Bioenergetic Changes during Differentiation of Human Embryonic Stem Cells along the Hepatic Lineage.

Mitochondrial dysfunction has been demonstrated to result in premature aging due to its effects on stem cells. Nevertheless, a full understanding of the role of mitochondrial bioenergetics through differentiation is still lacking. Here we show the bioenergetics profile of human stem cells of embryonic origin differentiating along the hepatic lineage. Our study reveals especially the transition between hepatic specification and hepatic maturation as dependent on mitochondrial respiration and demonstrates that even though differentiating cells are primarily dependent on glycolysis until induction of hepatocyte maturation, oxidative phosphorylation is essential at all stages of differentiation

Inflammatory bowel disease at a young age – implications for achieving upper secondary education

BACKGROUND: The incidence of inflammatory bowel disease (IBD) among children and adolescence is increasing worldwide. Having a chronic condition at a young age may affect educational achievement and later employment and self-support. The study aims to examine the impact of being diagnosed with IBD before 18 years of age on achieving an upper secondary education before 25 years of age. METHODS: Using the Danish National Patient Register (1980-2018) all patients (born 1970-1994) diagnosed with IBD at a young age (<18 years) were identified. The IBD-patients were matched on age and sex with 10 references without IBD at the index date (date of diagnosis of IBD). The outcome was achieving an upper secondary education using data from Danish Education Registers. The association between IBD diagnosis and achieving an upper secondary education was analyzed using Cox regression with robust variance estimation adjusting for parents’ highest educational level. Furthermore, stratified analyses were performed on parental socioeconomic status (education and income). RESULTS: We identified 3,178 patients with IBD: Crohn’s disease (CD) n = 1,344, Ulcerative colitis (UC) n = 1,834. Reference n = 28,220. The median age at diagnosis was 15.3 years (IQR: [13.0;16.9]). At the age of 25 74.0% (CI: 71.6-76.4) for CD, 75.8% (CI: 73.8-77.8) for UC, and 69.7% (CI: 69.2-70.3) for references had achieved an upper secondary education. The adjusted Hazard ratio (HR) of achieving an upper secondary education was 1.05 (CI: 1.00 -1.11) for CD and 1.09 (CI: 1.04 -1.15) for UC. When stratifying the IBD-patient with the lowest socioeconomic status performed better than their peers. CONCLUSIONS: Being diagnosed with IBD before 18 years of age did not reduce the chance of achieving an upper secondary education. Patients with low socioeconomic status performed better than their peers, however the study gives no explanation of this. KEY MESSAGES: • Children diagnosed with IBD before 18 years of age had at least the same chance of achieving an upper secondary education compared to references. • IBD patients with low social economic status performed better than their peers

Definition of the σW regulon of Bacillus subtilis in the absence of stress

Bacteria employ extracytoplasmic function (ECF) sigma factors for their responses to environmental stresses. Despite intensive research, the molecular dissection of ECF sigma factor regulons has remained a major challenge due to overlaps in the ECF sigma factor-regulated genes and the stimuli that activate the different ECF sigma factors. Here we have employed tiling arrays to single out the ECF σW regulon of the Gram-positive bacterium Bacillus subtilis from the overlapping ECF σX, σY, and σM regulons. For this purpose, we profiled the transcriptome of a B. subtilis sigW mutant under non-stress conditions to select candidate genes that are strictly σW-regulated. Under these conditions, σW exhibits a basal level of activity. Subsequently, we verified the σW-dependency of candidate genes by comparing their transcript profiles to transcriptome data obtained with the parental B. subtilis strain 168 grown under 104 different conditions, including relevant stress conditions, such as salt shock. In addition, we investigated the transcriptomes of rasP or prsW mutant strains that lack the proteases involved in the degradation of the σW anti-sigma factor RsiW and subsequent activation of the σW-regulon. Taken together, our studies identify 89 genes as being strictly σW-regulated, including several genes for non-coding RNAs. The effects of rasP or prsW mutations on the expression of σW-dependent genes were relatively mild, which implies that σW-dependent transcription under non-stress conditions is not strictly related to RasP and PrsW. Lastly, we show that the pleiotropic phenotype of rasP mutant cells, which have defects in competence development, protein secretion and membrane protein production, is not mirrored in the transcript profile of these cells. This implies that RasP is not only important for transcriptional regulation via σW, but that this membrane protease also exerts other important post-transcriptional regulatory functions

How can humans understand their automated cars? HMI principles, problems and solutions

As long as vehicles do not provide full automation, the design and function of the Human Machine Interface (HMI) is crucial for ensuring that the human “driver” and the vehicle-based automated systems collaborate in a safe manner. When the driver is decoupled from active control, the design of the HMI becomes even more critical. Without mutual understanding, the two agents (human and vehicle) will fail to accurately comprehend each other’s intentions and actions. This paper proposes a set of design principles for in-vehicle HMI and reviews some current HMI designs in the light of those principles. We argue that in many respects, the current designs fall short of best practice and have the potential to confuse the driver. This can lead to a mismatch between the operation of the automation in the light of the current external situation and the driver’s awareness of how well the automation is currently handling that situation. A model to illustrate how the various principles are interrelated is proposed. Finally, recommendations are made on how, building on each principle, HMI design solutions can be adopted to address these challenges

Internet use, needs and expectations of web-based information and communication in childbearing women with type 1 diabetes

<p>Abstract</p> <p>Background</p> <p>In the childbearing period women use the internet both to seek information and as an important source of communication. For women with type 1 diabetes, pregnancy and early motherhood constitute a more complex situation than for women in general. This implies need for support from various professionals and a way of bridging any discontinuity in care would be to develop a website providing complementary social support and information. The objective of this study was to explore internet use, needs, and expectations regarding web-based information and communication in childbearing women with type 1 diabetes.</p> <p>Methods</p> <p>Data were collected via a web-based survey with an explorative and descriptive design, in which 105 of 139 eligible mothers with type 1 diabetes and recent childbearing experience participated. The data were analyzed with descriptive and analytical statistics, and open answers with a directed content analysis.</p> <p>Results</p> <p>Of the 105 women, 22% never used the internet to search for information concerning pregnancy, childbirth, and parenthood. 12% searched for information every day, 29% one or more times a week, and 38% one or more times a month. Of the women 44% declared themselves to be passive participants on social websites, and 45% to be active participants. 45% had specific expectations of web-based support directed towards childbearing, especially those with higher educational level (<it>P </it>= .01). Expectations of instrumental and informational support included an expert-controlled website with reliable, updated, and information focused on childbearing and diabetes, improved access to diabetes care professionals and alternative ways to communicate and to receive childbearing-related support. The women also asked for online technical devices to manage the frequent monitoring of blood glucose during pregnancy. Informal, emotional, and appraisal support from women in similar situations was suggested as a way to provide an arena for belonging instead of creating feelings of alienation.</p> <p>Conclusions</p> <p>Our results add important knowledge about the web-based needs of women with type 1 diabetes in relation to childbearing. This user directed study indicates specific areas of development for the provision of effective web-based support that includes facilities for reliable information, interactive support and social networking in this population.</p

Inference of population splits and mixtures from genome-wide allele frequency data

Many aspects of the historical relationships between populations in a species are reflected in genetic data. Inferring these relationships from genetic data, however, remains a challenging task. In this paper, we present a statistical model for inferring the patterns of population splits and mixtures in multiple populations. In this model, the sampled populations in a species are related to their common ancestor through a graph of ancestral populations. Using genome-wide allele frequency data and a Gaussian approximation to genetic drift, we infer the structure of this graph. We applied this method to a set of 55 human populations and a set of 82 dog breeds and wild canids. In both species, we show that a simple bifurcating tree does not fully describe the data; in contrast, we infer many migration events. While some of the migration events that we find have been detected previously, many have not. For example, in the human data we infer that Cambodians trace approximately 16% of their ancestry to a population ancestral to other extant East Asian populations. In the dog data, we infer that both the boxer and basenji trace a considerable fraction of their ancestry (9% and 25%, respectively) to wolves subsequent to domestication, and that East Asian toy breeds (the Shih Tzu and the Pekingese) result from admixture between modern toy breeds and "ancient" Asian breeds. Software implementing the model described here, called TreeMix, is available at http://treemix.googlecode.comComment: 28 pages, 6 figures in main text. Attached supplement is 22 pages, 15 figures. This is an updated version of the preprint available at http://precedings.nature.com/documents/6956/version/

Gender-related differences of renal mass supply and metabolic demand after living donor kidney transplantation

Kidney donation from female donors to male recipients has been reported to be associated with decreased allograft survival. Whether there was a gender-related inadequacy between donor nephron supply and recipient functional demand was investigated in this study. One hundred ninety-five living donor kidney transplant recipients that had neither ischemic injury, episode of rejection, nor any complication were included. Weights and heights of both donors and recipients were recorded to calculate body surface area, lean body weight, and body mass index. The donated kidney was weighed just after cold flush, and the recipient's serum creatinine (Scr) was measured on a daily basis post-operatively. When the recipient's Scr reached the baseline, a 24-h urine was collected for the amount of proteinuria (Upr), creatinine excretion (Ucr) and creatinine clearance (Ccr) calculation. The effect of donor and recipient gender was analysed by independent sample t -test. On average, male donors and recipients were heavier and taller than females. However, the mass of kidneys donated from men and women were not statistically different. The gender-related differences in post-transplant Scr and Ucr of recipients were associated with the differences in the parameters of metabolic demands of recipients rather than with the weight of implanted kidney (renal mass supply) or with pre-operative renal functions of donors (functional supply). The early graft function is not determined by donor gender. The effect of recipient gender on the graft function depends on the metabolic demands, which are higher in male recipients.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73185/1/j.1399-0012.2005.00459.x.pd

Extraordinary exposed in early motherhood - a qualitative study exploring experiences of mothers with type 1 diabetes

<p>Abstract</p> <p>Background</p> <p>Women with type 1 diabetes face several challenges during pregnancy, childbirth and in relation to breastfeeding. It is therefore of utmost importance to consider their need for specific support, early postpartum as well as in daily life after discharge from maternity care. Few studies have investigated these aspects of healthcare. The aim of this study was to explore experiences after childbirth regarding breastfeeding, glycemic control, support and well-being in women with type 1 diabetes.</p> <p>Methods</p> <p>A hermeneutic reflective life world research approach was used in this qualitative study. Data was gathered through audio-recorded focus group discussions and individual interviews with 23 women with type 1 diabetes, 6-24 months after childbirth. After verbatim transcription, the text was analyzed in order to identify themes of meaning and a conclusive interpretation of the explored phenomenon.</p> <p>Results</p> <p>Experiences of extraordinary exposure challenged the women with type 1 diabetes in their transition to early motherhood. The exposure included a struggle with breastfeeding, although with a driving force to succeed. Everyday life was filled with uncertainty and unpredictability related to one's own unstable glycemic control and the women down-prioritized their own needs in favor of the child. A feeling of being disconnected from professional care further contributed to the experiences of extraordinary exposure.</p> <p>Conclusion</p> <p>In early motherhood women with type 1 diabetes have a great need for support in managing daily life postpartum, which requires contemporary approaches to overlap insufficient linkage between health care professionals in maternity and child health care, and diabetes care.</p

High prevalence of hyperglycaemia and the impact of high household income in transforming Rural China

<p>Abstract</p> <p>Background</p> <p>The prevalence of hyperglycaemia and its association with socioeconomic factors have been well studied in developed countries, however, little is known about them in transforming rural China.</p> <p>Methods</p> <p>A cross-sectional study was carried out in 4 rural communities of Deqing County located in East China in 2006-07, including 4,506 subjects aged 18 to 64 years. Fasting plasma glucose (FPG) was measured. Subjects were considered to have impaired fasting glucose (IFG) if FPG was in the range from 5.6 to 6.9 mmol/L and to have diabetes mellitus (DM) if FG was 7.0 mmol/L or above.</p> <p>Results</p> <p>The crude prevalences of IFG and DM were 5.4% and 2.2%, respectively. The average ratio of IFG/DM was 2.5, and tended to be higher for those under the age of 35 years than older subjects. After adjustment for covariates including age (continuous), sex, BMI (continuous), smoking, alcohol drinking, and regular leisure physical activity, subjects in the high household income group had a significantly higher risk of IFG compared with the medium household income group (OR: 1.74, 95% CI: 1.11-2.72) and no significant difference in IFG was observed between the low and medium household income groups. Education and farmer occupation were not significantly associated with IFG.</p> <p>Conclusions</p> <p>High household income was significantly associated with an increased risk of IFG. A high ratio of IFG/DM suggests a high risk of diabetes in foreseeable future in the Chinese transforming rural communities.</p

Cataract research using electronic health records

<p>Abstract</p> <p>Background</p> <p>The eMERGE (electronic MEdical Records and Genomics) network, funded by the National Human Genome Research Institute, is a national consortium formed to develop, disseminate, and apply approaches to research that combine DNA biorepositories with electronic health record (EHR) systems for large-scale, high-throughput genetic research. Marshfield Clinic is one of five sites in the eMERGE network and primarily studied: 1) age-related cataract and 2) HDL-cholesterol levels. The purpose of this paper is to describe the approach to electronic evaluation of the epidemiology of cataract using the EHR for a large biobank and to assess previously identified epidemiologic risk factors in cases identified by electronic algorithms.</p> <p>Methods</p> <p>Electronic algorithms were used to select individuals with cataracts in the Personalized Medicine Research Project database. These were analyzed for cataract prevalence, age at cataract, and previously identified risk factors.</p> <p>Results</p> <p>Cataract diagnoses and surgeries, though not type of cataract, were successfully identified using electronic algorithms. Age specific prevalence of both cataract (22% compared to 17.2%) and cataract surgery (11% compared to 5.1%) were higher when compared to the Eye Diseases Prevalence Research Group. The risk factors of age, gender, diabetes, and steroid use were confirmed.</p> <p>Conclusions</p> <p>Using electronic health records can be a viable and efficient tool to identify cataracts for research. However, using retrospective data from this source can be confounded by historical limits on data availability, differences in the utilization of healthcare, and changes in exposures over time.</p