A practical approach to continuous glucose monitoring (rtCGM) and FreeStyle Libre systems (isCGM) in children and young people with Type 1 diabetes

Real-time continuous glucose monitoring (rtCGM) and FreeStyle Libre glucose monitoring systems (isCGM) are new evolving technologies used in the management of Type 1 diabetes. They offer potential to improve diabetes control and reduce hypoglycaemia. rtCGM can be linked to insulin pump providing hybrid closed loop therapy. Families of children and young people are keen to have the benefit from these technologies. These are relatively expensive so it is important that health care professionals, families of children and young people (CYP) with diabetes are adequately trained in the use of these devices. Health care professionals need to be able to make patient selection based on individual needs and preferences to achieve maximum benefit. Association of Children’s Diabetes Clinicians (ACDC) developed a comprehensive guideline in 2017 to help identify which patients may be most likely to benefit and how these technologies may be practically implemented. Since then new technologies have been introduced and the use of GCM has expanded in routine clinical practice. This article, aims to provide a practical approach and help identify which patients may be most likely to benefit and how the technology may be implemented in order to maximise the clinical benefits

Infection-Associated Nuclear Degeneration in the Rice Blast Fungus Magnaporthe oryzae Requires Non-Selective Macro-Autophagy

addresses: School of Biosciences, University of Exeter, Exeter, Devon, United Kingdom.notes: PMCID: PMC3308974Freely-available open access article.The rice blast fungus Magnaporthe oryzae elaborates a specialized infection structure called an appressorium to breach the rice leaf surface and gain access to plant tissue. Appressorium development is controlled by cell cycle progression, and a single round of nuclear division occurs prior to appressorium formation. Mitosis is always followed by programmed cell death of the spore from which the appressorium develops. Nuclear degeneration in the spore is known to be essential for plant infection, but the precise mechanism by which it occurs is not known

Genome-wide transcriptional profiling of appressorium development by the rice blast fungus Magnaporthe oryzae.

addresses: College of Life and Environmental Sciences, University of Exeter, Exeter, United Kingdom.notes: PMCID: PMC3276559The rice blast fungus Magnaporthe oryzae is one of the most significant pathogens affecting global food security. To cause rice blast disease the fungus elaborates a specialised infection structure called an appressorium. Here, we report genome wide transcriptional profile analysis of appressorium development using next generation sequencing (NGS). We performed both RNA-Seq and High-Throughput SuperSAGE analysis to compare the utility of these procedures for identifying differential gene expression in M. oryzae. We then analysed global patterns of gene expression during appressorium development. We show evidence for large-scale gene expression changes, highlighting the role of autophagy, lipid metabolism and melanin biosynthesis in appressorium differentiation. We reveal the role of the Pmk1 MAP kinase as a key global regulator of appressorium-associated gene expression. We also provide evidence for differential expression of transporter-encoding gene families and specific high level expression of genes involved in quinate uptake and utilization, consistent with pathogen-mediated perturbation of host metabolism during plant infection. When considered together, these data provide a comprehensive high-resolution analysis of gene expression changes associated with cellular differentiation that will provide a key resource for understanding the biology of rice blast disease

Metal on metal hip resurfacing versus uncemented custom total hip replacement - early results

<p>Abstract</p> <p>Introduction</p> <p>There is no current consensus on the most appropriate prosthesis for treating symptomatic osteoarthritis (OA) of the hip in young, active patients. Modern metal on metal hip resurfacing arthroplasty (HR) has gained popularity as it is theoretically more stable, bone conserving and easier to revise than total hip arthroplasty. Early results of metal on metal resurfacing have been encouraging. We have compared two well matched cohorts of patients with regard to function, pain relief and patient satisfaction.</p> <p>Methods</p> <p>This prospective study compares 2 cohorts of young, active patients treated with hip resurfacing (137 patients, 141 hips) and custom uncemented (CADCAM) stems (134 patients, 141 hips). All procedures were performed by a single surgeon. Outcome measures included Oxford, WOMAC and Harris hip scores as well as an activity score. Statistical analysis was performed using the unpaired student's t-test.</p> <p>Results</p> <p>One hundred and thirty four and 137 patients were included in the hip replacement and resurfacing groups respectively. The mean age of these patients was 54.6 years. The mean duration of follow up for the hip resurfacing group was 19.2 months compared to 13.4 months for the total hip replacement group.</p> <p>Pre operative oxford, Harris and WOMAC scores in the THA group were 41.1, 46.4 and 50.9 respectively while the post operative scores were 14.8, 95.8 and 5.0. In the HR group, pre- operative scores were 37.0, 54.1 and 45.9 respectively compared to 15.0, 96.8 and 6.1 post operatively. The degree of improvement was similar in both groups.</p> <p>Conclusion</p> <p>There was no significant clinical difference between the patients treated with hip resurfacing and total hip arthroplasty in the short term.</p

Glycogen metabolic genes are involved in trehalose-6-phosphate synthase-mediated regulation of pathogenicity by the rice blast fungus Magnaporthe oryzae.

© 2013 Badaruddin et al.Editor - Peter N. Dodds, Commonwealth Scientific and Industrial Research Organisation (CSIRO), AustraliaThis work was funded by the Biotechnology and Biological Sciences Research Council and a European Research Council Advanced Investigator Award to NJT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The filamentous fungus Magnaporthe oryzae is the causal agent of rice blast disease. Here we show that glycogen metabolic genes play an important role in plant infection by M. oryzae. Targeted deletion of AGL1 and GPH1, which encode amyloglucosidase and glycogen phosphorylase, respectively, prevented mobilisation of glycogen stores during appressorium development and caused a significant reduction in the ability of M. oryzae to cause rice blast disease. By contrast, targeted mutation of GSN1, which encodes glycogen synthase, significantly reduced the synthesis of intracellular glycogen, but had no effect on fungal pathogenicity. We found that loss of AGL1 and GPH1 led to a reduction in expression of TPS1 and TPS3, which encode components of the trehalose-6-phosphate synthase complex, that acts as a genetic switch in M. oryzae. Tps1 responds to glucose-6-phosphate levels and the balance of NADP/NADPH to regulate virulence-associated gene expression, in association with Nmr transcriptional inhibitors. We show that deletion of the NMR3 transcriptional inhibitor gene partially restores virulence to a Δagl1Δgph1 mutant, suggesting that glycogen metabolic genes are necessary for operation of the NADPH-dependent genetic switch in M. oryzae.Biotechnology and Biological Sciences Research Council (BBSRC)European Research Council (ERC

Single Nucleotide Polymorphisms in IL1B and the Risk of Acute Coronary Syndrome: A Danish Case-Cohort Study

BACKGROUND: Interleukin-1B (IL-1B) is a key pro-inflammatory cytokine that has been associated with the development of atherosclerosis and myocardial infarction. However, the prospective associations between functional single nucleotide polymorphisms (SNPs) in IL1B and incident acute coronary syndrome (ACS) have not been thoroughly investigated. The aims of this study were to examine the associations between individual SNPs in and SNP haplotypes of the promoter region of IL1B and incident ACS in a prospective study. Furthermore, we wanted to explore potential interactions with other risk factors for ACS on an additive scale. METHODOLOGY/PRINCIPAL FINDINGS: The present study was based on the Danish prospective study Diet, Cancer and Health comprising more than 57 000 participants aged 50-64 at baseline. During a median follow-up of 7.2 years we identified 989 cases of incident ACS (755 men and 234 women). All cases were validated by review of medical records, and information on covariates was collected by study technicians. The study was conducted according to a case-cohort study design including ACS cases and a sex-stratified sub cohort of 1663 participants drawn randomly from the entire cohort. Weighted Cox proportional hazard models with age as time axis were used in the statistical analyses. Individual IL1B SNPs, SNP haplotypes, or haplotype combinations were not significantly associated with incident ACS, and, likewise, we found no evidence of interaction on an additive scale between IL1B haplotypes and risk factors, respectively. CONCLUSIONS/SIGNIFICANCE: Genetic variation in the promoter region of IL1B may not be associated with incident ACS in men or women above the age of 50 years

Yeast Methylotrophy and Autophagy in a Methanol-Oscillating Environment on Growing Arabidopsis thaliana Leaves

The yeast Candida boidinii capable of growth on methanol proliferates and survives on the leaves of Arabidopsis thaliana. The local methanol concentration at the phyllosphere of growing A. thaliana exhibited daily periodicity, and yeast cells responded by altering both the expression of methanol-inducible genes and peroxisome proliferation. Even under these dynamically changing environmental conditions, yeast cells proliferated 3 to 4 times in 11 days. Among the C1-metabolic enzymes, enzymes in the methanol assimilation pathway, but not formaldehyde dissimilation or anti-oxidizing enzymes, were necessary for yeast proliferation at the phyllosphere. Furthermore, both peroxisome assembly and pexophagy, a selective autophagy pathway that degrades peroxisomes, were necessary for phyllospheric proliferation. Thus, the present study sheds light on the life cycle and physiology of yeast in the natural environment at both the molecular and cellular levels

Ultrasound-assessed perirenal fat is related to increased ophthalmic artery resistance index in HIV-1 patients

<p>Abstract</p> <p>Background</p> <p>The introduction of highly active antiretroviral therapy (HAART) has dramatically changed the prognosis of human immunodeficiency virus (HIV) infection, with a significant decline in morbidity and mortality.</p> <p>Changes in body fat distribution are a common finding in individuals with HIV infection being treated with antiretrovirals, and this condition (collectively termed lipodystrophy syndrome) is associated with depletion of subcutaneous fat, increased triglycerides and insulin resistance. Obesity, particularly visceral obesity, is associated with increased risk of cardiovascular disease. Therefore, estimating visceral fat distribution is important in identifying subjects at high risk for cardiovascular disease.</p> <p>The aim of our study was to evaluate whether perirenal fat thickness (PRFT), a parameter of central obesity, is related to ophthalmic artery resistance index (OARI), an index of occlusive carotid artery disease in HIV-1 infected patients.</p> <p>Methods</p> <p>We enrolled 88 consecutive HIV-1-infected patients receiving highly active antiretroviral therapy for more than 12 months, in a prospective cohort study. Echographically measured PRFT and OARI, as well as serum metabolic parameters, were evaluated. PRFT and OARI were measured by 3.75 MHz convex and 7.5 MHz linear probe, respectively.</p> <p>Results</p> <p>The means of PRFT and OARI in HIV-1-infected patients with visceral obesity was considerably higher than in patients without it (p < 0.0001 and p < 0.001, respectively). Using the average OARI as the dependent variable, total serum cholesterol level, HDL, triglycerides, glycemia, sex, blood pressure, age and PRFT were independent factors associated with OARI. A PRFT of 6.1 mm was the most discriminatory value for predicting an OARI > 0.74 (sensitivity 78.9%, specificity 82.8%).</p> <p>Conclusions</p> <p>Our data indicate that ultrasound assessment of PRFT may have potential as a marker of increased endothelial damage with specific involvement of the ocular vascular region in HIV-1-infected patients.</p

Genome-Wide Analysis of Glucocorticoid Receptor Binding Regions in Adipocytes Reveal Gene Network Involved in Triglyceride Homeostasis

Glucocorticoids play important roles in the regulation of distinct aspects of adipocyte biology. Excess glucocorticoids in adipocytes are associated with metabolic disorders, including central obesity, insulin resistance and dyslipidemia. To understand the mechanisms underlying the glucocorticoid action in adipocytes, we used chromatin immunoprecipitation sequencing to isolate genome-wide glucocorticoid receptor (GR) binding regions (GBRs) in 3T3-L1 adipocytes. Furthermore, gene expression analyses were used to identify genes that were regulated by glucocorticoids. Overall, 274 glucocorticoid-regulated genes contain or locate nearby GBR. We found that many GBRs were located in or nearby genes involved in triglyceride (TG) synthesis (Scd-1, 2, 3, GPAT3, GPAT4, Agpat2, Lpin1), lipolysis (Lipe, Mgll), lipid transport (Cd36, Lrp-1, Vldlr, Slc27a2) and storage (S3-12). Gene expression analysis showed that except for Scd-3, the other 13 genes were induced in mouse inguinal fat upon 4-day glucocorticoid treatment. Reporter gene assays showed that except Agpat2, the other 12 glucocorticoid-regulated genes contain at least one GBR that can mediate hormone response. In agreement with the fact that glucocorticoids activated genes in both TG biosynthetic and lipolytic pathways, we confirmed that 4-day glucocorticoid treatment increased TG synthesis and lipolysis concomitantly in inguinal fat. Notably, we found that 9 of these 12 genes were induced in transgenic mice that have constant elevated plasma glucocorticoid levels. These results suggested that a similar mechanism was used to regulate TG homeostasis during chronic glucocorticoid treatment. In summary, our studies have identified molecular components in a glucocorticoid-controlled gene network involved in the regulation of TG homeostasis in adipocytes. Understanding the regulation of this gene network should provide important insight for future therapeutic developments for metabolic diseases

Do obese but metabolically normal women differ in intra-abdominal fat and physical activity levels from those with the expected metabolic abnormalities? A cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Obesity remains a major public health problem, associated with a cluster of metabolic abnormalities. However, individuals exist who are very obese but have normal metabolic parameters. The aim of this study was to determine to what extent differences in metabolic health in very obese women are explained by differences in body fat distribution, insulin resistance and level of physical activity.</p> <p>Methods</p> <p>This was a cross-sectional pilot study of 39 obese women (age: 28-64 yrs, BMI: 31-67 kg/m²) recruited from community settings. Women were defined as 'metabolically normal' on the basis of blood glucose, lipids and blood pressure. Magnetic Resonance Imaging was used to determine body fat distribution. Detailed lifestyle and metabolic profiles of participants were obtained.</p> <p>Results</p> <p>Women with a healthy metabolic profile had lower intra-abdominal fat volume (geometric mean 4.78 l [95% CIs 3.99-5.73] vs 6.96 l [5.82-8.32]) and less insulin resistance (HOMA 3.41 [2.62-4.44] vs 6.67 [5.02-8.86]) than those with an abnormality. The groups did not differ in abdominal subcutaneous fat volume (19.6 l [16.9-22.7] vs 20.6 [17.6-23.9]). A higher proportion of those with a healthy compared to a less healthy metabolic profile met current physical activity guidelines (70% [95% CIs 55.8-84.2] vs 25% [11.6-38.4]). Intra-abdominal fat, insulin resistance and physical activity make independent contributions to metabolic status in very obese women, but explain only around a third of the variance.</p> <p>Conclusion</p> <p>A sub-group of women exists who are metabolically normal despite being very obese. Differences in fat distribution, insulin resistance, and physical activity level are associated with metabolic differences in these women, but account only partially for these differences. Future work should focus on strategies to identify those obese individuals most at risk of the negative metabolic consequences of obesity and on identifying other factors that contribute to metabolic status in obese individuals.</p