A maternal higher-complex carbohydrate diet increases bifidobacteria and alters early life acquisition of the infant microbiome in women with gestational diabetes mellitus

Gestational diabetes mellitus (GDM) is associated with considerable imbalances in intestinal microbiota that may underlie pathological conditions in both mothers and infants. To more definitively identify these alterations, we evaluated the maternal and infant gut microbiota through the shotgun metagenomic analysis of a subset of stool specimens collected from a randomized, controlled trial in diet-controlled women with GDM. The women were fed either a CHOICE diet (60% complex carbohydrate/25% fat/15% protein, n=18) or a conventional diet (CONV, 40% complex carbohydrate/45% fat/15% protein, n=16) from 30 weeks’ gestation through delivery. In contrast to other published studies, we designed the study to minimize the influence of other dietary sources by providing all meals, which were eucaloric and similar in fiber content. At 30 and 37 weeks’ gestation, we collected maternal stool samples; performed the fasting measurements of glucose, glycerol, insulin, free fatty acids, and triglycerides; and administered an oral glucose tolerance test (OGTT) to measure glucose clearance and insulin response. Infant stool samples were collected at 2 weeks, 2 months, and 4–5 months of age. Maternal glucose was controlled to conventional targets in both diets, with no differences in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). No differences in maternal alpha or beta diversity between the two diets from baseline to 37 weeks’ gestation were observed. However, women on CHOICE diet had higher levels of Bifidobacteriaceae, specifically Bifidobacterium adolescentis, compared with women on CONV. Species-level taxa varied significantly with fasting glycerol, fasting glucose, and glucose AUC after the OGTT challenge. Maternal diet significantly impacted the patterns of infant colonization over the first 4 months of life, with CHOICE infants showing increased microbiome alpha diversity (richness), greater Clostridiaceae, and decreased Enterococcaceae over time. Overall, these results suggest that an isocaloric GDM diet containing greater complex carbohydrates with reduced fat leads to an ostensibly beneficial effect on the maternal microbiome, improved infant gut microbiome diversity, and reduced opportunistic pathogens capable of playing a role in obesity and immune system development. These results highlight the critical role a maternal diet has in shaping the maternal and infant microbiome in women with GDM

Design and feasibility testing of a novel group intervention for young women who binge drink in groups

BackgroundYoung women frequently drink alcohol in groups and binge drinking within these natural drinking groups is common. This study describes the design of a theoretically and empirically based group intervention to reduce binge drinking among young women. It also evaluates their engagement with the intervention and the acceptability of the study methods.MethodsFriendship groups of women aged 18–35 years, who had two or more episodes of binge drinking (>6 UK units on one occasion; 48g of alcohol) in the previous 30 days, were recruited from the community. A face-to-face group intervention, based on the Health Action Process Approach, was delivered over three sessions. Components of the intervention were woven around fun activities, such as making alcohol free cocktails. Women were followed up four months after the intervention was delivered. Results The target of 24 groups (comprising 97 women) was recruited. The common pattern of drinking was infrequent, heavy drinking (mean consumption on the heaviest drinking day was UK 18.1 units). Process evaluation revealed that the intervention was delivered with high fidelity and acceptability of the study methods was high. The women engaged positively with intervention components and made group decisions about cutting down. Twenty two groups set goals to reduce their drinking, and these were translated into action plans. Retention of individuals at follow up was 87%.ConclusionsThis study successfully recruited groups of young women whose patterns of drinking place them at high risk of acute harm. This novel approach to delivering an alcohol intervention has potential to reduce binge drinking among young women. The high levels of engagement with key steps in the behavior change process suggests that the group intervention should be tested in a full randomised controlled trial

Gestational Diabetes Is Characterized by Reduced Mitochondrial Protein Expression and Altered Calcium Signaling Proteins in Skeletal Muscle

The rising prevalence of gestational diabetes mellitus (GDM) affects up to 18% of pregnant women with immediate and long-term metabolic consequences for both mother and infant. Abnormal glucose uptake and lipid oxidation are hallmark features of GDM prompting us to use an exploratory proteomics approach to investigate the cellular mechanisms underlying differences in skeletal muscle metabolism between obese pregnant women with GDM (OGDM) and obese pregnant women with normal glucose tolerance (ONGT). Functional validation was performed in a second cohort of obese OGDM and ONGT pregnant women. Quantitative proteomic analysis in rectus abdominus skeletal muscle tissue collected at delivery revealed reduced protein content of mitochondrial complex I (C-I) subunits (NDUFS3, NDUFV2) and altered content of proteins involved in calcium homeostasis/signaling (calcineurin A, α1-syntrophin, annexin A4) in OGDM (n = 6) vs. ONGT (n = 6). Follow-up analyses showed reduced enzymatic activity of mitochondrial complexes C-I, C-III, and C-IV (−60–75%) in the OGDM (n = 8) compared with ONGT (n = 10) subjects, though no differences were observed for mitochondrial complex protein content. Upstream regulators of mitochondrial biogenesis and oxidative phosphorylation were not different between groups. However, AMPK phosphorylation was dramatically reduced by 75% in the OGDM women. These data suggest that GDM is associated with reduced skeletal muscle oxidative phosphorylation and disordered calcium homeostasis. These relationships deserve further attention as they may represent novel risk factors for development of GDM and may have implications on the effectiveness of physical activity interventions on both treatment strategies for GDM and for prevention of type 2 diabetes postpartum

The Importance of Nutrition in Pregnancy and Lactation: Lifelong Consequences.

Most women in the United States do not meet the recommendations for healthful nutrition and weight before and during pregnancy. Women and providers often ask what a healthy diet for a pregnant woman should look like. The message should be “eat better, not more.” This can be achieved by basing diet on a variety of nutrient-dense, whole foods, including fruits, vegetables, legumes, whole grains, healthy fats with omega-3 fatty acids that include nuts and seeds, and fish, in place of poorer quality highly processed foods. Such a diet embodies nutritional density and is less likely to be accompanied by excessive energy intake than the standard American diet consisting of increased intakes of processed foods, fatty red meat, and sweetened foods and beverages. Women who report “prudent” or “health-conscious” eating patterns before and/or during pregnancy may have fewer pregnancy complications and adverse child health outcomes. Comprehensive nutritional supplementation (multiple micronutrients plus balanced protein energy) among women with inadequate nutrition has been associated with improved birth outcomes, including decreased rates of low birthweight. A diet that severely restricts any macronutrient class should be avoided, specifically the ketogenic diet that lacks carbohydrates, the Paleo diet because of dairy restriction, and any diet characterized by excess saturated fats. User-friendly tools to facilitate a quick evaluation of dietary patterns with clear guidance on how to address dietary inadequacies and embedded support from trained healthcare providers are urgently needed. Recent evidence has shown that although excessive gestational weight gain predicts adverse perinatal outcomes among women with normal weight, the degree of prepregnancy obesity predicts adverse perinatal outcomes to a greater degree than gestational weight gain among women with obesity. Furthermore, low body mass index and insufficient gestational weight gain are associated with poor perinatal outcomes. Observational data have shown that first-trimester gain is the strongest predictor of adverse outcomes. Interventions beginning in early pregnancy or preconception are needed to prevent downstream complications for mothers and their children. For neonates, human milk provides personalized nutrition and is associated with short- and long-term health benefits for infants and mothers. Eating a healthy diet is a way for lactating mothers to support optimal health for themselves and their infants

Calling by Concluding Sentinels: Coordinating Cooperation or Revealing Risk?

Efficient cooperation requires effective coordination of individual contributions to the cooperative behaviour. Most social birds and mammals involved in cooperation produce a range of vocalisations, which may be important in regulating both individual contributions and the combined group effort. Here we investigate the role of a specific call in regulating cooperative sentinel behaviour in pied babblers (Turdoides bicolor). ‘Fast-rate chuck’ calls are often given by sentinels as they finish guard bouts and may potentially coordinate the rotation of individuals as sentinels, minimising time without a sentinel, or may signal the presence or absence of predators, regulating the onset of the subsequent sentinel bout. We ask (i) when fast-rate chuck calls are given and (ii) what effect they have on the interval between sentinel bouts. Contrary to expectation, we find little evidence that these calls are involved in regulating the pied babbler sentinel system: observations revealed that their utterance is influenced only marginally by wind conditions and not at all by habitat, while observations and experimental playback showed that the giving of these calls has no effect on inter-bout interval. We conclude that pied babblers do not seem to call at the end of a sentinel bout to maximise the efficiency of this cooperative act, but may use vocalisations at this stage to influence more individually driven behaviours

Why do General Practitioners Decline Training to Improve Management of Medically Unexplained Symptoms?

BACKGROUND: General practitioners’ (GPs) communication with patients presenting medically unexplained symptoms (MUS) has the potential to somatize patients’ problems and intensify dependence on medical care. Several reports indicate that GPs have negative attitudes about patients with MUS. If these attitudes deter participation in training or other methods to improve communication, practitioners who most need help will not receive it. OBJECTIVE: To identify how GPs’ attitudes to patients with MUS might inhibit their participation with training to improve management. DESIGN: Qualitative study. PARTICIPANTS: GPs (N = 33) who had declined or accepted training in reattribution techniques in the context of a research trial. APPROACH: GPs were interviewed and their accounts analysed qualitatively. RESULTS: Although attitudes that devalued patients with MUS were common in practitioners who had declined training, these coexisted, in the same practitioners, with evidence of intuitive and elaborate psychological work with these patients. However, these practitioners devalued their psychological skills. GPs who had accepted training also described working psychologically with MUS but devalued neither patients with MUS nor their own psychological skills. CONCLUSIONS: GPs’ attitudes that suggested disengagement from patients with MUS belied their pursuit of psychological objectives. We therefore suggest that, whereas negative attitudes to patients have previously been regarded as the main barrier to involvement in measures to improve patient management, GPs devaluing of their own psychological skills with these patients may be more important

Use of communities of practice in business and health care sectors: A systematic review

<p>Abstract</p> <p>Background</p> <p>Since being identified as a concept for understanding knowledge sharing, management, and creation, communities of practice (CoPs) have become increasingly popular within the health sector. The CoP concept has been used in the business sector for over 20 years, but the use of CoPs in the health sector has been limited in comparison.</p> <p>Objectives</p> <p>First, we examined how CoPs were defined and used in these two sectors. Second, we evaluated the evidence of effectiveness on the health sector CoPs for improving the uptake of best practices and mentoring new practitioners.</p> <p>Methods</p> <p>We conducted a search of electronic databases in the business, health, and education sectors, and a hand search of key journals for primary studies on CoP groups. Our research synthesis for the first objective focused on three areas: the authors' interpretations of the CoP concept, the key characteristics of CoP groups, and the common elements of CoP groups. To examine the evidence on the effectiveness of CoPs in the health sector, we identified articles that evaluated CoPs for improving health professional performance, health care organizational performance, professional mentoring, and/or patient outcome; and used experimental, quasi-experimental, or observational designs.</p> <p>Results</p> <p>The structure of CoP groups varied greatly, ranging from voluntary informal networks to work-supported formal education sessions, and from apprentice training to multidisciplinary, multi-site project teams. Four characteristics were identified from CoP groups: social interaction among members, knowledge sharing, knowledge creation, and identity building; however, these were not consistently present in all CoPs. There was also a lack of clarity in the responsibilities of CoP facilitators and how power dynamics should be handled within a CoP group. We did not find any paper in the health sector that met the eligibility criteria for the quantitative analysis, and so the effectiveness of CoP in this sector remained unclear.</p> <p>Conclusion</p> <p>There is no dominant trend in how the CoP concept is operationalized in the business and health sectors; hence, it is challenging to define the parameters of CoP groups. This may be one of the reasons for the lack of studies on the effectiveness of CoPs in the health sector. In order to improve the usefulness of the CoP concept in the development of groups and teams, further research will be needed to clarify the extent to which the four characteristics of CoPs are present in the mature and emergent groups, the expectations of facilitators and other participants, and the power relationship within CoPs.</p

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts