Longitudinal associations of leptin and adiponectin with heart rate variability in children

For early prevention of cardiovascular disease, early detection and risk factor insights are necessary. The autonomic balance reflects cardiovascular risk and can be measured by heart rate variability (HRV). Therefore, our purpose is to examine associations between HRV and the energy-related biomarkers leptin and adiponectin in children. Participants of this study were Belgian children recruited for the longitudinal ChiBS study (year 2010-2012). HRV was measured and fasting blood samples were taken in 249 children at baseline (4.4-11.0 y) and 223 children at follow-up (6.7-12.2 y). Cross-sectional and longitudinal linear regression analyses were separated by sex and adjusted for age, socio-economic status, body fat%, negative emotions, puberty, and mean heart rate. Leptin was a negative cross-sectional and longitudinal predictor of parasympathetic activity in boys; while leptin in girls was cross-sectionally associated with higher LF and LF/HF suggesting sympathetic predominance. Adiponectin was a negative cross-sectional and longitudinal predictor of parasympathetic activity in boys; but when adjusting for mean heart rate, this effect disappeared and adiponectin was a positive cross-sectional and longitudinal predictor of parasympathetic activity in girls. These results stress the importance of considering sex differences and adjustment for heart rate in testing HRV predictors. Leptin seemed disadvantageous for the autonomic balance, while adiponectin seemed advantageous for the autonomic balance in girls only. More research is needed to see whether leptin and adiponectin are interesting in cardiovascular screening/prevention or in determining the cardiovascular gain during weight loss follow-up

Pathophysiology in postterm pregnancy : Epidemiology, risk factors and cervical ripening

Background: Postterm pregnancy, defined as a pregnancy of 42 or more completed weeks of gestation, occurs in approximately 5-10 % of all pregnancies. The condition is associated with increased maternal and fetal morbidity as well as an increased risk of perinatal mortality. The risk of postterm pregnancy is higher among women who are nulliparous and of advanced maternal age. Genetic predispositions may also contribute to an increased risk of postterm pregnancy. Certain characteristics, notably obesity, advanced maternal age and nulliparity are common in women with delayed parturition and are also common among women with polycystic ovary syndrome (PCOS). However, outcomes of pregnancy among women with PCOS have been difficult to investigate due to confounding variables. Normal and delayed parturition is a complex and poorly understood process. A key component of normal parturition is the inflammatory process in the cervix, termed “cervical ripening”, which precedes normal labor. The physiology of cervical ripening, the causes of absent cervical ripening postterm, and why some women do not respond with adequate cervical ripening after administration of prostaglandins, are not properly understood. This thesis aims to describe risk factors for postterm pregnancy and failed labor induction, to investigate expression of prostaglandin receptors and cytokines in postterm women with failed and successful labor induction, as well as investigating the association between polycystic ovary syndrome, postterm pregnancy and adverse pregnancy outcomes. Methods: In paper I, risk factors for postterm pregnancy were determined using data from the Swedish Medical Birth Registry (MBR) where a cohort of term and postterm singleton births, taking place between 1992 to 2006 (total n=1,176,131), was identified. In paper II, a cohort of singleton births from 1995 to 2008 (n=1,191,336) was identified in the Swedish Medical Birth Registry, out of which 3,787 were born to a mother with a previous diagnosis of PCOS. In paper III and IV, transvaginal cervical biopsies were taken from non-pregnant, term pregnant and postpartal women as well as from postterm women with failed and successful labor induction. The biopsies were analyzed for mRNA expression with real-time PCR (RT-PCR). Immunohistochemistry was performed to analyze expression and distribution of cytokines (IL- 1β, IL-6, IL-8, IL-10 and IL-18), prostaglandin receptors (EP1-4 and FP) and stroma factors (CTGF, calgranulin B, furin and ALOX 15). Results: We identified advanced maternal age, nulliparity and BMI > 30.0 kg/m2as risk factors for postterm pregnancy and cesarean section following labor induction postterm. We found that a previous diagnosis of PCOS was not associated with postterm pregnancy. However, we found that independently from assisted reproductive technology and BMI, infants born to women with PCOS were at increased risk of adverse pregnancy outcome. In paper III and IV, we found that impaired cervical ripening in postterm women with failed labor induction was associated with a an elevated value of the ratio in the mRNA expression of EP3 and EP4. We also found an overall down-regulation of pro- and anti-inflammatory cytokines. Conclusions: The results imply that pregnant women with PCOS should be considered as a high risk group of adverse pregnancy outcomes and the obstetric guidelines should be reviewed. Women with postterm pregnancy are obese, nulliparous and of advanced age as compared to others. Down-regulation of pro- and anti-inflammatory cytokines among women with impaired cervical ripening as well as differences between women in the expression of EP3 and EP4 provides important information for an improved understanding of the physiology of normal and delayed parturition

The pan-genome of Lactobacillus reuteri strains originating from the pig gastrointestinal tract

Background Lactobacillus reuteri is a gut symbiont of a wide variety of vertebrate species that has diversified into distinct phylogenetic clades which are to a large degree host-specific. Previous work demonstrated host specificity in mice and begun to determine the mechanisms by which gut colonisation and host restriction is achieved. However, how L. reuteri strains colonise the gastrointestinal (GI) tract of pigs is unknown. Results To gain insight into the ecology of L. reuteri in the pig gut, the genome sequence of the porcine small intestinal isolate L. reuteri ATCC 53608 was completed and consisted of a chromosome of 1.94 Mbp and two plasmids of 138.5 kbp and 9.09 kbp, respectively. Furthermore, we generated draft genomes of four additional L. reuteri strains isolated from pig faeces or lower GI tract, lp167-67, pg-3b, 20-2 and 3c6, and subjected all five genomes to a comparative genomic analysis together with the previously completed genome of strain I5007. A phylogenetic analysis based on whole genomes showed that porcine L. reuteri strains fall into two distinct clades, as previously suggested by multi-locus sequence analysis. These six pig L. reuteri genomes contained a core set of 1364 orthologous gene clusters, as determined by OrthoMCL analysis, that contributed to a pan-genome totalling 3373 gene clusters. Genome comparisons of the six pig L. reuteri strains with 14 L. reuteri strains from other host origins gave a total pan-genome of 5225 gene clusters that included a core genome of 851 gene clusters but revealed that there were no pig-specific genes per se. However, genes specific for and conserved among strains of the two pig phylogenetic lineages were detected, some of which encoded cell surface proteins that could contribute to the diversification of the two lineages and their observed host specificity. Conclusions This study extends the phylogenetic analysis of L. reuteri strains at a genome-wide level, pointing to distinct evolutionary trajectories of porcine L. reuteri lineages, and providing new insights into the genomic events in L. reuteri that occurred during specialisation to their hosts. The occurrence of two distinct pig-derived clades may reflect differences in host genotype, environmental factors such as dietary components or to evolution from ancestral strains of human and rodent origin following contact with pig populations

Developing global indicators for quality of maternal and newborn care: a feasibility assessment

Objective To assess the feasibility of applying the World Health Organization’s proposed 15 indicators of quality of care for maternal and newborn health at health-facility level in low- and middle-income settings. Methods Six of the indicators are about maternal health, five are for newborn health and four are general cross-cutting indicators. We used data collected routinely in facility registers and obtained as part of facility assessments from 963 health-care facilities specializing in maternity services in 10 countries in Africa and Asia. We made a feasibility assessment of the availability of data and the clarity of indicator definitions and identified additional information and data collection processes needed to apply the proposed indicators in real-life settings. Findings Of the indicators evaluated, 10 were clearly defined, of which four could be applied directly in the field and six would require revisions to operationalize them. The other five indicators require further development, with one of them being ready for implementation by using information readily available in registers and four requiring further information before deployment. For indicators that measure coverage of care or availability of services or products, there is a need to further strengthen measurement. Information on emergency obstetric complications was not recorded in a standard manner, thus limiting the reliability of the information. Conclusion While some of the proposed indicators can already be applied, other indicators need to be refined or will need additional sources and methods of data collection to be applied in real-world settings

Physiological mechanisms of the impact of heat during pregnancy and the clinical implications: review of the evidence from an expert group meeting

Many populations experience high seasonal temperatures. Pregnant women are considered vulnerable to extreme heat because ambient heat exposure has been linked to pregnancy complications including preterm birth and low birthweight. The physiological mechanisms that underpin these associations are poorly understood. We reviewed the existing research evidence to clarify the mechanisms that lead to adverse pregnancy outcomes in order to inform public health actions. A multi-disciplinary expert group met to review the existing evidence base and formulate a consensus regarding the physiological mechanisms that mediate the efect of high ambient temperature on pregnancy. A literature search was conducted in advance of the meeting to identify existing hypotheses and develop a series of questions and themes for discussion. Numerous hypotheses have been generated based on animal models and limited observational studies. There is growing evidence that pregnant women are able to appropriately thermoregulate; however, when exposed to extreme heat, there are a number of processes that may occur which could harm the mother or fetus including a reduction in placental blood fow, dehydration, and an infammatory response that may trigger preterm birth. There is a lack of substantial evidence regarding the processes that cause heat exposure to harm pregnant women. Research is urgently needed to identify what causes the adverse outcomes in pregnancy related to high ambient temperatures so that the impact of climate change on pregnant women can be mitigated

Ambient temperature during pregnancy and risk of maternal hypertensive disorders: A time-to-event study in Johannesburg, South Africa

Hypertensive disorders in pregnancy are a leading cause of maternal and perinatal mortality and morbidity. We evaluate the effects of ambient temperature on risk of maternal hypertensive disorders throughout pregnancy. We used birth register data for all singleton births (22–43 weeks\u27 gestation) recorded at a tertiary-level hospital in Johannesburg, South Africa, between July 2017–June 2018. Time-to-event analysis was combined with distributed lag non-linear models to examine the effects of mean weekly temperature, from conception to birth, on risk of (i) high blood pressure, hypertension, or gestational hypertension, and (ii) pre-eclampsia, eclampsia, or HELLP (hemolysis, elevated liver enzymes, low platelets). Low and high temperatures were defined as the 5th and 95th percentiles of daily mean temperature, respectively. Of 7986 women included, 844 (10.6%) had a hypertensive disorder of which 432 (51.2%) had high blood pressure/hypertension/gestational hypertension and 412 (48.8%) had pre-eclampsia/eclampsia/HELLP. High temperature in early pregnancy was associated with an increased risk of pre-eclampsia/eclampsia/HELLP. High temperature (23 °C vs 18 °C) in the third and fourth weeks of pregnancy posed the greatest risk, with hazard ratios of 1.76 (95% CI 1.12–2.78) and 1.79 (95% CI 1.19–2.71), respectively. Whereas, high temperatures in mid-late pregnancy tended to protect against pre-eclampsia/eclampsia/HELLP. Low temperature (11°) during the third trimester (from 29 weeks’ gestation) was associated with an increased risk of high blood pressure/hypertension/gestational hypertension, however the strength and statistical significance of low temperature effects were reduced with model adjustments. Our findings support the hypothesis that high temperatures in early pregnancy increase risk of severe hypertensive disorders, likely through an effect on placental development. This highlights the need for greater awareness around the impacts of moderately high temperatures in early pregnancy through targeted advice, and for increased monitoring of pregnant women who conceive during periods of hot weather

Coping with Environmental Constraints: Geographically Divergent Adaptive Evolution and Germination Plasticity in the Transcontinental \u3cem\u3ePopulus tremuloides\u3c/em\u3e

Societal Impact Statement Syntheses clearly show that global warming is affecting ecosystems and biodiversity around the world. New methods and measures are needed to predict the climate resilience of plant species critical to ecosystem stability, to improve ecological management and to support habitat restoration and human well-being. Widespread keystone species such as aspen are important targets in the study of resilience to future climate conditions because they play a crucial role in maintaining various ecosystem functions and may contain genetic material with untapped adaptive potential. Here, we present a new framework in support of climate-resilient revegetation based on comprehensively understood patterns of genetic variation in aspen. Summary Elucidating species\u27 genetic makeup and seed germination plasticity is essential to inform tree conservation efforts in the face of climate change. Populus tremuloides Michx. (aspen) occurs across diverse landscapes and reaches from Alaska to central Mexico, thus representing an early-successional model for ecological genomics. Within drought-affected regions, aspen shows ploidy changes and/or shifts from sexual to clonal reproduction, and reduced diversity and dieback have already been observed. We genotyped over 1000 individuals, covering aspen\u27s entire range, for approximately 44,000 single-nucleotide polymorphisms (SNPs) to assess large-scale and fine-scale genetic structure, variability in reproductive type (sexual/clonal), polyploidy and genomic regions under selection. We developed and implemented a rapid and reliable analysis pipeline (FastPloidy) to assess the presence of polyploidy. To gain insights into plastic responses, we contrasted seed germination from western US and eastern Canadian natural populations under elevated temperature and water stress. Four major genetic clusters were identified range wide; a preponderance of triploids and clonemates was found within western and southern North American regions, respectively. Genomic regions involving approximately 1000 SNPs under selection were identified with association to temperature and precipitation variation. Under drought stress, western US genotypes exhibited significantly lower germination rates compared with those from eastern North America, a finding that was unrelated to differences in mutation load (ploidy). This study provided new insights into the adaptive evolution of a key indicator tree that provisions crucial ecosystem services across North America, but whose presence is steadily declining within its western distribution. We uncovered untapped adaptive potential across the species\u27 range which can form the basis for climate-resilient revegetation

Personal Genomes in Practice:Exploring Citizen and Healthcare Professionals’ Perspectives on Personalized Genomic Medicine and Personal Health Data Spaces Using a Mixed-Methods Design

Ongoing health challenges, such as the increased global burden of chronic disease, are increasingly answered by calls for personalized approaches to healthcare. Genomic medicine, a vital component of these personalization strategies, is applied in risk assessment, prevention, prognostication, and therapeutic targeting. However, several practical, ethical, and technological challenges remain. Across Europe, Personal Health Data Space (PHDS) projects are under development aiming to establish patient-centered, interoperable data ecosystems balancing data access, control, and use for individual citizens to complement the research and commercial focus of the European Health Data Space provisions. The current study explores healthcare users’ and health care professionals’ perspectives on personalized genomic medicine and PHDS solutions, in casu the Personal Genetic Locker (PGL). A mixed-methods design was used, including surveys, interviews, and focus groups. Several meta-themes were generated from the data: (i) participants were interested in genomic information; (ii) participants valued data control, robust infrastructure, and sharing data with non-commercial stakeholders; (iii) autonomy was a central concern for all participants; (iv) institutional and interpersonal trust were highly significant for genomic medicine; and (v) participants encouraged the implementation of PHDSs since PHDSs were thought to promote the use of genomic data and enhance patients’ control over their data. To conclude, we formulated several facilitators to implement genomic medicine in healthcare based on the perspectives of a diverse set of stakeholders.</p

Too hot to thrive: a qualitative inquiry of community perspectives on the effect of high ambient temperature on postpartum women and neonates in Kilifi, Kenya

Objective: To understand community perspectives on the effects of high ambient temperature on the health and wellbeing of neonates, and impacts on post-partum women and infant care in Kilifi. Design: Qualitative study using key informant interviews, in-depth interviews and focus group discussions with pregnant and postpartum women (n = 22), mothers-in-law (n = 19), male spouses (n = 20), community health volunteers (CHVs) (n = 22) and stakeholders from health and government ministries (n = 16). Settings: We conducted our research in Kilifi County in Kenya’s Coast Province. The area is largely rural and during summer, air temperatures can reach 37˚C and rarely go below 23˚C. Data analysis: Data were analyzed in NVivo 12, using both inductive and deductive approaches. Results: High ambient temperature is perceived by community members to have direct and indirect health pathways in pregnancy and postpartum periods, including on the neonates. The direct impacts include injuries on the neonate’s skin and in the mouth, leading to discomfort and affecting breastfeeding and sleeping. Participants described babies as “having no peace”. Heat effects were perceived to be amplified by indoor air pollution and heat from indoor cooking fires. Community members believed that exclusive breastfeeding was not practical in conditions of extreme heat because it lowered breast milk production, which was, in turn, linked to a low scarcity of food and time spend by mothers away from their neonates performing household chores. Kangaroo Mother Care (KMC) was also negatively affected. Participants reported that postpartum women took longer to heal in the heat, were exhausted most of the time and tended not to attend postnatal care. Conclusions: High ambient temperatures affect postpartum women and their neonates through direct and indirect pathways. Discomfort makes it difficult for the mother to care for the baby. Multi-sectoral policies and programs are required to mitigate the negative impacts of high ambient temperatures on maternal and neonatal health in rural Kilifi and similar settings

Frequent IgE recognition of Blomia tropicalis allergen molecules in asthmatic children and young adults in equatorial Africa

BackgroundAsthma is not well investigated in equatorial Africa and little is known about the disease-associated allergen molecules recognized by IgE from patients in this area. The aim was to study the molecular IgE sensitization profile of asthmatic children and young adults in a semi-rural area (Lambaréné) of an equatorial African country (Gabon), to identify the most important allergen molecules associated with allergic asthma in equatorial Africa.MethodsFifty-nine asthmatic patients, mainly children and few young adults, were studied by skin prick testing to Dermatophagoides pteronyssinus (Der p), D. farinae (Der f), cat, dog, cockroach, grass, Alternaria and peanut. Sera were obtained from a subset of 35 patients, 32 with positive and 3 with negative skin reaction to Der p and tested for IgE reactivity to 176 allergen molecules from different allergen sources by ImmunoCAP ISAC microarray technology and to seven recombinant Blomia tropicalis (Blo t) allergens by IgE dot blot assay.ResultsThirty-three of the 59 patients (56%) were sensitized to Der p and 23 of them (39%) were also sensitized to other allergen sources, whereas 9 patients (15%) were only sensitized to allergen sources other than Der p. IgE serology analyses (n=35) showed high IgE-binding frequencies to the Blo t allergens Blo t 5 (43%), Blo t 21 (43%) and Blo t 2 (40%), whereas the Der p allergens rDer p 2, rDer p 21 and rDer p 5 (34%, 29% and 26%) were less frequently recognized. Only few patients showed IgE reactivity to allergens from other allergen sources, except to allergens containing carbohydrate determinants (CCDs) or to wasp venom allergens (i.e., antigen 5).ConclusionOur results thus demonstrate that IgE sensitization to mite allergens is very prevalent in asthmatics in Equatorial Africa with B. tropicalis allergen molecules representing the most important ones associated with allergic asthma