The Antagonistic Gene Paralogs Upf3a and Upf3b Govern Nonsense-Mediated RNA Decay.

Gene duplication is a major evolutionary force driving adaptation and speciation, as it allows for the acquisition of new functions and can augment or diversify existing functions. Here, we report a gene duplication event that yielded another outcome--the generation of antagonistic functions. One product of this duplication event--UPF3B--is critical for the nonsense-mediated RNA decay (NMD) pathway, while its autosomal counterpart--UPF3A--encodes an enigmatic protein previously shown to have trace NMD activity. Using loss-of-function approaches in vitro and in vivo, we discovered that UPF3A acts primarily as a potent NMD inhibitor that stabilizes hundreds of transcripts. Evidence suggests that UPF3A acquired repressor activity through simple impairment of a critical domain, a rapid mechanism that may have been widely used in evolution. Mice conditionally lacking UPF3A exhibit "hyper" NMD and display defects in embryogenesis and gametogenesis. Our results support a model in which UPF3A serves as a molecular rheostat that directs developmental events.

Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest.

BACKGROUND: Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes. METHODS: We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months. RESULTS: A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).

Progression of the pluripotent epiblast depends upon the NMD factor UPF2.

Nonsense-mediated RNA decay (NMD) is a highly conserved RNA turnover pathway that degrades RNAs harboring in-frame stop codons in specific contexts. Loss of NMD factors leads to embryonic lethality in organisms spanning the phylogenetic scale, but the mechanism remains unknown. Here, we report that the core NMD factor, UPF2, is required for expansion of epiblast cells within the inner cell mass of mice in vivo. We identify NMD target mRNAs in mouse blastocysts - both canonical and alternatively processed mRNAs - including those encoding cell cycle arrest and apoptosis factors, raising the possibility that NMD is essential for embryonic cell proliferation and survival. In support, the inner cell mass of Upf2-null blastocysts rapidly regresses with outgrowth and is incompetent for embryonic stem cell derivation in vitro. In addition, we uncovered concordant temporal- and lineage-specific regulation of NMD factors and mRNA targets, indicative of a shift in NMD magnitude during peri-implantation development. Together, our results reveal developmental and molecular functions of the NMD pathway in the early embryo.

Area-based disparities in non-small-cell lung cancer survival.

BACKGROUND: In the Nordic countries, universal healthcare access has been effective in reducing socioeconomic disparities in non-small-cell lung cancer (NSCLC) management. However, other factors, such as proximity to healthcare facilities, may still affect access to care. This study aimed at investigating the influence of residential area on NSCLC survival. METHODS: This population-based study utilized hospital records to identify NSCLC patients who underwent their initial treatment at Vaasa Central Hospital between January 1, 2016, and December 31, 2020. Patients were categorized based on their postal codes into urban areas (≤50 km from the hospital) and rural areas (>50 km from the hospital). Survival rates between these two groups were compared using Cox regression analysis. RESULTS: A total of 321 patients were included in the study. Patients residing in rural areas (n = 104) exhibited poorer 12-month survival rates compared to their urban counterparts (n = 217) (unadjusted Hazard Ratio [HR]: 1.38; 95% Confidence Interval [CI]: 1.01-1.89; p = 0.042). After adjusting for factors such as performance status, frailty, and stage at diagnosis in a multivariate Cox regression model, the adjusted HR increased to 1.47 (95% CI: 1.07-2.01; p = 0.017) for patients living in rural areas compared to those in urban areas. INTERPRETATION: The study findings indicate that the distance to the hospital is associated with increased lung cancer mortality. This suggests that geographical proximity may play a crucial role in the disparities observed in NSCLC survival rates. Addressing these disparities should involve strategies aimed at improving healthcare accessibility, particularly for patients residing in rural areas, to enhance NSCLC outcomes and reduce mortality.

Agreement between self-reported and registered age at asthma diagnosis in Finland.

INTRODUCTION: In epidemiological studies, the age at asthma onset is often defined by patients' self-reported age at diagnosis. The reliability of this report might be questioned. Our objective was to evaluate the agreement between self-reported and registered age at asthma diagnosis and assess features contributing to the agreement. METHODS: As part of the FinEsS respiratory survey in 2016, randomly selected population samples of 13,435 from Helsinki and 8000 from Western Finland were studied. Self-reported age at asthma diagnosis was compared to age at asthma diagnosis registered in the Finnish register on special reimbursement for asthma medication. The reimbursement right is based on lung function criteria according to GINA and Finnish guidelines. If the difference was less than 5 years, self-reported diagnosis was considered reliable. Features associated with the difference between self-reported and registered age at asthma diagnosis were evaluated. RESULTS: Altogether 197 subjects from Helsinki and 144 from Western Finland were included. Of these, 61.9% and 77.8%, respectively, reported age at diagnosis reliably. Median difference between self-reported and registered age at diagnoses was - 2.0 years (IQR - 9.0 to 0) in Helsinki and - 1.0 (IQR - 4.3 to 0) in Western Finland indicating earlier self-reported age at diagnosis. More reliable self-report was associated with non-allergic subjects and subjects who reported having asthma diagnosis more recently. CONCLUSIONS: Agreement between self-reported and registered age at asthma diagnosis was good especially with adult-onset asthma patients. Poor agreement in early-onset asthma could be related to delay in registration due to reimbursement criteria.

Cytotoxic Natural Products from the Jurassic Relict Osmunda regalis L.

The Jurassic relict Royal fern, Osmunda regalis L., is widely distributed across temperate zones in the Northern and Southern hemispheres. Even though this species has been utilised for centuries as a medicinal plant, its phytochemical composition mainly remains unknown. As part of our ongoing research to identify potential lead compounds for future anticancer drugs, 17 natural products were characterised from the aerial parts of Osmunda regalis L. Fifteen of these compounds were identified in this species for the first time, including the six previously undescribed compounds kaempferol 3-O-(2''-O-(2'''-α-rhamnopyranosyl)-ß-glucopyranosyl)-ß-glucopyranoside, quercetin 3-O-(2''-O-(2'''-α-rhamnopyranosyl)-ß-glucopyranosyl)-ß-glucopyranoside, kaempferol 3-O-(2''-O-(2'''-α-rhamnopyranosyl-6'''-O-(E)-caffeoyl-)-ß-glucopyranosyl)-ß-glucopyranoside, 3-methoxy-5-hydroxy-4-olide, 4-hydroxy-3-(3'-hydroxy-4'-(hydroxyethyl)-oxotetrafuranone-5-methyl tetrahydropyranone, and 4-O-(5-hydroxy-4-oxohexanoyl) osmundalactone. The molecular structures were determined by combining several 1D and 2D NMR experiments, circular dichroism spectroscopy, and HRMS. Determination of cytotoxicity against AML MOLM-13, H9c2, and NRK cell lines showed that two isolated lactones exhibited significant cytotoxic activity.

Socioeconomic inequalities in asthma and respiratory symptoms in a high-income country: changes from 1996 to 2016.

Objective: Low socioeconomic status based both on educational level and income has been associated with asthma and respiratory symptoms, but changes over time in these associations have rarely been studied. The aim was to study the associations between educational or income inequality and asthma and respiratory symptoms among women and men over a 20-year period in northern Sweden. Methods: The study was performed within the Obstructive Lung disease in Northern Sweden (OLIN) research program. Mailed questionnaire surveys were administered to a random sample of adults (20-69 years of age) living in Sweden, in 1996, 2006 and 2016. Data on educational level and income were collected from the national integrated database for labor market research. Results: The educational inequality associated with asthma and asthmatic wheeze tended to decrease from 1996 to 2016, while it increased for productive cough, the latter among men not among women. The income inequality decreased for productive cough, especially for women, while no clear overall trends were found for asthmatic wheeze and asthma, apart from a decrease in income inequality regarding asthma among men. Conclusion: The patterns for socioeconomic inequality differed for asthma and wheeze compared to productive cough, and the results emphasize that education and income do not mirror the same aspects of socioeconomic inequality in a high-income country. Our findings are important for decision makers, not the least on a political level, as reduced inequality, e.g. through education, could lead to reduced morbidity.

Socioeconomic status and lifestyle patterns in the most common cancer types-community-based research.

INTRODUCTION: As the global burden of chronic cancer increases, its correlation to lifestyle, socioeconomic status (SES) and health equity becomes more important. The aim of the present study was to provide a snapshot of the socioeconomic and lifestyle patterns for different cancer types in patients at a Nordic tertiary cancer clinic. MATERIALS AND METHODS: In a descriptive observational study, questionnaires addressed highest-attained educational level, occupational level, economy, relationship status, exposures, and lifestyle habits. The questionnaire was distributed to all cancer patients attending the cancer clinic. Treating physicians added further information about the cancer disease, including primary origin, pathology report, TNM-classification and stage. RESULTS: Patients with lung cancer had the lowest SES, and patients with gastrointestinal (GI) cancer, other cancer types and prostate cancer had the second, third and fourth lowest SES, respectively. However, breast cancer patients had the highest SES. Lifestyle and exposure patterns differed among the major cancer types. Lung cancer patients reported the highest proportion of unfavourable lifestyle and exposure patterns, and patients with GI cancer, prostate cancer and other cancer types had the second, third and fourth highest proportion of unfavourable lifestyle and exposure patterns, respectively. The most favourable exposure and lifestyle patterns were observed in breast cancer patients. CONCLUSIONS: The present study indicated significant socioeconomic and lifestyle differences among cancer types at a Nordic cancer centre, with differences in lifestyle being more prominent than socioeconomic differences.

Women's reflections on timing of motherhood: a meta-synthesis of qualitative evidence.

INTRODUCTION: Fertility declines with increasing age, especially in women. In recent decades women's age at the birth of their first child has risen markedly in many countries, and an increasing number of women do not establish a family until their late-twenties to mid-thirties. Although there can be various reasons that couples experience fertility problems, advanced maternal age is the most frequent cause for difficulties with achieving pregnancy. OBJECTIVE: In this meta-synthesis, we investigated reflections on timing of motherhood in women who have not yet had children. METHODS: A systematic literature search of six electronic databases and manual searches of reference lists identified eight qualitative studies published between 2011 and 2018 that focused on women's reflections on timing of motherhood. The studies were assessed with the Critical Assessment Skills Programme (CASP) quality appraisal tool. The results were synthesized using Noblit and Hare's meta-ethnographic approach as described by Malterud. FINDINGS: An overall theme of 'Timing of motherhood' and four overlapping subthemes were identified: Making a life-changing decision, The right time, Fear of regret, and Plan B. The dilemmas associated with timing of motherhood leave women of reproductive age balancing their priorities and values against a biological deadline for having children naturally or through assisted reproductive technology. CONCLUSIONS: Women of reproductive age are aware that they must make a life-changing decision as to if or when to have children, but they consider having children at 'the right time' to be important. Simultaneously, while some women are reluctant to have children for various reasons, they express fear that waiting too long could result in their regretting not having children later in life. Although women of reproductive age express concern about their ability to achieve pregnancy, they have limited focus on the medical risks associated with postponing motherhood. There is a need to establish preventive health initiatives to support women of reproductive age in their considerations regarding timing of motherhood. TRIAL REGISTRATION NUMBER: PROSPERO: CRD42020175151.

In many countries, women's age at the birth of their first child has risen markedly, and an increasing number of women do not establish a family until their late-twenties to mid-thirties. This causes risk of couples experiencing fertility problems, as fertility declines with increasing age. Although fertility problems can be caused by various reasons, advanced maternal age is the most frequent cause for women having difficulties achieving pregnancy. In this study, we investigated reflections on timing of motherhood in women who have not yet had children. Through a systematic literature search we identified eight qualitative studies published between 2011 and 2018 that focused on women's reflections on timing of motherhood. The included studies were synthesized using a meta-ethnographic approach. We identified an overall theme 'Timing of motherhood' and four overlapping subthemes: Making a life-changing decision, The right time, Fear of regret, and Plan B. The dilemmas associated with timing of motherhood leave women of reproductive age balancing their priorities and values against a biological deadline for having children naturally or through assisted reproductive technology. Women of reproductive age are aware that they must make a life-changing decision as to if or when to have children, but they consider having children at 'the right time' to be important. Simultaneously, while some women are reluctant to have children for various reasons, they express fear that waiting too long could result in their regretting not having children later in life. Although women of reproductive age express concern about their ability to achieve pregnancy, they have limited focus on the medical risks associated with postponing motherhood, which emphasizes the need for establishing preventive health initiatives to support women of reproductive age in their considerations regarding timing of motherhood.

Community nurse specialists' translation of newly learned knowledge in primary healthcare: A mixed methods study.

AIM: To investigate how graduates of a Nurse Specialist Education in Community and Primary Healthcare Nursing programme self-assess their competencies and possibilities to translate knowledge into practice. METHODS: A mixed methods design based on the triangulation convergence model was used. Thirty-four community nurse specialists, who had graduated from a Nurse Specialist Education in Community and Primary Healthcare Nursing programme, participated in a cross-sectional survey and of these; seven nurses participated in a semi-structured interview. Data from the survey were analysed using descriptive statistics and data from the interviews underwent a thematic analysis. All results were combined and compared according to the study design. FINDINGS: The combined comparison of the results from the survey and the findings from the interviews showed, how the community nurse specialists self-assessed their competencies in direct clinical practice, professional development, ethical decision-making, clinical leadership, cooperation and collaboration, and critical thinking as high. However, they experienced very few opportunities to translate their new knowledge in practice due to low alignment between the statutory purpose of the education and their own expectations. CONCLUSIONS: Competent clinical nurses working in community care settings who completed an education in advanced community care experienced few opportunities to use their new knowledge in practice. The community nurse specialists' expectations of how to use their new knowledge in practice after graduation does not align with the statutory order of the specialist education, which is directed towards combining direct and specialised patient care with coordination of care trajectories for the most fragile patients. It is important to include the managers in coordination of the community nurse specialists' usage of their new knowledge in practice.

Cytotoxic Natural Products Isolated from Cryptogramma crispa (L.) R. Br.

Parsley fern, Cryptogramma crispa, is a common fern in arctic-alpine regions, and even though this species has been known since ancient times and has been presumed to cause the poisoning of horses, its natural products have not previously been investigated. Here, we characterise 15 natural products isolated from the aerial parts of Cryptogramma crispa, including the previously undescribed compound 3-malonyl pteroside D. The structure determinations were based on several advanced 1D and 2D NMR spectroscopic techniques, Circular Dichroism spectroscopy and high-resolution mass spectrometry. The pteroside derivatives exhibited selective moderate cytotoxic activity against the acute myeloid leukaemia MOLM13 cell line and no cytotoxicity against the normal heart and kidney cell lines, suggesting that their potential anticancer effect should be further investigated.

Natural Products from Leaves of the Ancient Iranian Medicinal Plant Echium amoenum Fisch. & C. A. Mey.

For several millennia, leaves of Echium amoenum Fisch. & C. A. Mey., an important Iranian medicinal plant with nutritional value as nutraceutical, have been used as tea for the treatment of several conditions, including inflammation. The nutritional value of intake of E. amoenum tea has mainly been correlated to its rich content of mainly water-soluble antioxidants. Although the entire plant is utilized, only natural products of the flowers have previously been thoroughly investigated. The rare natural products bis(3-(3,4-dihydroxyphenyl)-1-methoxy-1-oxopropan-2-yl)-1-(3,4-dihydroxyphenyl)-6,7-dihydroxy-1,2-dihydronaphthalene-2,3-dicarboxylate, 4-Oxy-(E)-caffeoyl-2,3-dihydroxybutanoic acid methyl ester and 4-Oxy-(Z)-caffeoyl-2,3-dihydroxybutanoic acid methyl ester, in addition to the widely distributed compounds rosmarinic acid methyl ester and (E)-caffeic acid, were purified and characterized from leaves of Echium amoenum. The structures were determined by a combination of several 2D NMR spectroscopic techniques, circular dichroism spectroscopy and high-resolution mass spectrometry. The fact that bis(3-(3,4-dihydroxyphenyl)-1-methoxy-1-oxopropan-2-yl)-1-(3,4-dihydroxyphenyl)-6,7-dihydroxy-1,2-dihydronaphthalene-2,3-dicarboxylate belongs to a rare group of natural products which have previously been patented for their significant anti-inflammatory activity may rationalize the traditional treatment of inflammations with E. amoenum.

A microRNA cluster in the Fragile-X region expressed during spermatogenesis targets FMR1.

Testis-expressed X-linked genes typically evolve rapidly. Here, we report on a testis-expressed X-linked microRNA (miRNA) cluster that despite rapid alterations in sequence has retained its position in the Fragile-X region of the X chromosome in placental mammals. Surprisingly, the miRNAs encoded by this cluster (Fx-mir) have a predilection for targeting the immediately adjacent gene, Fmr1, an unexpected finding given that miRNAs usually act in trans, not in cis Robust repression of Fmr1 is conferred by combinations of Fx-mir miRNAs induced in Sertoli cells (SCs) during postnatal development when they terminate proliferation. Physiological significance is suggested by the finding that FMRP, the protein product of Fmr1, is downregulated when Fx-mir miRNAs are induced, and that FMRP loss causes SC hyperproliferation and spermatogenic defects. Fx-mir miRNAs not only regulate the expression of FMRP, but also regulate the expression of eIF4E and CYFIP1, which together with FMRP form a translational regulatory complex. Our results support a model in which Fx-mir family members act cooperatively to regulate the translation of batteries of mRNAs in a developmentally regulated manner in SCs.

The Nordic perspective on migration and empowerment.

International migration is a complex phenomenon that touches on a multiplicity of economic, social and security aspects affecting our daily lives. In the Nordic countries' migration is a contentious political topic as the number of migrants has significantly increased in recent decades. The aim of this study is to analyse governmental policy documents on migrants in Denmark, Finland, Norway and Sweden and to identify and compare how they are described within an empowerment perspective. A critical discourse analysis was undertaken of each Nordic country. The findings revealed that all four documents placed migrants in a passive position in regard to decision-making and that an empowerment perspective was lacking. Migrants are similarly treated in each Nordic country as a problem to deal with rather than as a possible resource for the society and the approach seeks to protect the welfare state and the culture of the country. The lack of empowerment perspective may be having a negative impact on the health and well-being of migrants and on their integration in the Nordic society. The article concludes by raising several questions in regard to migration and empowerment in the Nordic context.

Improving Oral Health and Modulating the Oral Microbiome to Reduce Bloodstream Infections from Oral Organisms in Pediatric and Young Adult Hematopoietic Stem Cell Transplantation Recipients: A Randomized Controlled Trial.

Bloodstream infections (BSIs) from oral organisms are a significant cause of morbidity and mortality in hematopoietic stem cell transplantation (HSCT) recipients. There are no proven strategies to decrease BSIs from oral organisms. The aim of this study was to evaluate the impact of daily xylitol wipes in improving oral health, decreasing BSI from oral organisms, and modulating the oral microbiome in pediatric HSCT recipients. This was a single-center 1:1 randomized controlled trial in pediatric HSCT recipients age >2 years. Age-matched healthy children were enrolled to compare the oral microbiome. The oral hygiene standard of care (SOC) group continued to receive the standard oral hygiene regimen. The xylitol group received daily oral xylitol wipes (with .7 g xylitol) in addition to the SOC. The intervention started from the beginning of the transplantation chemotherapy regimen and extended to 28 days following transplantation. The primary outcome was oral health at interval time points, and secondary outcomes included BSIs from oral organisms in the first 30 days following transplantation, oral microbiome abundance, and diversity and oral pathogenic organism abundance. The study was closed early due to efficacy after an interim analysis of the first 30 HSCT recipients was performed (SOC group, n = 16; xylitol group, n = 14). The xylitol group had a significantly lower rate of gingivitis at days 7, 14, and 28 following transplantation (P = .031, .0039, and .0005, respectively); oral plaque at days 7 and 14 (P = .045 and .0023, respectively); and oral ulcers >10 mm at day 14 (P = .049) compared with the SOC group. The xylitol group had no BSI from oral organisms compared with the SOC group, which had 4 (P = .04). The xylitol group had significantly lower abundance of potential BSI pathogens, such as Staphylococcus aureus (P = .036), Klebsiella pneumoniae (P = .033), and Streptococcus spp (P = .011) at the day after transplantation compared with the SOC group. Healthy children and young adults had significantly increased oral microbiome diversity compared with all HSCT recipients (P < .001). The addition of xylitol to standard oral care significantly improves oral health, decreases BSI from oral organisms, and decreases the abundance of pathogenic oral organisms in pediatric and young adult HSCT recipients.

Evaluation of a change in cytomegalovirus prevention strategy following pediatric solid organ transplantation.

BACKGROUND: An optimal cytomegalovirus (CMV) prevention strategy following solid organ transplantation (SOT) remains uncertain. This study reports on the rates of CMV events following a change in a local prevention guideline involving increased surveillance, earlier transition to oral valganciclovir, and decreased CMV-immunoglobulin use. METHODS: A retrospective cohort study utilizing historical controls evaluated the rates of CMV invasive disease pre- and post-intervention among pediatric heart, liver, and kidney recipients. Outcomes were recorded for the 4 years pre- and post-intervention, 9/2009-10/2017. Logistic regression was used to estimate the risk of a CMV event. RESULTS: There was no difference in the rates of CMV invasive disease between the two study groups (P = 1). An increase in the detection of CMV events occurred (P = .04), predominantly asymptomatic CMV infection. This increase was independently associated with increased surveillance testing among high-risk heart and liver recipients, aOR 1.08 (1.06-1.12). Surprisingly, 28.9% of CMV events occurred during antiviral prophylaxis. CONCLUSIONS: Modification of the local CMV prevention guideline did not result in an increase in CMV invasive disease. CMV events occurred while on prophylaxis, highlighting a potential difference from adult solid organ transplant (SOT) and emphasizing the potential need for monitoring on prophylaxis in the pediatric population.

Age-specific incidence of allergic and non-allergic asthma.

BACKGROUND: Onset of allergic asthma has a strong association with childhood but only a few studies have analyzed incidence of asthma from childhood to late adulthood in relation to allergy. The purpose of the study was to assess age-specific incidence of allergic and non-allergic asthma. METHODS: Questionnaires were sent to 8000 randomly selected recipients aged 20-69 years in Finland in 2016. The response rate was 52.3% (n = 4173). The questionnaire included questions on e.g. atopic status, asthma and age at asthma diagnosis. Asthma was classified allergic if also a physician-diagnosed allergic rhinitis was reported. RESULTS: The prevalence of physician-diagnosed asthma and allergic rhinitis were 11.2 and 17.8%, respectively. Of the 445 responders with physician-diagnosed asthma, 52% were classified as allergic and 48% as non-allergic. Median ages at diagnosis of allergic and non-allergic asthma were 19 and 35 years, respectively. Among subjects with asthma diagnosis at ages 0-9, 10-19, 20-29, 30-39, 40-49, 50-59 and 60-69 years, 70, 62, 58, 53, 38, 19 and 33%, respectively, were allergic. For non-allergic asthma, the incidence rate was lowest in children and young adults (0.7/1000/year). It increased after middle age and was highest in older age groups (2.4/1000/year in 50-59 years old). CONCLUSIONS: The incidence of allergic asthma is highest in early childhood and steadily decreases with advancing age, while the incidence of non-allergic asthma is low until it peaks in late adulthood. After approximately 40 years of age, most of the new cases of asthma are non-allergic.

Multiple bloodstream infections in pediatric stem cell transplant recipients: A case series.

Bacterial bloodstream infections (BSIs) are associated with poor outcomes following stem cell transplantation (SCT). We describe the demographics, treatment, complications, and outcome of 23 pediatric SCT recipients who developed three or more BSIs in the first year after SCT at our center from 2011 through 2016. The majority underwent allogeneic SCT (n = 22/23;96%), mainly from an unrelated donor (n = 19/22,86%); developed grade 2-4 graft versus host disease (GVHD; n = 14/23, 61%), all steroid refractory; and were diagnosed with thrombotic microangiopathy (n = 21/23, 91%). One-year overall survival was 56% (n = 13/23). We observed a high rate of transplant-associated thrombotic microangiopathy and steroid-refractory acute GVHD in patients with three or more BSIs.

Health promotion in context: A reflective-analytical model.

Health promotion constitutes a complex field of study, as it addresses multifaceted problems and involves a range of methods and theories. Students in the field of health promotion can find this challenging. To raise their level of reflexivity and support learning we have developed the "context model," which is presented in this article. The model provides a framework for the analysis of health-promotion initiatives, employing eight perspectives each intertwined with the others. It is based on the assumption that health and health inequities are contextual and that the theoretically inspired understanding of contexts is central for health promoters. Contexts for health are seen as more than the local setting; they are embedded in societal and global conditions-which, vice versa, influence the local setting. A Danish community health project is used to exemplify how the model can be used in relation to educational purposes.