Look at the future -perceptions of fertility counseling and decision-making among adolescents and their parents in the context of hematopoietic stem cell transplantation—experience of one major center for pediatric stem cell transplantation

IntroductionIncreasing survival rates after hematopoietic stem cell transplantation (HSCT) in childhood should put focus on improving the quality of life as adults. An essential aspect is fertility and its preservation. In order to take advantage of the possibility of fertility preservation, fertility counseling should be provided to patients and their parents prior to gonadotoxic therapies.MethodsThe aim of this survey was to analyze the impact of fertility counseling in pediatric stem cell transplantation in patients and their parents using questionnaires designed for the study questions. Fifty-one parents and 7 adolescent patients were interviewed between February 2019 and October 2021 about the counseling, their perceptions of fertility issues, and the nature of decision- making concerning fertility preservation. The study included patients with malignant (e.g., leukemia, lymphoma, neuroblastoma) and nonmalignant diseases (e.g., thalassemia, sickle cell disease, immunodeficiency) who received counseling on fertility preservation before HSCT based on an in-house standard and analysed the impact for both groups.ResultsTwo-thirds of the study participants were concerned about having children and grandchildren respectively; for half of all respondents, the topic of fertility and fertility preservation proved to be hopeful. Forty percent of the study participants were burdened by the risk of possible fertility limitations after HSCT. Concerns about fertility was particularly significant for parents whose children were advised to undergo fertility preservation. Parents of children <12 years found deciding on appropriate measures more difficult. Parents with children >7 years involved their children in the decision. All study participants agreed that fertility counseling had not negatively affected the parent-child relationship. More than 90% of all study participants were in favor of addressing fertility, its potential limitations and fertility preservation measures before HSCT. There was no significant difference between the malignant and the non-malignant cohort in all study questions.DiscussionOverall, the standardized fertility counseling provided in our center of pediatric stem cell transplantation resulted in high satisfaction among patients and their parents. Multiple counseling on infertility risk, including the younger patients in the decision-making and further options after gonadotoxic therapy may increase the satisfaction of the counseled patients and their parents

Inhibition of IL-1beta improves Glycaemia in a Mouse Model for Gestational Diabetes

Gestational diabetes mellitus (GDM) is one of the most common diseases associated with pregnancy, however, the underlying mechanisms remain unclear. Based on the well documented role of inflammation in type 2 diabetes, the aim was to investigate the role of inflammation in GDM. We established a mouse model for GDM on the basis of its two major risk factors, obesity and aging. In these GDM mice, we observed increased Interleukin-1β (IL-1β) expression in the uterus and the placenta along with elevated circulating IL-1β concentrations compared to normoglycemic pregnant mice. Treatment with an anti-IL-1β antibody improved glucose-tolerance of GDM mice without apparent deleterious effects for the fetus. Finally, IL-1β antagonism showed a tendency for reduced plasma corticosterone concentrations, possibly explaining the metabolic improvement. We conclude that IL-1β is a causal driver of impaired glucose tolerance in GDM

Data from the German TwinLife Study: Genetic and Social Origins of Educational Predictors, Processes, and Outcomes

The major aim of the German TwinLife study is the investigation of gene-environment interplay driving educational and other inequalities across developmental trajectories from childhood to early adulthood. TwinLife encompasses an 8-year longitudinal, cross-sequential extended twin family design with data from same-sex twins of four age cohorts (5, 11, 17, and 23 years) and their parents, as well as their non-twin siblings, partners, and children, if available, altogether containing N = 4,096 families. As such, TwinLife includes unique and openly accessible data that allows, but is not limited to, genetically informative and environmentally sensitive research on sources of inequalities regarding educational attainment, school achievement, and skill development

Targeting colonic macrophages as a potential therapeutic option in metabolic disease

Obesity is characterized by chronic low-grade inflammation. However, the initiating mechanisms remain poorly understood. Here, we characterized intestinal macrophage subpopulations and their role in high-fat diet (HFD)-induced obesity in mice and humans. Pro-inflammatory/monocyte-derived intestinal macrophages transiently increased upon food intake and became chronically elevated upon HFD, suggesting a link between macrophage numbers and glycemia. Indeed, pharmacological dose-dependent or genetic ablation of macrophages improved glucose homeostasis. In particular, colon-specific macrophage depletion improved glycemic control and ameliorated β-cell function. Intestinal macrophage activation upon HFD was characterized by a strong interferon signature and metabolic shift, potentially via mTOR activation. Accordingly, colon-specific mTOR-inhibition enhanced insulin and GLP-1 secretion. In obese humans, pro-inflammatory intestinal macrophages were also increased, potentially by enhanced monocyte recruitment. Taken together, these data reveal that intestinal innate immunity contributes to glycemic dysfunction in obesity. Therefore, specifically targeting colonic macrophages or their activation might be a novel therapeutic avenue to improve glycemic control

Comparing Perceptual Speed Between Educational Contexts

<jats:p> Abstract. Perceptual speed is a basic component of cognitive functioning that allows people to efficiently process novel visual stimuli and quickly react to them. In educational studies, tests measuring perceptual speed are frequently developed using students from regular schools without considering students with special educational needs. Therefore, it is unclear whether these instruments allow valid comparisons between different school tracks. The present study on N = 3,312 students from the National Educational Panel Study evaluated differential item functioning (DIF) of a short test of perceptual speed between four school tracks in Germany (special, basic, intermediate, and upper secondary schools). Bayesian Rasch Poisson counts modeling identified negligible DIF that did not systematically disadvantage specific students. Moreover, the test reliabilities were comparable between school tracks. These results highlight that perceptual speed can be comparably measured in special schools, thus enabling educational researchers to study schooling effects in the German educational system. </jats:p&gt

Documentation TwinLife Data: Report Cards

Instinske J, Rohm T, Mattheus S, Starr A, Riemann R. Documentation TwinLife Data: Report Cards. TwinLife Technical Report Series. Vol 04 v2.0.0. Bielefeld: Project TwinLife "Genetic and social causes of life chances" (Universität Bielefeld / Universität Bremen/ Universität des Saarlandes); 2022

Inflammation in obesity, diabetes, and related disorders

Obesity leads to chronic, systemic inflammation and can lead to insulin resistance (IR), β-cell dysfunction, and ultimately type 2 diabetes (T2D). This chronic inflammatory state contributes to long-term complications of diabetes, including non-alcoholic fatty liver disease (NAFLD), retinopathy, cardiovascular disease, and nephropathy, and may underlie the association of type 2 diabetes with other conditions such as Alzheimer's disease, polycystic ovarian syndrome, gout, and rheumatoid arthritis. Here, we review the current understanding of the mechanisms underlying inflammation in obesity, T2D, and related disorders. We discuss how chronic tissue inflammation results in IR, impaired insulin secretion, glucose intolerance, and T2D and review the effect of inflammation on diabetic complications and on the relationship between T2D and other pathologies. In this context, we discuss current therapeutic options for the treatment of metabolic disease, advances in the clinic and the potential of immune-modulatory approaches

Obesity in Humans Is Characterized by Gut Inflammation as Shown by Pro-Inflammatory Intestinal Macrophage Accumulation

Chronic low-grade inflammation is a hallmark of obesity and associated with cardiovascular complications. However, it remains unclear where this inflammation starts. As the gut is constantly exposed to food, gut microbiota, and metabolites, we hypothesized that mucosal immunity triggers an innate inflammatory response in obesity. We characterized five distinct macrophage subpopulations (P1-P5) along the gastrointestinal tract and blood monocyte subpopulations (classical, non-classical, intermediate), which replenish intestinal macrophages, in non-obese (BMI32kg/m2). To elucidate factors that potentially trigger gut inflammation, we correlated these subpopulations with cardiovascular risk factors and lifestyle behaviors. In obese individuals, we found higher pro-inflammatory macrophages in the stomach, duodenum, and colon. Intermediate blood monocytes were also increased in obesity, suggesting enhanced recruitment to the gut. We identified unhealthy lifestyle habits as potential triggers of gut and systemic inflammation (i.e., low vegetable intake, high processed meat consumption, sedentary lifestyle). Cardiovascular risk factors other than body weight did not affect the innate immune response. Thus, obesity in humans is characterized by gut inflammation as shown by accumulation of pro-inflammatory intestinal macrophages, potentially via recruited blood monocytes. Understanding gut innate immunity in human obesity might open up new targets for immune-modulatory treatments in metabolic disease. Keywords: Obesity; chronic inflammation; diabetes; intestinal inflammation; macrophages; metabolic disease; monocytes; mucosal immunity

Imatinib reduces non-alcoholic fatty liver disease in obese mice by targeting inflammatory and lipogenic pathways in macrophages and liver

Macrophages have been recognized as key players in non-alcoholic fatty liver disease (NAFLD). Our aim was to assess whether pharmacological attenuation of macrophages can be achieved by imatinib, an anti-leukemia drug with known anti-inflammatory and anti-diabetic properties, and how this impacts on NAFLD. We analyzed the pro- and anti-inflammatory gene expression of murine macrophages and human monocytes in vitro in the presence or absence of imatinib. In a time-resolved study, we characterized metabolic disease manifestations such as hepatic steatosis, systemic and adipose tissue inflammation as well as lipid and glucose metabolism in obese mice at one and three months of imatinib treatment. Our results showed that imatinib lowered pro-inflammatory markers in murine macrophages and human monocytes in vitro. In obese mice, imatinib reduced TNFα-gene expression in peritoneal and liver macrophages and systemic lipid levels at one month. This was followed by decreased hepatic steatosis, systemic and adipose tissue inflammation and increased insulin sensitivity after three months. As the transcription factor sterol regulatory element-binding protein (SREBP) links lipid metabolism to the innate immune response, we assessed the gene expression of SREBPs and their target genes, which was indeed downregulated in the liver and partially in peritoneal macrophages. In conclusion, targeting both inflammatory and lipogenic pathways in macrophages and liver as shown by imatinib could represent an attractive novel therapeutic strategy for patients with NAFLD