Preconception care of women with diabetes: a review of current guideline recommendations

<p>Abstract</p> <p>Background</p> <p>The prevalence of type 2 diabetes mellitus (T2DM) continues to rise worldwide. More women from developing countries who are in the reproductive age group have diabetes resulting in more pregnancies complicated by T2DM, and placing both mother and foetus at higher risk. Management of these risks is best achieved through comprehensive preconception care and glycaemic control, both prior to, and during pregnancy. The aim of this review was to compare the quality and content of current guidelines concerned with the preconception care of women with diabetes and to develop a summary of recommendations to assist in the management of diabetic women contemplating pregnancy.</p> <p>Methods</p> <p>Relevant clinical guidelines were identified through a search of several databases (MEDLINE, SCOPUS and The Cochrane Library) and relevant websites. Five guidelines were identified. Each guideline was assessed for quality using the AGREE instrument. Guideline recommendations were extracted, compared and contrasted.</p> <p>Results</p> <p>All guidelines were assessed as being of high quality and strongly recommended for use in practice. All were consistent in counselling about the risk of congenital malformation related to uncontrolled blood sugar preconceptionally, ensuring adequate contraception until glycaemic control is achieved, use of HBA1C to monitor metabolic control, when to commence insulin and switching from ACE inhibitors to other antihypertensives. Major differences were in the targets recommended for optimal metabolic control and opinion regarding the usage of metformin as an adjunct or alternative treatment before or during pregnancy.</p> <p>Conclusions</p> <p>International guidelines for the care of women with diabetes who are contemplating pregnancy are consistent in their recommendations; however some are more comprehensive than others. Having established current standards for the preconception care of diabetic women, there is now a need to focus on guideline implementation through an examination of the barriers and enablers to successful implementation, and the applicability of the recommendations in the local setting.</p

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Stimulated monocyte IL-6 secretion predicts survival of patients with head and neck squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>This study was performed in order to determine whether monocyte <it>in vitro </it>function is associated with presence, stage and prognosis of head and neck squamous cell carcinoma (HNSCC) disease.</p> <p>Methods</p> <p>Prospective study describing outcome, after at least five years observation, of patients treated for HNSCC disease in relation to their monocyte function. Sixty-five patients with newly diagnosed HNSCC and eighteen control patients were studied. Monocyte responsiveness was assessed by measuring levels of monocyte <it>in vitro </it>interleukin (IL)-6 and monocyte chemotactic peptide (MCP)-1 secretion after 24 hours of endotoxin stimulation in cultures supplied either with 20% autologous serum (AS) or serum free medium (SFM). Survival, and if relevant, cause of death, was determined at least 5 years following primary diagnosis.</p> <p>Results</p> <p>All patients, as a group, had higher <it>in vitro </it>monocyte responsiveness in terms of IL-6 (AS) (<it>t </it>= 2.03; <it>p </it>< 0.05) and MCP-1 (SFM) (<it>t </it>= 2.49; <it>p </it>< 0.05) compared to controls. Increased <it>in vitro </it>monocyte IL-6 endotoxin responsiveness under the SFM condition was associated with decreased survival rate (Hazard ratio (HR) = 2.27; Confidence interval (CI) = 1.05–4.88; <it>p </it>< 0.05). The predictive value of monocyte responsiveness, as measured by IL-6, was also retained when adjusted for age, gender and disease stage of patients (HR = 2.67; CI = 1.03–6.92; <it>p </it>< 0.05). With respect to MCP-1, low endotoxin-stimulated responsiveness (AS), analysed by Kaplan-Meier method, predicted decreased survival (χ = 4.0; <it>p </it>< 0.05).</p> <p>Conclusion</p> <p>In HNSCC patients, changed monocyte <it>in vitro </it>response to endotoxin, as measured by increased IL-6 (SFM) and decreased MCP-1 (AS) responsiveness, are negative prognostic factors.</p

Spo0A∼P Imposes a Temporal Gate for the Bimodal Expression of Competence in Bacillus subtilis

ComK transcriptionally controls competence for the uptake of transforming DNA in Bacillus subtilis. Only 10%–20% of the cells in a clonal population are randomly selected for competence. Because ComK activates its own promoter, cells exceeding a threshold amount of ComK trigger a positive feedback loop, transitioning to the competence ON state. The transition rate increases to a maximum during the approach to stationary phase and then decreases, with most cells remaining OFF. The average basal rate of comK transcription increases transiently, defining a window of opportunity for transitions and accounting for the heterogeneity of competent populations. We show that as the concentration of the response regulator Spo0A∼P increases during the entry to stationary phase it first induces comK promoter activity and then represses it by direct binding. Spo0A∼P activates by antagonizing the repressor, Rok. This amplifies an inherent increase in basal level comK promoter activity that takes place during the approach to stationary phase and is a general feature of core promoters, serving to couple the probability of competence transitions to growth rate. Competence transitions are thus regulated by growth rate and temporally controlled by the complex mechanisms that govern the formation of Spo0A∼P. On the level of individual cells, the fate-determining noise for competence is intrinsic to the comK promoter. This overall mechanism has been stochastically simulated and shown to be plausible. Thus, a deterministic mechanism modulates an inherently stochastic process

Eaten out of house and home:impacts of grazing on ground-dwelling reptiles in Australian grasslands and grassy woodlands

Large mammalian grazers can alter the biotic and abiotic features of their environment through their impacts on vegetation. Grazing at moderate intensity has been recommended for biodiversity conservation. Few studies, however, have empirically tested the benefits of moderate grazing intensity in systems dominated by native grazers. Here we investigated the relationship between (1) density of native eastern grey kangaroos, Macropus giganteus, and grass structure, and (2) grass structure and reptiles (i.e. abundance, richness, diversity and occurrence) across 18 grassland and grassy Eucalyptus woodland properties in south-eastern Australia. There was a strong negative relationship between kangaroo density and grass structure after controlling for tree canopy cover. We therefore used grass structure as a surrogate for grazing intensity. Changes in grazing intensity (i.e. grass structure) significantly affected reptile abundance, reptile species richness, reptile species diversity, and the occurrence of several ground-dwelling reptiles. Reptile abundance, species richness and diversity were highest where grazing intensity was low. Importantly, no species of reptile was more likely to occur at high grazing intensities. Legless lizards (Delma impar, D. inornata) were more likely to be detected in areas subject to moderate grazing intensity, whereas one species (Hemiergis talbingoensis) was less likely to be detected in areas subject to intense grazing and three species (Menetia greyii, Morethia boulengeri, and Lampropholis delicata) did not appear to be affected by grazing intensity. Our data indicate that to maximize reptile abundance, species richness, species diversity, and occurrence of several individual species of reptile, managers will need to subject different areas of the landscape to moderate and low grazing intensities and limit the occurrence and extent of high grazing

Biochemical Characterization of a Structure-Specific Resolving Enzyme from Sulfolobus islandicus Rod-Shaped Virus 2

Sulfolobus islandicus rod shaped virus 2 (SIRV2) infects the archaeon Sulfolobus islandicus at extreme temperature (70°C–80°C) and acidity (pH 3). SIRV2 encodes a Holliday junction resolving enzyme (SIRV2 Hjr) that has been proposed as a key enzyme in SIRV2 genome replication. The molecular mechanism for SIRV2 Hjr four-way junction cleavage bias, minimal requirements for four-way junction cleavage, and substrate specificity were determined. SIRV2 Hjr cleaves four-way DNA junctions with a preference for cleavage of exchange strand pairs, in contrast to host-derived resolving enzymes, suggesting fundamental differences in substrate recognition and cleavage among closely related Sulfolobus resolving enzymes. Unlike other viral resolving enzymes, such as T4 endonuclease VII or T7 endonuclease I, that cleave branched DNA replication intermediates, SIRV2 Hjr cleavage is specific to four-way DNA junctions and inactive on other branched DNA molecules. In addition, a specific interaction was detected between SIRV2 Hjr and the SIRV2 virion body coat protein (SIRV2gp26). Based on this observation, a model is proposed linking SIRV2 Hjr genome resolution to viral particle assembly

Effects of Protein Deficiency on Perinatal and Postnatal Health Outcomes

There are a variety of environmental insults that can occur during pregnancy which cause low birth weight and poor fetal health outcomes. One such insult is maternal malnutrition, which can be further narrowed down to a low protein diet during gestation. Studies show that perinatal protein deficiencies can impair proper organ growth and development, leading to long-term metabolic dysfunction. Understanding the molecular mechanisms that underlie how this deficiency leads to adverse developmental outcomes is essential for establishing better therapeuticstrategies that may alleviate or prevent diseases in later life. This chapter reviews how perinatal protein restriction in humans and animals leads to metabolic disease, and it identifies the mechanisms that have been elucidated, to date. These include alterations in transcriptional and epigenetic mechanisms, as well as indirect means such as endoplasmic reticulum (ER) stress and oxidative stress. Furthermore, nutritional and pharmaceutical interventions are highlighted to illustrate that the plasticity of the underdeveloped organs during perinatal life can be exploited to prevent onset of long-term metabolic disease