Interaction between Metformin, Folate and Vitamin B 12 and the Potential Impact on Fetal Growth and Long-Term Metabolic Health in Diabetic Pregnancies

From MDPI via Jisc Publications RouterHistory: accepted 2021-05-25, pub-electronic 2021-05-28Publication status: PublishedFunder: Medical Research Council; Grant(s): MR/R023166/1, MR/T001828/1Funder: British Heart Foundation; Grant(s): FS/4yPhD/F/20/34130Metformin is the first-line treatment for many people with type 2 diabetes mellitus (T2DM) and gestational diabetes mellitus (GDM) to maintain glycaemic control. Recent evidence suggests metformin can cross the placenta during pregnancy, thereby exposing the fetus to high concentrations of metformin and potentially restricting placental and fetal growth. Offspring exposed to metformin during gestation are at increased risk of being born small for gestational age (SGA) and show signs of ‘catch up’ growth and obesity during childhood which increases their risk of future cardiometabolic diseases. The mechanisms by which metformin impacts on the fetal growth and long-term health of the offspring remain to be established. Metformin is associated with maternal vitamin B12 deficiency and antifolate like activity. Vitamin B12 and folate balance is vital for one carbon metabolism, which is essential for DNA methylation and purine/pyrimidine synthesis of nucleic acids. Folate:vitamin B12 imbalance induced by metformin may lead to genomic instability and aberrant gene expression, thus promoting fetal programming. Mitochondrial aerobic respiration may also be affected, thereby inhibiting placental and fetal growth, and suppressing mammalian target of rapamycin (mTOR) activity for cellular nutrient transport. Vitamin supplementation, before or during metformin treatment in pregnancy, could be a promising strategy to improve maternal vitamin B12 and folate levels and reduce the incidence of SGA births and childhood obesity. Heterogeneous diagnostic and screening criteria for GDM and the transient nature of nutrient biomarkers have led to inconsistencies in clinical study designs to investigate the effects of metformin on folate:vitamin B12 balance and child development. As rates of diabetes in pregnancy continue to escalate, more women are likely to be prescribed metformin; thus, it is of paramount importance to improve our understanding of metformin’s transgenerational effects to develop prophylactic strategies for the prevention of adverse fetal outcomes

Sexually dimorphic patterns in maternal circulating microRNAs in pregnancies complicated by fetal growth restriction

From Springer Nature via Jisc Publications RouterHistory: received 2021-08-18, accepted 2021-10-27, registration 2021-11-01, pub-electronic 2021-11-17, online 2021-11-17, collection 2021-12Publication status: PublishedFunder: tommy's baby charity; doi: http://dx.doi.org/10.13039/501100000306Funder: medical research foundation; doi: http://dx.doi.org/10.13039/501100009187; Grant(s): MR/R023166/1Abstract: Background: Current methods fail to accurately predict women at greatest risk of developing fetal growth restriction (FGR) or related adverse outcomes, including stillbirth. Sexual dimorphism in these adverse pregnancy outcomes is well documented as are sex-specific differences in gene and protein expression in the placenta. Circulating maternal serum microRNAs (miRNAs) offer potential as biomarkers that may also be informative of underlying pathology. We hypothesised that FGR would be associated with an altered miRNA profile and would differ depending on fetal sex. Methods: miRNA expression profiles were assessed in maternal serum (> 36 weeks’ gestation) from women delivering a severely FGR infant (defined as an individualised birthweight centile (IBC) < 3rd) and matched control participants (AGA; IBC = 20–80th), using miRNA arrays. qPCR was performed using specific miRNA primers in an expanded cohort of patients with IBC < 5th (n = 15 males, n = 16 females/group). Maternal serum human placental lactogen (hPL) was used as a proxy to determine if serum miRNAs were related to placental dysfunction. In silico analyses were performed to predict the potential functions of altered miRNAs. Results: Initial analyses revealed 11 miRNAs were altered in maternal serum from FGR pregnancies. In silico analyses revealed all 11 altered miRNAs were located in a network of genes that regulate placental function. Subsequent analysis demonstrated four miRNAs showed sexually dimorphic patterns. miR-28-5p was reduced in FGR pregnancies (p < 0.01) only when there was a female offspring and miR-301a-3p was only reduced in FGR pregnancies with a male fetus (p < 0.05). miR-454-3p was decreased in FGR pregnancies (p < 0.05) regardless of fetal sex but was only positively correlated to hPL when the fetus was female. Conversely, miR-29c-3p was correlated to maternal hPL only when the fetus was male. Target genes for sexually dimorphic miRNAs reveal potential functional roles in the placenta including angiogenesis, placental growth, nutrient transport and apoptosis. Conclusions: These studies have identified sexually dimorphic patterns for miRNAs in maternal serum in FGR. These miRNAs may have potential as non-invasive biomarkers for FGR and associated placental dysfunction. Further studies to determine if these miRNAs have potential functional roles in the placenta may provide greater understanding of the pathogenesis of placental dysfunction and the differing susceptibility of male and female fetuses to adverse in utero conditions

Marconi, masculinity and the heroic age of science: wireless telegraphy at the British Association meeting at Dover in 1899

In September 1899, at the annual meeting of the British Association for the Advancement of Science (BAAS) in Dover, Guglielmo Marconi’s wireless telegraphy system was used to transmit messages across the English Channel (and across a national border) for the first time. This achievement represented a highly effective performance of scientific masculinity and constitutes a key turning point in an important struggle between competing interpretations of invention and innovation as masculine practices within British science. The British Association tended to favor a narrative of scientific research as a collectivist, international, gentlemanly-amateur pursuit, largely confined to the laboratory. Marconi, by contrast, explained the development of wireless telegraphy as the achievement of his own genius. Appealing not only to the established scientific elite but to a range of non-traditional audiences, and stressing the possibilities or ‘imagined uses’ of his technology even more so than his actual results, he succeeded in commanding unprecedented influence

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Saturation in qualitative research: exploring its conceptualization and operationalization

Deposited on 20 October 2017 in Keele University Repository at: http://eprints.keele.ac.uk/4122/Saturation has attained widespread acceptance as a methodological principle in qualitative research. It is commonly taken to indicate that, on the basis of the data that have been collected or analysed hitherto, further data collection and/or analysis are unnecessary. However, there appears to be uncertainty as to how saturation should be conceptualized, and inconsistencies in its use. In this paper, we look to clarify the nature, purposes and uses of saturation, and in doing so add to theoretical debate on the role of saturation across different methodologies.Weidentify four distinct approaches to saturation, which differ in terms of the extent to which an inductive or a deductive logic is adopted, and the relative emphasis on data collection, data analysis, and theorizing. We explore the purposes saturation might serve in relation to these different approaches, and the implications for how and when saturation will be sought. In examining these issues, we highlight the uncertain logic underlying saturation- as essentially a predictive statement about the unobserved based on the observed, a judgement that, we argue, results in equivocation, and may in part explain the confusion surrounding its use.Weconclude that saturation should be operationalized in a way that is consistent with the research question(s), and the theoretical position and analytic framework adopted, but also that there should be some limit to its scope, so as not to risk saturation losing its coherence and potency if its conceptualization and uses are stretched too widely.sch_die52pub5265pub

How Patients Perceive Their Doctors’ Communication: Implications for Patient Willingness to Communicate

By emphasizing the value of health professionals’ communication skills in creating positive health care experiences, researchers have tended to study health communication as an interpersonal encounter. Interactions in the health context, though, are inherently intergroup. Using the language and social psychology approach, this study emphasizes those intergroup features of health communication. We used mixed methods and applied communication accommodation theory and the willingness to communicate construct to the health context. Participants in Canada and Australia (N = 371) were asked about their perceptions of their health consultations. Multiple regression analyses revealed that health communication competence was the best predictor of patient willingness to communicate. Differences between patients’ accounts of positive and negative health care experiences were clearly differentiated by their perceptions of the health professionals’ communication strategies. The potential effects of these strategies on patient participation are discussed

Understanding the health communication process: advancing the research agenda to improve health care interactions and patient care

The articles presented in this special issue bring attention to important sociocultural variables and language strategies present in the ever-changing and complex health care system. These articles were selected from the health communication symposium of the 14th International Conference of Language and Social Psychology held in Hawaii in 2014. The articles each concentrate on different aspects of health communication and employ different theoretical and analytical approaches, but they all call for more education and better interventions to improve relations in the health context and patient care

Exploring intercultural communication problems in health care with a communication accommodation competence approach

In this chapter, we explore intercultural health communication in doctor-patient and interprofessional interactions. Traditionally, intercultural health communication research has focused on interpersonal issues. We argue here that, although interpersonal aspects are present, intergroup issues are often likely more salient and have a greater impact on communicative behavior. Consequently, we propose that intercultural communication competence (ICC) training programs must consider both interpersonal and intergroup characteristics of intercultural health communication. We invoke Communication Accommodation Theory (CAT), which takes into account how interpersonal and intergroup aspects of the health context influence motivations and subsequent communicative behavior. CAT is ideally suited to inform ICC training programs