The role of insulin receptor substrate 2 in hypothalamic and β cell function

Insulin receptor substrate 2 (Irs2) plays complex roles in energy homeostasis. We generated mice lacking Irs2 in β cells and a population of hypothalamic neurons (RIPCreIrs2KO), in all neurons (NesCreIrs2KO), and in proopiomelanocortin neurons (POMCCreIrs2KO) to determine the role of Irs2 in the CNS and β cell. RIPCreIrs2KO mice displayed impaired glucose tolerance and reduced β cell mass. Overt diabetes did not ensue, because β cells escaping Cre-mediated recombination progressively populated islets. RIPCreIrs2KO and NesCreIrs2KO mice displayed hyperphagia, obesity, and increased body length, which suggests altered melanocortin action. POMCCreIrs2KO mice did not display this phenotype. RIPCreIrs2KO and NesCreIrs2KO mice retained leptin sensitivity, which suggests that CNS Irs2 pathways are not required for leptin action. NesCreIrs2KO and POMCCreIrs2KO mice did not display reduced β cell mass, but NesCreIrs2KO mice displayed mild abnormalities of glucose homeostasis. RIPCre neurons did not express POMC or neuropeptide Y. Insulin and a melanocortin agonist depolarized RIPCre neurons, whereas leptin was ineffective. Insulin hyperpolarized and leptin depolarized POMC neurons. Our findings demonstrate a critical role for IRS2 in β cell and hypothalamic function and provide insights into the role of RIPCre neurons, a distinct hypothalamic neuronal population, in growth and energy homeostasis

Moral courage in the workplace: moving to and from the desire and decision to act

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72135/1/j.1467-8608.2007.00484.x.pd

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

An assessment of CCAMLR measures employed to mitigate seabird mortality in longlining operations for Dissostichus eleginoides around South Georgia

Longlining operations for Dissostichus eleginoides off South Georgia were assessed for interactions with seabirds and the effectiveness of measures employed by CCAMLR to mitigate seabird mortality. Following an agreement between the Governments of the United Kingdom and Chile, a UK observer was placed aboard a Chilean longliner, the BF Cisne Verde, fishing in CCAMLR Subarea 48.3 during the 1996/97 season. In this study 61 lines were laid from March to May 1997 using the Spanish double-line method. In accordance with CCAMLR conservation measures, lines were set at night, weights (6-7 kg) were set at 50 m intervals along the line, all deck lights were extinguished and no offal was discarded during setting. A streamer line made to CCAMLR specifications was also used, except during an experiment that attempted to assess the effectiveness of the streamer line in mitigating incidental mortality of seabirds during night-time setting. Data were recorded during hauling using a randomised cluster sampling method, developed to allow representative data to be collected when 100% observer coverage could not be achieved: A total of 12 dead seabirds were recorded, giving an average mortality rate/night of 0.099 birds/l 000 observed hooks, substantially lower than other vessels fishing around South Georgia during the same period. Mortalities consisted of nine white-chinned petrels, two black-browed albatrosses and one unidentifiable bird caught on hooks. One giant petrel was also killed as a result of flying into the side of the vessel. Generally, few birds were seen following the vessel during setting operations. During April, however, large numbers of white-chinned petrels were seen occasionally, and large numbers of black-browed albatrosses were seen when the moon was full. Live birds were observed to become caught on hooks during hauling on 23 occasions; all birds were released alive. Black-browed albatrosses concentrated on taking returning bait off the line and accounted for 18 birds caught; giant petrels concentrated on taking discarded offal, and accounted for five birds caught

A method for preparing large numbers of otolith sections for viewing by scanning electron microscope

In an investigation of the age structure of a population of Notothenia coriiceps Richardson at the South Orkney Islands, Antarctica, the microstructure of otoliths was examined. Progress is reported on a method used for processing large numbers of otoliths using a scanning electron microscope (SEM). Compared with previous SEM techniques, which normally prepare otoliths individually for viewing, this allowed larger sample sizes to be examined. Compared with similar light microscope techniques, this method gave enhanced resolution, particularly for discerning edge structure, and thus may facilitate present methods of ageing fish populations, especially for fishery work in the Antarctic where otoliths are often small and difficult to interpret using conventional techniques

Review: Microglia in motor neuron disease

Motor Neuron Disease (MND) is a fatal neurodegenerative condition, which is characterized by the selective loss of the upper and lower motor neurons. At the sites of motor neuron injury, accumulation of activated microglia, the primary immune cells of the central nervous system, is commonly observed in both human post mortem studies and animal models of MND. Microglial activation has been found to correlate with many clinical features and importantly, the speed of disease progression in humans. Both anti‐inflammatory and pro‐inflammatory microglial responses have been shown to influence disease progression in humans and models of MND. As such, microglia could both contribute to and protect against inflammatory mechanisms of pathogenesis in MND. While murine models have characterized the microglial response to MND, these studies have painted a complex and often contradictory picture, indicating a need for further characterization in humans. This review examines the potential role microglia play in MND in human and animal studies. Both the pro‐inflammatory and anti‐inflammatory responses will be addressed, throughout the course of disease, followed by the potential of microglia as a target in the development of disease‐modifying treatments for MND

Seabird interactions with longlining operations for Dissostichus eleginoides around South Georgia, April to May 1994

Longlining operations for Dissostichus eleginoides off South Georgia were assessed for incidental mortality and interactions with seabirds. Twenty-seven line sets were observed and 98 deaths of seabirds were recorded over 20 sets; no deaths occurred during hauls. The 16 sets made at night contributed 15% of overall mortality, all of white-chinned petrels (Procellaria aequinoctialis); the four day sets contributed 85% of deaths, with giant petrels (Macronectes sp.), grey-headed albatrosses (Diomedea chrysostoma) and black-browed albatrosses (D. melanophrys) predominating. Grey-headed albatrosses, whose populations (at South Georgia are in serious decline, were disproportionately affected in relation to their numbers near the fishing vessel; giant petrels may be disproportionately affected in relation to the size of their breeding population at South Georgia when compared to albatrosses. The average mortality rate for the 20 sets was 0.48 birds/1 000 hooks and maximum mortality 3.12 birds/1 000 hooks. Mortality and interactions of birds with operations varied with site and time of day, and was affected by behavioural interactions between birds. Setting only at night would dramatically reduce the number of albatross deaths, and restrict mortality to white-chinned petrels. A streamer line made to CCAMLR specifications may reduce mortality but may be less effective during calm weather, intense feeding activity by seabirds, or when incorrectly constructed