Exploring parental perspectives after commencement of flash glucose monitoring for type 1 diabetes in adolescents and young adults not meeting glycaemic targets: a qualitative study.

AIMS: To explore parental perspectives after flash glucose monitoring commencement in adolescents and young adults with type 1 diabetes who were not meeting glycaemic targets. METHODS: Twelve semi-structured interviews were conducted among parents of adolescents and young adults between the ages of 14 and 20 years (inclusive) with type 1 diabetes and not meeting glycaemic targets [HbA1c 81-130 mmol/mol (9.6-14.0%)] participating in a randomized controlled trial. Interviews were transcribed, then thematic analysis was performed to identify themes regarding parental experiences. RESULTS: Four key themes were found: flash glucose monitoring improved parental emotional well-being; flash glucose monitoring reduced diabetes-specific conflict within families; flash glucose monitoring facilitated the parental role in diabetes management; and sensor-related challenges, particularly sensors falling off, interfered with using flash glucose monitoring for diabetes management. The cost of self-funded sensors was the only barrier to continuing flash glucose monitoring that parents reported. CONCLUSIONS: This study provides new insights into the potential benefits and challenges of flash glucose monitoring use, drawn from the perspective of parents of adolescents and young adults not meeting glycaemic targets. As parents are often key partners in obtaining or purchasing this technology, these findings can be used to further inform parental expectations of this technology.

The ups and downs of low-carbohydrate diets in the management of Type 1 diabetes: a review of clinical outcomes.

Dietary management has been a mainstay of care in Type 1 diabetes since before the discovery of insulin when severe carbohydrate restriction was advocated. The use of insulin facilitated re-introduction of carbohydrate into the diet. Current management guidelines focus on a healthy and varied diet with consideration of glycaemic load, protein and fat. As a result of frustration with glycaemic outcomes, low-carbohydrate diets have seen a resurgence in popularity. To date, low-carbohydrate diets have not been well studied in the management of Type 1 diabetes. Studies looking at glycaemic outcomes from low-carbohydrate diets have largely been cross-sectional, without validated dietary data and with a lack of control groups. The participants have been highly motivated self-selected individuals who follow intensive insulin management practices, including frequent blood glucose monitoring and additional insulin corrections with tight glycaemic targets. These confounders limit the ability to determine the extent of the impact of dietary carbohydrate restriction on glycaemic outcomes. Carbohydrate-containing foods including grains, fruit and milk are important sources of nutrients. Hence, low-carbohydrate diets require attention to vitamin and energy intake to avoid micronutrient deficiencies and growth issues. Adherence to restricted diets is challenging and can have an impact on social normalcy. In individuals with Type 1 diabetes, adverse health risks such as diabetic ketoacidosis, hypoglycaemia, dyslipidaemia and glycogen depletion remain clinical concerns. In the present paper, we review studies published to date and provide clinical recommendations for ongoing monitoring and support for individuals who choose to adopt a low-carbohydrate diet. Strategies to optimize postprandial glycaemia without carbohydrate restriction are presented.

Inhibiting connexin channels protects against cryopreservation-induced cell death in human blood vessels.

OBJECTIVES: Cryopreserved blood vessels are being increasingly employed in vascular reconstruction procedures but freezing/thawing is associated with significant cell death that may lead to graft failure. Vascular cells express connexin proteins that form gap junction channels and hemichannels. Gap junction channels directly connect the cytoplasm of adjacent cells and may facilitate the passage of cell death messengers leading to bystander cell death. Two hemichannels form a gap junction channel but these channels are also present as free non-connected hemichannels. Hemichannels are normally closed but may open under stressful conditions and thereby promote cell death. We here investigated whether blocking gap junctions and hemichannels could prevent cell death after cryopreservation. MATERIALS AND METHODS: Inclusion of Gap27, a connexin channel inhibitory peptide, during cryopreservation and thawing of human saphenous veins and femoral arteries was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assays and histological examination. RESULTS: We report that Gap27 significantly reduces cell death in human femoral arteries and saphenous veins when present during cryopreservation/thawing. In particular, smooth muscle cell death was reduced by 73% in arteries and 71% in veins, while endothelial cell death was reduced by 32% in arteries and 51% in veins. CONCLUSIONS: We conclude that inhibiting connexin channels during cryopreservation strongly promotes vascular cell viability.

Measurement performance assessment for the ITER CXRS Edge diagnostic system.

Measurement performance assessment has been carried out for the latest design of the ITER Charge Exchange Recombination Spectroscopy (CXRS) Edge diagnostic system. Several plasma scenarios, covering all expected baseline operation regimes for ITER, were used. Various impurity (He, Be, C, and Ne) concentrations for the system whole spatial range (0.5 < r/a < 1.0) were considered. Statistical errors for the measurements of low-Z impurity temperature, density, and rotation velocity were calculated. Other non-statistical error sources were reviewed, including the presence of wall reflections, effects on the active charge-exchange line shape, calibration, and positioning uncertainties. Minimal impurity concentrations, allowing measurements with required accuracy, were obtained. It was shown that the CXRS Edge system will be able to measure primary plasma parameters with required accuracy, space, and time resolution.

Efficacy, safety, and user experience of DIY or open-source artificial pancreas systems: a systematic review.

The do-it-yourself artificial pancreas system (DIYAPS) is a patient-driven initiative with the potential to revolutionise diabetes management, automating insulin delivery with existing pumps and CGM combined with open-source algorithms. Given the considerable interest in this topic within the diabetes community, we have conducted a systematic review of DIYAPS efficacy, safety, and user experience. Following recognised procedures and reporting standards, we identified 10 eligible publications of 730 participants within the peer-reviewed literature. Overall, studies reported improvements in time in range, HbA1c (glycated haemoglobin), reduced hypoglycaemia, and improved quality of life with DIYAPS use. While results were positive, the identified studies were small, and the majority were observational and at high risk of bias. Further research including well-designed randomised trials comparing DIYAPS with appropriate comparators is recommended.

Dehydroascorbate and glucose are taken up into Arabidopsis thaliana cell cultures by two distinct mechanisms.

The possible involvement of glucose (Glc) carriers in the uptake of vitamin C in plant cells is still a matter of debate. For the first time, it was shown here that plant cells exclusively take up the oxidised dehydroascorbate (DHA) form. DHA uptake is not affected by 6-bromo-6-deoxy-ascorbate, an ascorbate (ASC) analogue, specifically demonstrating ASC uptake in animal cells. There is no competition between Glc and DHA uptake. Moreover, DHA and Glc carriers respond in the opposite manner to different inhibitors (cytochalasin B, phloretin and genistein). In conclusion, the plant plasma membrane DHA carrier is distinct from the plant Glc transporters.

Prevalence of 'Candidatus Helicobacter suis' in pigs of different ages.

Samples from the antrum and fundus of the stomachs of 457 pigs from 22 different herds were screened for the presence of 'Candidatus Helicobacter suis' by pcr, and samples from the antrum and/or fundus of 222 of the stomachs were tested for urease activity. The prevalence of the infection was very low before weaning, increased rapidly after weaning and reached 90 per cent in the adult boars and sows. The agreement between the results obtained with the pcr test and the urease test was very good for some age groups and sampling sites, but poor for other age groups and sampling sites.

Experimental infection of pigs with 'Candidatus Helicobacter suis'.

'Candidatus Helicobacter suis' is a spiral-shaped bacterium that colonizes the stomach of more than 60% of slaughter pigs. The role of 'Candidatus Helicobacter suis' in gastric disease of pigs is still unclear. Experimental studies in pigs are lacking because this bacterium is unculturable until now. An inoculation protocol using 'Candidatus Helicobacter suis' infected mouse stomach homogenate was used to reproduce the infection in pigs. Control animals were inoculated using negative mouse stomach homogenate. Pigs were inoculated three times with one-week intervals and euthanized 6 weeks post inoculation. Tissue samples were taken from different mucosal stomach regions to detect 'Candidatus Helicobacter suis' by PCR and urease test. Mucosal inflammation was evaluated on formalin-fixed tissue samples. Lesions in the pars oesophagea were scored macroscopically. Infection was successful in all challenged animals, with the antrum and the fundus being predominantly positive. Infection was associated with infiltration of lymphocytes and plasma cells in the antral mucosa, evolving to follicular gastritis. No apparent inflammation of the fundic stomach region was detected in the infected animals. A clear link between 'Candidatus Helicobacter suis' and pars oesophageal lesions could not be found.

The effect of Helicobacter felis and Helicobacter bizzozeronii on the gastric mucosa in Mongolian gerbils: a sequential pathological study.

In contrast to Helicobacter(H.) pylori, little is known about the pathogenic mechanisms of gastric non-H. pylori Helicobacter species. Mongolian gerbils were inoculated intragastrically with H. felis or H. bizzozeronii and killed at different timepoints post-inoculation (p.i.), stomach tissue being taken for light and transmission electron microscopy (TEM) and polymerase chain reaction (PCR) analysis. Parietal cells (PCs), apoptosis, cell proliferation and nuclear factor-kappaB (NF-kappaB) activation were "visualized" immunohistochemically. Inflammation consisted of neutrophilic granulocytes, mainly in the antrum, and lymphocytic infiltrates around the limiting ridge and throughout the stomach mucosa and submucosa. From day 11 p.i. onwards, H. felis-inoculated animals showed moderate to severe loss of PCs extending from the limiting ridge into the fundus. Apoptotic cells, spiral bacteria, cell proliferation, and NF-kappaB activation were detected at the transition zone between affected and normal PCs. TEM revealed interaction of H. felis flagella with PCs and chief cells. Moreover, H. felis was seen in proximity to, and inside, necrotic cells. At 10 weeks p.i., some H. felis-infected gerbils showed complete loss of fundic glands, and mucous metaplasia of the epithelium. H. bizzozeronii, which made no flagellar contact with epithelial cells, was associated with only mild PC loss. The mechanism by which H. felis induces PC necrosis and apoptosis remains unclear. The observed flagellar contact and NF-kappaB activation may play an important role in H. felis-associated inflammation.

A photoelastic-modulator-based motional Stark effect polarimeter for ITER that is insensitive to polarized broadband background reflections.

A motional Stark effect polarimeter insensitive to polarized broadband light is proposed. Partially polarized background light is anticipated to be a significant source of systematic error for the ITER polarimeter. The proposed polarimeter is based on the standard dual photoelastic modulator approach, but with the introduction of a birefringent delay plate, it generates a sinusoidal spectral filter instead of the usual narrowband filter. The period of the filter is chosen to match the spacing of the orthogonally polarized Stark effect components, thereby increasing the effective signal level, but resulting in the destructive interference of the broadband polarized light. The theoretical response of the system to an ITER like spectrum is calculated and the broadband polarization tolerance is verified experimentally.

The inflammatory response in the mouse stomach to Helicobacter bizzozeronii, Helicobacter salomonis and two Helicobacter felis Strains.

The inflammatory response in the mouse stomach was evaluated as a means of distinguishing different non-pylori Helicobacter (H.) strains in terms of virulence. Mice of four strains (BALB/c, SJL, C57BL/6 and CFW) were infected intragastrically with four bacterial strains (H. felis ATCC 49179 and CCUG 37471, H. bizzozeronii and H. salomonis). The animals were killed for gastric examination at 3, 9 or 16 weeks post-inoculation. H. salomonis could not be detected by the polymerase chain reaction, but the other three organisms were detected in all stomach samples at all timepoints. SJL mice consistently showed particularly severe gastric inflammation regardless of bacterial strain. Lymphocytes and occasionally neutrophils were seen in submucosa and lamina propria mucosae. BALB/c mice showed the least severe inflammatory changes. H. bizzozeronii differed from the two H. felis strains in producing less striking pathological changes in mice. Of the two H. felis strains, ATCC 49179 produced the more severe inflammatory changes in SJL mice.

Fluoxetine suppresses calcium signaling in human T lymphocytes through depletion of intracellular calcium stores.

Selective serotonin reuptake inhibitors, such as fluoxetine, have recently been shown to exert anti-inflammatory and immunosuppressive effects. Although the effects on cytokine secretion, proliferation and viability of T lymphocytes have been extensively characterized, little is known about the mechanism behind these effects. It is well known that Ca(2+) signaling is an important step in the signaling transduction pathway following T cell receptor activation. Therefore, we investigated if fluoxetine interferes with Ca(2+) signaling in Jurkat T lymphocytes. Fluoxetine was found to suppress Ca(2+) signaling in response to T cell receptor activation. Moreover, fluoxetine was found to deplete intracellular Ca(2+) stores, thereby leaving less Ca(2+) available for release upon IP3- and ryanodine-receptor activation. The Ca(2+)-modifying effects of fluoxetine are not related to its capability to block the serotonin transporter, as even a large excess of 5HT did not abolish the effects. In conclusion, these data show that fluoxetine decreases IP3- and ryanodine-receptor mediated Ca(2+) release in Jurkat T lymphocytes, an effect likely to be at the basis of the observed immunosuppression.

Long-term intrathecal infusion of morphine and morphine/bupivacaine mixtures in the treatment of cancer pain: a retrospective analysis of 51 cases.

A retrospective analysis of 51 patients with cancer pain treated with a continuous i.t. morphine infusion through a tunnelled percutaneous catheter was undertaken. Because of insufficient pain relief with morphine only, 17 of these patients received a morphine/bupivacaine mixture. Pain relief subsequently improved significantly in 10 patients and a moderate improvement was present in 4 patients. An additional analgesic effect of bupivacaine was not shown in 3 patients with clinical signs of severe mental depression. Bupivacaine-induced side effects were absent below a daily dosage of 30 mg by continuous infusion. In all patients a gradual dose increment was observed. No serious complications, neurologic sequelae or meningitis occurred. It is concluded that long-term i.t. infusion of morphine through a tunnelled catheter can provide adequate pain relief in cancer patients with an acceptable risk-benefit ratio. The effects of long-term intrathecal co-administration of local anesthetics, especially bupivacaine, await further prospective evaluation.

Does it make sense to use two internal thoracic arteries?

Retrospectively, the first 143 patients who were operated on with bilateral internal thoracic arteries (BITA group) were matched with 143 patients operated on with only one left internal thoracic artery anastomosed on the left anterior descending artery and additional vein grafts (LITA group) and followed up for a maximum of 8 years. At 5 years follow-up there were no significant differences in event-free survival between the groups. After 8 years, the overall survival was 96% and 92% (not significant [NS]), cardiac survival 99% and 97% (NS), angina-free cardiac survival 51% and 35% (NS), infarction-free cardiac survival 95% and 78% (NS), reintervention-free cardiac survival 87% and 88% (NS), and all cardiac event-free survival 49% and 31% (NS) for the BITA and LITA groups, respectively. The incidence of late pulmonary, wound, and other complications was comparable. Cox proportional hazards analysis showed that a higher left ventricular end-diastolic pressure and female sex were predictors of recurrent angina and late cardiac events. During this intermediate-term follow-up, the use of one or two internal thoracic arteries was of no value in predicting angina-free or cardiac event-free survival.

[Anaphylactic shock after injection of patent blue for sentinel lymph node biopsy]. / Anafylactische shock na injectie van patentblauw voor schildwachtklieronderzoek.

After being diagnosed with a melanoma, an 18-year-old woman developed anaphylactic shock following an intracutaneous injection of patent blue during a sentinel lymph node biopsy procedure. Intracutaneous allergy tests revealed positive reactions with patent blue (Bleu patenté V 'Guerbet') as well as with several anaesthetics and morphine. It was concluded that patent blue was the most probable causative agent for the anaphylactic reaction and that the possibility of such a reaction should be taken into consideration during sentinel node procedures. After a few days the operation was completed under epidural anaesthesia with technetium Tc 99m sulphur colloid being used to detect the sentinel node.

Instrumentation for a multichord motional Stark effect diagnostic in KSTAR.

The motional Stark effect (MSE) diagnostic is used to measure the radial magnetic pitch angle profile in neutral beam heated plasmas. This information is used to calculate the safety factor, q, with magnetic equilibrium reconstruction codes such as EFIT. The MSE diagnostic is important during active shaping of the q profile to optimize confinement and stability, and it has become a key diagnostic in high performance tokamaks. A multichord photo-elastic modulator (PEM) based MSE system is being developed for a real-time plasma current profile control in Korea Superconducting Tokamak Advanced Research (KSTAR). The PEM-based approach is a standard method that measures the polarization direction of a single Stark line with narrow tunable bandpass filters. A tangential view of the heating beam provides good spatial resolution of 1-3 cm, which provides an opportunity to install 25 spatial channels spanning the major radius from 1.74 m to 2.84 m. Application of real-time control is a long-term technical goal after commissioning the diagnostic in KSTAR, which is expected in 2015. In this paper, we describe the design of this newly-constructed multichord MSE diagnostic in KSTAR.

Real-time MSE measurements for current profile control on KSTAR.

To step up from current day fusion experiments to power producing fusion reactors, it is necessary to control long pulse, burning plasmas. Stability and confinement properties of tokamak fusion reactors are determined by the current or q profile. In order to control the q profile, it is necessary to measure it in real-time. A real-time motional Stark effect diagnostic is being developed at Korean Superconducting Tokamak for Advanced Research for this purpose. This paper focuses on 3 topics important for real-time measurements: minimize the use of ad hoc parameters, minimize external influences and a robust and fast analysis algorithm. Specifically, we have looked into extracting the retardance of the photo-elastic modulators from the signal itself, minimizing the influence of overlapping beam spectra by optimizing the optical filter design and a multi-channel, multiharmonic phase locking algorithm.

Transfer of IP3 through gap junctions is critical, but not sufficient, for the spread of apoptosis.

Decades of research have indicated that gap junction channels contribute to the propagation of apoptosis between neighboring cells. Inositol 1,4,5-trisphosphate (IP3) has been proposed as the responsible molecule conveying the apoptotic message, although conclusive results are still missing. We investigated the role of IP3 in a model of gap junction-mediated spreading of cytochrome C-induced apoptosis. We used targeted loading of high-molecular-weight agents interfering with the IP3 signaling cascade in the apoptosis trigger zone and cell death communication zone of C6-glioma cells heterologously expressing connexin (Cx)43 or Cx26. Blocking IP3 receptors or stimulating IP3 degradation both diminished the propagation of apoptosis. Apoptosis spread was also reduced in cells expressing mutant Cx26, which forms gap junctions with an impaired IP3 permeability. However, IP3 by itself was not able to induce cell death, but only potentiated cell death propagation when the apoptosis trigger was applied. We conclude that IP3 is a key necessary messenger for communicating apoptotic cell death via gap junctions, but needs to team up with other factors to become a fully pro-apoptotic messenger.

A comparison of two stomatal conductance models for ozone flux modelling using data from two Brassica species.

In this study we tested and compared a multiplicative stomatal model and a coupled semi-empirical stomatal-photosynthesis model in their ability to predict stomatal conductance to ozone (gst) using leaf-level data from oilseed rape (Brassica napus L.) and broccoli (Brassica oleracea L. var. italica Plenck). For oilseed rape, the multiplicative model and the coupled model were able to explain 72% and 73% of the observed gst variance, respectively. For broccoli, the models were able to explain 53% and 51% of the observed gst variance, respectively. These results support the coupled semi-empirical stomatal-photosynthesis model as a valid alternative to the multiplicative stomatal model for O3 flux modelling, in terms of predictive performance.