Tolerogenic dendritic cell reporting: Has a minimum information model made a difference?

Minimum information models are reporting frameworks that describe the essential information that needs to be provided in a publication, so that the work can be repeated or compared to other work. In 2016, Minimum Information about Tolerogenic Antigen-Presenting cells (MITAP) was created to standardize the reporting on tolerogenic antigen-presenting cells, including tolerogenic dendritic cells (tolDCs). tolDCs is a generic term for dendritic cells that have the ability to (re-)establish immune tolerance; they have been developed as a cell therapy for autoimmune diseases or for the prevention of transplant rejection. Because protocols to generate these therapeutic cells vary widely, MITAP was deemed to be a pivotal reporting tool by and for the tolDC community. In this paper, we explored the impact that MITAP has had on the tolDC field. We did this by examining a subset of the available literature on tolDCs. Our analysis shows that MITAP is used in only the minority of relevant papers (14%), but where it is used the amount of metadata available is slightly increased over where it is not. From this, we conclude that MITAP has been a partial success, but that much more needs to be done if standardized reporting is to become common within the discipline.

Genomic analysis of a novel Rhodococcus (Prescottella) equi isolate from a bovine host.

Rhodococcus (Prescottella) equi causes pneumonia-like infections in foals with high mortality rates and can also infect a number of other animals. R. equi is also emerging as an opportunistic human pathogen. In this study, we have sequenced the genome of a novel R. equi isolate, B0269, isolated from the faeces of a bovine host. Comparative genomic analyses with seven other published R. equi genomes, including those from equine or human sources, revealed a pangenome comprising of 6876 genes with 4141 genes in the core genome. Two hundred and 75 genes were specific to the bovine isolate, mostly encoding hypothetical proteins of unknown function. However, these genes include four copies of terA and five copies of terD genes that may be involved in responding to chemical stress. Virulence characteristics in R. equi are associated with the presence of large plasmids carrying a pathogenicity island, including genes from the vap multigene family. A BLAST search of the protein sequences from known virulence-associated plasmids (pVAPA, pVAPB and pVAPN) revealed a similar plasmid backbone on two contigs in bovine isolate B0269; however, no homologues of the main virulence-associated genes, vapA, vapB or vapN, were identified. In summary, this study confirms that R. equi genomes are highly conserved and reports the presence of an apparently novel plasmid in the bovine isolate B0269 that needs further characterisation to understand its potential involvement in virulence properties.

The Role of Dietary Protein and Fat in Glycaemic Control in Type 1 Diabetes: Implications for Intensive Diabetes Management.

A primary focus of the management of type 1 diabetes has been on matching prandial insulin therapy with carbohydrate amount consumed. However, even with the introduction of more flexible intensive insulin regimes, people with type 1 diabetes still struggle to achieve optimal glycaemic control. More recently, dietary fat and protein have been recognised as having a significant impact on postprandial blood glucose levels. Fat and protein independently increase the postprandial glucose excursions and together their effect is additive. This article reviews how the fat and protein in a meal impact the postprandial glycaemic response and discusses practical approaches to managing this in clinical practice. These insights have significant implications for patient education, mealtime insulin dose calculations and dosing strategies.

Extended insulin boluses cannot control postprandial glycemia as well as a standard bolus in children and adults using insulin pump therapy.

INTRODUCTION: Insulin pumps are able to deliver bolus insulin as a standard, extended or combination bolus. There is minimal research to determine which bolus is preferable in different settings. Anecdotally, many patients utilizes only the standard bolus (SB) due to uncertainty regarding when and how to program the different bolus types. We compared postprandial glycemia when five different extended boluses (EBs) and an SB were used following a test meal. We sought to determine the impact of varying rates of insulin delivery from an EB on early postprandial glycemia. METHODS: We conducted a randomized, repeated measures trial of 20 children and adults comparing postprandial glycemic excursions following EBs given at five different rates with SB as a control. All EBs were delivered over 2 h. Rates of EBs were chosen to reflect EBs used in clinical practice: EB1HR=100% of insulin:carbohydrate ratio (ICR) per hour (200% ICR total dose); EB2HR=50% of ICR per hour; EB3HR=33% of ICR per hour; EB4HR=25% of ICR per hour; EB6HR=16% ICR per hour. A standardized breakfast was given and activity was standardized. Continuous glucose monitoring was used to assess glycemia for 2 h after the meal. RESULTS: The mean postprandial glycemic excursions were lower at 30, 60, and 90 min (p<0.05) for SB compared with all EBs. The mean peak postprandial glycemic excursion and the area under the curve was lower for SB compared with all EBs (p<0.05). DISCUSSION: EBs resulted in higher postprandial glycemic excursions than SB for 2 h after the meal. For a moderate glycemic index meal EBs are unable to control glycemia for 2 h after a meal as well as SB. Further studies with different meal types are required to determine the impact of differential delivery of the EB on postprandial glycemia. TRIAL REGISTRATION NUMBER: ACTRN12612000609853.

Changes in altitude cause unintended insulin delivery from insulin pumps: mechanisms and implications.

OBJECTIVE: Children and adults with type 1 diabetes who receive insulin pump therapy have reported hypoglycemia during air travel. We studied the effects of atmospheric pressure on insulin pump delivery. RESEARCH DESIGN AND METHODS: Ten insulin pumps were connected to capillary tubes. The effects of changes in ambient pressure on insulin delivery, bubble formation, bubble size, and cartridge plunger movement were analyzed. RESULTS: During a flight (200 mmHg pressure decrease), excess insulin delivery of 0.623% of the cartridge volume occurred (P < 0.001, Student t test). In hypobaric chamber studies, bubbles developed in the insulin when the pressure decreased and displaced the insulin out of the cartridge. Pre-existing bubbles changed in size consistent with Boyle law. Cartridge plunger movement did not occur in normal flight conditions but did occur when catastrophic plane depressurization was mimicked. CONCLUSIONS: Atmospheric pressure reduction causes predictable, unintended insulin delivery in pumps by bubble formation and expansion of existing bubbles.

A 'radical' new rural model for pediatric diabetes care.

OBJECTIVE: The purpose of the study was to evaluate a new rural Australian multidisciplinary model of pediatric diabetes care. METHODS: In 2007, in response to insurmountable obstructions to establish an effective multidisciplinary team within the public health system, an Australian rural pediatric practice created a private multidisciplinary diabetes care model. The 'Rural Australian Diabetes -Inspiring Control Activity & Lifestyle' model -'RADICAL'-comprised a locally based, co-located core team of general pediatrician, diabetes educator, and mental health nurse. Regular diabetes clinics were established, including team meetings where each individual patient was discussed. Therapy included proactive child and family emotional support and promotion of insulin regimes that aimed to match patient lifestyle, especially insulin pump therapy. By 2009, 56 of 61 children and adolescents with type 1 diabetes across a broad regional area had access to the model of care. The model was evaluated in terms of metabolic control, patient satisfaction, and quality of life. RESULTS: Since the RADICAL model was established, the average HbA1c has fallen from mean 9.6% +/- 1.81 (median 9.7%) in 2006 to mean 8.1% +/- 1.25 (median 7.9%) in 2009 (p < 0.001). Patient satisfaction with the model was overwhelming. The previously demonstrated reduced quality of life of Australian rural diabetic youth compared with urban diabetic youth was eliminated. CONCLUSION: Multidisciplinary child diabetes care can be successfully achieved in rural settings using local resources with results comparable to international tertiary multidisciplinary diabetes units.