Short linear peptides can overcome certain limitations of small molecules for targeting protein–protein interactions (PPIs). Herein, the interaction between the human chemokine CCL19 with chemokine ...receptor CCR7 was investigated to obtain receptor‐derived CCL19‐binding peptides. After identifying a linear binding site of CCR7, five hexapeptides binding to CCL19 in the low micromolar to nanomolar range were designed, guided by pharmacophore and lipophilicity screening of computationally generated peptide libraries. The results corroborate the applicability of the computational approach and the chosen selection criteria to obtain short linear peptides mimicking a protein–protein interaction site.
Fragmentation of the chemokine‐receptor CCL19/CCR7 binding domain led to a hexapeptide as a template for de novo peptide design. Computer‐generated peptides were characterized in terms of their binding to CCl19. Potent ligands were identified as starting points for developing innovative protein–protein interaction modulators.
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Biorelevant media are commonly used to simulate the physiological composition of human intestinal fluids (HIF) in in vitro solubility and dissolution investigations. In comparison ...with the surfactant solutions or blank buffers, these media are able to better reflect the physiological solubility and dissolution behavior of poorly soluble active pharmaceutical ingredients (APIs). The aim of this investigation was to review the composition of FaSSIF and FaSSIF-V2 according to recently summarized data about the physiological composition of fasted state human intestinal fluid and propose an updated version, FaSSIF-V3. Furthermore the surface tension was considered as a possible surrogate parameter to gauge the physiological correctness of new versions of biorelevant media.
Various prototypes of FaSSIF-V3 were prepared with each of the following five bile salts: taurocholate (TC), glycocholate (GC), tauroursodeoxycholate (TUDC), taurochenodeoxycholate (TCDC) and glycochenodeoxycholate (GCDC) as well as replacing lecithin with its hydrolysis products, lysolecithin and sodium oleate. Two additional media consisting of a mixture of glycocholate (GC) and taurocholate (TG), with or without 0.2mM cholesterol, were also investigated.
Solubilities of ten model compounds in various prototypes of FaSSIF-V3 were measured using HPLC-UV and compared to the solubilities in the existing biorelevant media (FaSSIF and FaSSIF-V2), fasted HIF, blank buffer and a 0.5% sodium dodecyl sulfate (SDS) solution. Additionally, the influence on the surface tension properties of various combinations of bile salts, phospholipids and their hydrolysis products and cholesterol in these media was investigated and an attempt was made to calculate the CMC of the various generations of FaSSIF.
The results demonstrated that the amount and the type of phospholipids as well as the type of bile salt had a significant influence on the solubility and surface tension in the various FaSSIF-V3 prototypes and existing biorelevant media. In contrast to results with biorelevant media, it was demonstrated that blank buffers generally underestimate and SDS solutions highly overestimate the physiological relevant solubilities of all investigated APIs.
The prototype containing FaSSIF-V3-GC/TC_Chol was able to better reflect the solubilities of the most investigated APIs in fasted HIF than the existing media, and it also matched the physiological surface tension reported for the fasted human gut, and was designated FaSSIF-V3.
Syngas fermentation processes with acetogenic bacteria like
have been proven to be a promising approach for the conversion of CO-rich waste gases into short- and medium-chain alcohols. The challenge ...of synthesis gas impurities, on the other hand, has always been a major concern for establishing an industrial-scale process, since some of the trace components in waste gases, such as NH
, H
S, and NO
, can have inhibiting or even toxic effects on microbial growth and product formation. Thus, this study aims to identify the effects of the main trace impurities in syngas from gasification of biogenic residues by the supply of defined concentrations of trace impurities to the cultivation medium. Autotrophic gas fermentation studies were performed with
in batch-operated fully-controlled stirred-tank bioreactors with continuous gas supply (80% CO and 20% CO
). The syngas components NH
and H
S had a positive effect on both growth and alcohol formation (ethanol, 1-butanol, and 1-hexanol). The maximum biomass concentration was increased by more than 50%, and the maximum ethanol concentration was more than doubled with 5.0 g L
NH
Cl or 1.0 g L
H
S provided by the addition of 2.2 g L
thioacetamide. The addition of the nitrogen oxide species nitrate and nitrite, on the other hand, reduced biomass growth as well as alcohol concentrations. Already, the supply of 0.1 g L
NaNO
resulted in reduced growth and 25% reduction of the maximum ethanol concentration. The production of the longer chain alcohols 1-butanol and 1-hexanol was reduced as well. All NaNO
concentrations tested showed a strong toxic effect on the metabolism of
, and neither CO consumption nor product formation was observed after addition. As a consequence, NO
components in syngas from the gasification of biogenic residues should be reduced by the gasification process and/or selectively removed from the syngas after gasification.
Interprofessional Education (IPE) aims to improve students' attitudes towards collaboration, teamwork, and leads to improved patient care upon graduation. However, the best time to introduce IPE into ...the undergraduate curriculum is still under debate.
We used a mixed-methods design based on a sequential explanatory model. Medical students from all six years at the University of Bern, Switzerland (n = 683) completed an online survey about attitudes towards interprofessional learning using a scale validated for German speakers (G-IPAS). Thirty-one medical students participated in nine semi-structured interviews focusing on their experience in interprofessional learning and on the possible impact it might have on their professional development.
Women showed better attitudes in the G-IPAS across all years (p = 0,007). Pre-clinical students showed more positive attitudes towards IPE Year 1 to Year 3 (p = 0.011). Students correctly defined IPE and its core dimensions. They appealed for more organized IPE interventions throughout the curriculum. Students also acknowledged the relevance of IPE for their future professional performance.
These findings support an early introduction of IPE into the medical curriculum. Although students realise that interprofessional learning is fundamental to high-quality patient care, there are still obstacles and stereotypes to overcome.
ISRCTN 41715934.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The COVID-19 pandemic hit healthcare professionals (HCPs) hard, potentially leading to mental health deterioration. This longitudinal study investigated the 1-year evolution of psychological health ...of acute care HCPs during the COVID-19 pandemic and explored possible differences between high and low resilient HCPs. From April 2020 to April 2021, a convenience sample of 520 multinational HCPs completed an online survey every 3 months, up to five times. We used mixed linear models to examine the association between resilience and the variation of COVID-19-related anxiety, depressiveness, perceived vulnerability, and psychological trauma symptomatology. We demonstrated "u-shaped" trajectories for all mental health symptoms. We also explored differences in the abovementioned variables between front-line and second-line acute care HCPs. In contrast to HCP.s with lower levels of resilience (-1SD), those with higher levels of resilience (+1SD) showed increased COVID-19 anxiety and perceived vulnerability over time. Front-line and second-line HCPs differed in their depressiveness and psychological trauma variation during the 1-year analysis. High and average resilient second-line HCPs showed steeper depressiveness increases with time than high and average resilient front-line HCPs. Acute care HCPs reported their most elevated clinical symptoms of depressiveness (5-7%) and psychological trauma symptomatology (26-46%) in April 2020. During the first year of the COVID-19 pandemic, second-line HCPs with more resilience showed a steeper worsening of their depressiveness than more resilient front-line HCPs. HCPs with low resilience may benefit from interventions at the beginning of a pandemic, whereas HCPs with high resilience might benefit from resilience-enhancing interventions at later phases.
The study protocol was pre-registered with the International Standard Randomised Controlled Trial Number (ISRCTN13694948) published (Fuchs et al., 2020).
There is agreement among educators and professional bodies that interprofessional education needs to be implemented at the pre-registration level. We performed a systematic review assessing ...interprofessional learning interventions, measuring attitudes towards interprofessional education and involving pre-registration medical students across all years of medical education.
A systematic literature review was performed using PubMed, PsycINFO, EThOS, EMBASE, PEDro and SCOPUS. Search terms were composed of interprofession*, interprofessional education, inter professional, inter professionally, IPE, and medical student. Inclusion criteria were 1) the use of a validated scale for assessment of attitudes towards IPE, and results for more than 35 medical students; 2) peer-reviewed articles in English and German, including medical students; and 3) results for IPE interventions published after the 2011 Interprofessional Education Collaborative (IPEC) report. We identified and screened 3995 articles. After elimination of duplicates or non-relevant topics, 278 articles remained as potentially relevant for full text assessment. We used a data extraction form including study designs, training methods, participant data, assessment measures, results, and medical year of participants for each study. A planned comprehensive meta-analysis was not possible.
This systematic review included 23 articles with a pre-test-post-test design. Interventions varied in their type and topic. Duration of interventions varied from 25 min to 6 months, and interprofessional groups ranged from 2 to 25 students. Nine studies (39%) reported data from first-year medical students, five (22%) from second-year students, six (26%) from third-year students, two (9%) from fourth-year students and one (4%) from sixth-year students. There were no studies including fifth-year students. The most frequently used assessment method was the Readiness for Interprofessional Learning Scale (RIPLS) (n = 6, 26%). About half of study outcomes showed a significant increase in positive attitudes towards interprofessional education after interventions across all medical years.
This systematic review showed some evidence of a post-intervention change of attitudes towards IPE across different medical years studied. IPE was successfully introduced both in pre-clinical and clinical years of the medical curriculum. With respect to changes in attitudes to IPE, we could not demonstrate a difference between interventions delivered in early and later years of the curriculum.
PROSPERO registration number: CRD42020160964 .
This contribution presents a framework for Numerical Material Testing (NMT) of textile reinforced concrete based on the mesomechanical analysis of a Representative Volume Element (RVE). Hence, the ...focus of this work is on the construction of a proper RVE representing the dominant mechanical characteristics of Textile Reinforced Concrete (TRC). For this purpose, the RVE geometry is derived from the periodic mesostructure. Furthermore, sufficient constitutive models for the individual composite constituents as well as their interfacial interactions are considered, accounting for the particular mechanical properties. The textile yarns are modeled as elastic transversal isotropic unidirectional layers. For the concrete matrix, an advanced gradient enhanced microplane model is utilized considering the complex plasticity and damage behavior at multiaxial loading conditions. The mechanical interactions of the constituents are modeled by an interface formulation considering debonding and friction as well as contact. These individual constitutive models are calibrated by corresponding experimental results. Finally, the damage mechanisms as well as the load bearing behavior of the constructed TRC-RVE are analyzed within an NMT procedure based on a first-order homogenization approach. Moreover, the effective constitutive characteristics of the composite at macroscale are derived. The numerical results are discussed and compared to experimental results.
IntroductionThe unprecedented COVID-19 pandemic has exposed healthcare professionals (HCPs) to exceptional situations that can lead to increased anxiety (ie, infection anxiety and perceived ...vulnerability), traumatic stress and depression. We will investigate the development of these psychological disturbances in HCPs at the treatment front line and second line during the COVID-19 pandemic over a 12-month period in different countries. Additionally, we will explore whether personal resilience factors and a work-related sense of coherence influence the development of mental health problems in HCPs.Methods and analysisWe plan to carry out a sequential qualitative–quantitative mixed-methods design study. The quantitative phase consists of a longitudinal online survey based on six validated questionnaires, to be completed at three points in time. A qualitative analysis will follow at the end of the pandemic to comprise at least nine semistructured interviews. The a priori sample size for the survey will be a minimum of 160 participants, which we will extend to 400, to compensate for dropout. Recruitment into the study will be through personal invitations and the ‘snowballing’ sampling technique. Hierarchical linear regression combined with qualitative data analysis, will facilitate greater understanding of any associations between resilience and mental health issues in HCPs during pandemics.Ethics and disseminationThe study participants will provide electronic informed consent. All recorded data will be stored on a secured research server at the study site, which will only be accessible to the investigators. The Bern Cantonal Ethics Committee has waiv ed the need for ethical approval (Req-2020–00355, 1 April 2020). There are no ethical, legal or security issues regarding the data collection, processing, storage and dissemination in this project.Trial registration numberISRCTN13694948.
Introduction
Continuous professional development is essential for maintaining competencies in healthcare. This applies to medical device knowledge and safe handling, which are fundamental for patient ...safety. Little is known about the efficiency of self-directed learning with an integrated video in medical device education. This study investigates whether anaesthesia providers acquire their medical device competencies on an anaesthesia workstation differently via self-directed learning than traditional teacher-led workshops.
Methods and analysis
This single-centre, non-inferiority, randomised, controlled trial aims to enrol at least 224 anaesthesia providers (ie, certified nurses and physicians). Participants will be randomised to (1) self-directed learning with an integrated learning video (intervention) or (2) a traditional teacher-led workshop (control), for a 1-hour session on a new anaesthesia workstation. The two educational approaches and their effect on medical device competence will be assessed concerning 12 competencies in the same 10 min, objective, structured, clinical examination-like station for both groups. The primary endpoint will be an assessment score of ≥60%. Non-inferiority will be declared if the upper limit of a 90% two-sided CI excludes a difference of more than 10% in favour of the control group. Secondary endpoints will be: (1) the score achieved in the study assessment, (2) the number of open questions after the training, (3) training time in minutes, (4) use of resources and (5) costs, all of which are compared between both groups.
Ethics and dissemination
Study participants will provide written informed consent. All recorded data will be stored on a password-protected research server at the study site accessible only to the investigators. The Bern Cantonal Ethics Committee waived the need for ethical approval (Req-2021–00837; 25 July 2021). There are no ethical, legal or security issues regarding data collection, processing, storage or dissemination.
Trial registration number
NCT05530382
, 7 September 2022; ClinicalTrials.gov
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