Single-channel measurements of an N-acetylneuraminic acid-inducible outer membrane channel in Escherichia coli

NanC is an Escherichia coli outer membrane protein involved in sialic acid (Neu5Ac, i.e., N-acetylneuraminic acid) uptake. Expression of the NanC gene is induced and controlled by Neu5Ac. The transport mechanism of Neu5Ac is not known. The structure of NanC was recently solved (PDB code: 2WJQ) and includes a unique arrangement of positively charged (basic) side chains consistent with a role in acidic sugar transport. However, initial functional measurements of NanC failed to find its role in the transport of sialic acids, perhaps because of the ionic conditions used in the experiments. We show here that the ionic conditions generally preferred for measuring the function of outer-membrane porins are not appropriate for NanC. Single channels of NanC at pH 7.0 have: (1) conductance 100 pS to 800 pS in 100 mM: KCl to 3 M: KCl), (2) anion over cation selectivity (V (reversal) = +16 mV in 250 mM: KCl || 1 M: KCl), and (3) two forms of voltage-dependent gating (channel closures above ±200 mV). Single-channel conductance decreases by 50% when HEPES concentration is increased from 100 ?M: to 100 mM: in 250 mM: KCl at pH 7.4, consistent with the two HEPES binding sites observed in the crystal structure. Studying alternative buffers, we find that phosphate interferes with the channel conductance. Single-channel conductance decreases by 19% when phosphate concentration is increased from 0 mM: to 5 mM: in 250 mM: KCl at pH 8.0. Surprisingly, TRIS in the baths reacts with Ag|AgCl electrodes, producing artifacts even when the electrodes are on the far side of agar-KCl bridges. A suitable baseline solution for NanC is 250 mM: KCl adjusted to pH 7.0 without buffer

Conocimiento del profesional de enfermería en el proceso de cuidado de enfermería en los servicios del Hospital Regional – Tumbes, 2022

El objetivo de la investigación fue determinar el nivel de conocimiento del profesional de enfermería en el proceso de cuidado de enfermería (PCE) en los servicios del Hospital Regional, Tumbes - 2022, se utilizó la investigación tipo básica, con enfoque cuantitativo de diseño no experimental, la recolección de datos se realizó a través de la técnica de la entrevista y como instrumento el cuestionario que costo de 20 preguntas, aplicado a 48 profesionales. Los resultados muestran que los profesionales de enfermería presentan un nivel de conocimiento medio con el 70%, respecto al (PCE), en conocimientos de aspectos básicos, predominó el nivel de conocimiento alto en los servicios de emergencia cirugía, ginecología y medicina, con el 100%, 90% y 70% respectivamente, en la etapa de la Valoración nivel alto 80% en ginecología, nivel medio en emergencia medicina con el 50%; la etapa de diagnóstico el nivel bajo lo obtuvo medicina y pediatría con el 80%, ginecología nivel medio con el 50%; en la etapa de la planificación emergencia cirugía con el nivel medio alcanzo el 100%, cirugía y medicina nivel alto con el 70% y ginecología nivel bajo 70%; en la etapa de ejecución emergencia cirugía, medicina, obtuvieron nivel alto con el 100% y 70% respectivamente, pediatría, emergencia medicina y ginecología iguales porcentajes 60% nivel alto; la etapa de evaluación, ginecología, cirugía, emergencia cirugía y emergencia medicina niveles altos del 90%, 70% y 60% respectivamente. Se concluye que los profesionales en enfermería alcanzaron el nivel medio en un 70% sobre el PCE y sólo el 30% presenta un nivel alto

Making Sense of the Epigenome Using Data Integration Approaches

Epigenetic research involves examining the mitotically heritable processes that regulate gene expression, independent of changes in the DNA sequence. Recent technical advances such as whole-genome bisulfite sequencing and affordable epigenomic array-based technologies, allow researchers to measure epigenetic profiles of large cohorts at a genome-wide level, generating comprehensive high-dimensional datasets that may contain important information for disease development and treatment opportunities. The epigenomic profile for a certain disease is often a result of the complex interplay between multiple genetic and environmental factors, which poses an enormous challenge to visualize and interpret these data. Furthermore, due to the dynamic nature of the epigenome, it is critical to determine causal relationships from the many correlated associations. In this review we provide an overview of recent data analysis approaches to integrate various omics layers to understand epigenetic mechanisms of complex diseases, such as obesity and cancer. We discuss the following topics: (i) advantages and limitations of major epigenetic profiling techniques, (ii) resources for standardization, annotation and harmonization of epigenetic data, and (iii) statistical methods and machine learning methods for establishing data-driven hypotheses of key regulatory mechanisms. Finally, we discuss the future directions for data integration that shall facilitate the discovery of epigenetic-based biomarkers and therapies.Peer reviewe

Combined gene essentiality scoring improves the prediction of cancer dependency maps

Correction: Volume: 51 Article Number: UNSP 102594 DOI: 10.1016/j.ebiom.2019.12.003Peer reviewe

Hand hygiene compliance and environmental contamination with gram-negative bacilli in a rural hospital in Madarounfa, Niger

Abstract Background Healthcare-associated infections pose a major, yet often preventable risk to patient safety. Poor hand hygiene among healthcare personnel and unsanitary hospital environments may contribute to this risk in low-income settings. We aimed to describe hand hygiene behaviour and environmental contamination by season in a rural, sub-Saharan African hospital setting. Methods We conducted a concurrent triangulation mixed-methods study combining three types of data at a hospital in Madarounfa, Niger. Hand hygiene observations among healthcare personnel during two seasons contributed quantitative data describing hand hygiene frequency and its variability in relation to seasonal changes in caseload. Semistructured interviews with healthcare personnel contributed qualitative data on knowledge, attitudes and barriers to hand hygiene. Biweekly environmental samples evaluated microbial contamination from October 2016 to December 2017. Triangulation identified convergences, complements and contradictions across results. Results Hand hygiene compliance, or the proportion of actions (handrubbing or handwashing) performed out of all actions required, was low (11% during non-peak and 36% during peak caseload seasons). Interviews with healthcare personnel suggesting good general knowledge of hand hygiene contradicted the low hand hygiene compliance. However, compliance by healthcare activity was convergent with poor knowledge of precise hand hygiene steps and the motivation to prevent personal acquisition of infection identified during interviews. Contamination of environmental samples with gram-negative bacilli was high (45%), with the highest rates of contamination observed during the peak caseload season. Conclusion Low hand hygiene compliance coupled with high contamination rates of hospital environments may increase the risk of hospital-acquired infections in sub-Saharan African settings. </jats:sec

Bipartite network models to design combination therapies in acute myeloid leukaemia

Combination therapy is preferred over single-targeted monotherapies for cancer treatment due to its efficiency and safety. However, identifying effective drug combinations costs time and resources. We propose a method for identifying potential drug combinations by bipartite network modelling of patient-related drug response data, specifically the Beat AML dataset. The median of cell viability is used as a drug potency measurement to reconstruct a weighted bipartite network, model drug-biological sample interactions, and find the clusters of nodes inside two projected networks. Then, the clustering results are leveraged to discover effective multi-targeted drug combinations, which are also supported by more evidence using GDSC and ALMANAC databases. The potency and synergy levels of selective drug combinations are corroborated against monotherapy in three cell lines for acute myeloid leukaemia in vitro. In this study, we introduce a nominal data mining approach to improving acute myeloid leukaemia treatment through combinatorial therapy.Peer reviewe

Digital cognitive behavioural therapy intervention in the workplace:study protocol for a feasibility randomised waitlist-controlled trial to improve employee mental well-being, engagement and productivity

INTRODUCTION: One in six workers experience some form of mental health problems at work costing the UK economy an estimated £70 billion/year. Digital interventions provide low cost and easily scalable delivery methods to implement psychological interventions in the workplace. This trial tests the feasibility of implementing a self-guided 8-week digital cognitive behavioural therapy intervention for subthreshold to clinical depression and/or anxiety versus waitlist control (ie, life as usual) in the workplace. METHODS AND ANALYSIS: Feasibility of implementation will be tested using a mixed-methods evaluation of the two-arm randomised waitlist-control trial. Evaluation will include examination of organisational buy-in, and the engagement of employees through the trial indicated by the completion of outcome measures. In addition, we also explore how participants use the platform, the appropriateness of the analysis both with reference to the outcome measures and linear modelling. Finally, we examine the acceptability of the intervention based on participants experiences using qualitative interviews. Assessments take place at baseline (T0), at 8 weeks post-treatment (T1), at short-term follow-up 4 weeks post-treatment (T2) and long-term follow-ups (6 and 12 months after-end of treatment). We will recruit from 1 July 2021 to 31 December 2021 for employees and self-employed workers with depression and anxiety symptoms (subclinical and clinical levels) who are not seeking or engaged in treatment at the time of the trial. ETHICS AND DISSEMINATION: Full approval was given by the University of Warwick Biomedical and Research Ethics Committee (BSREC 45/20–21). The current protocol version is 2.8 (August 2021). Publication of results in peer-reviewed journals will inform the scientific, clinical and business communities. We will disseminate results through webinars, conferences, newsletter as well as a lay summary of results on the study website (mhpp.me). TRIAL REGISTRATION NUMBER: ISRCTN31161020

An XMCD study of magnetism and valence state in iron-substituted strontium titanate

Room temperature ferromagnetism was characterized for thin films of SrTi$_{0.6}$Fe$_{0.4}$O$_{3-{\delta}}$ grown by pulsed laser deposition on SrTiO$_{3}$ and Si substrates under different oxygen pressures and after annealing under oxygen and vacuum conditions. X-ray magnetic circular dichroism demonstrated that the magnetization originated from Fe$^{2+}$ cations, whereas Fe$^{3+}$ and Ti$^{4+}$ did not contribute. Films with the highest magnetic moment (0.8 {\mu}B per Fe) had the highest measured Fe$^{2+}$:Fe${^3+}$ ratio of 0.1 corresponding to the largest concentration of oxygen vacancies ({\delta} = 0.19). Post-growth annealing treatments under oxidizing and reducing conditions demonstrated quenching and partial recovery of magnetism respectively, and a change in Fe valence states. The study elucidates the microscopic origin of magnetism in highly Fe-substituted SrTi$_{1-x}$Fe$_x$O$_{3-{\delta}}$ perovskite oxides and demonstrates that the magnetic moment, which correlates with the relative content of Fe$^{2+}$ and Fe$^{3+}$, can be controlled via the oxygen content, either during growth or by post-growth annealing