239 research outputs found

    Improved pregnancy outcomes in women with type 1 and type 2 diabetes but substantial clinic-to-clinic variations: a prospective nationwide study

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    Aims/hypothesis: The aim of this prospective nationwide study was to examine antenatal pregnancy care and pregnancy outcomes in women with type 1 and type 2 diabetes, and to describe changes since 2002/2003. Methods: This national population-based cohort included 3036 pregnant women with diabetes from 155 maternity clinics in England and Wales who delivered during 2015. The main outcome measures were maternal glycaemic control, preterm delivery (before 37 weeks), infant large for gestational age (LGA), and rates of congenital anomaly, stillbirth and neonatal death. Results: Of 3036 women, 1563 (51%) had type 1, 1386 (46%) had type 2 and 87 (3%) had other types of diabetes. The percentage of women achieving HbA1c < 6.5% (48 mmol/mol) in early pregnancy varied greatly between clinics (median [interquartile range] 14.3% [7.7–22.2] for type 1, 37.0% [27.3–46.2] for type 2). The number of infants born preterm (21.7% vs 39.7%) and LGA (23.9% vs 46.4%) were lower for women with type 2 compared with type 1 diabetes (both p < 0.001). The prevalence rates for congenital anomaly (46.2/1000 births for type 1, 34.6/1000 births for type 2) and neonatal death (8.1/1000 births for type 1, 11.4/1000 births for type 2) were unchanged since 2002/2003. Stillbirth rates are almost 2.5 times lower than in 2002/2003 (10.7 vs 25.8/1000 births for type 1, p = 0.0012; 10.5 vs 29.2/1000 births for type 2, p = 0.0091). Conclusions/interpretation: Stillbirth rates among women with type 1 and type 2 diabetes have decreased since 2002/2003. Rates of preterm delivery and LGA infants are lower in women with type 2 compared with type 1 diabetes. In women with type 1 diabetes, suboptimal glucose control and high rates of perinatal morbidity persist with substantial variations between clinics

    Evolutionary genomics of Staphylococcus aureus reveals insights into the origin and molecular basis of ruminant host adaptation

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    Phenotypic biotyping has traditionally been used to differentiate bacteria occupying distinct ecological niches such as host species. For example, the capacity of Staphylococcus aureus from sheep to coagulate ruminant plasma, reported over 60 years ago, led to the description of small ruminant and bovine S. aureus ecovars. The great majority of small ruminant isolates are represented by a single, widespread clonal complex (CC133) of S. aureus, but its evolutionary origin and the molecular basis for its host tropism remain unknown. Here, we provide evidence that the CC133 clone evolved as the result of a human to ruminant host jump followed by adaptive genome diversification. Comparative whole-genome sequencing revealed molecular evidence for host adaptation including gene decay and diversification of proteins involved in host-pathogen interactions. Importantly, several novel mobile genetic elements encoding virulence proteins with attenuated or enhanced activity in ruminants were widely distributed in CC133 isolates, suggesting a key role in its host-specific interactions. To investigate this further, we examined the activity of a novel staphylococcal pathogenicity island (SaPIov2) found in the great majority of CC133 isolates which encodes a variant of the chromosomally encoded von Willebrand-binding protein (vWbp(Sov2)), previously demonstrated to have coagulase activity for human plasma. Remarkably, we discovered that SaPIov2 confers the ability to coagulate ruminant plasma suggesting an important role in ruminant disease pathogenesis and revealing the origin of a defining phenotype of the classical S. aureus biotyping scheme. Taken together, these data provide broad new insights into the origin and molecular basis of S. aureus ruminant host specificity.This work was funded by grant BB/D521222/1 from the Biotechnology and Biological Sciences Research Council (to J.R.F.). The Bacterial Microarray Group at St Georges is funded by The Wellcome Trust

    Dental general anaesthetic receipt among Australians aged 15+ years, 1998–1999 to 2004–2005

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    Background Adults receive dental general anaesthetic (DGA) care when standard dental treatment is not possible. Receipt of DGA care is resource-intensive and not without risk. This study explores DGA receipt among 15+-year-old Australians by a range of risk indicators. Methods DGA data were obtained from Australia's Hospital Morbidity Database from 1998–1999 to 2004–2005. Poisson regression modeling was used to examine DGA rates in relation to age, sex, Indigenous status, location and procedure. Results The overall DGA rate was 472.79 per 100,000 (95% CI 471.50–474.09). Treatment of impacted teeth (63.7%) was the most common reason for DGA receipt, followed by dental caries treatment (12.4%), although marked variations were seen by age-group. After adjusting for other covariates, DGA rates among 15–19-year-olds were 13.20 (95% CI 12.65–13.78) times higher than their 85+-year-old counterparts. Females had 1.46 (95% CI 1.45–1.47) times the rate of their male counterparts, while those living in rural/remote areas had 2.70 (95% CI 2.68–2.72) times the rate of metropolitan-dwellers. DGA rates for non-Indigenous persons were 4.88 (95% CI 4.73–5.03) times those of Indigenous persons. The DGA rate for 1+ extractions was 461.9 per 100,000 (95% CI 460.6–463.2), compared with a rate of 23.6 per 100,000 (95% CI 23.3–23.9) for 1+ restorations. Conclusion Nearly two-thirds of DGAs were for treatment of impacted teeth. Persons aged 15–19 years were disproportionately represented among those receiving DGA care, along with females, rural/remote-dwellers and those identifying as non-Indigenous. More research is required to better understand the public health implications of DGA care among 15+-year-olds, and how the demand for receipt of such care might be reduced.Lisa M Jamieson and Kaye F Roberts-Thomso

    Health-seeking behaviours of older black women living with non-communicable diseases in an urban township in South Africa

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    BACKGROUND: Various studies have shown that non-communicable diseases (NCDs) especially diabetes and hypertension are prevalent among older women living in South African urban areas, placing a heavy burden on the healthcare system. This study aimed to understand the health-seeking behaviour, healthcare practices and prevalence of traditional herbal medicine (THM) use among older women self-reporting NCDs from the Prospective Urban Rural Epidemiology study (PURE). METHOD: A homogenous purposive sampling of PURE participants was used to recruit women who were 50 years or older (n = 250). Descriptive statistics were used to examine the number of NCDs reported by the study sample, health seeking behaviour and practices as well as THM use. Logistic regression was also employed to investigate possible associations between reported conditions and THM use or medical pluralism. RESULTS: Within the study sample, 72 % self-reported an NCD. Of those with self-reported NCDs, 46 % had one, and 54 % had two or more NCDs. Those with NCDs usually visited public clinics (80 %), relied on doctors (90 %) and nurses (85 %) for health information, and mostly used conventional medicine (CM) to manage high blood pressure (81 %). About 30 % of those with NCDs indicated using THM, of whom 29 (53 %) reported practicing medical pluralism. Participants with dental problems (OR: 3.24, 95 % CI: 1.30–8.20), headaches (OR: 2.42, 95 % CI: 1.24–4.94), heart burn (OR: 2.30, 95 % CI: 1.18–4.48) and severe tiredness (OR: 2.05, 95 % CI: 1.08–3.99) were more likely to use THM. Anxiety and allergies increased the likelihood to practise medical pluralism by five and 20 times, respectively. CONCLUSION: Self-reported NCD with co-morbidities was prevalent among the participants in the study. Most of the study participants utilized state-owned clinics and hospitals for the management of their chronic conditions. THM use was not very common. However, among those who used THM, medical pluralism was prevalent. Family history was the most common reason for THM use, with many THM patrons utilizing these for treatment of a health condition. Older black women with anxiety and allergies were more likely to practise medical pluralism

    Developing adaptive control:Age-related differences in task choices and awareness of proactive and reactive control demands

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    Developmental changes in executive function are often explained in terms of core cognitive processes and associated neural substrates. For example, younger children tend to engage control reactively in the moment as needed, whereas older children increasingly engage control proactively, in anticipation of needing it. Such developments may reflect increasing capacities for active maintenance dependent upon dorsolateral prefrontal cortex. However, younger children will engage proactive control when reactive control is made more difficult, suggesting that developmental changes may also reflect decisions about whether to engage control, and how. We tested awareness of temporal control demands and associated task choices in 5-year-olds and 10-year-olds and adults using a demand selection task. Participants chose between one task that enabled proactive control and another task that enabled reactive control. Adults reported awareness of these different control demands and preferentially played the proactive task option. Ten-year-olds reported awareness of control demands but selected task options at chance. Five-year-olds showed neither awareness nor task preference, but a subsample who exhibited awareness of control demands preferentially played the reactive task option, mirroring their typical control mode. Thus, developmental improvements in executive function may in part reflect better awareness of cognitive demands and adaptive behavior, which may in turn reflect changes in dorsal anterior cingulate in signaling task demands to lateral prefrontal cortex

    New Insights into the Mechanisms of Embryonic Stem Cell Self-Renewal under Hypoxia: A Multifactorial Analysis Approach

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    Previous reports have shown that culturing mouse embryonic stem (mES) cells at different oxygen tensions originated different cell proliferation patterns and commitment stages depending on which signaling pathways are activated or inhibited to support the pluripotency state. Herein we provide new insights into the mechanisms by which oxygen is influencing mES cell self-renewal and pluripotency. A multifactorial approach was developed to rationally evaluate the singular and interactive control of MEK/ERK pathway, GSK-3 inhibition, and LIF/STAT3 signaling at physiological and non-physiological oxygen tensions. Collectively, our methodology revealed a significant role of GSK-3-mediated signaling towards maintenance of mES cell pluripotency at lower O2 tensions. Given the central role of this signaling pathway, future studies will need to focus on the downstream mechanisms involved in ES cell self-renewal under such conditions, and ultimately how these findings impact human models of pluripotency

    Universal Alcohol/Drug Screening in Prenatal Care: A Strategy for Reducing Racial Disparities? Questioning the Assumptions

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    Agencies and organizations promoting universal screening for alcohol and drug use in prenatal care argue that universal screening will reduce White versus Black racial disparities in reporting to Child Protective Services (CPS) at delivery. Yet, no published research has assessed the impact of universal screening on reporting disparities or explored plausible mechanisms. This review defines two potential mechanisms: Equitable Surveillance and Effective Treatment and identifies assumptions underlying each mechanism. It reviews published literature relating to each assumption. Research relating to assumptions underlying each mechanism is primarily inconclusive or contradictory. Thus, available research does not support the claim that universal screening for alcohol and drug use in prenatal care reduces racial disparities in CPS reporting at delivery. Reducing these reporting disparities requires more than universal screening

    Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR

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    We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR −/−) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37°C for up to 9 days and displayed a terminal half-life (T1/2β) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that 125I-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of' 111In-labelled ch806 was demonstrated with uptake of 31%ID g−1 and a tumour to blood ratio of 5 : 1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent
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