Distribution of Alarin Immunoreactivity in the Mouse Brain

Alarin is a 25 amino acid peptide that belongs to the galanin peptide family. It is derived from the galanin-like peptide gene by a splice variant, which excludes exon 3. Alarin was first identified in gangliocytes of neuroblastic tumors and later shown to have a vasoactive function in the skin. Recently, alarin was demonstrated to stimulate food intake as well as the hypothalamic–pituitary–gonadal axis in rodents, suggesting that it might be a neuromodulatory peptide in the brain. However, the individual neurons in the central nervous system that express alarin have not been identified. Here, we determined the distribution of alarin-like immunoreactivity (alarin-LI) in the adult murine brain. The specificity of the antibody against alarin was demonstrated by the absence of labeling after pre-absorption of the antiserum with synthetic alarin peptide and in transgenic mouse brains lacking neurons expressing the GALP gene. Alarin-LI was observed in different areas of the murine brain. A high intensity of alarin-LI was detected in the accessory olfactory bulb, the medial preoptic area, the amygdala, different nuclei of the hypothalamus such as the arcuate nucleus and the ventromedial hypothalamic nucleus, the trigeminal complex, the locus coeruleus, the ventral chochlear nucleus, the facial nucleus, and the epithelial layer of the plexus choroideus. The distinct expression pattern of alarin in the adult mouse brain suggests potential functions in reproduction and metabolism

Biogeographical Survey Identifies Consistent Alternative Physiological Optima and a Minor Role for Environmental Drivers in Maintaining a Polymorphism

The contribution of adaptive mechanisms in maintaining genetic polymorphisms is still debated in many systems. To understand the contribution of selective factors in maintaining polymorphism, we investigated large-scale (>1000 km) geographic variation in morph frequencies and fitness-related physiological traits in the damselfly Nehalennia irene. As fitness-related physiological traits, we investigated investment in immune function (phenoloxidase activity), energy storage and fecundity (abdomen protein and lipid content), and flight muscles (thorax protein content). In the first part of the study, our aim was to identify selective agents maintaining the large-scale spatial variation in morph frequencies. Morph frequencies varied considerably among populations, but, in contrast to expectation, in a geographically unstructured way. Furthermore, frequencies co-varied only weakly with the numerous investigated ecological parameters. This suggests that spatial frequency patterns are driven by stochastic processes, or alternatively, are consequence of highly variable and currently unidentified ecological conditions. In line with this, the investigated ecological parameters did not affect the fitness-related physiological traits differently in both morphs. In the second part of the study, we aimed at identifying trade-offs between fitness-related physiological traits that may contribute to the local maintenance of both colour morphs by defining alternative phenotypic optima, and test the spatial consistency of such trade-off patterns. The female morph with higher levels of phenoloxidase activity had a lower thorax protein content, and vice versa, suggesting a trade-off between investments in immune function and in flight muscles. This physiological trade-off was consistent across the geographical scale studied and supports widespread correlational selection, possibly driven by male harassment, favouring alternative trait combinations in both female morphs

Closed-loop management of inpatient hyperglycaemia.

The prevalence of diabetes in the inpatient setting is increasing, and suboptimal glucose control in hospital is associated with increased morbidity and mortality. Attaining the recommended glucose levels is challenging with standard insulin therapy. Hypoglycaemia and hyperglycaemia are common and diabetes management in hospital can be a considerable workload burden for health-care professionals. Fully automated insulin delivery (closed-loop) has been shown to be safe, and achieves superior glucose control than standard insulin therapy in the hospital, including in those patients receiving haemodialysis and enteral or parenteral nutrition where glucose control can be particularly challenging. Evidence that the improved glucose control achieved using closed-loop systems can translate into improved clinical outcomes for patients is key to support widespread adoption of this technology. The closed-loop approach has the potential to provide a paradigm shift in the management of inpatient diabetes, particularly in the most challenging inpatient populations, and may reduce staff work burden and the health-care costs associated with inpatient diabetes

Is an artificial pancreas (closed-loop system) for Type 1 diabetes effective?

The artificial pancreas is now a viable treatment option for people with Type 1 diabetes and has demonstrated improved glycaemic outcomes while also reducing the onus of self-management of Type 1 diabetes. Closed-loop glucose-responsive insulin delivery guided by real-time sensor glucose readings can accommodate highly variable day-to-day insulin requirements and reduce the hypoglycaemia risk observed with tight glycaemic control in Type 1 diabetes. In 2011, the James Lind Alliance research priorities for Type 1 diabetes were produced and priority 3 was to establish whether an artificial pancreas (closed-loop system) for Type 1 diabetes is effective. This review focuses on the progress that has been made in the evolution of closed-loop systems as an effective treatment option for Type 1 diabetes. Development of closed-loop systems has advanced from feasibility evaluations in highly supervised settings over short periods, to clinical studies in free-living, unsupervised conditions lasting several months. The approval in the USA of the first hybrid closed-loop system (MiniMed® 670G pump, Medtronic, Northridge, CA, USA) in 2016 for use in Type 1 diabetes reflects these advancements. We discuss the evidence from clinical studies that closed-loop systems are effective with improved glycaemic outcomes, reduced hypoglycaemia and had positive end-user acceptance in children, adolescents, adults and pregnant women with Type 1 diabetes. We also present the outlook for future closed-loop systems in the treatment of Type 1 diabetes and identify the challenges facing the wide-spread clinical adoption of this technology

Closed-loop technology: a practical guide

Hybrid closed-loop insulin delivery has been shown to be safe and effective in improving time in target glucose range and reducing the risk of hypoglycaemia for people with type 1 diabetes. Benefits in terms of reduction in diabetes burden have also been demonstrated. After decades of research and development, four hybrid closed-loop systems are now commercially available in the UK with more expected soon. We review the hybrid closed-loop systems currently available – Tandem t:slim with Control-IQ, CamAPS FX, Medtronic MiniMed 670G and second generation, Medtronic MiniMed 780G – and discuss the components and key features of these technologies. As hybrid closed-loop systems become more widely available, education and training of health care professionals and users will be pivotal in ensuring the research benefits are translated into real-world outcomes. Users need to be supported to make appropriate choices about the different systems available and be guided in realistic expectations regarding outcomes. Attention must be given to the key training and education requirements and how these differ from traditional insulin pump therapy. Training and interpretation in reviewing closed-loop data are essential for post-initiation reviews and optimisation. Developments in diabetes technology are progressing rapidly and other hybrid closed-loop systems currently in pivotal clinical trials may soon become commercially available. We also consider other important progress in this field including the use of faster-acting insulin analogues, adjunctive therapies such as SGLT2 inhibitors and dual hormone closed-loop systems

The importance of prandial insulin bolus timing with hybrid closed-loop systems.

Attainment of glycaemic targets for people with type 1 diabetes (T1D) is challenging and management of post-prandial hyperglycaemia is one key contributing factor. Due to delays in subcutaneous insulin absorption, administering rapid‐acting insulin boluses 15–20 minutes before a meal leads to approximately 30% reduction in post‐prandial glucose compared with boluses delivered immediately before the meal [1-3]. There is also a greater risk of post-prandial hypoglycaemia when people administer insulin boluses post-meal. People with T1D who routinely bolus rapid-acting insulin pre‐meal have better HbA1c values, according to large registry data [4]

Closed-loop insulin delivery in end-of-life care: a case report.

BACKGROUND: Glucose management for people with diabetes approaching the end of life can be very challenging. The aim is to balance a minimally invasive approach with avoidance of symptomatic hypo- and hyperglycaemia. CASE REPORT: We present a case of a hospitalized individual whose glucose was managed with closed-loop insulin delivery within a randomized controlled trial setting during a period of terminal illness. During the time in which closed-loop insulin delivery was used, glucose control was safe, with no glucose-related harm. The mean ± sd sensor glucose for this individual was 11.3 ± 4.3 mmol/l, percentage of time spent in target glucose range between 6 and 15 mmol/l was 70.5%, time spent in hypoglycaemia was 2.0% and time spent in significant hyperglycaemia >20 mmol/l was 2.6%. CONCLUSION: Closed-loop systems can accommodate personalized glucose targets and highly variable insulin requirements. Factory-calibrated continuous glucose sensors and insulin pump therapy are less intrusive than finger-stick glucose measurements and insulin injections, respectively. Closed-loop systems may provide a safer and less burdensome approach to glucose management towards the end of life