Predicting intensive care need in women with preeclampsia using machine learning - a pilot study.

BACKGROUND: Predicting severe preeclampsia with need for intensive care is challenging. To better predict high-risk pregnancies to prevent adverse outcomes such as eclampsia is still an unmet need worldwide. In this study we aimed to develop a prediction model for severe outcomes using routine biomarkers and clinical characteristics. METHODS: We used machine learning models based on data from an intensive care cohort with severe preeclampsia (n=41) and a cohort of preeclampsia controls (n=40) with the objective to find patterns for severe disease not detectable with traditional logistic regression models. RESULTS: The best model was generated by including the laboratory parameters aspartate aminotransferase (ASAT), uric acid and body mass index (BMI) with a cross-validation accuracy of 0.88 and an area under the curve (AUC) of 0.91. Our model was internally validated on a test-set where the accuracy was lower, 0.82, with an AUC of 0.85. CONCLUSION: The clinical routine blood parameters ASAT and uric acid as well as BMI, were the parameters most indicative of severe disease. Aspartate aminotransferase reflects liver involvement, uric acid might be involved in several steps of the pathophysiologic process of preeclampsia, and obesity is a well-known risk factor for development of both severe and non-severe preeclampsia likely involving inflammatory pathways..[Figure: see text].

Changes in self-perceived performance and satisfaction with performance of daily activities following interdisciplinary rehabilitation in people with late effects of polio.

BACKGROUND: People with late effects of polio (LEoP) may need rehabilitation to manage everyday life but knowledge of the benefits of interdisciplinary rehabilitation is limited. OBJECTIVE: To evaluate changes in performance and satisfaction with performance of activities among people with LEoP following interdisciplinary rehabilitation. METHODS: A pre-post retrospective study based on data on 102 participants with LEoP from a rehabilitation clinic. Changes in performance and satisfaction with performance of daily activities before and after interdisciplinary rehabilitation were assessed with the Canadian Occupational Performance Measure (COPM). RESULTS: There were statistically significant increases in the mean performance and mean satisfaction with performance COPM scores from admission to discharge. Twenty-three percent and 19% of the participants, respectively, had improved their performance and satisfaction with performance, 25% and 26% of the participants had no changes, and 19% and 22% of the participants, respectively, rated their performance and satisfaction lower at discharge compared to admission. CONCLUSION: Interdisciplinary rehabilitation can enhance self-rated performance and satisfaction with performance of daily activities among people with LEoP. Future studies of rehabilitation for people with LEoP should use a prospective design and capture the participants' process of change related to their rehabilitation period.

Electronic medication administration record (eMAR) in Swedish home healthcare-Implications for Nurses' and nurse Assistants' Work environment: A qualitative study.

BACKGROUND: The electronic medication administration record (eMAR) is an eHealth system that has replaced the traditional paper-based medication administration used in many healthcare settings. Research has highlighted that eHealth technologies can change working methods and professional roles in both expected and unexpected ways. To date, there is sparse research that has explored how nurses and nurse assistants (NA) in home healthcare experience eMAR in relation to their work environment. AIM: The aim was to explore how nurses and nurse assistants experienced their work environment, in terms of job-demand, control, and support in a Swedish home healthcare setting where an electronic medication administration record had been implemented to facilitate delegation of medical administration. METHOD: We took a qualitative approach, where focus groups were used as data collection method. The focus groups included 16 nurses and nine NAs employed in a Swedish municipality where an eMAR had been implemented 6 months before the first focus groups were performed. The analysis adapted the job-demand-control-support model, by condensing the professionals' experiences into the three categories of demand, control, and support, in alignment with the model. RESULTS: NAs experienced high levels of job demand and low levels of job control. The use of the eMAR limited NAs' ability to control their work, in terms of priorities, content, and timing. In contrast, the nurses described demands as high but manageable, and described having a high level of control. Both professions found the eMar supportive. CONCLUSION: Nurses and NAs in home healthcare experienced changes in their work environment regarding demand, control, and support when an eMAR was implemented to facilitate delegation of medical administration. In general, nurses were satisfied with the eMAR. However, NAs felt that the eMAR did not cover all aspects of their daily work. Healthcare organisations should be aware of the changes that digitalisation processes entail in the work environment of nurses and NAs in home healthcare.

Preliminary evidence that blocking the uptake of placenta-derived preeclamptic extracellular vesicles protects the vascular endothelium and prevents vasoconstriction.

Preeclampsia (PE) is a pregnancy syndrome characterized by hypertension and organ damage manifesting after 20 gestational weeks. The etiology is of multifactorial origin, where placental stress causes increased levels of placenta-derived extracellular vesicles (STBEVs) in the maternal circulation, shown to cause inflammation, endothelial activation, vasoconstriction, and anti-angiogenic activity. General endothelial dysfunction is believed to be initiated by endothelial insult during pregnancy that alters vascular function resulting in increased arterial stiffness, cardiac dysfunction, and increased risk of cardiovascular disease later in life. We compared the effect of normal and PE derived STBEVs in vitro on vascular contractility of human subcutaneous arteries using wire myography. Cellular structures of exposed vessels were investigated by transmission electron microscopy. We explored strategies to pharmacologically block the effects of the STBEVs on human vessels. The PE STBEVs caused significantly stronger angiotensin II-mediated contractions and extended structural damage to human subcutaneous arteries compared to normal STBEVs. These negative effects could be reduced by blocking vesicle uptake by endothelial cells, using chlorpromazine or specific antibodies towards the LOX-1 receptor. The therapeutic potential of blocking vesicle uptake should be further explored, to reduce the permanent damage caused on the vasculature during PE pregnancy to prevent future cardiovascular risk.

Taking control of one's everyday life - a qualitative study of experiences described by participants in an occupational intervention.

BACKGROUND: Sick leave due to stress-related ill-health is increasing and is often caused by occupational imbalance. These types of issues tend to affect both the ability to work and cope with everyday life, as well as the overall experience of health, negatively. There is still little knowledge on how to prepare people and workplaces for the return-to-work process after participation in a work rehabilitation program due to stress and occupational ill-health. Therefore, this study aimed to describe what is needed to achieve a balanced everyday life that includes paid work as experienced by individuals who had participated in a ReDO® intervention due to occupational imbalance and ill-health. METHODS: The concluding notes from 54 informants' medical records were used for qualitative content analysis. The informants had participated in an occupational therapy group intervention to promote occupational health and regain full work capacity. RESULTS: The analysis resulted in one major theme and four categories describing how the informants perceive that they must take control of their everyday life as a whole. By doing so, they need to work with structurization and prioritization, social interaction, boundary setting, and occupational meaningfulness. CONCLUSION: The study indicates a highly relational process, where it is impossible to divide life into private and work, and presupposes balance in everyday life in multiple dimensions. Its contribution includes the formulation of perceived needs in the transition between intervention and return to work and could, through further research, be used to generate a more effective and sustainable return- and rehabilitation models.

Gut Micro- and Mycobiota in Preeclampsia: Bacterial Composition Differences Suggest Role in Pathophysiology.

Preeclampsia is a severe pregnancy-related inflammatory disease without an effective treatment. The pathophysiology remains partly unknown. However, an increased inflammatory response and oxidative stress are part of the maternal systemic reaction. Recent data have suggested that dysbiosis of the gut microbiome plays a role in preeclampsia as well as other inflammatory diseases. However, dysbiosis in preeclampsia has not been studied in a Scandinavian population. Furthermore, although the fungal flora may also have anti-inflammatory properties, it has never been studied in preeclampsia. We included 25 preeclamptic and 29 healthy third-trimester women for the ITS and 16S sequencing of fungal and bacterial microbiota, respectively. Calprotectin was measured to assess systemic and intestinal inflammatory responses. The fungal diversity differed with BMI and gestational length, suggesting a link between fungi and the immune changes seen in pregnancy. An LEfSe analysis showed 18 significantly differentially abundant bacterial taxa in PE, including enriched Bacteroidetes and depleted Verrucomicrobia and Syntergistota at the phylum level and depleted Akkermansia at the genus level, suggesting a role in the pathophysiology of PE.

Assessing erythroferrone and iron homeostasis in preeclamptic and normotensive pregnancies: A retrospective study.

INTRODUCTION: Preeclampsia (PE) is a pregnancy-related disorder associated with maternal hypertension and placental dysfunction. A significant micronutrient during pregnancy is iron, which is important in cellular functions. While iron absorption increases in pregnancy, little is known about the exact mechanisms regulating maternal iron levels and transfer through the placenta in normal and complicated pregnancies. METHODS: In this retrospective study, we investigated the regulation of maternal and placental iron availability and storage, in normotensive and pregnancies complicated by early- or late-onset PE. Methods used were analysis of clinical records, ELISA analysis on plasma samples, immunofluorescent and Prussian Blue analysis on placenta biopsies. RESULTS: Focusing on erythroferrone (ERFE) as a new marker and hormonal regulator of iron, our results demonstrated altered maternal ERFE levels in PE. We are the first to report the expression of ERFE in trophoblasts and indicate its lower levels in early-onset PE placentas. These changes were associated with lower placental transferrin receptor 1 (TfR1) in syncytiotrophoblasts in both early- and late-onset PE. In addition, maternal plasma ERFE levels were elevated in both early- and late-onset PE and hepcidin levels reduced in early-onset PE. Unaltered maternal plasma IL-6 levels suggest mechanism other than inflammation being involved in altered iron regulation in PE pregnancy. DISCUSSION: Our data supports a deregulation in maternal iron bioavailability in early- and late-onset PE vs normotensive pregnancies. The exact role of placental ERFE in regulating maternal-placental-fetal iron transport axis requires further investigation.

Intensive care patients with preeclampsia - Clinical risk factors and biomarkers for oxidative stress and angiogenic imbalance as discriminators for severe disease.

BACKGROUND: Approximately 180 mothers are treated in Swedish Intensive Care Units (ICU) due to preeclampsia each year. Although several clinical risk factors are known, prediction of critical disease is challenging. Two scavenger proteins, hemopexin (Hpx) and alpha-1-microglobulin (A1M) have been suggested to be associated with the oxidative stress seen in preeclampsia. The ratio of two other biomarkers, soluble fms-like tyrosine kinase (sFlt-1) to placental growth factor (PIGF), is predictive of adverse pregnancy outcomes. METHODS: In total 121 women were included in this study where we compared risk factors for preeclampsia, plasma levels of Hpx and A1M in ICU-patients with preeclampsia (n = 41) compared to uncomplicated preeclampsia cases (n = 40) and normotensive pregnancies (n = 40), with the objective to identify clinical risk patterns for severe disease. The sFlt-1/PIGF ratio was investigated in early and late onset preeclampsia ICU-patients. Blood samples were collected at admission to ICU and within 27 h postpartum for all groups. RESULTS: Hemopexin and A1M levels were significantly lower in the preeclampsia ICU-cohort compared to uncomplicated preeclampsia patients. The sFlt-1/PIGF-ratio was elevated in the ICU-patients but there was no difference between early and late onset preeclampsia. The ICU-patients had more clinical risk factors, refractory hypertension, and an increased rate of emergency Caesarean section. CONCLUSION: Intensive care patients have more clinical risk factors and a Hpx and A1M profile suggestive of depletion and thereby a reduced capacity to respond to oxidative stress. The ratios of sFlt-1/PIGF were high in the ICU-cohort and in accordance with pre-delivery levels predictive of adverse pregnancy outcomes.

How does ReDO®-10 work? Understanding the mechanisms of action of an intervention focused on daily activities and health from the perspective of participants.

Evaluation of a complex healthcare intervention should include careful exploration of the mechanisms through which it brings about change. This paper describes a qualitative evaluation of the Redesigning Daily Occupations (ReDO®-10) programme as it was implemented for the first time with women with stress-related issues in a primary care setting in Ireland. The ReDO®-10 is a 10-week group intervention designed to support participants make changes to their daily activity patterns to have a more satisfying and balanced daily life. Fourteen women were interviewed after completing the programme. The aim was to explore changes that participants perceived they experienced and to understand how the content of ReDO®-10 was thought to bring about this change (if it did). Directed content analysis was used to analyse the qualitative data using the Behaviour Change Wheel and Theoretical Domains Framework as a coding framework. Overall, four BCW functions of ReDO® -10 were identified: Education, Persuasion, Modelling and Enablement. Participants described improved belief in their own capabilities, knowledge and goals around life changes. Many behaviour changes were also described, particularly in relation to doing more restorative activities in daily life. Behaviour change techniques that were identified as important for change were practicing new, restorative occupations in group sessions and as homework and the use of self-analysis activities to understand the relationship between activities and health for these participants. Modelling, support and other effects of group dynamics were also vital in changes that occurred.

Maternal and fetal haemopexin and α1-microglobulin concentrations in pre-eclamptic IVF pregnancies according to presence of corpus luteum at embryo transfer.

RESEARCH QUESTION: Do pregnancies with corpus luteum show different maternal and fetal plasma concentrations of the scavenger proteins haemopexin and α1-microglobulin compared with pregnancies without corpus luteum in preeclampsia? DESIGN: Case-control study of 160 singleton pregnancies: 54 naturally conceived, 50 by IVF after fresh embryo transfer or frozen embryo transfer (FET) in natural cycle (presence of corpus luteum) and 56 after fresh oocyte donation or FET in programmed cycles (absence of corpus luteum). Pregnancies were subclassified into normotensive, preeclampsia and severe preeclampsia cases. Heme-scavenger concentrations were measured by ELISA in maternal and cord plasma collected at delivery. RESULTS: After adjustment, maternal haemopexin was higher in IVF with corpus luteum than in naturally conceived pregnancies in normotensive (P = 0.038) and preeclampsia (P = 0.011) populations, and lower in preeclampsia for IVF pregnancies lacking corpus luteum compared with IVF with corpus luteum (P = 0.002). Maternal α1-microglobulin levels were higher in the absence of corpus luteum only in severe cases of preeclampsia compared with naturally conceived pregnancies (P = 0.014) and IVF with corpus luteum pregnancies (P = 0.041). In cord blood, haemopexin was higher in IVF with corpus luteum compared with naturally conceived pregnancies in preeclampsia (P = 0.039) and α1-microglobulin was higher in the group lacking corpus luteum compared with IVF with corpus luteum in the normotensive population (P < 0.001). CONCLUSIONS: The physiological differences shown for these heme-scavengers between pregnancies after embryo transfer in the presence or absence of corpus luteum support the hypothesis that corpus luteum activity could influence perinatal outcomes. Future research is needed on whether applying potential strategies to develop a corpus luteum might reduce the perinatal complications associated with programmed cycles of IVF.

Nurses' Perspectives on an Electronic Medication Administration Record in Home Health Care: Qualitative Interview Study.

BACKGROUND: eHealth is considered by policy makers as a prerequisite for meeting the demands of health care from the growing proportion of older people worldwide. The expectation about what the efficiency of eHealth can bring is particularly high in the municipal home health care sector, which is facing pressure regarding resources because of, for example, earlier discharges from hospitals and a growing number of patients receiving medications and treatments at home. Common eHealth services in home health care are electronic medication administration records (eMARs) that aim to communicate delegated tasks between professionals. However, there is an extensive gap in the research on how technology affects and is experienced by home health care professionals. OBJECTIVE: The objective of this paper is to shed light on how home care nurses experience eMARs in a Swedish municipality. METHODS: This qualitative interview study was conducted among home health care nurses using eMARs to facilitate communication and signing of delegated nursing tasks. The analysis of the interviews was performed using constructivist grounded theory, according to Charmaz. RESULTS: Of the 19 day-employed nurses in the municipality where an eMAR was used, 16 (84%) nurses participated in the study. The following two categories were identified from the focus group interviews: nurses become monitors and slip away from the point of care. The nurses experienced that they became monitors of health care through the increased transparency provided by the eMAR and the measurands they also applied, focusing on the quantitative aspects of the delegated nursing tasks rather than the qualitative aspects. The nurses experienced that their monitoring changed the power relations between the professions, reinforcing the nurses' superior position. The experience of the eMAR was regarded as transitioning the nurses' professional role-away from the point of care and toward more administration-and further strengthened the way of managing work through delegation to health care assistants. CONCLUSIONS: Previous analyses of eHealth services in health care showed that implementation is a complex process that changes health care organizations and the work of health care professionals in both intended and unintended ways. This study adds to the literature by examining how users of a specific eHealth service experience its impacts on their daily work. The results indicate that the inscribed functions in an eHealth service may affect the values and priorities where the service is in use. This presents an opportunity for future research and for health care organizations to assess the impacts of specific eHealth services on health care professionals' work and to further examine the effects of inscribed functions in relation to how they may affect actions and priorities at individual and organizational levels.

Exploring risk factors for developing occupational ill health - departing from an occupational perspective.

BACKGROUND: Sick leave due to stress-related mental ill health increases in society. In occupational therapy, occupational balance is considered important for experiencing health and well-being. Thus, knowledge regarding occupational balance and occupational value constitute essential parts of occupational therapists' work with people suffering from occupational ill health. OBJECTIVE: The aim of this study is to analyse the relationships between sociodemographic factors, occupational value, occupational balance and perceived health in people suffering from occupational ill health. METHODS: In a quantitative cross-sectional study data from a total of 218 individuals were included, 192 women, 22 men and 4 individuals who did not specify their gender. Data were collected by means of surveys prior to an occupational therapy intervention. The instruments used included OVal-pd, OBQ, EQ5D and a sociodemographic questionnaire. Data were analysed using regression and decision tree analysis. RESULTS: The results show that individuals who experience an imbalance in their everyday life and who have few or no experiences of daily occupations imprinted by socio-symbolic occupational value experienced lower perceived health. CONCLUSIONS: Low level of experiences of balance in daily life and occupational value seems to be the main risk factors for the development of occupational ill health, rather than sociodemographic factors.

Assessing the use of a portable time-geographic diary for detecting patterns of daily occupations.

BACKGROUND: A time-geographic diary approach is of interest in occupational therapy due to the inclusion of the diarist's subjective experiences. There are several methods for detecting doing in time, but details needed for analysis are still lacking. The smartphone application POrtable Diary Data collector (PODD), a 24-hr diary based on the time-geographic diary has recently been introduced. AIM: To test the usability of PODD as a tool for diary data collection to detect and visualize sequences of daily activities. MATERIAL AND METHODS: An exploratory sequential design was used, where diary data was first collected and then followed by a questionnaire assessing usefulness. Thirty-one occupational therapy students participated. Usability testing was applied, exploring how participants experienced the use of the device. Data was analysed qualitatively and quantitatively. RESULTS: The PODD visually presents activity sequences and thus assists in detecting patterns of daily occupations (PDO). The students agreed on the supportive statements concerning learnability, efficiency and memorability. Regarding errors and satisfaction, participants agreed that the device was easy to use. CONCLUSIONS: Using a mobile application to collect data about students' daily activities was effective. However, the PODD needs to be further evaluated among other groups and contexts as well as for its usefulness for PDO analyses.

A feasibility study of the Redesigning Daily Occupations (ReDOTM-10) programme in an Irish context.

BACKGROUND: Despite high demand, mental health services in primary care in Ireland are underdeveloped. People with mild/moderate anxiety, depression and unspecified psychological distress are frequently seen in primary care settings, mostly by general practitioners (GPs). Occupational therapists have the potential to contribute to service-provision with interventions specially designed for the targeted group e.g. the Redesigning Daily Occupations programme (ReDO-10). AIMS/OBJECTIVES: This study aimed to explore the feasibility of a future RCT of the ReDO-10 programme in Ireland and the contextual factors that would influence future implementation. MATERIAL AND METHODS: Using a multi-phase, mixed-method design, qualitative and quantitative data were gathered from key stakeholders: ReDO-10 participants (n = 10), GPs (n = 9) and occupational therapists (n = 2). Acceptability, satisfaction, cultural fit and demand were explored, as well as methodological issues such as appropriateness of recruitment methods, outcome measures and randomization. RESULTS: ReDO-10 was acceptable to participants who reported improvements in their occupational patterns and valued the group-based format. GPs and occupational therapists welcomed the intervention, but acknowledged the limitations of time and resources in the Irish primary care context. CONCLUSIONS: ReDO-10 is feasible to explore in a future RCT in Ireland and this study provides important context for future implementation and/or research.

Early Pregnancy Exposure to Ambient Air Pollution among Late-Onset Preeclamptic Cases Is Associated with Placental DNA Hypomethylation of Specific Genes and Slower Placental Maturation.

Exposure to ambient air pollution during pregnancy has been associated with an increased risk of preeclampsia (PE). Some suggested mechanisms behind this association are changes in placental DNA methylation and gene expression. The objective of this study was to identify how early pregnancy exposure to ambient nitrogen oxides (NOx) among PE cases and normotensive controls influence DNA methylation (EPIC array) and gene expression (RNA-seq). The study included placentas from 111 women (29 PE cases/82 controls) in Scania, Sweden. First-trimester NOx exposure was assessed at the participants' residence using a dispersion model and categorized via median split into high or low NOx. Placental gestational epigenetic age was derived from the DNA methylation data. We identified six differentially methylated positions (DMPs, q < 0.05) comparing controls with low NOx vs. cases with high NOx and 14 DMPs comparing cases and controls with high NOx. Placentas with female fetuses showed more DMPs (N = 309) than male-derived placentas (N = 1). Placentas from PE cases with high NOx demonstrated gestational age deceleration compared to controls with low NOx (p = 0.034). No differentially expressed genes (DEGs, q < 0.05) were found. In conclusion, early pregnancy exposure to NOx affected placental DNA methylation in PE, resulting in placental immaturity and showing sexual dimorphism.

The BELE program: The development of a holistic interdisciplinary health-promoting program enhancing work-life balance among female employees working in human service organizations in Sweden.

BACKGROUND: Despite an increase in work-life balance literature, the development of successful support to help employees manage their work -life balance is slow. Moreover, there are few interventions with a comprehensive approach to workplace health promotion focusing on work-life balance. OBJECTIVE: This paper aims to present the development and building blocks of a holistic interdisciplinary health-promoting program, the BELE program, to enhance female employees working in human service organizations health and well-being with a focus on work-life balance. METHODS: The planning and development of the program was done through an intervention mapping and research circles methodology. RESULTS: The planning- and development process of the program resulted in a theoretical framework, and a program structure with a program content. The intervention program was named "The Balance in Everyday Life Empowerment program" (BELE program). CONCLUSIONS: The BELE program adds to the existing body of work-life balance knowledge, so far often based on a conflict approach. Interventions focusing on a comprehensive approach to health and work-life balance with a salutogenic approach are rare. Furthermore, the integration with occupational therapy and health promotion in a workplace health promotion framework is innovative. In a previous study, the BELE program has shown that it enhances women's well-being and balance in their everyday life.

The roles of free iron, heme, haemoglobin, and the scavenger proteins haemopexin and alpha-1-microglobulin in preeclampsia and fetal growth restriction.

BACKGROUND: Preeclampsia (PE) is a complex pregnancy syndrome characterised by maternal hypertension and organ damage after 20 weeks of gestation and is associated with an increased risk of cardiovascular disease later in life. Extracellular haemoglobin (Hb) and its metabolites heme and iron are highly toxic molecules and several defence mechanisms have evolved to protect the tissue. OBJECTIVES: We will discuss the roles of free iron, heme, Hb, and the scavenger proteins haemopexin and alpha-1-microglobulin in pregnancies complicated by PE and fetal growth restriction (FGR). CONCLUSION: In PE, oxidative stress causes syncytiotrophoblast (STB) stress and increased shedding of placental STB-derived extracellular vesicles (STBEV). The level in maternal circulation correlates with the severity of hypertension and supports the involvement of STBEVs in causing maternal symptoms in PE. In PE and FGR, iron homeostasis is changed, and iron levels significantly correlate with the severity of the disease. The normal increase in plasma volume taking place during pregnancy is less for PE and FGR and therefore have a different impact on, for example, iron concentration, compared to normal pregnancy. Excess iron promotes ferroptosis is suggested to play a role in trophoblast stress and lipotoxicity. Non-erythroid α-globin regulates vasodilation through the endothelial nitric oxide synthase pathway, and hypoxia-induced α-globin expression in STBs in PE placentas is suggested to contribute to hypertension in PE. Underlying placental pathology in PE with and without FGR might be amplified by iron and heme overload causing oxidative stress and ferroptosis. As the placenta becomes stressed, the release of STBEVs increases and affects the maternal vasculature.

Hypoxia-Induced Alpha-Globin Expression in Syncytiotrophoblasts Mimics the Pattern Observed in Preeclamptic Placentas.

Preeclampsia (PE) is a pregnancy disorder associated with placental dysfunction and elevated fetal hemoglobin (HbF). Early in pregnancy the placenta harbors hematopoietic stem and progenitor cells (HSPCs) and is an extramedullary source of erythropoiesis. However, globin expression is not unique to erythroid cells and can be triggered by hypoxia. To investigate the role of the placenta in increasing globin levels previously reported in PE, flow cytometry, histological and immunostaining and in situ analyses were used on placenta samples and ex vivo explant cultures. Our results indicated that in PE pregnancies, placental HSPC homing and erythropoiesis were not affected. Non-erythroid alpha-globin mRNA and protein, but not gamma-globin, were detected in syncytiotrophoblasts and stroma of PE placenta samples. Similarly, alpha-globin protein and mRNA were upregulated in normal placenta explants cultured in hypoxia. The upregulation was independent of HIF1 and NRF2, the two main candidates of globin transcription in non-erythroid cells. Our study is the first to demonstrate alpha-globin mRNA expression in syncytiotrophoblasts in PE, induced by hypoxia. However, gamma-globin was only expressed in erythrocytes. We conclude that alpha-globin, but not HbF, is expressed in placental syncytiotrophoblasts in PE and may contribute to the pathology of the disease.

Association of Prenatal Ambient Air Pollution Exposure With Placental Mitochondrial DNA Copy Number, Telomere Length and Preeclampsia.

Background: Studies have shown that ambient air pollution is linked to preeclampsia (PE), possibly via generation of oxidative stress in the placenta. Telomere length and mitochondrial DNA copy number (mtDNAcn) are sensitive to oxidative stress damage. Objective: To study the association between prenatal exposure to ambient nitrogen oxides (NOx, a marker for traffic-related air pollution), and PE, as well as potential mediation effects by placental telomere length and mtDNAcn. Methods: This is a cross-sectional study of 42 preeclamptic and 95 arbitrarily selected normotensive pregnant women with gestational ambient NOx exposure assessment in southern Scania, Sweden. Hourly concentrations of NOx were estimated at the residential addresses by a Gaussian-plume dispersion model with 100 × 100 m spatial resolutions and aggregated into trimester-specific mean concentrations. Placental relative mtDNAcn and telomere length were measured using qPCR. Linear and logistic regression models were used to investigate associations, adjusted for perinatal and seasonal characteristics. Results: Exposure was categorized into low and high exposures by median cut-offs during first [11.9 µg/m3; interquartile range (IQR) 7.9, 17.9], second (11.6 µg/m3; IQR: 7.1, 21.1), third trimesters (11.9 µg/m3; IQR: 7.7, 19.5) and entire pregnancy (12.0 µg/m3; IQR: 7.6, 20.1). Increased risk of PE was found for high prenatal NOx exposure during the first trimester (OR 4.0; 95% CI: 1.4, 11.1; p = 0.008), and entire pregnancy (OR 3.7; 95% CI: 1.3, 10.4; p = 0.012). High exposed group during the first trimester had lower placental relative mtDNAcn compared with low exposed group (-0.20; 95% CI: -0.36, -0.04; p = 0.01). Changes in relative mtDNAcn did not mediate the association between prenatal NOx exposure and PE. No statistically significant association was found between placental relative telomere length, prenatal NOx exposure and PE. Conclusion: In this region with relatively low levels of air pollution, ambient NOx exposure during the first trimester was associated with reduced placental relative mtDNAcn and an increased risk of PE. However, we did not find any evidence that mtDNAcn or TL mediated the association between air pollution and PE. Future research should further investigate the role of mtDNAcn for pregnancy complications in relation to exposure to ambient air pollution during pregnancy.

Knockout of the radical scavenger α1-microglobulin in mice results in defective bikunin synthesis, endoplasmic reticulum stress and increased body weight.

α1-microglobulin (A1M) is a ubiquitous protein with reductase and radical- and heme-binding properties. The protein is mainly expressed in the liver and encoded by the α1-microglobulin-bikunin precursor (AMBP) gene together with the plasma proteinase inhibitor bikunin. The AMBP polypeptide is translated, glycosylated and the C-terminal bikunin part linked via a chondroitin sulfate glycosaminoglycan chain to one or two heavy chains in the endoplasmic reticulum (ER) and Golgi compartments. After proteolytic cleavage, the A1M protein and complexed bikunin parts are secreted separately. The complete physiological role of A1M, and the reason for the co-synthesis with bikunin, are both still unknown. The aim of this work was to develop an A1M knockout (A1M-KO) mouse model lacking expression of A1M, but with a preserved bikunin expression, and to study the phenotypic traits in these mice, with a focus on hepatic endoplasmic reticulum (ER) function. The bikunin expression was increased in the A1M-KO mouse livers, while the bikunin levels in plasma were decreased, indicating a defective biosynthesis of bikunin. The A1M-KO livers also showed an increased expression of transducers of the unfolded protein response (UPR), indicating an increased ER-stress in the livers. At twelve months of age, the A1M-KO mice also displayed an increased body weight, and an increased liver weight and lipid accumulation. Moreover, the KO mice showed an increased expression of endogenous antioxidants in the liver, but not in the kidneys. Together, these results suggest a physiological role of A1M as a regulator of the intracellular redox environment and more specifically the ER folding and posttranslational modification processes, particularly in the liver.