Contraceptive Use and Pregnancy Outcomes among Opioid Drug-Using Women: A Retrospective Cohort Study

Objective

The contraceptive needs of illicit opioid users differ from non-drug users but are poorly understood. The aim of this study was to describe contraceptive use and pregnancy outcomes in opioid-using women, and to examine their association with a range of risk factors.

Method

This retrospective cohort study used UK general practice records, Treatment Outcomes Profile and National Drug Treatment Monitoring System data, and a nested data validation exercise. A cohort of 376 women aged 20–61 years were in active treatment for opioid addiction in October 2010 at two specialised primary care practices in North-East England. Outcomes were age-adjusted prevalence estimates for contraceptive use and pregnancy outcomes in users of illicit opioids. The association between lifestyle-related risk factors and contraception was explored.

Results

Drug-using women made lower use of planned (non-condom) contraception (24% vs 50%, p<0.001), had more frequent pregnancy terminations (0.46 vs. 0.025, p = 0.004) and higher annual incidence of chlamydia (1.1% vs. 0.33%, p<0.001), when compared with age-matched population data. Specifically, there was low use of oral contraceptives (4% vs. 25%, p<0.001), IUCD (1% vs. 6%, p<0.001), and sterilisation (7% vs. 6%, p = 0.053), but higher rates of injectable contraceptives (6% vs. 3%, p = 0.003). A total of 64% of children aged <16 years born to this group did not live with their mother. No individual risk factor (such as sex-working) significantly explained the lower use or type of non-condom contraception.

Conclusions

This is the first study to describe planned contraceptive use among drug-users, as well as the association with a range of risk factors and pregnancy outcomes. The low uptake of planned contraception, set against high rates of terminations and sexually transmitted disease demonstrates the urgent clinical need to improve contraceptive services, informed by qualitative work to explore the values and beliefs influencing low contraceptive uptake.     

The Relationship between Cranial Structure,Biomechanical Performance and Ecological Diversity in Varanoid Lizards

Skull structure is intimately associated with feeding ability in vertebrates, both in terms of specific performance measures and general ecological characteristics. This study quantitatively assessed variation in the shape of the cranium and mandible in varanoid lizards, and its relationship to structural performance (von Mises strain) and interspecific differences in feeding ecology. Geometric morphometric and linear morphometric analyses were used to evaluate morphological differences, and finite element analysis was used to quantify variation in structural performance (strain during simulated biting, shaking and pulling). This data was then integrated with ecological classes compiled from relevant scientific literature on each species in order to establish structure-function relationships. Finite element modelling results showed that variation in cranial morphology resulted in large differences in the magnitudes and locations of strain in biting, shaking and pulling load cases. Gracile species such as Varanus salvadorii displayed high strain levels during shaking, especially in the areas between the orbits. All models exhibit less strain during pull back loading compared to shake loading, even though a larger force was applied (pull =30N, shake = 20N). Relationships were identified between the morphology, performance, and ecology. Species that did not feed on hard prey clustered in the gracile region of cranial morphospace and exhibited significantly higher levels of strain during biting (P = 0.0106). Species that fed on large prey clustered in the elongate area of mandible morphospace. This relationship differs from those that have been identified in other taxonomic groups such as crocodiles and mammals. This difference may be due to a combination of the open ‘space-frame’ structure of the varanoid lizard skull, and the ‘pull back’ behaviour that some species use for processing large prey.     

Cross-cultural consensus for waist–hip ratio and women's attractiveness

In women of reproductive age, a gynoid body fat distribution as measured by the size of waist–hip ratio (WHR) is a reliable indicator of their sex hormone profile, greater success in pregnancy and less risk for major diseases. According to evolutionary mate selection theory, such indicators of health and fertility should be judged as attractive. Previous research has confirmed this prediction. In this current research, we use the same stimulus for diverse racial groups (Bakossiland, Cameroon, Africa; Komodo Island, Indonesia; Samoa; and New Zealand) to examine the universality of relationships between WHR and attractiveness. As WHR is positively correlated with body mass index (BMI), we controlled BMI by using photographs of women who have gone through micrograft surgery for cosmetic reasons. Results show that in each culture participants selected women with low WHR as attractive, regardless of increases or decreases in BMI. This cross-cultural consensus suggests that the link between WHR and female attractiveness is due to adaptation shaped by the selection process.     

The identification of a series of novel, soluble non-peptidic neuropeptide Y Y2 receptor antagonists

The identification and subsequent optimisation of a selective non-peptidic NPY Y2 antagonist series is described. This led to the development of amine 2, a selective, soluble NPY Y2 receptor antagonist with enhanced CNS exposure.     

ERp57 is essential for efficient folding of glycoproteins sharing common structural domains

ERp57 is a member of the protein disulphide isomerase family of oxidoreductases, which are involved in native disulphide bond formation in the endoplasmic reticulum of mammalian cells. This enzyme has been shown to be associated with both calnexin and calreticulin and, therefore, has been proposed to be a glycoprotein-specific oxidoreductase. Here, we identify endogenous substrates for ERp57 by trapping mixed disulphide intermediates between enzyme and substrate. Our results demonstrate that the substrates for this enzyme are mostly heavily glycosylated, disulphide bonded proteins. In addition, we show that the substrate proteins share common structural domains, indicating that substrate specificity may involve specific structural features as well as the presence of an oligosaccharide side chain. We also show that the folding of two of the endogenous substrates for ERp57 is impaired in ERp57 knockout cells and that prevention of an interaction with calnexin or calreticulin perturbs the folding of some, but not all, substrates with multiple disulphide bonds. These results suggest a specific role for ERp57 in the isomerisation of non-native disulphide bonds in specific glycoprotein substrates.     

Enhancing yeast cell viability after dehydration by modification of the lipid profile

In the present study, we analysed metabolite features during the dehydration-rehydration process for different yeast species genetically closely related to S. cerevisiae, in order to determine whether metabolites might play a role in cell viability. We ranked the species S. cerevisiae, S. paradoxus, S. kudriavzevii, L. kluyveri, N. castellii, S. mikatae, S. bayanus, and S. servazzii according to their viability rate after the dehydration-rehydration process, and showed that desiccation tolerance across the species did not correlate with the intracellular content of trehalose or glycogen. Cell lipid composition was also investigated during this process, to see whether the content of triacylglycerols and phosphatidylcholine showed significant variations across the species. The increase of phosphatidylcholine level increase in both S. paradoxus and S. bayanus cells grown in supplemented media enhanced both their cell viability after stress imposition and lipid storage.     

Influence of wine-like conditions on arginine utilization by lactic acid bacteria

Wine can contain trace amounts of ethyl carbamate (EC), a carcinogen formed when ethanol reacts with carbamyl compounds such as citrulline. EC is produced from arginine by lactic acid bacteria (LAB), e.g., Lactobacillus and Pediococcus. Although the amounts of EC in wine are usually negligible, over the last few years there has been a slight but steady increase, as climate change has increased temperatures and alcohol levels have become proportionately higher, both of which favor EC formation. In this study, resting cells of LAB were used to evaluate the effects of ethanol, glucose, malic acid, and low pH on the ability of non-oenococcal strains of these bacteria to degrade arginine and excrete citrulline. Malic acid was found to clearly inhibit arginine consumption in all strains. The relation between citrulline produced and arginine consumed was clearly higher in the presence of ethanol (10-12%) and at low pH (3.0), which is consistent with both the decreased amount of ornithine produced from arginine and the reduction in arginine degradation. In L. brevis and L. buchneri strains isolated from wine and beer, respectively, the synthesis of citrulline from arginine was highest.     

Efficient suspension bioreactor expansion of murine embryonic stem cells on microcarriers in serum-free medium

Large numbers of cells will be required for successful embryonic stem cell (ESC)-based cellular therapies or drug discovery, thus raising the need to develop scaled-up bioprocesses for production of ESCs and their derived progeny. Traditionally, ESCs have been propagated in adherent cultures in static flasks on fibroblasts layers in serum-containing medium. Direct translation of two-dimensional flatbed cultures to large-scale production of the quantities of cells required for therapy simply by increasing the number of dishes or flasks is not practical or economical. Here, we describe successful scaled-up production of ESCs on microcarriers in a stirred culture system in a serum-free medium. Cells expanded on CultiSpher S, Cytodex 3, and Collagen microcarriers showed superior cell-fold expansions of 439, 193, and 68, respectively, without excessive agglomeration, compared with 27 in static culture. In addition, the ESCs maintained their pluripotency after long-term culture (28 days) in serum-free medium. This is the first time mESCs have been cultured on microcarriers without prior exposure to serum and/or fibroblasts, while also eliminating the excessive agglomeration plaguing earlier studies. These protocols provide an economical, practical, serum-free means for expanding ESCs in a stirred suspension bioprocess.