Maternal Obesity and the Fetal Origins of the Metabolic Syndrome

Over recent decades there has been a rapid rise in metabolic disorders throughout the world. Whilst lifestyle and societal habits have contributed to the obesity epidemic, there is now increasing evidence that the early developmental environment of an infant can play a pivotal role in the ‘programming’ of an adverse physiological phenotype in later life. Clinical evidence highlights that maternal over-nutrition and/or obesity during pregnancy presents not only adverse effects on maternal health, but also persistent and deleterious effects in the developing child. Animal models are providing essential information into the underlying cellular and molecular mechanisms that contribute to this adverse phenotype. The use of this information will aid our understanding of the programming signals related to maternal and paternal over-nutrition and the improved healthcare for both mother and infant

Mindfulness practice correlates with reduced exam-induced stress and improved exam performance in preclinical medical students with the “acting with awareness”, “non-judging” and “non-reacting” facets of mindfulness particularly associated with improved exam performance

Abstract: Background: Medical students demonstrate higher levels of psychological distress compared with the general population and other student groups, especially at exam times. Mindfulness interventions show promise in stress reduction for this group, and in the reduction of cortisol, an established clinical marker of the body’s stress response. This study investigated the relationship of mindfulness to exam-induced stress, salivary cortisol and exam performance in undergraduate medical students. Methods: A controlled pre-post analysis design with within-groups comparisons. 67 medical students completed the five facet mindfulness questionnaire (FFMQ) and provided saliva samples, from which cortisol was extracted, during group work (control/baseline) and immediately prior to end of year 2 examinations (experimental). Academic performance data was extracted for comparison with measures. Results: Exam-induced salivary cortisol concentration showed a significant negative relation with exam performance. Total FFMQ score showed a significant positive relation with exam performance and a significant negative relation with exam-induced salivary cortisol. The specific mindfulness facets of acting with awareness, non-judging and non-reacting also showed a positive correlation with exam performance. Conclusions: This study suggests that there exists an important relationship between mindfulness and the physiological biomarker of stress, cortisol, and this manifests into improved assessment outcomes potentially through healthier, more adaptive coping and stress management strategies. In particular, this study identifies the acting with awareness, non-judging and non-reacting facets of mindfulness to be significantly associated with exam performance suggesting that these may be important facets for clinical educators to target when helping students with mindfulness practice

A systematic review and taxonomy of tools for evaluating evidence-based medicine teaching in medical education

Background: The importance of teaching the skills and practice of evidence-based medicine (EBM) for medical professionals has steadily grown in recent years. Alongside this growth is a need to evaluate the effectiveness of EBM curriculum as assessed by competency in the five ‘A’s’: asking, acquiring, appraising, applying and assessing (impact and performance). EBM educators in medical education will benefit from a compendium of existing assessment tools for assessing EBM competencies in their settings. The purpose of this review is to provide a systematic review and taxonomy of validated tools that evaluate EBM teaching in medical education. Methods: We searched MEDLINE, EMBASE, Cochrane library, Educational Resources Information Centre (ERIC), Best Evidence Medical Education (BEME) databases and references of retrieved articles published between January 2005 and March 2019. We have presented the identified tools along with their psychometric properties including validity, reliability and relevance to the five domains of EBM practice and dimensions of EBM learning. We also assessed the quality of the tools to identify high quality tools as those supported by established interrater reliability (if applicable), objective (non-self-reported) outcome measures and achieved ≥ 3 types of established validity evidence. We have reported our study in accordance with the PRISMA guidelines. Results: We identified 1719 potentially relevant articles of which 63 full text articles were assessed for eligibility against inclusion and exclusion criteria. Twelve articles each with a unique and newly identified tool were included in the final analysis. Of the twelve tools, all of them assessed the third step of EBM practice (appraise) and four assessed just that one step. None of the twelve tools assessed the last step of EBM practice (assess). Of the seven domains of EBM learning, ten tools assessed knowledge gain, nine assessed skills and-one assessed attitude. None addressed reaction to EBM teaching, self-efficacy, behaviours or patient benefit. Of the twelve tools identified, six were high quality. We have also provided a taxonomy of tools using the CREATE framework, for EBM teachers in medical education. Conclusions: Six tools of reasonable validity are available for evaluating most steps of EBM and some domains of EBM learning. Further development and validation of tools that evaluate all the steps in EBM and all educational outcome domains are needed

Correlates of dermis thickness in mouse models with a range of obesity, insulin resistance and diabetic states

Diabetic complications of the skin regarding skin structure have been well documented and researched, notably in relation to wound healing. Recently it has also been discovered that dermis thickness may also be reduced in type 2 diabetic patients. Peripheral damage in diabetes has been attributed to inflammation, as well as hyperglycaemia resulting from insulin resistance. However, this has not been investigated specifically in relation to dermis thickness. This study used mouse models with a range of obesity, insulin resistance and diabetic states to investigate the extent of reduction in dermis thickness that results from these conditions and to elucidate the correlation of dermis thickness with both biomarkers of insulin resistance and whole-body and local proinflammatory cytokine levels, which can both directly damage tissues and be the causative factor of the insulin resistance. The results suggest that the reduced dermis thickness observed in type 2 diabetes is likely a result of hyperglycaemia resulting from insulin resistance rather than the increased proinflammatory milieu resulting from insulin resistance and obesity

Patient-centered medical education: A proposed definition

Multiple papers have been presented to define patient-centered care, with regulatory bodies such as the General Medical Council mapping this in their professional standards. Educational institutions clearly value instilling appreciation of patient-centredness in medical training, and attempts have been made to make medical education more patient-centered in practice. Such attempts are often limited to expert patients sharing personal stories, and public involvement in teaching. Despite the drive towards patient-centered care and medical education, there has been no attempt to formally define what patient-centered medical education is and what it means to medical educators globally. This paper proposes a definition of patient-centered medical education that is about the patients, with the patients, and for the patients, to ensure current and future doctors remain sensitive to all of the needs of the people they care for. This should be considered at both the micro and macro community levels

Non-Acidic Free Fatty Acid Receptor 4 Agonists with Antidiabetic Activity

The free fatty acid receptor 4 (FFA4 or GPR120) has appeared as an interesting potential target for the treatment of metabolic disorders. At present, most FFA4 ligands are carboxylic acids that are assumed to mimic the endogenous long-chain fatty acid agonists. Here, we report preliminary structure-activity relationship studies of a previously disclosed nonacidic sulfonamide FFA4 agonist. Mutagenesis studies indicate that the compounds are orthosteric agonists despite the absence of a carboxylate function. The preferred compounds showed full agonist activity on FFA4 and complete selectivity over FFA1, although a significant fraction of these noncarboxylic acids also showed partial antagonistic activity on FFA1. Studies in normal and diet-induced obese (DIO) mice with the preferred compound 34 showed improved glucose tolerance after oral dosing in an oral glucose tolerance test. Chronic dosing of 34 in DIO mice resulted in significantly increased insulin sensitivity and a moderate but significant reduction in bodyweight, effects that were also present in mice lacking FFA1 but absent in mice lacking FFA4

Schwartz rounds in undergraduate medical education facilitates active reflection and individual identification of learning need

Strategies applying Schwartz Rounds to improve wellbeing of medical students has focused on the clinical years of study. This pilot study investigates whether Schwartz Rounds could be effective in developing students’ reflective practice in Year 2 undergraduates. Engagement with the Schwartz Round was high with over 50% of the students identifying learning needs through reflection on the Round. Schwartz Rounds promoted recognition of the value of reflective practice and increased self-awareness of student needs

Prolonged treatment of genetically obese mice with conjugated linoleic acid improves glucose tolerance and lowers plasma insulin concentration: possible involvement of PPAR activation

BACKGROUND: Studies in rodents and some studies in humans have shown that conjugated linoleic acid (CLA), especially its trans-10, cis-12 isomer, reduces body fat content. However, some but not all studies in mice and humans (though none in rats) have found that CLA promotes insulin resistance. The molecular mechanisms responsible for these effects are unclear, and there are conflicting reports on the effects of CLA on peroxisomal proliferator-activated receptor-γ (PPARγ) activation and expression. We have conducted three experiments with CLA in obese mice over three weeks, and one over eleven weeks. We have also investigated the effects of CLA isomers in PPARγ and PPARα reporter gene assays. RESULTS: Inclusion of CLA or CLA enriched with its trans-10, cis-12 isomer in the diet of female genetically obese (lep(ob)/lep(ob)) mice for up to eleven weeks reduced body weight gain and white fat pad weight. After two weeks, in contrast to beneficial effects obtained with the PPARγ agonist rosiglitazone, CLA or CLA enriched with its trans-10, cis-12 isomer raised fasting blood glucose and plasma insulin concentrations, and exacerbated glucose tolerance. After 10 weeks, however, CLA had beneficial effects on glucose and insulin concentrations. At this time, CLA had no effect on the plasma TNFα concentration, but it markedly reduced the plasma adiponectin concentration. CLA and CLA enriched with either isomer raised the plasma triglyceride concentration during the first three weeks, but not subsequently. CLA enriched with its trans-10, cis-12 isomer, but not with its cis-9, trans-11 isomer, stimulated PPARγ-mediated reporter gene activity; both isomers stimulated PPARα-mediated reporter gene activity. CONCLUSIONS: CLA initially decreased but subsequently increased insulin sensitivity in lep(ob)/lep(ob )mice. Activation of both PPARγ and PPARα may contribute to the improvement in insulin sensitivity. In the short term, however, another mechanism, activated primarily by trans-10, cis-12-CLA, which probably leads to reduced adipocyte number and consequently reduced plasma adiponectin concentration, may decrease insulin sensitivity

5-HT2A and 5-HT2C receptors as hypothalamic targets of developmental programming in male rats.

Although obesity is a global epidemic, the physiological mechanisms involved are not well understood. Recent advances reveal that susceptibility to obesity can be programmed by maternal and neonatal nutrition. Specifically, a maternal low-protein diet during pregnancy causes decreased intrauterine growth, rapid postnatal catch-up growth and an increased risk for diet-induced obesity. Given that the synthesis of the neurotransmitter 5-hydroxytryptamine (5-HT) is nutritionally regulated and 5-HT is a trophic factor, we hypothesised that maternal diet influences fetal 5-HT exposure, which then influences development of the central appetite network and the subsequent efficacy of 5-HT to control energy balance in later life. Consistent with our hypothesis, pregnant rats fed a low-protein diet exhibited elevated serum levels of 5-HT, which was also evident in the placenta and fetal brains at embryonic day 16.5. This increase was associated with reduced levels of 5-HT2CR, the primary 5-HT receptor influencing appetite, in the fetal, neonatal and adult hypothalamus. As expected, a reduction of 5-HT2CR was associated with impaired sensitivity to 5-HT-mediated appetite suppression in adulthood. 5-HT primarily achieves effects on appetite by 5-HT2CR stimulation of pro-opiomelanocortin (POMC) peptides within the arcuate nucleus of the hypothalamus (ARC). We show that 5-HT2ARs are also anatomically positioned to influence the activity of ARC POMC neurons and that mRNA encoding 5-HT2AR is increased in the hypothalamus ofin uterogrowth-restricted offspring that underwent rapid postnatal catch-up growth. Furthermore, these animals at 3 months of age are more sensitive to appetite suppression induced by 5-HT2AR agonists. These findings not only reveal a 5-HT-mediated mechanism underlying the programming of susceptibility to obesity, but also provide a promising means to correct it, by treatment with a 5-HT2AR agonist