Ineffective control of Epstein-Barr-virus-induced autoimmunity increases the risk for multiple sclerosis.

Multiple sclerosis (MS) is a demyelinating disease of the CNS. Epstein-Barr virus (EBV) contributes to the MS pathogenesis because high levels of EBV EBNA386-405-specific antibodies cross react with the CNS-derived GlialCAM370-389. However, it is unclear why only some individuals with such high autoreactive antibody titers develop MS. Here, we show that autoreactive cells are eliminated by distinct immune responses, which are determined by genetic variations of the host, as well as of the infecting EBV and human cytomegalovirus (HCMV). We demonstrate that potent cytotoxic NKG2C+ and NKG2D+ natural killer (NK) cells and distinct EBV-specific T cell responses kill autoreactive GlialCAM370-389-specific cells. Furthermore, immune evasion of these autoreactive cells was induced by EBV-variant-specific upregulation of the immunomodulatory HLA-E. These defined virus and host genetic pre-dispositions are associated with an up to 260-fold increased risk of MS. Our findings thus allow the early identification of patients at risk for MS and suggest additional therapeutic options against MS.

Natural killer cell functional genetics and donor-specific antibody-triggered microvascular inflammation.

Antibody-mediated rejection (ABMR) is a leading cause of graft failure. Emerging evidence suggests a significant contribution of natural killer (NK) cells to microvascular inflammation (MVI). We investigated the influence of genetically determined NK cell functionality on ABMR development and activity. The study included 86 kidney transplant recipients subjected to systematic biopsies triggered by donor-specific antibody detection. We performed killer immunoglobulin-like receptor typing to predict missing self and genotyped polymorphisms determining NK cell functionality (FCGR3AV/F158 [rs396991], KLRC2wt/del, KLRK1HNK/LNK [rs1049174], rs9916629-C/T). Fifty patients had ABMR with considerable MVI and elevated NK cell transcripts. Missing self was not related to MVI. Only KLRC2wt/wt showed an association (MVI score: 2 [median; interquartile range: 0-3] vs 0 [0-1] in KLRC2wt/del recipients; P = .001) and remained significant in a proportional odds multivariable model (odds ratio, 7.84; 95% confidence interval, 2.37-30.47; P = .001). A sum score incorporating all polymorphisms and missing self did not outperform a score including only KLRC2 and FCGR3A variants, which were predictive in univariable analysis. NK cell genetics did not affect graft functional decline and survival. In conclusion, a functional KLRC2 polymorphism emerged as an independent determinant of ABMR activity, without a considerable contribution of missing self and other NK cell gene polymorphisms.

Comparison of clinical outcomes in hospitalized patients with COVID-19 or non-COVID-19 community-acquired pneumonia in a prospective observational cohort study.

PURPOSE: Coronavirus disease 2019 (COVID-19) and non-COVID-19 community-acquired pneumonia (NC-CAP) often result in hospitalization with considerable risks of mortality, ICU treatment, and long-term morbidity. A comparative analysis of clinical outcomes in COVID-19 CAP (C-CAP) and NC-CAP may improve clinical management. METHODS: Using prospectively collected CAPNETZ study data (January 2017 to June 2021, 35 study centers), we conducted a comprehensive analysis of clinical outcomes including in-hospital death, ICU treatment, length of hospital stay (LOHS), 180-day survival, and post-discharge re-hospitalization rate. Logistic regression models were used to examine group differences between C-CAP and NC-CAP patients and associations with patient demography, recruitment period, comorbidity, and treatment. RESULTS: Among 1368 patients (C-CAP: n = 344; NC-CAP: n = 1024), C-CAP showed elevated adjusted probabilities for in-hospital death (aOR 4.48 [95% CI 2.38-8.53]) and ICU treatment (aOR 8.08 [95% CI 5.31-12.52]) compared to NC-CAP. C-CAP patients were at increased risk of LOHS over seven days (aOR 1.88 [95% CI 1.47-2.42]). Although ICU patients had similar in-hospital mortality risk, C-CAP was associated with length of ICU stay over seven days (aOR 3.59 [95% CI 1.65-8.38]). Recruitment period influenced outcomes in C-CAP but not in NC-CAP. During follow-up, C-CAP was linked to a reduced risk of re-hospitalization and mortality post-discharge (aOR 0.43 [95% CI 0.27-0.70]). CONCLUSION: Distinct clinical trajectories of C-CAP and NC-CAP underscore the need for adapted management to avoid acute and long-term morbidity and mortality amid the evolving landscape of CAP pathogens.

Analysis of acute COVID-19 including chronic morbidity: protocol for the deep phenotyping National Pandemic Cohort Network in Germany (NAPKON-HAP).

BACKGROUND: The severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) pandemic causes a high burden of acute and long-term morbidity and mortality worldwide despite global efforts in containment, prophylaxis, and therapy. With unprecedented speed, the global scientific community has generated pivotal insights into the pathogen and the host response evoked by the infection. However, deeper characterization of the pathophysiology and pathology remains a high priority to reduce morbidity and mortality of coronavirus disease 2019 (COVID-19). METHODS: NAPKON-HAP is a multi-centered prospective observational study with a long-term follow-up phase of up to 36 months post-SARS-CoV-2 infection. It constitutes a central platform for harmonized data and biospecimen for interdisciplinary characterization of acute SARS-CoV-2 infection and long-term outcomes of diverging disease severities of hospitalized patients. RESULTS: Primary outcome measures include clinical scores and quality of life assessment captured during hospitalization and at outpatient follow-up visits to assess acute and chronic morbidity. Secondary measures include results of biomolecular and immunological investigations and assessment of organ-specific involvement during and post-COVID-19 infection. NAPKON-HAP constitutes a national platform to provide accessibility and usability of the comprehensive data and biospecimen collection to global research. CONCLUSION: NAPKON-HAP establishes a platform with standardized high-resolution data and biospecimen collection of hospitalized COVID-19 patients of different disease severities in Germany. With this study, we will add significant scientific insights and provide high-quality data to aid researchers to investigate COVID-19 pathophysiology, pathology, and chronic morbidity.

Children extract a new linguistic rule more quickly than adults.

Children achieve better long-term language outcomes than adults. However, it remains unclear whether children actually learn language more quickly than adults during real-time exposure to input-indicative of true superior language learning abilities-or whether this advantage stems from other factors. To examine this issue, we compared the rate at which children (8-10 years) and adults extracted a novel, hidden linguistic rule, in which novel articles probabilistically predicted the animacy of associated nouns (e.g., "gi lion"). Participants categorized these two-word phrases according to a second, explicitly instructed rule over two sessions, separated by an overnight delay. Both children and adults successfully learned the hidden animacy rule through mere exposure to the phrases, showing slower response times and decreased accuracy to occasional phrases that violated the rule. Critically, sensitivity to the hidden rule emerged much more quickly in children than adults; children showed a processing cost for violation trials from very early on in learning, whereas adults did not show reliable sensitivity to the rule until the second session. Children also showed superior generalization of the hidden animacy rule when asked to classify nonword trials (e.g., "gi badupi") according to the hidden animacy rule. Children and adults showed similar retention of the hidden rule over the delay period. These results provide insight into the nature of the critical period for language, suggesting that children have a true advantage over adults in the rate of implicit language learning. Relative to adults, children more rapidly extract hidden linguistic structures during real-time language exposure. RESEARCH HIGHLIGHTS: Children and adults both succeeded in implicitly learning a novel, uninstructed linguistic rule, based solely on exposure to input. Children learned the novel linguistic rules much more quickly than adults. Children showed better generalization performance than adults when asked to apply the novel rule to nonsense words without semantic content. Results provide insight into the nature of critical period effects in language, indicating that children have an advantage over adults in real-time language learning.

The influence of movement-related costs when searching to act and acting to search.

Real-world search behavior often involves limb movements, either during search or after search. Here we investigated whether movement-related costs influence search behavior in two kinds of search tasks. In our visual search tasks, participants made saccades to find a target object among distractors and then moved a cursor, controlled by the handle of a robotic manipulandum, to the target. In our manual search tasks, participants moved the cursor to perform the search, placing it onto objects to reveal their identity as either a target or a distractor. In all tasks, there were multiple targets. Across experiments, we manipulated either the effort or time costs associated with movement such that these costs varied across the search space. We varied effort by applying different resistive forces to the handle, and we varied time costs by altering the speed of the cursor. Our analysis of cursor and eye movements during manual and visual search, respectively, showed that effort influenced manual search but did not influence visual search. In contrast, time costs influenced both visual and manual search. Our results demonstrate that, in addition to perceptual and cognitive factors, movement-related costs can also influence search behavior.NEW & NOTEWORTHY Numerous studies have investigated the perceptual and cognitive factors that influence decision making about where to look, or move, in search tasks. However, little is known about how search is influenced by movement-related costs associated with acting on an object once it has been visually located or acting during manual search. In this article, we show that movement time costs can bias visual and manual search and that movement effort costs bias manual search.

Rapid, Label-Free Screening of Diverse Biotransformations by Flow-Injection Mass Spectrometry.

Mass spectrometry-based high-throughput screening methods combine the advantages of photometric or fluorometric assays and analytical chromatography, as they are reasonably fast (throughput ≥1 sample/min) and broadly applicable, with no need for labelled substrates or products. However, the established MS-based screening approaches require specialised and expensive hardware, which limits their broad use throughout the research community. We show that a more common instrumental platform, a single-quadrupole HPLC-MS, can be used to rapidly analyse diverse biotransformations by flow-injection mass spectrometry (FIA-MS), that is, by automated infusion of samples to the ESI-MS detector without prior chromatographic separation. Common organic buffers can be employed as internal standard for quantification, and the method provides readily validated activity and selectivity information with an analytical run time of one minute per sample. We report four application examples that cover a broad range of analyte structures and concentrations (0.1-50 mM before dilution) and diverse biocatalyst preparations (crude cell lysates and whole microbial cells). Our results establish FIA-MS as a versatile and reliable alternative to more traditional methods for screening enzymatic reactions.

Steric hindrance, ligand ejection and associated photocytotoxic properties of ruthenium(II) polypyridyl complexes.

Two ruthenium(II) polypyridyl complexes were prepared with the {Ru(phen)2}2+ moiety and a third sterically non-hindering bidentate ligand, namely 2,2'-dipyridylamine (dpa) and N-benzyl-2,2'-dipyridylamine (Bndpa). Hence, complexes [Ru(phen)2(dpa)](PF6)2 (1) and [Ru(phen)2(Bndpa)](PF6)2 (2) were characterized and their photochemical behaviour in solution (acetonitrile and water) was subsequently investigated. Compounds 1 and 2, which do not exhibit notably distorted octahedral coordination environments, contrarily to the homoleptic "parent" compound [Ru(phen)3](PF6)2, experience two-step photoejection of the dpa and Bndpa ligand upon irradiation (1050-430 nm) for several hours. DNA-binding studies revealed that compounds 1 and 2 affect the biomolecule differently upon irradiation; while 2 solely modifies its electrophoretic mobility, complex 1 is also capable of cleaving it. In vitro cytotoxicity studies with two cancer-cell lines, namely A549 (lung adenocarcinoma) and A375 (melanoma), showed that both 1 and 2 are not toxic in the dark, while only 1 is significantly cytotoxic if irradiated, 2 remaining non-toxic under these conditions. Light irradiation of the complex cation [Ru(phen)2(dpa)]2+ leads to the generation of transient Ru species that is present in the solution medium for several hours, and that is significantly cytotoxic, ultimately producing non-toxic free dpa and [Ru(phen)(OH2)2]2+.

The unique contributions of day and night sleep to infant motor problem solving.

The current study sought to tease apart the unique contributions of napping and nighttime sleep to infant learning, specifically in the context of motor problem solving. We challenged 54 walking infants to solve a novel locomotor problem at three time points-training, test, and follow-up the next morning. One group of infants napped during the delay between training and test. Another group did not sleep during the delay. A third group received the test immediately after training with no delay. Only the Nap group's strategy choices continued to improve through the follow-up session, suggesting that daytime sleep has an active role in strengthening otherwise fragile memory. Although group did not affect strategy maintenance, walk experience did, suggesting that task difficulty may shape the impact of sleep on learning. Thus, day sleep and night sleep make independent contributions to the consolidation of motor problem-solving strategies during infancy.

Ethical and coordinative challenges in setting up a national cohort study during the COVID-19 pandemic in Germany.

With the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), global researchers were confronted with major challenges. The German National Pandemic Cohort Network (NAPKON) was launched in fall 2020 to effectively leverage resources and bundle research activities in the fight against the coronavirus disease 2019 (COVID-19) pandemic. We analyzed the setup phase of NAPKON as an example for multicenter studies in Germany, highlighting challenges and optimization potential in connecting 59 university and nonuniversity study sites. We examined the ethics application process of 121 ethics submissions considering durations, annotations, and outcomes. Study site activation and recruitment processes were investigated and related to the incidence of SARS-CoV-2 infections. For all initial ethics applications, the median time to a positive ethics vote was less than two weeks and 30 of these study sites (65%) joined NAPKON within less than three weeks each. Electronic instead of postal ethics submission (9.5 days (Q1: 5.75, Q3: 17) vs. 14 days (Q1: 11, Q3: 26), p value = 0.01) and adoption of the primary ethics vote significantly accelerated the ethics application process. Each study center enrolled a median of 37 patients during the 14-month observation period, with large differences depending on the health sector. We found a positive correlation between recruitment performance and COVID-19 incidence as well as hospitalization incidence. Our analysis highlighted the challenges and opportunities of the federated system in Germany. Digital ethics application tools, adoption of a primary ethics vote and standardized formal requirements lead to harmonized and thus faster study initiation processes during a pandemic.

Agreement of Computerized QT and QTc Interval Measurements Between Both Bedside and Expert Nurses Using Electronic Calipers.

BACKGROUND: In hospitalized patients, QT/QTc (heart rate corrected) prolongation on the electrocardiogram (ECG) increases the risk of torsade de pointes. Manual measurements are time-consuming and often inaccurate. Some bedside monitors automatically and continuously measure QT/QTc; however, the agreement between computerized versus nurse-measured values has not been evaluated. OBJECTIVE: The aim of this study was to examine the agreement between computerized QT/QTc and bedside and expert nurses who used electronic calipers. METHODS: This was a prospective observational study in 3 intensive care units. Up to 2 QT/QTc measurements (milliseconds) per patient were collected. Bland-Altman test was used to analyze measurement agreement. RESULTS: A total of 54 QT/QTc measurements from 34 patients admitted to the ICU were included. The mean difference (bias) for QT comparisons was as follows: computerized versus expert nurses, -11.04 ± 4.45 milliseconds (95% confidence interval [CI], -2.3 to -19.8; P = .016), and computerized versus bedside nurses, -13.72 ± 6.70 (95% CI, -0.70 to -26.8; P = .044). The mean bias for QTc comparisons was as follows: computerized versus expert nurses, -12.46 ± 5.80 (95% CI, -1.1 to -23.8; P = .035), and computerized versus bedside nurses, -18.49 ± 7.90 (95% CI, -3.0 to -33.9; P = .022). CONCLUSION: Computerized QT/QTc measurements calculated by bedside monitor software and measurements performed by nurses were in close agreement; statistically significant differences were found, but differences were less than 20 milliseconds (on-half of a small box), indicating no clinical significance. Computerized measurements may be a suitable alternative to nurse-measured QT/QTc. This could reduce inaccuracies and nurse burden while increasing adherence to practice recommendations. Further research comparing computerized QT/QTc from bedside monitoring to standard 12-lead electrocardiogram in a larger sample, including non-ICU patients, is needed.

Infant motor development predicts the dynamics of movement during sleep.

The characteristics of infant sleep change over the first year. Generally, infants wake and move less at night as they grow older. However, acquisition of new motor skills leads to temporary increases in night waking and movement at night. Indeed, sleep-dependent movement at night is important for sensorimotor development. Nevertheless, little is known about how movement during sleep changes as infants accrue locomotor experience. The current study investigated whether infant sleep and movement during sleep were predicted by infants' walking experience. Seventy-eight infants wore an actigraph to measure physical activity during sleep. Parents reported when their infants first walked across a room >10 feet without stopping or falling. Infants in the midst of walking skill acquisition had worse sleep than an age-group estimate. Infants with more walk experience had more temporally sporadic movement during sleep and a steeper hourly increase in physical activity over the course of the night. Ongoing motor skill consolidation changes the characteristics of movement during sleep and may alter sleep state-dependent memory consolidation. We propose a model whereby changes in gross motor activity during night sleep reflect movement-dependent consolidation.

Encountering uncertainty and complexity in decision-making: an observational study of clinical reasoning among medical and interprofessional groups of health care students.

Poor teamwork and clinical decisions have a major impact on patient outcomes and safety. Clinical decision-making rarely occurs under ideal conditions, but complex health care environments make this particularly challenging for new graduate health professionals as beginner practitioners. Recent evidence indicates that effective collaboration also enhances quality of clinical decisions for patients with complex needs. However, collaborative decision-making is not standard in educational curricula, where clinical decision-making is usually taught in profession-specific courses emphasizing individual rationality and cognition. The aim of this study was to gain detailed insights into the practice of clinical decision-making by small groups of medical and other health care students. A qualitative observational study design was used. Students (n = 45) took part in a short role-play of a hospital clinical ethics committee meeting discussing three complex patient cases, considering clinical and ethical aspects of care, and made a group decision about priorities for treatment. Audio-recorded data were transcribed verbatim and inductively analyzed based on Strauss's "Theoretical Coding" approach. Coding and interpretation of transcripts resulted in three key themes: a) values/beliefs as a basis for negotiation; b) encountering obstacles; c) overcoming obstacles. All groups benefited from shared knowledge, assisting each other in dealing with uncertainty and perceived emotional burden. In small groups, they were able to overcome challenges and fulfil a goal potentially beyond many of them as individuals. Provision of learning opportunities where students learn to share expertise and decision-making responsibilities has the potential to optimize their learning in preparation for challenges in future practice.

Translation and psychometric properties of the German version of the "Interprofessional Socialization and Valuing Scale" (ISVS-21-D).

Understanding of the processes associated with socialization into collaborative work plays an important role in interprofessional education and collaborative practice. In order to evaluate changes in socialization toward interprofessional collaborative practice a measure is needed that captures professional beliefs, attitudes and behaviors of individuals in learning activities and in workplace practice. This article presents the translation and psychometric properties of the German Version of the Interprofessional Socialization and Valuing Scale (ISVS-21). Following translation from English to German, data of the German version of the questionnaire (ISVS-21-D) was collected in six different interprofessional education and practice settings amongst undergraduate students and health professionals. In total, 494 responses were analyzed. Results showed high reliability with Cronbach's alpha .90. Although not all fit indices are in the desired range, results give preliminary indication of the underlying single factor of the ISVS-21-D and suggest that the German version of the ISVS-21-D is a reliable instrument that can be used to measure interprofessional socialization in German health professionals and health care students as well as within other disciplines.

Prevalence of peripheral intravenous catheters and policy adherence: A point prevalence in a tertiary care university hospital.

AIMS AND OBJECTIVES: To determine prevalence and policy adherence for peripheral intravenous catheters (PIVC) in adult inpatients at a tertiary care university hospital (with about 83,000 inpatient admissions annually). BACKGROUND: Up to 80% of hospitalised patients receive intravenous therapy, most commonly via PIVCs. However, these devices are not risk-free. Studies indicate that PIVC management standards in clinical practice are inadequate despite established policies promoting best practice. This leads to premature failure resulting in treatment delays, extended length of stay and potential compromised venous access for subsequent IV therapy. DESIGN: Observational point prevalence study. METHODS: Study undertaken on all adult acute care medical, surgical and oncology wards. Data were collected by senior registered nurses working in pairs on a single day. Descriptive statistics used to analyse data. SQUIRE 2.0 checklist for quality improvement reporting used. RESULTS: There were 449 adult inpatients in 19 wards on survey day. One hundred and ninety-seven had one or more PIVCs in situ. The total number of PIVCs in-situ was 212. PIVC Prevalence was 47%. PIVCs were inserted in points of flexion such as antecubital fossa, back of hand or wrist in 52% of patients. Only 19% of cases had documented assessment of 8-hourly visual infusion phlebitis (VIP) score. Patients had local signs of phlebitis in 14.4% of cases. Patients were not aware of the reason/need for their PIVC in 44% of cases. CONCLUSIONS: Discrepancies between evidence-based guidelines and local policy in clinical practice were identified including high rates of PIVC insertion in points of flexion and poor documentation. These quality problems increase likelihood of adverse patient outcomes especially when associated with limited patient awareness of the reason for their PIVC. RELEVANCE TO CLINICAL PRACTICE: Poor adherence to best practice standards is 'accepted but unacceptable'. PIVC failure is costly to both patients and health systems. A strong focus on improvement in PIVC care and management is needed.

Keeping nurses in nursing: a qualitative study of German nurses' perceptions of push and pull factors to leave or stay in the profession.

BACKGROUND: The increasing nursing shortages worldwide has focused attention on the need to find more effective ways to recruit and retain nurses. The aim of this study was to gain understanding of factors that keep German nurses in nursing and explore their perceptions of factors that contribute to nurses leaving or staying in the profession. METHODS: An explorative qualitative study was undertaken at four different hospitals (two university hospitals and two public hospitals) in Baden-Wuerttemberg, a state in South Germany. Semi-structured face-to-face or telephone interviews were conducted with 21 state-qualified nurses who had graduated from a German nursing program. Each interview was pseudonymized and transcribed. Transcripts were coded according to Qualitative Content Analysis with data structured into themes and subthemes. The study was reported according to the Consolidated Criteria for Reporting Qualitative Studies (COREQ) checklist for qualitative research. RESULTS: Two themes emerged from the analysis and each theme had several subthemes: a) PUSH FACTORS i.e. factors that may push nurses to consider leaving the profession included limited career prospects, generational barriers, poor public image of nursing, and workplace pressures; b) PULL FACTORS i.e. factors that nurses wished for and could keep them in the profession included professional pride, improved remuneration, recognition of nursing, professionalisation, and improving the image of nursing as a profession. CONCLUSION: The decision to leave or stay in nursing is influenced by a complex range of dynamic push and pull factors. Nurse Managers responsible for stabilizing the workforce and maintaining their health system will continue to have to navigate challenges until working conditions, appropriate wages and career development opportunities are addressed. A key to tackling nursing shortages may be focusing on pull factors and nurse managers listening in particular to the perspectives of junior nurses directly involved in patient care, as giving them opportunity to further develop professionally, reinforcing a strong and supportive workplace relationships, paying an appropriate salary, and improving the public image of nursing profession. REGISTRATION NUMBER: The study has been prospectively registered (27 June 2019) at the German Clinical Trial Register ( DRKS00017465 ).

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 during Border Quarantine and Air Travel, New Zealand (Aotearoa).

The strategy in New Zealand (Aotearoa) to eliminate coronavirus disease requires that international arrivals undergo managed isolation and quarantine and mandatory testing for severe acute respiratory syndrome coronavirus 2. Combining genomic and epidemiologic data, we investigated the origin of an acute case of coronavirus disease identified in the community after the patient had spent 14 days in managed isolation and quarantine and had 2 negative test results. By combining genomic sequence analysis and epidemiologic investigations, we identified a multibranched chain of transmission of this virus, including on international and domestic flights, as well as a probable case of aerosol transmission without direct person-to-person contact. These findings show the power of integrating genomic and epidemiologic data to inform outbreak investigations.

Making the process of strategy choice visible: Inhibition and motor demands impact preschoolers' real-time problem solving.

To examine the real-time process of strategy choice and execution and the role of inhibition in problem solving, 4- to 6-year-old children were asked to navigate a ball around a maze board under high- and low-precision motor demands. Employing a motor problem-solving task made normally hidden cognitive processes observable. Sequential analysis revealed two subtypes of inhibition (response and attentional) that are involved in problem solving and different developmental trajectories for each. Cognition-action trade-offs due to motor and inhibition demands adversely impacted children's strategy choices, but contributed to heightened variability of strategies. Children used fewer strategies with age, reflecting more efficient problem solving due to increasing inhibitory control. When solutions required precision, preschoolers were more likely to have difficulty inhibiting irrelevant and distracting strategies and maintaining appropriate strategies. By preschool age, executive functioning serves to make strategic motor control possible. A video abstract of this article can be viewed at https://www.youtube.com/watch?v=TCLxK7dvheE.

Internationally trained nurses and host nurses' perceptions of safety culture, work-life-balance, burnout, and job demand during workplace integration: a cross-sectional study.

BACKGROUND: The shortage of qualified nurses is a problem of growing concern in many countries. Recruitment of internationally trained nurses has been used to address this shortage, but successful integration in the workplace is complex and resource intensive. For effective recruitment and retention, it is important to identify why nurses migrate and if their expectations are met to ensure their successful integration and promote a satisfying work climate for the entire nursing team. The aim of this study was to examine the perceptions of safety culture, work-life-balance, burnout and job demand of internationally trained nurses and associated host nurses in German hospitals. METHODS: A multicentric, cross-sectional study was conducted with internationally trained nurses (n = 64) and host nurses (n = 103) employed at two university hospitals in the state of Baden-Wuerttemberg, Germany. An anonymous paper-based survey was conducted between August 2019 and April 2020. The questionnaire included sociodemographic questions, questions regarding factors related to migration, and the German version of the Assessment of your work setting Safety, Communication, Operational Reliability, and Engagement (SCORE) questionnaire. SCORE is divided into three sections: Safety Culture Domains (six subscales), Work-Life-Balance (one subscale), and Engagement Assessment Tool (four subscales). RESULTS: Nurses who migrated to Germany were primarily seeking better working conditions, a higher standard of living, and professional development opportunities. Internationally trained nurses reported lower work-related burnout climate (Mean 55.4 (SD 22.5)) than host nurses (Mean 66.4 (SD 23.5)) but still at a moderately high degree (Safety Culture Domains). Host nurses indicated a higher workload (Mean 4.06 (SD 0.65)) (Engagement Assessment Tool) and a lower Work-Life-Balance (Mean 2.31 (SD 0.66)) (Work-Life-Balance) compared to nurses who trained abroad (Mean 3.67 (SD 0.81) and Mean 2.02 (SD 0.86), respectively). No differences were detected for the other subscales. The Safety Culture Domains and Engagement Assessment Tool showed room for improvement in both groups. CONCLUSION: The study suggest that the expectations migrant nurses had prior to migration may not be met and that in turn could have a negative impact on the integration process and their retention. With increasing recruitment of internationally trained nurses from within Europe but also overseas, it is crucial to identify factors that retain migrant nurses and assist integration. TRIAL REGISTRATION: The study has been prospectively registered (27 June 2019) at the German Clinical Trial Register ( DRKS00017465 ).

Computational backbone design enables soluble engineering of transferrin receptor apical domain.

Supply of iron into human cells is achieved by iron carrier protein transferrin and its receptor that upon complex formation get internalized by endocytosis. Similarly, the iron needs to be delivered into the brain, and necessitates the transport across the blood-brain barrier. While there are still unanswered questions about these mechanisms, extensive efforts have been made to use the system for delivery of therapeutics into biological compartments. The dimeric form of the receptor, where each subunit consists of three domains, further complicates the detailed investigation of molecular determinants responsible for guiding the receptor interactions with other proteins. Especially the apical domain's biological function has been elusive. To further the study of transferrin receptor, we have computationally decoupled the apical domain for soluble expression, and validated the design strategy by structure determination. Besides presenting a methodology for solubilizing domains, the results will allow for study of apical domain's function.