoxicity was assessed on HeLa cells. Our data suggest that the dendritic compound ArCO 2 G 2 (SNMe 3 I) 4 could represent an alternative to control the infections caused by this pathogen.

The application of siRNA in gene therapy is mainly limited because of the problems with its transport into cells. Utilization of cationic dendrimers as siRNA carriers seems to be a promising solution in overcoming these issues, due to their positive charge and ability to penetrate cell membranes. The following two types of carbosilane dendrimers were examined: CBD-1 and CBD-2. Dendrimers were complexed with pro-apoptotic siRNA (Mcl-1 and Bcl-2) and the complexes were characterized by measuring their zeta potential, circular dichroism and fluorescence of ethidium bromide associated with dendrimers. CBD-2/siRNA complexes were also examined by agarose gel electrophoresis. Both dendrimers form complexes with siRNA. Moreover, the cellular uptake and influence on the cell viability of the dendrimers and dendriplexes were evaluated using microscopic methods and XTT assay on MCF-7 cells. Microscopy showed that both dendrimers can transport siRNA into cells; however, a cytotoxicity assay showed differences in the toxicity of these dendrimers.

Income support programs introduced for workers during the first wave of coronavirus disease 2019 (COVID-19) lockdowns faced criticism for their negative labour supply effects. We propose that these concerns about work disincentives are embedded in restrictive assumptions about work and led to suboptimal design of crisis support policies. We describe a framework for analyzing alternative crisis income support programs predicated on more realistic assumptions of labour markets and human motivation. Our framework proposes that balancing efficiency, equity, and voice objectives should be the goal of crisis labour market policies. We argue that adoption of a basic income targeted toward low-income workers, in combination with Canada's pre-existing Employment Insurance program, would have balanced efficiency, equity, and voice better than the combination of the Canada Emergency Response Benefit and Canada Emergency Wage Subsidy. A targeted basic income would also have been more effective at achieving stated public health objectives., (© Canadian Public Policy / Analyse de politiques.)

The unavailability of effective and safe human immunodeficiency virus (HIV) vaccines incites several approaches for development of the efficient antigen/adjuvant vaccination composite. In this study, three different dendronized gold nanoparticles (AuNPs 13-15) were investigated for a complexation ability with gp160 synthetic peptides derived from an HIV envelope. It has been shown that HIV peptides interacted with nanoparticles as evident from the changes in their secondary structures, restricted the mobility of the attached fluorescence dye, and enhanced peptide helicity confirmed by the fluorescence polarization and circular dichroism results. Transmission electron microscopy visualized complexes as cloud-like structures with attached nanoparticles. AuNP 13-15 nanoparticles bind negatively charged peptides depending on the number of functional groups; the fastest saturation and peptide retardation were observed for the most dendronized nanoparticle as indicated from dynamic light scattering, laser Doppler velocimetry, and agarose gel electrophoresis experiments. Dendronized gold nanoparticles can be considered one of the potential HIV peptide-based vaccination platforms.

An experimental characterization of crop residue biomass blends to evaluate their energy potential was conducted using an experimental approach in a commercial scale downdraft gasifier. Corncobs, rice husks, sesame stalks and cotton gin refuse were used to study the effect of mixture proportions on equivalence ratio, gasification temperature, syngas lower heating value (LHV), and cold gas efficiency (CGE). Using an experimental mixture design, thirty-two sample blends were evaluated in an Ankur WBG-30 downdraft gasifier with 30 kg/h feed supply coupled with a syngas purification system, temperature sensors and a gas chromatograph. Syngas composition CO, H 2 , CH 4 , N 2 and CO 2 are presented for each blend. It was found that temperature, syngas composition, syngas lower heating value and cold gas efficiency were negatively affected as the proportion of rice husks in the mixture was increased. It was possible to reach CGE values up to 57.91% and LHV up to 4460 kJ/kg under certain blending conditions. A higher percentages of rice husks caused a considerable increase in the variability of the equivalence ratio resulting in suboptimal gasification conditions., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors have declared that no competing interests exist.

In renal failure, hyperphosphatemia is common and correlates with increased mortality making phosphate removal a key priority for dialysis therapy. We investigated phosphate clearance, removal and serum level, and factors associated with phosphate control in patients undergoing continuous ambulatory (CAPD), continuous cyclic (CCPD) and automated (APD) peritoneal dialysis (PD). In 154 prevalent PD patients (mean age 53.2 ± 17.6 year, 59% men, 47% anuric), 196 daily collections of urine and 368 collections of dialysate were evaluated in terms of renal, peritoneal and total (renal plus peritoneal) phosphorus removal (g/week), phosphate and creatinine clearances (L/week) and urea KT/V. Dialytic removal of phosphorus was lower in APD (1.34 ± 0.62 g/week) than in CAPD (1.89 ± 0.73 g/week) and CCPD (1.91 ± 0.63 g/week) patients; concomitantly, serum phosphorus was higher in APD than in CAPD (5.55 ± 1.61 vs. 4.84 ± 1.23 mg/dL; p < 0.05). Peritoneal and total phosphate clearances correlated with peritoneal (rho = 0.93) and total (rho = 0.85) creatinine clearances (p < 0.001) but less with peritoneal and total urea KT/V (rho = 0.60 and rho = 0.65, respectively, p < 0.001). Phosphate removal, clearance and serum levels differed between PD modalities. CAPD was associated with higher peritoneal removal and lower serum level of phosphate than APD.

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is considered as the master regulator of antioxidant and cytoprotective gene expressions. Moreover, it plays a pivotal role in cancer progression. Nrf2 mediates the adaptive response which contributes to the resistance to chemotherapeutic pro-oxidant drugs, such as cisplatin (CDDP), in various tumors, including bladder cancers. For this reason, Nrf2 could be a promising target to overcome chemoresistance. There are several known Nrf2 pharmacological inhibitors; however, most of them are not specific. The use of a specific small interfering RNA (siRNA) targeting the Nrf2 gene (siNrf2) loaded into nanovehicles is an attractive alternative, since it can increase specificity. This study aimed to evaluate the biological activity of siNrf2 loaded on guanidine-terminated carbosilane dendrimers (GCDs) in overcoming CDDP resistance in bladder cancer cells with a high level of Nrf2. Parameters such as viability, proliferation, apoptosis, migration, and oxidative stress level were taken into account. Results demonstrated that siNrf2-GCD treatment sensitized CDDP-resistant cells to CDDP treatment. Moreover, data obtained by treating the non-cancerous human kidney HK-2 cell line strongly suggest a good safety profile of the carbosilane dendrimers loaded with siNrf2. In conclusion, we suggest that siNrf2-GCD is a promising drug delivery system for gene therapy to be used in vivo; and it may represent an important tool in the therapy of CDDP-resistant cancer.

Lung cancer, the leading cause of cancer mortality, exhibits heterogeneity that enables adaptability, limits therapeutic success, and remains incompletely understood. Single-cell RNA sequencing (scRNA-seq) of metastatic lung cancer was performed using 49 clinical biopsies obtained from 30 patients before and during targeted therapy. Over 20,000 cancer and tumor microenvironment (TME) single-cell profiles exposed a rich and dynamic tumor ecosystem. scRNA-seq of cancer cells illuminated targetable oncogenes beyond those detected clinically. Cancer cells surviving therapy as residual disease (RD) expressed an alveolar-regenerative cell signature suggesting a therapy-induced primitive cell-state transition, whereas those present at on-therapy progressive disease (PD) upregulated kynurenine, plasminogen, and gap-junction pathways. Active T-lymphocytes and decreased macrophages were present at RD and immunosuppressive cell states characterized PD. Biological features revealed by scRNA-seq were biomarkers of clinical outcomes in independent cohorts. This study highlights how therapy-induced adaptation of the multi-cellular ecosystem of metastatic cancer shapes clinical outcomes., Competing Interests: Declaration of Interests C.E.M., advisory board–Genentech; honoraria–Novartis, Guardant, Research Funding: Novartis, Revolution Medicines; J.K.R., advisory board: AstraZeneca, consulting: Takeda; E.L.S., employee – editorial contributor, Elsevier, PracticeUpdate.com; speakers fees: Takeda, Roche/Genentech, Physicians’ Education Resource, Medscape; Consultant: AbbVie; R.G.S., stock ownership in Celgene Corporation (Bristol-Myers Squibb); IP licensing: Newomics; S.B. consults with and/or receives research funding from Pfizer, Ideaya Biosciences and Revolution Medicines; M.G., research funding (to institution) for Celgene, Merck, Novartis, OncoMed, Roche; R.C.D., Advisory Board: Rain Therapeutics, Blueprint Medicines, Anchiano, Green Peptide, Genentech/Roche, Bayer, AstraZeneca; Intellectual Property Licensing: Rain Therapeutics, Foundation Medicine, Abbott Molecular, Black Diamond, Pearl River, Voronoi; Stock Ownership: Rain Therapeutics; J.W., Scientific Advisory Board member for Tenaya Therapeutics and Amgen. Founder and Consultant of KSQ Therapeutics and Maze Therapeutics. Venture Partner of 5AM Ventures; C.M.B., Consulting: Amgen, Foundation Medicine, Blueprint Medicines, Revolution Medicines; Research Funding: Novartis, AstraZeneca, Takeda; Institutional Research Funding: Mirati, Spectrum, MedImmune, Roche; T.G.B., Advisor to Novartis, Astrazeneca, Revolution Medicines, Array/Pfizer, Springworks, Strategia, Relay, Jazz, Rain and receives research funding from Novartis and Revolution Medicines and Strategia., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Local anaesthetics are being combined clinically with amikacin in intravenous regional limb perfusion (IVRLP), with limited knowledge on the analgesia provided and its onset and duration of action after tourniquet application and release., Objective: To evaluate the systemic clinical effect, limb withdrawal to nociceptive stimulation, and plasma and synovial fluid concentrations after IVRLP with lidocaine or mepivacaine in standing sedated horses., Study Design: Prospective, controlled, randomised, cross-over study., Methods: Six healthy adult horses were sedated and received IVRLP with lidocaine, mepivacaine or saline (negative control), or perineural anaesthesia of the medial and lateral palmar and palmar metacarpal nerves (positive control) in one forelimb with a 3-week washout period between trials. Electrical and mechanical stimuli were used to test nociceptive threshold of the limb before and after IVRLP/perineural anaesthesia. For lidocaine and mepivacaine trials, blood was collected from the jugular vein and synovial fluid from the radiocarpal joint before, during and out to 24 hours after IVRLP. Drug concentrations were measured using high-performance liquid chromatography., Results: Nociceptive thresholds for lidocaine, mepivacaine and perineural anaesthesia trials were significantly increased compared with saline and baseline values at 10, 20 and 30 minutes, with no differences between anaesthetic trials. During this time, horses had lower heart rates than IVRLP with saline. After tourniquet release at 30 minutes, nociceptive thresholds for lidocaine and mepivacaine trials gradually returned to baselines, whereas perineural anaesthesia trial remained unchanged out to an hour. Plasma lidocaine and mepivacaine concentrations were ≤50 ng/mL while the tourniquet was in place, significantly increasing 10 minutes after tourniquet release. Maximal lidocaine and mepivacaine concentrations in synovial fluid were reached 25 minutes after IVRLP injection., Main Limitations: Amikacin was not included in the perfusate., Conclusion: Similar to perineural anaesthesia, IVRLP with lidocaine or mepivacaine provides anti-nociception to the distal limb in standing sedated horses while a tourniquet is applied with concentrations remaining below toxic levels in plasma and synovial fluid., (© 2020 EVJ Ltd.)

Dendrimers as drug carriers can be utilized for drugs and siRNA delivery in central nervous system (CNS) disorders, including various types of cancers, such as neuroblastomas and gliomas. They have also been considered as drugs per se, for example as anti-Alzheimer's disease (AD), anti-cancer, anti-prion or anti-inflammatory agents. Since the influence of carbosilane-viologen-phosphorus dendrimers (SMT1 and SMT2) on the basic cellular processes of nerve cells had not been investigated, we examined the impact of two generations of these hybrid macromolecules on two murine cell lines-cancer cell line N2a (mouse neuroblastoma) and normal immortalized cell line mHippoE-18 (embryonic mouse hippocampal cell line). We examined alterations in cellular responses including the activity of mitochondrial dehydrogenases, the generation of reactive oxygen species (ROS), changes in mitochondrial membrane potential, and morphological modifications and fractions of apoptotic and dead cells. Our results show that both dendrimers at low concentrations affected the cancer cell line more than the normal one. Also, generation-dependent effects were found: the highest generation induced greater cytotoxic effects and morphological modifications. The most promising is that the changes in mitochondrial membrane potential and transmission electron microscopy (TEM) images indicate that dendrimer SMT1 can reach mitochondria. Thus, SMT1 and SMT2 seem to have potential as nanocarriers to mitochondria or anti-cancer drugs per se in CNS disorders.

Metallodendrimers-dendrimers with included metals-are widely investigated as biocompatible equivalents to metal nanoparticles. Applications can be expected in the fields of catalysis, as chemical sensors in molecular recognition and as anticancer drugs. Metallodendrimers can also mimic certain biomolecules, for example, haemoprotein in the case of using a dendrimer with a porphyrin core. In previous papers, we showed the promising anticancer effects of carbosilane ruthenium dendrimers. The present paper is devoted to studying biocompatibility and the cytotoxic effect on normal and cancer cells of carbosilane ruthenium dendrimers labelled with fluorescent probe fluorescein isothiocyanate (FITC). The addition of fluorescent probe allowed tracking the metallodendrimer in both normal and cancer cells. It was found that carbosilane ruthenium dendrimer labelled with FITC in concentration up to 10 µmol/L was more cytotoxic for cancer cells than for normal cells. Thus, FITC labelled carbosilane ruthenium dendrimer is a good candidate for diagnostic imaging and studying anticancer effects of metallodendrimers in cancer therapy.

Coordination of ruthenium arene fragments on carbosilane dendrimers' surface greatly increases their antitumor properties. Newly synthetized ruthenium dendrimers are water-soluble, monodisperse and stable. Since carbosilane dendrimers are good carriers of drugs and genes, the presence of ruthenium in their structure makes them promising candidates for new drug delivery systems with improved antitumor potential. Carbosilane ruthenium dendrimers are more toxic to cancer cells than normal cells. Results of several in vitro studies applied here indicate that carbosilane ruthenium dendrimers induce apoptosis in promyelocytic leukemia HL-60 cells.

Multiple sclerosis-related neurobehavioral abnormalities are one of the main components of disability in this disease. The same pathological processes that explain demyelination periods and neurodegeneration also allow the comprehension of neurobehavioral abnormalities. Inflammation in the central nervous system caused by cells of the immune system, especially lymphocytes, and by resident cells, such as astrocytes and microglia, directly modulate neurotransmission and synaptic physiology, resulting in behavioral changes (such as sickness behavior) and amplifying the degenerative mechanisms that occur in multiple sclerosis. In addition, neuronal death caused by glutamate-mediated excitotoxicity, alterations in GABAergic, serotonergic, and dopaminergic neurotransmission, and the mechanisms of axon damage are of foremost importance to explain the reduction in brain volume and the associated cognitive decline. Neuroinflammation and neurodegeneration are not isolated phenomena and various instances of interaction between them have been described. This presents attractive targets for the development of therapeutic strategies for this neglected component of multiple sclerosis related disability.

Patients with end-stage kidney disease (ESKD) have different options to replace the function of their failing kidneys. The "integrated care" model considers treatment pathways rather than individual renal replacement therapy (RRT) techniques. In such a paradigm, the optimal strategy to plan and enact transitions between the different modalities is very relevant, but so far, only limited data on transitions have been published. Perspectives of patients, caregivers, and health professionals on the process of transitioning are even less well documented. Available literature suggests that poor coordination causes significant morbidity and mortality.This review briefly provides the background, development, and scope of the INTErnational Group Research Assessing Transition Effects in Dialysis (INTEGRATED) initiative. We summarize the literature on the transition between different RRT modalities. Further, we present an international research plan to quantify the epidemiology and to assess the qualitative aspects of transition between different modalities., (Copyright © 2019 International Society for Peritoneal Dialysis.)

The efficiency of a rotor-stator device for water disinfection based on hydrodynamic cavitation is investigated. Water is infected with E. coli and E. faecalis with initial concentrations in the range 5 × 10 2 -1.2 × 10 6  CFU/ml. Various geometries of the cavitation channel between rotor and stator are tested, achieving bacterial annihilation in less than 10 min of treatment times. Microorganism permanent elimination is verified via micro-seeding to discard viable non-culturable bacteria; micro-seeding was done for those samples displaying no CFU growth via normalized cultures on a Petri dish. TEM photographs are analyzed and the extent of bacterial damages is tentatively correlated with the various cavitation mechanisms. Rotor-stator cavitation assemblies used in the current research are between one and two orders of magnitude more energy efficient than those tested by other investigators. Acoustic pressure spectra are measured to assess the implosion intensity. Parametric analyses are conducted changing the rotor diameter (110-155 mm), the cavitation channel contraction ratio, A max /A min (4.56-5.0), and the number of contractions (N r :58-80 rotor vanes; N s :8-16 stator vanes)., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Cell-to-cell transmission is the most effective pathway for the spread of human immunodeficiency virus (HIV-1). Infected cells expose virus-encoded fusion proteins on their surface as a consequence of HIV-1 replicative cycle that interacts with noninfected cells through CD4 receptor and CXCR4 coreceptor leading to the formation of giant multinucleated cells known as syncytia. Our group previously described the potent activity of dendrimers against CCR5-tropic viruses. Nevertheless, the study of G1-S4, G2-S16, and G3-S16 dendrimers in the context of X4-HIV-1 tropic cell-cell fusion referred to syncytium formation remains still unknown. These dendrimers showed a suitable biocompatibility in all cell lines studied and our results demonstrated that anionic carbosilane dendrimers G1-S4, G2-S16, and G3-S16 significantly inhibit the X4-HIV-1 infection, as well as syncytia formation, in a dose dependent manner. We also demonstrated that G2-S16 and G1-S4 significantly reduced syncytia formation in HIV-1 Env-mediated cell-to-cell fusion model. Molecular modeling and in silico models showed that G2-S16 dendrimer interfered with gp120-CD4 complex and demonstrated its potential use for a treatment.

Microfluidic technologies have been used across diverse disciplines ( e.g. high-throughput biological measurement, fluid physics, laboratory fluid manipulation) but widespread adoption has been limited in part due to the lack of openly disseminated resources that enable non-specialist labs to make and operate their own devices. Here, we report the open-source build of a pneumatic setup capable of operating both single and multilayer (Quake-style) microfluidic devices with programmable scripting automation. This setup can operate both simple and complex devices with 48 device valve control inputs and 18 sample inputs, with modular design for easy expansion, at a fraction of the cost of similar commercial solutions. We present a detailed step-by-step guide to building the pneumatic instrumentation, as well as instructions for custom device operation using our software, Geppetto, through an easy-to-use GUI for live on-chip valve actuation and a scripting system for experiment automation. We show robust valve actuation with near real-time software feedback and demonstrate use of the setup for high-throughput biochemical measurements on-chip. This open-source setup will enable specialists and novices alike to run microfluidic devices easily in their own laboratories.