Glucose-stimulated insulin response in pregnant sheep following acute suppression of plasma non-esterified fatty acid concentrations

BACKGROUND: Elevated non-esterified fatty acids (NEFA) concentrations in non-pregnant animals have been reported to decrease pancreatic responsiveness. As ovine gestation advances, maternal insulin concentrations fall and NEFA concentrations increase. Experiments were designed to examine if the pregnancy-associated rise in NEFA concentration is associated with a reduced pancreatic sensitivity to glucose in vivo. We investigated the possible relationship of NEFA concentrations in regulating maternal insulin concentrations during ovine pregnancy at three physiological states, non-pregnant, non-lactating (NPNL), 105 and 135 days gestational age (dGA, term 147+/- 3 days). METHODS: The plasma concentrations of insulin, growth hormone (GH) and ovine placental lactogen (oPL) were determined by double antibody radioimmunoassay. Insulin responsiveness to glucose was measured using bolus injection and hyperglycaemic clamp techniques in 15 non-pregnant, non-lactating ewes and in nine pregnant ewes at 105 dGA and near term at 135 dGA. Plasma samples were also collected for hormone determination. In addition to bolus injection glucose and insulin Area Under Curve calculations, the Mean Plasma Glucose Increment, Glucose Infusion Rate and Mean Plasma Insulin Increment and Area Under Curve were determined for the hyperglycaemic clamp procedures. Statistical analysis of data was conducted with Students t-tests, repeated measures ANOVA and 2-way ANOVA. RESULTS: Maternal growth hormone, placental lactogen and NEFA concentrations increased, while basal glucose and insulin concentrations declined with advancing gestation. At 135 dGA following bolus glucose injections, peak insulin concentrations and insulin area under curve (AUC) profiles were significantly reduced in pregnant ewes compared with NPNL control ewes (p < 0.001 and P < 0.001, respectively). In hyperglycaemic clamp studies, while maintaining glucose levels not different from NPNL ewes, pregnant ewes displayed significantly reduced insulin responses and a maintained depressed insulin secretion. In NPNL ewes, 105 and 135 dGA ewes, the Glucose Infusion Rate (GIR) was constant at approximately 5.8 mg glucose/kg/min during the last 40 minutes of the hyperglycaemic clamp and the Mean Plasma Insulin Increment (MPII) was only significantly (p < 0.001) greater in NPNL ewes. Following the clamp, NEFA concentrations were reduced by approximately 60% of pre-clamp levels in all groups, though a blunted and suppressed insulin response was maintained in 105 and 135 dGA ewes. CONCLUSIONS: Results suggest that despite an acute suppression of circulating NEFA concentrations during pregnancy, the associated steroids and hormones of pregnancy and possibly NEFA metabolism, may act to maintain a reduced insulin output, thereby sparing glucose for non-insulin dependent placental uptake and ultimately, fetal requirements

Surface effects of vapour-liquid-solid driven Bi surface droplets formed during molecular-beam-epitaxy of GaAsBi

Herein we investigate a (001)-oriented GaAs1−xBix/GaAs structure possessing Bi surface droplets capable of catalysing the formation of nanostructures during Bi-rich growth, through the vapourliquid-solid mechanism. Specifically, self-aligned “nanotracks” are found to exist trailing the Bi droplets on the sample surface. Through cross-sectional high-resolution transmission electron microscopy the nanotracks are revealed to in fact be elevated above surface by the formation of a subsurface planar nanowire, a structure initiated mid-way through the molecular-beam-epitaxy growth and embedded into the epilayer, via epitaxial overgrowth. Electron microscopy studies also yield the morphological, structural, and chemical properties of the nanostructures. Through a combination of Bi determination methods the compositional profile of the film is shown to be graded and inhomogeneous. Furthermore, the coherent and pure zincblende phase property of the film is detailed. Optical characterisation of features on the sample surface is carried out using polarised micro-Raman and micro-photoluminescence spectroscopies. The important light producing properties of the surface nanostructures are investigated through pump intensity-dependent micro PL measurements, whereby relatively large local inhomogeneities are revealed to exist on the epitaxial surface for important optical parameters. We conclude that such surface effects must be considered when designing and fabricating optical devices based on GaAsBi alloys

Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications

Endometriosis is a common, oestrogen driven chronic condition, where endometrium-like epithelial and stromal cells exist in ectopic sites. At present, no curative treatments are available and the existing evidence for disease progression is conflicting. The pathogenesis is still unknown and evidently complex, as mechanisms of initiation may depend on the anatomical distribution of endometriotic lesions. However, amongst the numerous theories and plethora of mechanisms, contributions of the fallopian tubes (FT) to endometriosis are rarely discussed. The FT are implicated in all endometriosis associated symptomatology and clinical consequences; they may contribute to the origin of endometriotic tissue, determine the sites for ectopic lesion establishment and act as conduits for the spread of proinflammatory media. Here, we examine the available evidence for the contribution of the human FT to the origin, pathogenesis and symptoms/clinical consequences of endometriosis. We also examine the broader topic linking endometriosis and the FT epithelium to the genesis of ovarian epithelial cancers. Further studies elucidating the distinct functional and phenotypical characteristics of FT mucosa may allow the development of novel treatment strategies for endometriosis that are potentially curative

'Choosing shoes': a preliminary study into the challenges facing clinicians in assessing footwear for rheumatoid patients

Background: Footwear has been accepted as a therapeutic intervention for the foot affected by rheumatoid arthritis (RA). Evidence relating to the objective assessment of footwear in patients with RA is limited. The aims of this study were to identify current footwear styles, footwear characteristics, and factors that influence footwear choice experienced by patients with RA. Methods: Eighty patients with RA were recruited from rheumatology clinics during the summer months. Clinical characteristics, global function, and foot impairment and disability measures were recorded. Current footwear, footwear characteristics and the factors associated with choice of footwear were identified. Suitability of footwear was recorded using pre-determined criteria for assessing footwear type, based on a previous study of foot pain. Results: The patients had longstanding RA with moderate-to severe disability and impairment. The foot and ankle assessment demonstrated a low-arch profile with both forefoot and rearfoot structural deformities. Over 50% of shoes worn by patients were opentype footwear. More than 70% of patients’ footwear was defined as being poor. Poor footwear characteristics such as heel rigidity and sole hardness were observed. Patients reported comfort (17%) and fit (14%) as important factors in choosing their own footwear. Only five percent (5%) of patients wore therapeutic footwear. Conclusions: The majority of patients with RA wear footwear that has been previously described as poor. Future work needs to aim to define and justify the specific features of footwear that may be of benefit to foot health for people with RA

A multicentre retrospective cohort comparison of aetiology and survival in patients with chronic hypersensitivity pneumonitis versus idiopathic pulmonary fibrosis

This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this recordWinter Meeting of the British Thoracic Society, 5-7 December 2018, London, U

Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays

We applied whole-genome single-nucleotide polymorphism arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range, 23-208) per tumor. LOH and gains averaged 33 (range, 3-83) and 31 (range, 11-73) per tumor, respectively. Copy neutral LOH events averaged 27 (range, 7-57) per EAC. We noted 126 homozygous deletions (HD) across the EAC panel (range, 0-11 in individual tumors). Frequent HDs within FHIT (17 of 23), WWOX (8 of 23), and DMD (6 of 23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 may be targeted. Frequent gains were noted around MYC (13 of 23), BCL9 (12 of 23), CTAGE1 (14 of 23), and ZNF217 (12 of 23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53, and MYC in EAC and identified additional genes of interest. Meta-analysis of previous genome-wide EAC studies together with the data presented here highlighted consistent regions of gain on 8q, 18q, and 20q and multiple LOH regions on 4q, 5q, 17p, and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development

Attitudes towards gender roles and prevalence of intimate partner violence perpetrated against pregnant and postnatal women: Differences between women immigrants from conflict-affected countries and women born in Australia

BACKGROUND: The aim was to compare, for the first time in a large systematic study, women born in conflict-affected countries who immigrated to Australia with women born in Australia for attitudes towards gender roles and men\u27s use of IPV and the actual prevalence of IPV. The study also examined if any associations remained across the two timepoints of pregnancy and postpartum. METHODS: Women were interviewed during their first visit to one of three Australian public hospital antenatal clinics and re-interviewed at home six months after giving birth. A total of 1111 women completed both interviews, 583 were born in conflict-affected countries and 528 born in Australia. Associations between attitudes towards gender roles and men\u27s use of IPV, socio-demographic characteristics and reported actual experiences of IPV were examined using bivariate and multiple logistic regression analyses. RESULTS: Attitudes toward inequitable gender roles including those that condone men\u27s use of IPV, and prevalence of IPV, were significantly higher (p \u3c 0.001) among women born in conflict-affected countries compared to Australia-born women. Women born in conflict-affected countries with the strongest held attitudes towards gender roles and men\u27s use of IPV had an adjusted odds ratio (aOR) of 3.18 for IPV at baseline (95% CI 1.85-5.47) and an aOR of 1.83 for IPV at follow-up (95% CI 1.11-3.01). Women born in Australia with the strongest held attitudes towards gender roles and IPV had an aOR of 7.12 for IPV at baseline (95% CI 2.12-23.92) and an aOR of 10.59 for IPV at follow-up (95% CI 2.21-50.75). CONCLUSIONS: Our results underscore the need for IPV prevention strategies sensitively targeted to communities from conflict-affected countries, and for awareness among clinicians of gender role attitudes that may condone men\u27s use of IPV, and the associated risk of IPV. The study supports the need for culturally informed national strategies to promote gender equality and to challenge practices and attitudes that condone men\u27s violence in spousal relationships

SiDCoN: A Tool to Aid Scoring of DNA Copy Number Changes in SNP Chip Data

The recent application of genome-wide, single nucleotide polymorphism (SNP) microarrays to investigate DNA copy number aberrations in cancer has provided unparalleled sensitivity for identifying genomic changes. In some instances the complexity of these changes makes them difficult to interpret, particularly when tumour samples are contaminated with normal (stromal) tissue. Current automated scoring algorithms require considerable manual data checking and correction, especially when assessing uncultured tumour specimens. To address these limitations we have developed a visual tool to aid in the analysis of DNA copy number data. Simulated DNA Copy Number (SiDCoN) is a spreadsheet-based application designed to simulate the appearance of B-allele and logR plots for all known types of tumour DNA copy number changes, in the presence or absence of stromal contamination. The system allows the user to determine the level of stromal contamination, as well as specify up to 3 different DNA copy number aberrations for up to 5000 data points (representing individual SNPs). This allows users great flexibility to assess simple or complex DNA copy number combinations. We demonstrate how this utility can be used to estimate the level of stromal contamination within tumour samples and its application in deciphering the complex heterogeneous copy number changes we have observed in a series of tumours. We believe this tool will prove useful to others working in the area, both as a training tool, and to aid in the interpretation of complex copy number changes

National Survey Highlights the Urgent Need for Standardisation of Embryo Transfer Techniques in the UK

Embryo transfer (ET) is one of the vital steps in the in vitro fertilisation (IVF) process, yet there is wide variation in ET technique throughout the UK, without a nationally approved standardised approach. The aim of this study was to gain contemporaneous information regarding the current clinical ET practice in the UK. Method: A 38-question electronic survey was distributed to the 79 UK Human Fertilisation and Embryology Authority (HFEA) registered clinics performing ETs. Results: In total, 59% (47/79) of units responded, 83% (39/47) performing ultrasound-guided transfers, with 42% (20/47) of units using a tenaculum; 22% (10/45) would proceed with transfer regardless of fluid in the endometrial cavity. In 91% (43/47) of units, embryos were deposited in the upper/middle portion of the uterine cavity, but interpretation of this area ranged from 0.5 to >2 cm from the fundus, with 68% (32/47) allowing patients to mobilise immediately after transfer. In 60% (27/45) of clinics, success rates were based on clinical pregnancy rates (CPR). Conclusion: Within the UK there is a wide range of variability in ET techniques, with >70% of discordance in survey-responses between clinics. Whilst there are areas of good practice, some disadvantageous techniques continue to persist. This survey emphasises the importance of developing a standardised, evidence-based approach to improve ET success rates