The effects of fluctuations in oestrogen and progesterone during the menstrual cycle on glucose homeostasis, energy balance, exercise and premenstrual syndrome

It is widely accepted that the loss of sex hormones after the menopause is strongly linked with cancer, insulin resistance and obesity, with variations in sex hormone concentrations being responsible in part, for the differences reported in energy metabolism and glycaemic control between genders. As such a greater understanding of the effects that oestrogen and progesterone may have on women's health and their potential long term consequences is required. This thesis reports evidence of three studies investigating the effects of oestrogen and progesterone during the menstrual cycle on glucose and insulin response, energy expenditure, substrate oxidation and premenstrual syndrome (PMS). The aim of the first study was to investigate glucose and insulin responses to a 75g glucose load during different phases of the menstrual cycle. Venous blood samples for baseline measurements of oestradiol and progesterone were collected every other week day from eighteen regularly menstruating women for one complete menstrul cycle. An oral glucose tolerance test (OGIT, 75g glucose) was performed on three separate days during the next complete menstrual cycle. The results report an increase in glucose area under the curve (AUC) and insulin AUC during the luteal phase (P<0.05) compared to the menstrual and follicular phase, but no significant differences in insulin sensitivity between phases. The findings indicate that both oestrogen and progesterone during the luteal phase may affect glycaemic response and this potentially has significant implications for the development of type 2 diabetes over prolonged periods of time. The second study investigated energy expenditure and substrate oxidation at rest and during a 30 minute moderate intensity walking exercise within the three phases of the menstrual cycle. Sex hormone concentrations were collected in the same manner as study 1. Nineteen women undertook resting measures and ten for exercise. The study reports a decrease in carbohydrate (CHO) oxidation (P<0.05) and a marginal increase in fat oxidation (P=0.06) during the follicular phase at rest, with no difference in energy expenditure at rest. No difference in energy expenditure or substrate oxidation between phases was reported during exercise. The results indicate high oestrogen concentrations during the follicular phase only may mediate the changes in substrate oxidation response reported at rest. I The final study investigated the effects of a 12 week moderate intensity exercise intervention on symptoms of PMS, quality of life and dietary intake and determined whether any such effect was associated with changes in oestrogen and progesterone concentrations in a randomised control trial. Twenty-five sedentary women, identified as suffering from PMS symptoms, were recruited to the trial spanning four menstrual cycles, the first serving as a baseline followed by three cycles of intervention. Participants were randomly assigned to either an exercise (EX) group (n= l 3), which involved three supervised 30-minute moderate­ intensity (70-80% HR max) treadmill walking exercise sessions per week, or to a control (CON) group (n=12), which involved attending a 90-minute, one-to-one meeting once per week with the investigator. The results report a reduction in PMS symptoms following the exercise intervention (P<0.05), with no differences in the control (CON) group. Averaged dietary intake over the three intervention cycles reports a decrease in CHO intake (% total energy intake, TEI) during the luteal phase, compared to the menstrual (45.5% vs. 50. l%) and follicular (45.5 vs. 49.9%) phases in the EX group, with no difference in the CON group. No significant difference was reported in overall energy intake in either group. In addition, no significant difference was reported in plasma oestrogen and progesterone concentrations over the four cycles in either group (EX and CON). The findings indicate that the exercise regime reduces PMS symptoms and CHO intake (%TEI), but that these are not mediated in response to changes in oestrogen and progesterone hormone concentrations. As such exercise may therefore be an effective symptom management tool for women suffering with PMS. Further studies are essential to determine the exact duration and intensity required for the most effective symptom relief. The results reported in this thesis provide evidence that the circulating reproductive hormones oestrogen and progesterone during the menstrual cycle have significant implications for energy regulation, glycaemic control and women suffering from PMS. As such, both hormones need to be investigated further in larger research studies to determine their potential long-term adverse effects on health and well-being in women

The sugar content of children’s and lunchbox beverages sold in the UK before and after the soft drink industry levy

Background: Childhood obesity is associated with an increased intake of sugary soft drinks and juice drinks. The aims of this study were (1) to report the sugar and energy content in commercial fruit juice (FJ), juice drinks (JD) and smoothies (S) specifically targeted at children in the UK, (2) to identify beverages liable for the Soft Drinks Industry Levy (SDIL) and (3) to compare the amount of sugar in these beverages before and after the levy. Methods: The beverages were retrieved using the online shopping tool my Supermarket, websites of nine major supermarket in the UK and manufacturers webpages. Comparisons of sugar content were taken before and after the introduction of the SDIL. Results: 131 FJJDS fulfilled the inclusion criteria. The mean sugar content of all the beverages was 6.3g±4.5/100mL. There was large variation in the sugar content from 0.1g/100mL to 15.2g/100mL, with smoothies found to contain the most sugar (11.55±1.62 g/mL). The beverages were reanalysed in September 2018 to determine their eligibility for the SDIL. Of the 131 products only 7 JD were eligible for the levy. Four of these beverages had reformulated their ingredients since the initial analysis resulting in a sugar content of <5g/100mL. Conclusions: The majority of the beverages targeted at children and children’s lunch boxes were not eligible for the SDIL. This study suggests the necessity to adapt the SDIL to include all FJJDS aimed at children as the total sugar content of these beverages are still above the recommended quantities for this age group

Women's dietary changes before and during pregnancy: A systematic review

Background: dietary intake before and during pregnancy has significant health outcomes for both mother and child, including a healthy gestational weight gain. To ensure effective interventions are successfully developed to improve dietary intake during pregnancy, it is important to understand what dietary changes pregnant women make without intervention. Aims: to systematically identify and review studies examining women's dietary changes before and during pregnancy and to identify characteristics of the women making these changes. Methods: a systematic search strategy was employed using three databases (Web of Science, CINAHL and PubMed) in May 2016. Search terms included those relating to preconception, pregnancy and diet. All papers were quality assessed using the Scottish Intercollegiate Guidelines Network methodology checklist for cohort studies.The search revealed 898 articles narrowed to full-text review of 23 studies. In total, 11 research articles were included in the review, describing nine different studies. The findings were narratively summarised in line with the aims of the review. Findings: the included studies showed marked heterogeneity, which impacts on the findings. However, the majority report an increase in energy intake (kcal or kJ) during pregnancy. Of the studies that reported changes through food group comparisons, a majority reported a significant increase in fruit and vegetable consumption, a decrease in egg consumption, a decrease in fried and fast food consumption and a decrease in coffee and tea consumption from before to during pregnancy. The characteristics of the women participating in these studies, suggest that age, education and pregnancy intention are associated with healthier dietary changes; however these factors were only assessed in a small number of studies. Key conclusions: the 11 included articles show varied results in dietary intake during pregnancy as compared to before. More research is needed regarding who makes these healthy changes, this includes consistency regarding measurement tools, outcomes and time points. Implications for practice: Midwives as well as intervention developers need to be aware of the dietary changes women may spontaneously engage in when becoming pregnant, so that care and interventions can build on these

Multi-centre parallel arm randomised controlled trial to assess the effectiveness and cost-effectiveness of a group-based cognitive behavioural approach to managing fatigue in people with multiple sclerosis

Abstract (provisional) Background Fatigue is one of the most commonly reported and debilitating symptoms of multiple sclerosis (MS); approximately two-thirds of people with MS consider it to be one of their three most troubling symptoms. It may limit or prevent participation in everyday activities, work, leisure, and social pursuits, reduce psychological well-being and is one of the key precipitants of early retirement. Energy effectiveness approaches have been shown to be effective in reducing MS-fatigue, increasing self-efficacy and improving quality of life. Cognitive behavioural approaches have been found to be effective for managing fatigue in other conditions, such as chronic fatigue syndrome, and more recently, in MS. The aim of this pragmatic trial is to evaluate the clinical and cost-effectiveness of a recently developed group-based fatigue management intervention (that blends cognitive behavioural and energy effectiveness approaches) compared with current local practice. Methods This is a multi-centre parallel arm block-randomised controlled trial (RCT) of a six session group-based fatigue management intervention, delivered by health professionals, compared with current local practice. 180 consenting adults with a confirmed diagnosis of MS and significant fatigue levels, recruited via secondary/primary care or newsletters/websites, will be randomised to receive the fatigue management intervention or current local practice. An economic evaluation will be undertaken alongside the trial. Primary outcomes are fatigue severity, self-efficacy and disease-specific quality of life. Secondary outcomes include fatigue impact, general quality of life, mood, activity patterns, and cost-effectiveness. Outcomes in those receiving the fatigue management intervention will be measured 1 week prior to, and 1, 4, and 12 months after the intervention (and at equivalent times in those receiving current local practice). A qualitative component will examine what aspects of the fatigue management intervention participants found helpful/unhelpful and barriers to change. Discussion This trial is the fourth stage of a research programme that has followed the Medical Research Council guidance for developing and evaluating complex interventions. What makes the intervention unique is that it blends cognitive behavioural and energy effectiveness approaches. A potential strength of the intervention is that it could be integrated into existing service delivery models as it has been designed to be delivered by staff already working with people with MS. Service users will be involved throughout this research. Trial registration: Current Controlled Trials ISRCTN7651747

The genome of a songbird

The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chickenthe only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat- based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour. © 2010 Macmillan Publishers Limited. All rights reserved

The genome of the green anole lizard and a comparative analysis with birds and mammals

The evolution of the amniotic egg was one of the great evolutionary innovations in the history of life, freeing vertebrates from an obligatory connection to water and thus permitting the conquest of terrestrial environments. Among amniotes, genome sequences are available for mammals and birds, but not for non-avian reptiles. Here we report the genome sequence of the North American green anole lizard, Anolis carolinensis. We find that A. carolinensis microchromosomes are highly syntenic with chicken microchromosomes, yet do not exhibit the high GC and low repeat content that are characteristic of avian microchromosomes. Also, A. carolinensis mobile elements are very young and diverse—more so than in any other sequenced amniote genome. The GC content of this lizard genome is also unusual in its homogeneity, unlike the regionally variable GC content found in mammals and birds. We describe and assign sequence to the previously unknown A. carolinensis X chromosome. Comparative gene analysis shows that amniote egg proteins have evolved significantly more rapidly than other proteins. An anole phylogeny resolves basal branches to illuminate the history of their repeated adaptive radiations.National Science Foundation (U.S.) (NSF grant DEB-0920892)National Science Foundation (U.S.) (NSF grant DEB-0844624)National Human Genome Research Institute (U.S.

A Systematically Improved High Quality Genome and Transcriptome of the Human Blood Fluke Schistosoma mansoni

Schistosomiasis is one of the most prevalent parasitic diseases, affecting millions of people in developing countries. Amongst the human-infective species, Schistosoma mansoni is also the most commonly used in the laboratory and here we present the systematic improvement of its draft genome. We used Sanger capillary and deep-coverage Illumina sequencing from clonal worms to upgrade the highly fragmented draft 380 Mb genome to one with only 885 scaffolds and more than 81% of the bases organised into chromosomes. We have also used transcriptome sequencing (RNA-seq) from four time points in the parasite's life cycle to refine gene predictions and profile their expression. More than 45% of predicted genes have been extensively modified and the total number has been reduced from 11,807 to 10,852. Using the new version of the genome, we identified trans-splicing events occurring in at least 11% of genes and identified clear cases where it is used to resolve polycistronic transcripts. We have produced a high-resolution map of temporal changes in expression for 9,535 genes, covering an unprecedented dynamic range for this organism. All of these data have been consolidated into a searchable format within the GeneDB (www.genedb.org) and SchistoDB (www.schistodb.net) databases. With further transcriptional profiling and genome sequencing increasingly accessible, the upgraded genome will form a fundamental dataset to underpin further advances in schistosome research

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

Livestock 2.0 – genome editing for fitter, healthier, and more productive farmed animals

Abstract The human population is growing, and as a result we need to produce more food whilst reducing the impact of farming on the environment. Selective breeding and genomic selection have had a transformational impact on livestock productivity, and now transgenic and genome-editing technologies offer exciting opportunities for the production of fitter, healthier and more-productive livestock. Here, we review recent progress in the application of genome editing to farmed animal species and discuss the potential impact on our ability to produce food