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The impact of the microenvironment on innate lymphoid cell (ILC)-mediated immunity in humans remains largely unknown. Here we used full-length Smart-seq2 single-cell RNA-sequencing to unravel tissue-specific transcriptional profiles and heterogeneity of CD127 + ILCs across four human tissues. Correlation analysis identified gene modules characterizing the migratory properties of tonsil and blood ILCs, and signatures of tissue-residency, activation and modified metabolism in colon and lung ILCs. Trajectory analysis revealed potential differentiation pathways from circulating and tissue-resident naïve ILCs to a spectrum of mature ILC subsets. In the lung we identified both CRTH2 + and CRTH2 − ILC2 with lung-specific signatures, which could be recapitulated by alarmin-exposure of circulating ILC2. Finally, we describe unique TCR-V(D)J-rearrangement patterns of blood ILC1-like cells, revealing a subset of potentially immature ILCs with TCR-δ rearrangement. Our study provides a useful resource for in-depth understanding of ILC-mediated immunity in humans, with implications for disease.

Background Automated measurement of blood pressure (BP) in designated BP kiosks have in recent years been introduced in primary care. If kiosk blood pressure (BP) monitoring provides results equivalent to in-office BP or daytime ambulatory BP monitoring (ABPM), follow-up of adult patients could be managed primarily by self-checks. We therefore designed a comparative trial and evaluated the diagnostic performance of kiosk- and office-based BP (nurse- versus physician-measured) compared with daytime ABPM. Methods A trial of automated BP monitoring in three settings: a designated BP kiosk, by nurses and physicians in clinic, and by ABPM. The primary outcome was systolic and diastolic BP, with respective diagnostic thresholds of ≥135 mmHg and/or ≥ 85 mmHg for daytime ABPM and kiosk BP and ≥ 140 mmHg and/or ≥ 90 mmHg for office BP (nurse- and physician-measured). Results Compared with daytime ABPM, mean systolic kiosk BP was higher by 6.2 mmHg (95% confidence interval [CI] 3.8–8.6) and diastolic by 7.9 mmHg (95% CI 6.2–9.6; p  < 0.001). Mean systolic BP taken by nurses was similar to daytime ABPM values (+ 2.0 mmHg; 95% CI − 0.2–4.2; p  = 0.071), but nurse-measured diastolic values were higher, by 7.2 mmHg (95% CI 5.9–9.6; p  < 0.001). Mean systolic and diastolic physician-measured BPs were higher compared with daytime ABPM (systolic, by 7.6 mmHg [95% CI 4.5–10.2] and diastolic by 5.8 mmHg [95% CI 4.1–7.6]; p  < 0.001). Receiver operating characteristic curves of BP monitoring across pairs of systolic/diastolic cut-off levels among the three settings, with daytime ABPM as reference, demonstrated overall similar diagnostic performance between kiosk and nurse-measured values and over the curve performance for physician-measured BP. Accuracy with nurse-measured BP was 69.2% (95% CI 60.0–77.4%), compared with 65.8% (95% CI 56.5–74.3%) for kiosk BP. Conclusions In this study kiosk BP monitoring was not comparable to daytime ABPM but could be an alternative to in-office BP monitoring by trained nurses. The diagnostic performance of kiosk and nurse-measured BP monitoring was similar and better than that of physician-measured BP. Trial registration ClinicalTrials.gov (NCT04488289) 27/07/2020.

Background Patients’ ideas, concerns, and expectations are three important concepts in consultation techniques. Limited studies on these concepts include responses from both health care providers and care recipients of the same consultation. Highlighting both perspectives provides an increased understanding of the consultation. This study aims to explore the perspectives of patients and health care professionals about patients’ expectations of primary health care during consultations with primary care physicians and compare the two sets of perspectives. Methods A cross-sectional study. Patients ( n  = 113) and physicians ( n  = 67) from five primary health care centers completed a questionnaire after planned consultations. Their responses to open-ended questions about patients’ expectations, from patients’ and physicians’ perspectives were analyzed with qualitative content analyses. Results The patients expected a personal journey, through the primary health care system where they were the subject of interest. A journey, with ready access to a health care provider followed by a consultation with the physician, medical measures administered, their outcomes discussed, and a plan developed for continued health care. The physicians observed patients’ expectations to concern the responsibilities placed on primary health care where patients were the object of interest. Patients’ short-term expectations were described in a similar way by both patients and physicians. Patients expressed their long-term expectations as more personal and interpersonal whereas physicians observed them from a more professional and organizational standpoint. Conclusions Patients and physicians have different views of what patients expect of primary health care. While patients’ short-term expectations were perceived by physicians, their long-term expectations were not. Patients expected more of a personal journey through the primary health care system while physicians observed patients’ expectations to concern the responsibilities placed on primary health care. Identifying and meeting patients’ expectations is an important part of patient-centered care, and a better understanding of patients’ expectations is needed to improve health professionals’ consultation skills.

Background: Mastocytosis is a disease characterized by accumulation of aberrant mast cells and mediator- related symptoms and is divided into systemic mastocytosis (SM) and cutaneous mastocytosis (CM). The epidemiology of mastocytosis remains incompletely understood. Objective: To estimate the incidence, prevalence, overall survival (OS) and burden of comorbidities in adult mastocytosis patients identified in Swedish population-based registries. Methods: Individuals (≥ 20 years of age) with a mastocytosis diagnosis in the National Patient Register (NPR) and/or the Swedish Cancer Register (SCR) between 2001 and 2018, were identified. In a matched cohort design, for each case five randomly selected mastocytosis-free comparators matched on age, sex, and county of residence were chosen from the Population Register. The Kaplan-Meier method was used to compare OS between individuals with mastocytosis and comparators. Information on concomitant disease at baseline was assessed by use of the Charlson Comorbidity Index (CCI). Results: We identified 2,040 adults with a mastocytosis diagnosis yielding an annual incidence of 1.56 per 100,000 (95% CI 1.29-1.87) and a prevalence of 23.9 per 100,000 (95% CI 22.8-25.0). The comorbidity burden was higher, and the OS lower, in patients with mastocytosis compared to comparators. Interpretation: We found a higher incidence and prevalence of mastocytosis compared to assessments in other settings and confirmed that the prognosis generally is favorable. Of special note was evidence of a higher comorbidity burden in mastocytosis patients compared to the background population. Limitations: Underreporting and inconsistencies in the use of diagnostic codes.

Mast cell-derived mediators mediate several of the pathological features of asthma. Microbial infections induce asthma exacerbations in which the contribution of mast cells remains incomprehensible. In this study we have investigated the characteristic expression pattern of Toll-like receptors (TLRs) 1-9 and the effect of TLR ligand treatment on IgE-receptor mediated mast cell reactivity. For the studies we employed in vitro differentiated connective tissue like mast cells (CTLMC) and mucosal like mast cells (MLMC) from mice. Both phenotypes were treated for 24 h or 96 h with ligands for TLR1/2, TLR2/6, TLR3 and TLR4, before activation with IgE and antigen. Prolonged exposure (96 h) with TLR-ligands promoted mast cell reactivity following IgE-receptor activation. TLR4 activation with LPS generated the most pronounced effect, with an enhanced degranulation and secretion of leukotrienes, cytokines and chemokines, in both CTLMC and MLMC. The effect of LPS was mediated through a Myd88-dependent pathway and the increased effect involved JNK-dependent pathway. We find that prolonged exposure of mast cells to pathogens/TLR-ligands modulates their effector responses by priming them for increased release of several inflammatory mediators when subsequently activated by IgE-receptors. These data suggest that infections might exaggerate the severity of allergic reactions such as in asthma, by enhancing mediator release from mast cells.

Background Multimorbidity, the co-existence of two or more chronic conditions in an individual, is present in most patients over 65 years. Primary health care (PHC) is uniquely positioned to provide the holistic and continual care recommended for this group of patients, including support for self-management. The aim of this study was to explore professionals’, patients’, and family caregivers’ perspectives on how PHC professionals should support self-management in patients with multimorbidity. This study also includes experiences of using telemedicine to support self-management. Methods A mixed qualitative method was used to explore regular self-management support and telemedicine as a tool to support self-management. A total of 42 participants (20 physicians, 3 registered nurses, 12 patients, and 7 family caregivers) were interviewed using focus group interviews (PHC professionals), pair interviews (patients and family caregivers), and individual interviews (registered nurses, patients, and family caregivers). The study was performed in urban areas in central Sweden and rural areas in southern Sweden between April 2018 and October 2019. Data were analyzed using content analysis. Results The main theme that emerged was “Standing on common ground enables individualized support.” To achieve such support, professionals needed to understand their own views on who bears the primary responsibility for patients’ self-management, as well as patients’ self-management abilities, needs, and perspectives. Personal continuity and trustful relationships facilitated this understanding. The findings also indicated that professionals should be accessible for patients with multimorbidity, function as knowledge translators (help patients understand their symptoms and how the symptoms correlated with diseases), and coordinate between levels of care. Telemedicine supported continual monitoring and facilitated patient access to PHC professionals. Conclusion Through personal continuity and patient-centered consultations, professionals could collaborate with patients to individualize self-management support. For some patients, this means that PHC professionals are in control and monitor symptoms. For others, PHC professionals play a less controlling role, empowering patients’ self-management. Development and improvement of eHealth tools for patients with multimorbidity should focus on improving the ability to set mutual goals, strengthening patients’ inner motivation, and including multiple caregivers to enhance information-sharing and care coordination.

Background Worldwide, physicians are migrating to new countries and want to practise their profession. However, they may experience difficulties doing so. To optimise and accelerate their entrance into and advancement within the Swedish healthcare system, there is an urgent need to explore how they are currently doing so, as their competences should be put to use without any unnecessary delay. The aim of the study was to explore how migrant physicians with a medical degree from outside EU/EEA enter and advance within the medical labour market in Sweden and to identify perceived barriers and facilitating aspects in the process. The empirical findings are discussed in light of Bourdieu’s concept symbolic capital as adapted in the Swedish medical field. Methods A cross-sectional study with a self-administrated questionnaire was disseminated. A sample of 498 migrant physicians were identified. Descriptive statistical analysis and qualitative thematic analysis were used to analyse the data. Results The response rate was 57% ( n  = 283). Respondents mainly found their first positions via spontaneous job applications, during internships, while participating in an educational intervention or via personal contacts. Perceived barriers to entering and advancing within the medical field in Sweden were mainly related to having a medical degree from and/or originating from another country, which could in turn represent discrimination and/or having one’s competence undervalued as a result. Facilitating aspects included having or developing contacts in Swedish healthcare and gaining proficiency or fluency in the Swedish language. Conclusions When MPs find their first positions, the contacts they have developed appear to play a role , and when advancing in their positions, the active development of a variety of contacts seems to be beneficial. MPs experience a variety of barriers to entering and advancing within the field that could be related to discrimination. Many MPs perceived having their competences undervalued due to their origin or to being educated abroad. Based on the respondents’ experiences, our interpretation is that MPs as a group are hierarchically positioned lower in the Swedish medical field than physicians trained in the country. Facilitating aspects included educational interventions, having contacts and developing language skills. For optimal entry into the labour market, it is vitally important for MPs to learn the new language and obtain a job or internship in the field as soon as possible.

Traumatic brain injury (TBI) is a devastating condition, often leading to life-long consequences for patients. Even though modern neurointensive care has improved functional and cognitive outcomes, efficient pharmacological therapies are still lacking. Targeting peripherally derived, or resident inflammatory, cells that are rapid responders to brain injury is promising, but complex, given that the contribution of inflammation to exacerbation versus improved recovery varies with time post-injury. The injury-induced inflammatory response is triggered by release of alarmins, and in the present study we asked whether interleukin-33 (IL-33), an injury-associated nuclear alarmin, is involved in TBI. Here, we used samples from human TBI microdialysate, tissue sections from human TBI, and mouse models of central nervous system injury and found that expression of IL-33 in the brain was elevated from nondetectable levels, reaching a maximum after 72 h in both human samples and mouse models. Astrocytes and oligodendrocytes were the main producers of IL-33. Post-TBI, brains of mice deficient in the IL-33 receptor, ST2, contained fewer microglia/macrophages in the injured region than wild-type mice and had an altered cytokine/chemokine profile in response to injury. These observations indicate that IL-33 plays a role in neuroinflammation with microglia/macrophages being cellular targets for this interleukin post-TBI.

The origin and functions of mast cells (MCs) have been debated since their description by Paul Ehrlich in 1879. MCs have long been considered 'reactive bystanders' and 'amplifiers' in inflammatory processes, allergic reactions, and host responses to infectious diseases. However, knowledge about the origin, phenotypes and functions of MCs has increased substantially over the past 50 years. MCs are now known to be derived from multipotent hematopoietic progenitors, which, through a process of differentiation and maturation, form a unique hematopoietic lineage residing in multiple organs. In particular, MCs are distinguishable from basophils and other hematopoietic cells by their unique phenotype, origin(s), and spectrum of functions, both in innate and adaptive immune responses and in other settings. The concept of a unique MC lineage is further supported by the development of a distinct group of neoplasms, collectively referred to as mastocytosis, in which MC precursors expand as clonal cells. The clinical consequences of the expansion and/or activation of MCs are best established in mastocytosis and in allergic inflammation. However, MCs have also been implicated as important participants in a number of additional pathologic conditions and physiological processes. In this article, we review concepts regarding MC development, factors controlling MC expansion and activation, and some of the fundamental roles MCs may play in both health and disease. We also discuss new concepts for suppressing MC expansion and/or activation using molecularly-targeted drugs.

Background Questionnaires and surveys are used throughout medical education. Nevertheless, measuring psychological attributes such as perceptions of a phenomenon among individuals may be difficult. The aim of this paper is to introduce the basic principles of Mokken scale analysis (MSA) as a method for the analysis of questionnaire data and to empirically apply MSA to a real-data example. Methods MSA provides a set of statistical tools for exploring the relationship between items and latent traits. MSA is a scaling method of item selection algorithms used to partition an array of items into scales. It employs various methods to probe the assumptions of two nonparametric item response theory models: the monotone homogeneity model and the double monotonicity model. The background and theoretical framework underlying MSA are outlined in the paper. MSA for polytomous items was applied to a real-life data example of 222 undergraduate students who had completed a 50-item self-administered inventory measuring the educational environment, the Dundee Ready Educational Measure (DREEM). Results A pragmatic and parsimonious approach to exploring questionnaires and surveys from an item response theory (IRT) perspective is outlined. The use of MSA to explore the psychometric properties of the Swedish version of the DREEM failed to yield strong support for the scalability and dimensional structure of the instrument. Conclusions MSA, a class of simple nonparametric IRT models – for which estimates can be easily obtained and whose fit to data is relatively easily investigated – was introduced, presented, and tested. Our real-data example suggests that the psychometric properties of DREEM are not adequately supported. Thus, the empirical application depicted a potential and feasible approach whereby MSA could be used as a valuable method for exploring the behavior of scaled items in response to varying levels of a latent trait in medical education research.