Temporal variations in maternal treatment requirements and early neonatal outcomes in patients with gestational diabetes

Funder: NIHR Cambridge Biomedical Research CentreAbstract: Aims: There is seasonal variation in the incidence of gestational diabetes (GDM) and delivery outcomes of affected patients. We assessed whether there was also evidence of temporal variation in maternal treatment requirements and early neonatal outcomes. Methods: We performed a retrospective analysis of women diagnosed with GDM (75 g oral glucose tolerance test, 0 h ≥ 5.1; 1 h ≥ 10.0; 2 h ≥ 8.5 mmol/L) in a UK tertiary obstetric centre (2015–2019) with a singleton infant. Data regarding demographic characteristics, total insulin requirements and neonatal outcomes were extracted from contemporaneous electronic medical records. Linear/logistic regression models using month of the year as a predictor of outcomes were used to assess annual variation. Results: In all, 791 women (50.6% receiving pharmacological treatment) and 790 neonates were included. The likelihood of requiring insulin treatment was highest in November (p < 0.05). The average total daily insulin dose was higher at peak (January) compared to average by 19 units/day (p < 0.05). There was no temporal variation in neonatal intensive care admission, or neonatal capillary blood glucose. However, rates of neonatal hypoglycaemia (defined as <2.6 mmol/L) were highest in December (40% above average; p < 0.05). Conclusions: Women with GDM diagnosed in winter are more likely to require insulin treatment and to require higher insulin doses. Neonates born to winter‐diagnosed mothers had a corresponding increased risk of neonatal hypoglycaemia. Maternal treatment requirements and neonatal outcomes of GDM vary significantly throughout the year, even in a relatively temperate climate

Markers for the identification of late breast cancer recurrence

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Impact of Scottish smoke-free legislation on smoking quit attempts and prevalence

&lt;p&gt;&lt;b&gt;Objectives:&lt;/b&gt; In Scotland, legislation was implemented in March 2006 prohibiting smoking in all wholly or partially enclosed public spaces. We investigated the impact on attempts to quit smoking and smoking prevalence.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We performed time series models using Box-Jenkins autoregressive integrated moving averages (ARIMA) on monthly data on the gross ingredient cost of all nicotine replacement therapy (NRT) prescribed in Scotland in 2003–2009, and quarterly data on self-reported smoking prevalence between January 1999 and September 2010 from the Scottish Household Survey.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; NRT prescription costs were significantly higher than expected over the three months prior to implementation of the legislation. Prescription costs peaked at £1.3 million in March 2006; £292,005.9 (95% CI £260,402.3, £323,609, p&#60;0.001) higher than the monthly norm. Following implementation of the legislation, costs fell exponentially by around 26% per month (95% CI 17%, 35%, p&#60;0.001). Twelve months following implementation, the costs were not significantly different to monthly norms. Smoking prevalence fell by 8.0% overall, from 31.3% in January 1999 to 23.7% in July–September 2010. In the quarter prior to implementation of the legislation, smoking prevalence fell by 1.7% (95% CI 2.4%, 1.0%, p&#60;0.001) more than expected from the underlying trend.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; Quit attempts increased in the three months leading up to Scotland's smoke-free legislation, resulting in a fall in smoking prevalence. However, neither has been sustained suggesting the need for additional tobacco control measures and ongoing support.&lt;/p&gt

Branch Mode Selection during Early Lung Development

Many organs of higher organisms, such as the vascular system, lung, kidney, pancreas, liver and glands, are heavily branched structures. The branching process during lung development has been studied in great detail and is remarkably stereotyped. The branched tree is generated by the sequential, non-random use of three geometrically simple modes of branching (domain branching, planar and orthogonal bifurcation). While many regulatory components and local interactions have been defined an integrated understanding of the regulatory network that controls the branching process is lacking. We have developed a deterministic, spatio-temporal differential-equation based model of the core signaling network that governs lung branching morphogenesis. The model focuses on the two key signaling factors that have been identified in experiments, fibroblast growth factor (FGF10) and sonic hedgehog (SHH) as well as the SHH receptor patched (Ptc). We show that the reported biochemical interactions give rise to a Schnakenberg-type Turing patterning mechanisms that allows us to reproduce experimental observations in wildtype and mutant mice. The kinetic parameters as well as the domain shape are based on experimental data where available. The developed model is robust to small absolute and large relative changes in the parameter values. At the same time there is a strong regulatory potential in that the switching between branching modes can be achieved by targeted changes in the parameter values. We note that the sequence of different branching events may also be the result of different growth speeds: fast growth triggers lateral branching while slow growth favours bifurcations in our model. We conclude that the FGF10-SHH-Ptc1 module is sufficient to generate pattern that correspond to the observed branching modesComment: Initially published at PLoS Comput Bio

Impact of gestational weight gain on obstetric and neonatal outcomes in obese diabetic women

Both obesity and gestational diabetes mellitus are increasing in prevalence, being a major health problem in pregnancy with independent and additive impact on obstetrics outcomes. It is recognized that inadequate gestational weight gain is an independent risk factor for pregnancy-related morbidity. The aim of this study was to evaluate the effect of gestational weight gain on obstetric and neonatal outcomes in obese women with gestational diabetes

Enteric Neurospheres Are Not Specific to Neural Crest Cultures: Implications for Neural Stem Cell Therapies

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Rapid Tooling Method for Soft Customized Removable Oral Appliances

Traditionally oral appliances i.e. removable orthodontic appliances, bite splints and snoring / sleep apnea appliances are made with alginate impressions and wax registrations. Our aim was to describe the process of manufacturing customized oral appliances with a new technique i.e. rapid tooling method. The appliance should ideally be custom made to match the teeth. An orthodontic patient, scheduled for conventional orthodontic treatment, served as a study subject. After a precise clinical and radiographic examination, the approach was to digitize the patient’s dental arches and then to correct them virtually by computer. Additive manufacturing was then used to fabricate a mould for a soft customized appliance. The mould was manufactured using stereolithography from Somos ProtoGen O-XT 18420 material. Casting material for the mould to obtain the final appliance was silicone. As a result we managed to create a customized soft orthodontic appliance. Also, the accuracy of the method was found to be adequate. Two versions of the described device were manufactured: one with small and one with moderate orthodontic force. The study person also gave information on the subjective patient adaptation aspects of the oral appliance

The Role of Alveolar Epithelial Cells in Initiating and Shaping Pulmonary Immune Responses: Communication between Innate and Adaptive Immune Systems

Macrophages and dendritic cells have been recognized as key players in the defense against mycobacterial infection. However, more recently, other cells in the lungs such as alveolar epithelial cells (AEC) have been found to play important roles in the defense and pathogenesis of infection. In the present study we first compared AEC with pulmonary macrophages (PuM) isolated from mice in their ability to internalize and control Bacillus Calmette-Guérin (BCG) growth and their capacity as APCs. AEC were able to internalize and control bacterial growth as well as present antigen to primed T cells. Secondly, we compared both cell types in their capacity to secrete cytokines and chemokines upon stimulation with various molecules including mycobacterial products. Activated PuM and AEC displayed different patterns of secretion. Finally, we analyzed the profile of response of AEC to diverse stimuli. AEC responded to both microbial and internal stimuli exemplified by TLR ligands and IFNs, respectively. The response included synthesis by AEC of several factors, known to have various effects in other cells. Interestingly, TNF could stimulate the production of CCL2/MCP-1. Since MCP-1 plays a role in the recruitment of monocytes and macrophages to sites of infection and macrophages are the main producers of TNF, we speculate that both cell types can stimulate each other. Also, another cell-cell interaction was suggested when IFNs (produced mainly by lymphocytes) were able to induce expression of chemokines (IP-10 and RANTES) by AEC involved in the recruitment of circulating lymphocytes to areas of injury, inflammation, or viral infection. In the current paper we confirm previous data on the capacity of AEC regarding internalization of mycobacteria and their role as APC, and extend the knowledge of AEC as a multifunctional cell type by assessing the secretion of a broad array of factors in response to several different types of stimuli