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Community engagement; Tuberculosis research Participación de la comunidad; Investigación de la tuberculosis Compromís comunitari; Recerca en tuberculosi Objectives: Community representatives are key to ensuring that tuberculosis (TB) research is relevant, culturally sensitive, and appropriate. For all trials (new drugs or treatment regimens, diagnostics, or vaccines) this can result in improvement of recruitment, retention, and adherence to the trial schedule. The early engagement of the community will, later in time, support the process of implementation of new policies designed for successful products. We aim at developing a structured protocol for the early engagement of TB community representatives developed in the context of the EU-Patient-cEntric clinicAl tRial pLatforms (EU-PEARL) project. Design: The EU-PEARL Innovative Medicine Initiative 2 (IMI2) project TB work package has developed a community engagement (CE) framework to ensure fair and efficient participation of the community in the design and implementation of TB clinical platform trials. Results: We showed that early engagement of the EU-PEARL community advisory board highly contributes to the process of development of a community-acceptable Master Protocol Trial and Intervention-Specific Appendixes. We identified capacity building and training as major gaps in advancing CE in the TB field. Conclusion: Developing strategies to address these needs can contribute to preventing tokenism and increase the acceptability and appropriateness of TB research. This work is partially supported by EU-PEARL. EU-PEARL has received funding from the InnovativeMedicines Initiative 2 Joint Undertaking under grant agreement No 853966. This Joint Undertaking receivessupport from the European Union’s Horizon 2020 research and innovation program and EFPIA and Children’sTumor Foundation, Global Alliance for TB Drug Development non-profit organization, SpringworksTherapeutics Inc. This publication reflects the authors’ views. Neither IMI nor the European Union,EFPIA,or any Associated Partners are responsible for any use that may be made of the information contained hereinDMC is the co-leader of EU-PEARL WP5. ASM is supported by a Juan Rodés (JR18/00022) postdoctoral fellowship from ISCIII. FS salary is supported by EU-PEARLgrant to UniSR.

Principado de Asturias, Spain [FC-GRUPIN-IDI/2021/000081]; Ministry of Science and Innovation, Spain [PID2019-109698GB-I00, PID2020-117282RB-I00]; Fundacion Española para la Ciencia y la Tecnología [MCIU-20-FCT-PRECIPITA]; Banco Santander; University of Oviedo [PAPI-19-PF22]

A deep eutectic solvent is presented as a sustainable, synthetically accessible, and non-toxic environment for the stabilisation of lysozyme over a wide concentration range, keeping the enzyme stable and functional even after long-term storage.

As restrictions ease and more people holiday overseas, the importance of providing accurate travel health advice increases. Jacqueline Spinks and colleagues provide an overview of current guidance The COVID-19 pandemic has led to a dramatic drop in people travelling to other countries for pleasure; however, now that restrictions across the UK are easing, more people are seeking a break and a long-awaited holiday overseas. Practice nurses are uniquely placed to provide travel advice not just in relation to COVID-19 requirements and restrictions, but also to remind travellers of the importance of being prepared for all other communicable diseases and travel-related hazards. This article aims to provide a summary of the latest and up to date information in England (links to guidance covering the Devolved Administrations of Scotland, Wales and Northern Ireland are found in Box 1 ) and covers a summary of COVID-19, current guidance on travel during the pandemic, information about pre-planning for overseas travel, return from travel and information about being identified as a contact during travel, general travel advice; and ends with links to the most relevant guidance and information available.

Security research has concentrated on converting operating system audit logs into suitable graphs, such as provenance graphs, for analysis. However, provenance graphs can grow very large requiring significant computational resources beyond what is necessary for many security tasks and are not feasible for resource constrained environments, such as edge devices. To address this problem, we present the \textit{resource-interaction graph} that is built directly from the audit log. We show that the resource-interaction graph's storage requirements are significantly lower than provenance graphs using an open-source data set with two container escape attacks captured from an edge device. We use a graph autoencoder and graph clustering technique to evaluate the representation for an anomaly detection task. Both approaches are unsupervised and are thus suitable for detecting zero-day attacks. The approaches can achieve f1 scores typically over 80\% and in some cases over 90\% for the selected data set and attacks., 15 pages, 11 figures, 6 tables, for dataset see https://github.com/jpope8/container-escape-dataset, for code see https://github.com/jpope8/container-escape-analysis

While the traditional consensus dictates that high ion concentrations lead to negligible long-range electrostatic interactions, we demonstrate that electrostatic correlations prevail in deep eutectic solvents where intrinsic ion concentrations often surpass 2.5 M. Here we present an investigation of intermicellar interactions in 1:2 choline chloride:glycerol and 1:2 choline bromide:glycerol using small-angle neutron scattering. Our results show that long-range electrostatic repulsions between charged colloidal particles occur in these solvents. Interestingly, micelle morphology and electrostatic interactions are modulated by specific counterion condensation at the micelle interface despite the exceedingly high concentration of the native halide from the solvent. This modulation follows the trends described by the Hofmeister series for specific ion effects. The results are rationalized in terms of predominant ion-ion correlations, which explain the reduction in the effective ionic strength of the continuum and the observed specific ion effects.

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer. The molecular pathogenesis of HCC varies due to the different etiologies and genotoxic insults. The development of HCC is characterized by complex interactions between several etiological factors that result in genetic and epigenetic changes in proto-onco and/or tumor suppressor genes. MicroRNAs (miRNAs) are short non-coding RNAs that also can act as oncomiRs or tumor suppressors regulating the expression of cancer-associated genes post-transcriptionally. Studies revealed that several microRNAs are directly or indirectly involved in cellular signaling, and dysregulation of those miRNAs in the body fluids or tissues potentially affects key signaling pathways resulting in carcinogenesis. Therefore, in this mini-review, we discussed recent progress in microRNA-mediated regulation of crucial signaling networks during HCC development, concentrating on the most relevant ones such as PI3K/Akt/mTOR, Hippo-YAP/TAZ, and Wnt/β-catenin, which might open new avenues in HCC management.

Hypothesis The anomeric configuration (α or β) of n-hexadecyl-d-maltopyranoside (C16G2) has been shown to affect the morphology of the micelle, from elongated for α-C16G2 to worm-like micelles for β-C16G2. The entanglement of worm-like micelles often leads to strong modifications of the rheological behavior of the system and, as such, the anomeric configuration of C16G2 could also provide the possibility of controlling this. Furthermore, mixing these surfactants are hypothesized to result in mixed micelles allowing to finely tune the rheology of a system containing these sustainable surfactants. Experiments The rheology of α- and β-C16G2, and mixtures of those, was determined by rotational and oscillatory rheology at different temperatures and surfactant concentrations. Micelle structure and composition for these systems were characterized using contrast variation small-angle neutron scattering and small-angle X-ray scattering. The results from these were connected in order to elaborate a molecular understanding of the rheological response of the system. Findings The self-assembly of these surfactants have been found to result in different rheological properties. β-C16G2 show a high viscosity with a non-Newtonian viscoelastic behavior, which was linked to the formation of worm-like micelles. In contrast, α-C16G2 self-assembled into short cylindrical micelles, resulting in a Newtonian fluid with low viscosity. Furthermore, mixtures of these two surfactants lead to systems with intermediate rheological properties as a result of the formation of micelles with intermediate morphology to those of the pure anomers. These results also show that the rheological properties of the system can be tuned to change the micelle morphology, which in turn depends on the anomeric configuration of the surfactant. Also, surfactant concentration, temperature of the system, and micelle composition for surfactant mixtures provide control over the rheological properties of the system in a wide temperature range. Therefore, these results open new possibilities in the development of sustainable excipients for formulation technology, where the characteristics of the system can be easily tailored through geometric variations in the monomer structure whilst maintaining the chemical composition of the system.

Hypothesis The self-assembly of ionic surfactants in deep eutectic solvents has recently been demonstrated, opening up new possibilities in terms of the development of formulated products and templating of nanostructured materials. As it occurs in an aqueous environment, the solvophobic effect drives the formation of micelles in these solvents and specific-ion interactions alter the resulting structures. We hypothesized that the presence of hydrotropic salts would greatly affect the micellar structure in deep eutectic solvents, ultimately leading to the formation of worm-like aggregates. Experiments A systematic investigation performed on hydrotrope-surfactant assemblies in neat and hydrated 1:2 choline chloride:glycerol is presented. The effect of choline salicylate on the micellization of hexadecyltrimethylammonium chloride at different hydrotrope-to-surfactant ratios was probed by contrast variation small-angle neutron scattering. Findings Here the first investigation on salt-induced micellar growth in deep eutectic solvents is presented. The microscopic characterization of the system shows that the micelle-hydrotrope interaction in pure and hydrated deep eutectic solvents results in a significant increase in micelle elongation. The condensation of the hydrotrope on the micelle, which alters the effective monomer packing, leads to the formation of worm-like micelles with tunable morphology and flexibility. The results presented here present new possibilities in terms of self-assembly and co-assembly in neoteric solvents, where micelle morphology can be controlled through surfactant-salt interactions.

Hypothesis: The self-assembly of long tail sugar-based surfactants into worm-like micelles has recently been demonstrated, and the rheological properties of such systems have been shown to be tuneable through subtle modifications of the molecular characteristics of the surfactant monomer. In particular, the anomeric configuration of the hexadecylmaltoside headgroup was shown to induce profound changes in the nanostructure and rheology of the system. The origin of such changes is hypothesised to arise from differences in the structure and relaxation of the micellar networks in the semi-dilute regime. Experiments: Here we explore the molecular background to the flow properties of the two anomers of hexadecylmaltoside (alpha- and beta-C(16)G(2)) by directly connecting their rheological behaviour to the micelle morphology. For this purpose, 1-3 plane rheo-small-angle neutron scattering measurements, using a Couette cell geometry, probed the structural changes in the micellar phase under shear. The effect of surfactant anomeric configuration, surfactant concentration, temperature and mixing ratio of the two anomers were investigated. The static micelle structure in the semi-dilute regime was determined using the polymer reference interaction site model. Findings: The segmental alignment of the micellar phase was studied under several flow conditions, showing that the shear-thinning behaviour relates to the re-arrangement of beta-C(16)G(2) worm-like micelles, whilst shorter alpha-C(16)G(2) micelles are considerably less affected by the flow. The results are rationalised in terms of micelle alignment and disruption of the entangled network, providing a detailed mechanism by which sugar-based surfactants control the rheology of the fluid. To further enable future studies, we provide the complete code for modelling micelle structure in the semi-dilute regime using the polymer reference interaction site model. (C) 2021 The Authors. Published by Elsevier Inc.

The molecular architecture of sugar-based surfactants strongly affects their self-assembled structure, i.e., the type of micelles they form, which in turn controls both the dynamics and rheological properties of the system. Here, we report the segmental and mesoscopic structure and dynamics of a series of C16 maltosides with differences in the anomeric configuration and degree of tail unsaturation. Neutron spin-echo measurements showed that the segmental dynamics can be modeled as a one-dimensional array of segments where the dynamics increase with inefficient monomer packing. The network dynamics as characterized by dynamic light scattering show different relaxation modes that can be associated with the micelle structure. Hindered dynamics are observed for arrested networks of worm-like micelles, connected to their shear-thinning rheology, while nonentangled diffusing rods relate to Newtonian rheological behavior. While the design of novel surfactants with controlled properties poses a challenge for synthetic chemistry, we demonstrate how simple variations in the monomer structure can significantly influence the behavior of surfactants The authors thank the Swedish Research Council Formas (Grant 2015-666) for funding J.L. The research was performed with financial support from the Vinnova─Swedish Governmental Agency for Innovation Systems within the NextBioForm Competence Centre. The authors also thank the Institut Laue-Langevin, France, for the awarded beamtime (Proposal No. 9-10-1652). NSE data is openly available at doi: 10.5291/ILL-DATA.9-10-1652 SI

Data integrity becomes paramount as the number of Internet of Things (IoT) sensor deployments increases. Sensor data can be altered by benign causes or malicious actions. Mechanisms that detect drifts and irregularities can prevent disruptions and data bias in the state of an IoT application. This paper presents LE3D, an ensemble framework of data drift estimators capable of detecting abnormal sensor behaviours. Working collaboratively with surrounding IoT devices, the type of drift (natural/abnormal) can also be identified and reported to the end-user. The proposed framework is a lightweight and unsupervised implementation able to run on resource-constrained IoT devices. Our framework is also generalisable, adapting to new sensor streams and environments with minimal online reconfiguration. We compare our method against state-of-the-art ensemble data drift detection frameworks, evaluating both the real-world detection accuracy as well as the resource utilisation of the implementation. Experimenting with real-world data and emulated drifts, we show the effectiveness of our method, which achieves up to 97% of detection accuracy while requiring minimal resources to run., Comment: IEEE CCNC 2023, Las Vegas, USA

Edge computing is rapidly changing the IoT-Cloud landscape. Various testbeds are now able to run multiple Docker-like containers developed and deployed by end-users on edge devices. However, this capability may allow an attacker to deploy a malicious container on the host and compromise it. This paper presents a dataset based on the Linux Auditing System, which contains malicious and benign container activity. We developed two malicious scenarios, a denial of service and a privilege escalation attack, where an adversary uses a container to compromise the edge device. Furthermore, we deployed benign user containers to run in parallel with the malicious containers. Container activity can be captured through the host system via system calls. Our time series auditd dataset contains partial labels for the benign and malicious related system calls. Generating the dataset is largely automated using a provided AutoCES framework. We also present a semi-supervised machine learning use case with the collected data to demonstrate its utility. The dataset and framework code are open-source and publicly available.

The common Deep Eutectic Solvent (DES) ‘ethaline’ (1:2 choline chloride:ethylene glycol) was examined here as a basis for the self-assembly of the surfactant dodecyltrimethylammonium bromide (C12TAB). A phase diagram was constructed, showing evidence for a L1 (micellar) phase, confirmed by tensiometry to have a room temperature critical micelle concentration (CMC) of 1.2 wt.%. Small angle neutron scattering (SANS) measurements indicate formation of interacting globular micelles with slightly smaller apparent radii than in water. The apparent mesophase/multiphase region was studied using SWAXS, demonstrating rich mesoscopic lyotropic liquid crystalline phase behaviour, with evidence for lamellar Lα peaks, alongside potential co-crystalline phases. We attempted to tailor the self-assembly by studying binary DES containing longer diols including 1,2-propanediol, 1,3-propanediol, 1,4-butanediol, and 1,5-pentanediol, and ternary DES where the HBD component was a 1:1 ethylene glycol:diol mixture. However, synchrotron SAXS showed that only ternary ‘propethaline’ mixtures displayed signs of self-assembly and micellization, perhaps due to the reduction in calculated Gordon parameter, which decreases linearly with increasing alkyl chain length. Systematic differences were thus observed in the ability of the solvents to modulate assembly, from globular micelles in ChCl:EG, to weaker assembly in long-tail DES, and complete solubilisation in butaline and pentaline.

Aim: The association between COVID-19 disease severity and certain medicines for the treatment of chronic diseases is currently under discussion. We herein evaluated if previous exposure to antihypertensive, hypoglycaemic, and lipid-lowering drugs increases the risk of poorer COVID-19 outcomes. Methods: We performed a retrospective study on three cohorts of COVID-19 adult patients between March 2020 and May 2020 at the Vall d’Hebron University Hospital. Information relating to the patient lifestyle, comorbidities, and chronic exposures was retrieved from primary healthcare electronic records. Three cohorts were examined, namely patients who had died or required intensive care treatment (ICU/Death [ICU-D] Cohort), patients who required hospitalisation (Hospitalisation [HOSP] Cohort), and patients who only attended the emergency department (Emergencies [EM] Cohort). Descriptive statistics and a multivariate logistic regression model were used to investigate associations with drug exposure, where EM was employed as the reference cohort. Results: We included 1,778 patients: 417 (23.5%) from the ICU-D Cohort, 1,052 (59.2%) from the HOSP Cohort, and 309 (17.4%) from the EM Cohort. After multiple imputations and data adjustment by potential confounders, no statistically significant association was observed between the COVID-19 severity and the use of antihypertensives, hypoglycaemic agents, or lipid-lowering agents, with the exception of calcium channel blockers (CCB) (ICU-D Cohort: OR 2.23; CI 95% [1.03–4.83]; P = 0.042). Conclusions: Most results on lifestyle characteristics and comorbidities related to COVID-19 severity were in agreement with current knowledge, although some associated factors are nowadays a matter of controversy and further investigation is required.

This paper proposes a protocol to ensure market equity in car-sharing applications where fares result fair and just, and actors cannot influence prices to their benefit. To achieve our proposal, we use homomorphic encryption to hide prices and opportunistic networking to avoid any central element that could alter the market. Both technologies are combined in a twoway communication protocol achieving fair price setting for both drivers and passengers. Results show that the proposal is feasible and mitigate price alteration attempts.

With the increase of global demand for food and with the adoption of the trends of local sourcing and locally grown produce, the need for gardening and farming automation solutions ranging from industrial to home level has been on the rise. In this paper, we propose an Internet of Things (IoT) farming control system based on the concept of Wireless Sensor and Actuator Networks (WSAN) that provides ideal growing conditions for user-defined crops. This is achieved by utilizing the information provided by a series of sensors monitoring the environmental (temperature, humidity, UV, etc.) and soil (moisture, nutrients, etc.) conditions to control the deployed actuators. To allow a wide range of deployment sizes, we use a two-stage system that combines a series of low-power sensor and actuator nodes with a communication and data processing gateway. The low-power microcontroller reads the data from the sensors and sends them to the data processing gateway, which then calculates the optimal actuator changes required to achieve the desired status. These changes are then feedbacked to the low-power microcontroller which actuates the control devices. The communication between the devices is performed via a bespoke LoRa-based communication protocol optimized for minimal overhead, flexibility, and guaranteed data delivery. This is presented to the user via a website to view the configuration of the system and the observation of the past and present environmental, soil, and actuator status of the system.

ObjectiveTo develop and validate a rapid scoring system at hospital admission for predicting in-hospital mortality in patients hospitalized with coronavirus disease 19 (COVID-19), and to compare this score with other existing ones.DesignCohort studySettingThe Brazilian COVID-19 Registry has been conducted in 36 Brazilian hospitals in 17 cities. Logistic regression analysis was performed to develop a prediction model for in-hospital mortality, based on the 3978 patients that were admitted between March-July, 2020. The model was then validated in the 1054 patients admitted during August-September, as well as in an external cohort of 474 Spanish patients.ParticipantsConsecutive symptomatic patients (≥18 years old) with laboratory confirmed COVID-19 admitted to participating hospitals. Patients who were transferred between hospitals and in whom admission data from the first hospital or the last hospital were not available were excluded, as well those who were admitted for other reasons and developed COVID-19 symptoms during their stay.Main outcome measuresIn-hospital mortalityResultsMedian (25th-75th percentile) age of the model-derivation cohort was 60 (48-72) years, 53.8% were men, in-hospital mortality was 20.3%. The validation cohorts had similar age distribution and in-hospital mortality. From 20 potential predictors, seven significant variables were included in the in-hospital mortality risk score: age, blood urea nitrogen, number of comorbidities, C-reactive protein, SpO2/FiO2ratio, platelet count and heart rate. The model had high discriminatory value (AUROC 0.844, 95% CI 0.829 to 0.859), which was confirmed in the Brazilian (0.859) and Spanish (0.899) validation cohorts. Our ABC2-SPH score showed good calibration in both Brazilian cohorts, but, in the Spanish cohort, mortality was somewhat underestimated in patients with very high (>25%) risk. The ABC2-SPH score is implemented in a freely available online risk calculator (https://abc2sph.com/).ConclusionsWe designed and validated an easy-to-use rapid scoring system based on characteristics of COVID-19 patients commonly available at hospital presentation, for early stratification for in-hospital mortality risk of patients with COVID-19.Summary boxesWhat is already known on this topic?Rapid scoring systems may be very useful for fast and effective assessment of COVID-19 patients in the emergency department.The majority of available scores have high risk of bias and lack benefit to clinical decision making.Derivation and validation studies in low- and middle-income countries, including Latin America, are scarce.What this study addsABC2-SPH employs seven well defined variables, routinely assessed upon hospital presentation: age, number of comorbidities, blood urea nitrogen, C reactive protein, Spo2/FiO2 ratio, platelets and heart rate.This easy-to-use risk score identified four categories at increasing risk of death with a high level of accuracy, and displayed better discrimination ability than other existing scores.A free web-based calculator is available and may help healthcare practitioners to estimate the expected risk of mortality for patients at hospital presentation.

Hypothesis The self-assembly of long-tail surfactants results in the formation of nanoscale structures, e.g. worm-like micelles, with the ability to modify the rheology of the system. However, micelle formation, and thus the alteration of the rheology, is subject to the high Krafft temperature of saturated long-tail surfactants. Hexadecylmaltosides are sustainable surfactants that, in solution, form tailorable viscoelastic fluids. The preparation of monounsaturated sugar-based surfactants is hypothesised to reduce the Krafft point compared to the saturated analogues, therefore increasing the temperature range where the surfactant remains in the micellar form. Experiments Here we report the synthesis and characterisation of a novel sugar-based surfactant with an unsaturated C16-tail, namely palmitoleyl-β- d -maltoside (β-C16-1G2). Differential scanning calorimetry was used to probe the temperature stability of the system. The rheology of β-C16-1G2 solutions was investigated by means of rotational and oscillatory rheology, and these results were connected to the mesoscopic structure of the system as shown by small-angle neutron and X-ray scattering, and dynamic light scattering. Findings The presence of a double bond on the alkyl chain moiety leads to a depression in the Krafft point, allowing the surfactant to form a thermodynamically stable micellar solution over a wide range of temperatures, i.e. 5–95 °C. The surfactant self-assembles into worm-like micelles which, upon entanglement in the semi-dilute regime, result in the formation of a non-Newtonian, viscoelastic fluid. These observations have important implications in the development of new sustainable formulated products, enabling the preparation of surfactant phases with remarkable thermal resilience.

The structure and dynamics of proteins in solution are closely related to their activity and, ultimately, to their performance in products and technologies, for example, drug formulations and enzymatic catalysis. With this in mind, the study of the fundamental behavior of proteins in deep eutectic solvents not only provides insight into a novel alternative to aqueous and molecular organic solvents, but also contributes to understanding the potential behavior of these macromolecules in non-aqueous environments. In particular, it has relevance for systems with high levels of dehydration, liquid phases for dispersions at cryogenic temperatures, or systems with high ionic strength. In this chapter, we will explore current knowledge of the physicochemical behavior of proteins in deep eutectic solvents. The local and global structure of proteins in these solvents will be presented and compared to those in aqueous solutions, organic solvents and ionic liquids. Furthermore, the characteristic behavior of proteins in deep eutectic solvents will be linked to solvation effects and the interaction of the macromolecules with the solvent, where specific electrostatic and hydrogen bond interactions can affect the structure and dynamics of proteins. Finally, challenges and opportunities in the field will be discussed, with the aim of guiding a common effort to develop a better understanding of the fundamental behavior of proteins in these interesting environments.

Facial plastic surgery and esthetic surgery are among the most challenging parts of the residency training. As a former fellow at Velthuis Kliniek Rotterdam with Dr. Van Der Meulen and Dr. Stevens, the author hereby present his unique 3-month experience offering actively participation in surgeries and consultation, academical education and research, and personal development for junior plastic surgeons who want to aspire to make facial and esthetic surgery their area of expertise.

Deep eutectic solvents (DES) are potentially greener solvents obtained through the complexation of simple precursors which, among other applications, have been investigated in recent years for their ability to support the self-assembly of amphiphilic molecules. It is crucial to understand the factors which influence surfactant solubility and self-assembly with respect to the interaction of the surfactant molecule with the DES components. In this work, small-angle neutron scattering (SANS) has been used to investigate the micellization of cationic (CnTAB) and anionic (SDS) surfactants in a ternary DES comprising choline chloride, urea, and glycerol, where the hydrogen bond donors are mixed in varying molar ratios. The results show that in each case either globular or rodlike micelles are formed with the degree of elongation being directly dependent on the composition of the DES. It is hypothesized that this composition dependence arises largely from the poor solubility of the counterions in the DES, especially at low glycerol content, leading to a tighter binding of the counterion to the micelle surface and giving rise to micelles with a high aspect ratio. This potential for accurate control over micelle morphology presents unique opportunities for rheology control or to develop templated syntheses of porous materials in DES, utilizing the solvent composition to tailor micelle shape and size, and hence the pore structure of the resulting material.

MicroRNAs (miRNAs) are a novel class of biomarkers that can be present in different biological samples, which can be related to many diseases. Controlled aggregation of gold nanoparticles (GNPs) in the presence of miRNAs can be used to perform a rapid detection of miRNAs based on color change. Sometimes the color change can be observed with the naked eye; however, this is not always possible. This work proposes the design of a novel instrumental prototype that allows performance of simultaneous transmittance measurements at different wavelengths. Once the signals are obtained, the system calculates the 525nm/650nm transmittance ratio and the miRNA concentration, displaying and recording the results in a smartphone. This prototype has been validated to detect the miRNA "miR146a," which is found in higher concentrations in milk and tissues in cases of bovine mastitis.

Palatal fistula after primary palatoplasty remains one of the most difficult complications that plastic surgeons have to face. Once the fistula has developed, the complexity of the reconstruction increases significantly, and the revisional surgery results are not promising. The recent use of acellular dermal matrix (ADM) provides a new perspective for the reconstructive surgeon. Our goal is to reduce and prevent the postoperative oronasal fistula in patients with cleft palate by placing an ADM in the zone 3 and 4 of Pittsburgh (hard palate and hard–soft palate junction), creating an extra layer for support of the cleft palate. Seven children diagnosed of palatal cleft with high risk of developing oronasal fistula were operated. The technique of choice was two-flap palatoplasty with lateral incisions and intravelar veloplasty and three-layered closure with ADM in the hard palate and hard–soft palate junction. One patient developed a 3-mm oronasal fistula at 3-month follow-up, with spontaneous closure at 12 months. The rest of the children had an uneventful evolution. Our rate of postoperative oronasal fistula was 0% at 12 months. The use of ADM in primary palatoplasty had been of great use to prevent complications in high-risk oronasal fistula patients.

The interactions between protein and surfactants play an important role in the stability and performance of formulated products. Due to the high complexity of such interactions, multi-technique approaches are required to study these systems. Here, an integrative approach is used to investigate the various interactions in a model system composed of human growth hormone and sodium dodecyl sulfate. Contrast variation small-angle neutron scattering was used to obtain information on the structure of the protein, surfactant aggregates and surfactant–protein complexes. 1H and 1H–13C HSQC nuclear magnetic resonance spectroscopy was employed to probe the local structure and dynamics of specific amino acids upon surfactant addition. Through the combination of these advanced methods with fluorescence spectroscopy, circular dichroism and isothermal titration calorimetry, it was possible to identify the interaction mechanisms between the surfactant and the protein in the pre- and post-micellar regimes, and interconnect the results from different techniques. As such, the protein was revealed to evolve from a partially unfolded conformation at low SDS concentration to a molten globule at intermediate concentrations, where the protein conformation and local dynamics of hydrophobic amino acids are partially affected compared to the native state. At higher surfactant concentrations the local structure of the protein appears disrupted, and a decorated micelle structure is observed, where the protein is wrapped around a surfactant assembly. Importantly, this integrative approach allows for the identification of the characteristic fingerprints of complex transitions as seen by each technique, and establishes a methodology for an in-detail study of surfactant–protein systems.

Introduction: Treatment of MDRTB is complex: regimens require microbiological data; adverse events are frequent; availability of drugs and authorization for new drugs varies. The aim of this study was to scope the available national resources. Method: A survey to determine whether practising physicians could access MDRTB advice was sent to TBnet members by email. The ERS Office also contacted national respiratory societies. Questions included the name and contact details for their national advisory service, whether it was national policy to use the service for each patient with MDRTB and whether advice was required to access bedaquiline and delaminid. Results: 65 replies were received (14 were uninformative). 26/31 EU/EEA and 10/19 other countries in the WHO European Region were represented. 7 countries referred all MDRTB to a tertiary centre; 12 countries had tertiary referral centres that also gave advice to physicians treating MDRTB. 11 countries had an electronic system for advice, 6 with multidisciplinary team meetings to review patients’ progress. Lead clinicians were identified for a further 8 countries, one of which had no national advisory service and the other 7 had not responded by the time of abstract submission. For 18 (58%) countries, discussion of MDRTB by a national /regional committee was national policy and most (15/18) required consultation to use bedaquiline or delamanid. Electronic platforms had a wide range of functionality but few retained anonymised data and audited patient outcomes. Conclusion: MDRTB management is often concentrated in tertiary centres. Clinical governance, regarding audit and outcome, are at an early stage in managing MDRTB.

Secondary bacterial pneumonias following influenza infections consistently rank within the top ten leading causes of death in the United States. To date, murine models of co-infection have been the primary tool developed to explore the pathologies of both the primary and secondary infections. Despite the prevalence of this model, considerable discrepancies regarding instillation procedures, dose volumes, and efficacies are prevalent among studies. Furthermore, these efforts have been largely incomplete in addressing how the pathogen may be directly influencing disease progression post-infection. Herein we provide a precise method of pathogen delivery, recovery, and analysis to be used in murine models of secondary bacterial pneumonia. We demonstrate that intratracheal instillation enables an efficient and accurate delivery of controlled volumes directly and evenly into the lower respiratory tract. Lungs can be excised to recover and quantify the pathogen burden. Following excision of the infected lungs, we describe a method to extract high quality pathogen RNA for subsequent transcriptional analysis. This procedure benefits from being a non-surgical method of delivery without the use of specialized laboratory equipment and provides a reproducible strategy to investigate pathogen contributions to secondary bacterial pneumonia.

In this work, we present the first example of the self-assembly of phospholipid monolayers at the interface between air and an ionic solvent. Deep eutectic solvents are a novel class of environmentally friendly non-aqueous room temperature liquids with tunable properties, that have wide ranging potential applications and are capable of promoting the self-assembly of surfactant molecules. We use a chemically-consistent Bayesian modelling of X-ray and neutron reflectometry measurements to show that these monolayers broadly behave as they do on water. This method allows for the monolayer structure to be determined, alongside the molecular volumes of the individual monolayer components without the need for water-specific constraints to be introduced. Furthermore, using this method we are able to better understand the correlations present between parameters in the analytical model. This example of a non-aqueous phospholipid monolayer has important implications for the potential uses of these solvents and for our understanding of how biomolecules behave in the absence of water., Comment: Electronic Supplementary Information (ESI) available: All analysis/plotting scripts and figures files, allowing for a fully reproducible, and automated, analysis workflow for the work presented is available at https://github.com/arm61/lipids_at_airdes (DOI: 10.5281/zenodo.2577796) under a CC-BY-SA 4.0 license

Low cost and in situ fluoride detection by non-experts is important for the determination of drinking water safety in developing countries. Colour reagents can provide results quickly without expensive equipment, but colorimetric fluoride indicators are often nonspecific, complex to use or do not work in water. Here we show that azulene–boronate indicators respond selectively to fluoride at concentrations relevant to the WHO limit of 1.5 mg L−1.

Resumen Introducción y Objetivo El desbridamiento enzimático es hoy una herramienta útil en el tratamiento precoz de las quemaduras profundas. Tras el mismo, existen diferentes protocolos de manejo de la herida en las distintas unidades de quemados, consiguiendo en algunos casos la curación espontánea y en otros necesitando injertos de piel. A día de hoy no existe ninguna herramienta objetiva para asegurar el éxito del desbridamiento, ya que el lecho de herida que deja se asemeja a una escara que puede generar confusión sobre la eficacia del producto y el manejo del paciente. El desarrollo de una técnica fiable y objetiva para la medición de la dermis remanente podría ayudar en la toma de decisiones postdesbridamiento y en consecuencia a lograr mejores resultados. Material y Método Realizamos ultrasonografía (US) cutánea a tiempo real con sondas de alta frecuencia en 15 pacientes, 12 horas tras desbridamiento enzimático con Nexobrid®, proporcionando imágenes precisas del remanente dérmico. Medimos el grosor de la dermis en regiones que no han sufrido quemaduras y las comparamos con áreas similares desbridadas. Resultados Todas las US de piel demostraron menor grosor dérmico en las áreas desbridadas que en las zonas no quemadas del mismo paciente. A pesar de que en todos los casos el diagnóstico visual del lecho fue similar a una escara, en un caso la US demostró la práctica ausencia de dermis y en otro persistencia de la escara. A los pocos días, ambos pacientes necesitaron injertos de piel. Todos los casos con suficiente dermis remanente curaron por epitelización espontánea. Conclusiones La evaluación del lecho de la herida con ultrasonografía tras desbridamiento enzimático, es un método objetivo para valorar la respuesta al tratamiento. Asimismo, la medición de la dermis remanente podría proporcionar parámetros reales para predecir las oportunidades de epitelización espontánea o la necesidad de injertos de piel en pacientes quemados.

The self-assembly of the two anomeric forms of n-hexadecyl-d-maltopyranoside (denoted α-C16G2 and β-C16G2) has been studied in dilute aqueous solution by means of surface tension measurements, scattering methods (dynamic light scattering, static light scattering, and small-angle X-ray and neutron scattering), and cryo-transmission electron microscopy at different surfactant concentrations and temperatures. Surface tension measurements demonstrate differences in the surfactant adsorption at the air–water interface, where α-C16G2 shows a lower CMC than β-C16G2. Similarly, micelle morphology was found to profoundly depend on anomerism. β-C16G2 preferentially forms very elongated micelles with large persistence lengths, whereas α-C16G2 assembles into smaller micelles for which the structure varies with concentration and temperature. The differences between the two surfactant anomers in terms of self-assembly can be attributed to the interaction between neighboring headgroups. Specifically, β-C16G2 allows for a closer packing in the palisade layer, hence reducing the micelle curvature and promoting the formation of more elongated micelles. Strong intermolecular headgroup interactions may also account for the observed rigidity of the micelles.

[Background] Sleep-disordered breathing (SDB) has been associated with cancer aggressiveness, but studies focused on specific tumors are lacking. In this pilot study we investigated whether SDB is associated with breast cancer (BC) aggressiveness., [Methods] 83 consecutive women, [Results] The mean (SD) age was 48.8 (8.8) years and body mass index was 27.4 (5.4) Kg/m2. 42 women (50.6%) were post-menopausal. The median (IQR) AHI was 5.1 (2–9.4), and ODI4 was 1.5 (0.5–5.8). The median (IQR) AHI did not differ between the groups with Ki67>28% and Ki6728% and Ki67, [Conclusion] Our results do not support an association between the presence or severity of SDB and BC aggressiveness., This study was supported by a grant from the Asociación de Neumología y Cirugía Torácica del Sur (NEUMOSUR) (Grant number 1/2015), awarded to F. C-R., https://www.neumosur.net/.

Micellisation of surfactants in deep eutectic solvents has been recently demonstrated to provide a controllable way to modify micelle morphology. Ion-pair interactions between the solvent and the surfactant headgroup were identified as affecting the micellisation by modifying the charge density of the micelle. Here we explore the micellisation of dodecylsulfate surfactants with different counterions (Li+, Cs+, Mg2+, Bmim+, Emim+, cholinium+) dissolved in two deep eutectic solvents: choline chloride:urea and choline chloride:glycerol. Surface tension results show a solvent and counterion dependence of the CMC of the surfactants. Small-angle neutron scattering was subsequently used to investigate the morphology of the micelles formed. The results show that the elongation of the micelles is strongly dependent on the solvent, showing more elongated aggregates in choline chloride:urea than in choline chloride:glycerol. The morphology of micelles in DES was also found to depend on the counterion, where the affinity of binding showed similarities to that in water.

In recent years many studies into green solvents have been undertaken and deep eutectic solvents (DES) have emerged as sustainable and green alternatives to conventional solvents since they may be formed from cheap non-toxic organic precursors. In this study we examine amphiphile behaviour in these novel media to test our understanding of amphiphile self-assembly within environments that have an intermediate polarity between polar and non-polar extremes. We have built on our recently published results to present a more detailed structural characterisation of micelles of sodium dodecylsulfate (SDS) within the eutectic mixture of choline chloride and urea. Here we show that SDS adopts an unusual cylindrical aggregate morphology, unlike that seen in water and other polar solvents. A new morphology transition to shorter aggregates was found with increasing concentration. The self-assembly of SDS was also investigated in the presence of water; which promotes the formation of shorter aggregates.

Deep eutectic solvents have shown the ability to promote the self-assembly of surfactants in solution. However, some differences have been found compared with self-assembly in pure water and other polar organic solvents. The behaviour of alkyltrimethylammonium bromides in choline chloride:glycerol deep eutectic solvent has been studied by means of surface tension, X-ray and neutron reflectivity and smallangle neutron scattering. The surfactants were found to remain surface active and showed comparable critical micelle concentrations to the same surfactants in water. Our scattering studies demonstrate that these surfactants form globular micelles with ellipsoidal shape in solution. The size, shape and aggregation number of the aggregates were found to vary with the chain length of the surfactant. Specific solventheadgroup interactions were not found in this system, unlike those we have previously postulated for anionic surfactants in choline chloride deep eutectic solvents.

Recent investigations have shown that deep eutectic solvents provide a suitable environment for self-organisation of biomolecules, in particular phospholipids and proteins. However, the solvation of complex lyophilic moieties by deep eutectic solvents still remains unclear. Here we explore the behaviour of zwitterionic surfactants in choline chloride:glycerol eutectic mixture. Dodecyl-2-(trimethylammonio)ethylphosphate and N-alkyl-N,N-dimethyl-3-ammonio-1-propanesulfonate (alkyl = dodecyl, tetradecyl) surfactants were investigated by means of surface tension, X-ray reflectivity and small-angle neutron scattering. These surfactants were found to remain surface active and form globular micelles in deep eutectic solvents. Still, the surface behaviour of these species was found to differ depending on the headgroup and tail structure. The morphology of the micelles also slightly varies between surfactants, demonstrating differences in the packing of individual monomers. The characteristics of mixtures of the dodecyl surfactants is also reported, showing a deviation from ideal mixing associated with attractive interactions between sulfobetaine and phosphocholine headgroups. Such non-ideality results in variation of the surface behaviour and self-assembly of these surfactant mixtures. The results presented here will potentially lead to the development of new alternatives for drug-delivery, protein solubilisation and biosensing through a better fundamental understanding of the behaviour of zwitterionic surfactants in deep eutectic solvents.

Deep eutectic solvents have been demonstrated to support amphiphile self-assembly, providing potential alternatives as structure-directing agents in the synthesis of nanostructures, and drug delivery. Here we have expanded on this recent research to investigate the self-assembly of alkyltrimethylammonium bromide surfactants in choline chloride:malonic acid deep eutectic solvent and mixtures of the solvent with water. Surface tension and small-angle neutron scattering were used to determine the behavior of the amphiphiles. Surfactants were found to remain active in the solvent, and surface tension measurements revealed changes in the behavior of the surfactants with different levels of hydration. Small-angle neutron scattering shows that in this solvent the micelle shape depends on the surfactant chain length, varying from globular micelles (aspect ratio ∼2) for short chain surfactants to elongated micelles (aspect ratio ∼14) for long chain surfactants even at low surfactant concentration. We suggest that the formation of elongated micelles can be explained through the interaction of the solvent with the surfactant headgroup, since ion-ion interactions between surfactant headgroups and solvent may modify the morphology of the micelles. The presence of water in the deep eutectic solvents promotes an increase in the charge density at the micelle interface and therefore the formation of less elongated, globular micelles.

Little is presently known about the unique nanostructure of deep eutectic solvents (DES). The order of the liquid-solid phase transition is contended and whether DES-water mixtures are merely aqueous solutions, or have properties dominated by the eutectic pair, is unclear. Here, we unambiguously show the structure of choline chloride-malic acid (malicine) as a liquid, and also in solid and hydrated forms, using neutron total scattering on D/H isotope-substituted samples, and quasi-elastic neutron scattering (QENS). Data were refined using empirical potential structure refinement. We show evidence for a stoichiometric complex ion cluster in the disordered liquid, with strong choline-chloride bonding and a hydrogen bond donor (HBD) contribution. The 1:1 eutectic stoichiometry makes these ionic domains more well-defined, with less HBD clustering than seen previously for reline. There is minimal structural difference for the solidified material, demonstrating that this DES solidification is a glass transition rather than a first order phase change. QENS data support this by showing a gradual change in solvent dynamics rather than a step change. The DES structure is mostly retained upon hydration, with water acting both as a secondary smaller HBD at closer range to choline than malic acid, and forming transient wormlike aggregates. This new understanding of DES structure will aid understanding of the properties of these novel green solvents on the molecular length scale in chemical processes, as well as giving an insight into the apparent role of natural DESs in plant physiology.

Deep eutectic solvents (DES) have recently been postulated as possible environments where protein structure may be preserved in the absence of water. Here we present our results towards understanding protein conformation in choline chloride-based DES and mixtures with water. Lysozyme and bovine serum albumin have been investigated by means of circular dichroism and small-angle neutron scattering.

Male pattern hair loss (MPHL) is exceedingly common. It is characterised by onset in early adulthood and progression with age. It has a strong heritable component. The reason for its existence remains unexplained. Given that MPHL is progressive and has its earliest manifestations in young adults it may be a barometer of age. Here we suggest that MPHL may have atavistically allowed women in our species and ancestor species to select younger (but not necessarily the youngest) adult mates. Evidence suggests that conceptions by younger fathers are more likely to lead to live births and less likely to result in miscarriage. Further children fathered by younger men may have improved health and be less likely to suffer from a number of co-morbidities. This is collectively known as the “paternal age affect”. Hence the selection of younger males mediated by the MPHL may improve the fitness of the population and of the species at the expense of the individual. Indeed MPHL may have been an evolutionary “nudge” directing women to favour younger partners. It is conceivable that for a species whose success is predicated upon co-operation, collaboration and altruism the gene cannot be exclusively selfish and must have a selfless allele.