General anesthesia alters CNS and astrocyte expression of activity-dependent and activity-independent genes.

General anesthesia represents a common clinical intervention and yet can result in long-term adverse CNS effects particularly in the elderly or dementia patients. Suppression of cortical activity is a key feature of the anesthetic-induced unconscious state, with activity being a well-described regulator of pathways important for brain health. However, the extent to which the effects of anesthesia go beyond simple suppression of neuronal activity is incompletely understood.

The consequences of neurodegenerative disease on neuron-astrocyte metabolic and redox interactions.

Brain metabolic pathways relating to bioenergetic and redox homeostasis are closely linked, and deficits in these pathways are thought to occur in many neurodegenerative diseases. Astrocytes play important roles in both processes, and growing evidence suggests that neuron-astrocyte intercellular signalling ensures brain bioenergetic and redox homeostasis in health. Moreover, alterations to this crosstalk have been observed in the context of neurodegenerative pathology.

Astrocyte-oligodendrocyte interaction regulates central nervous system regeneration.

Failed regeneration of myelin around neuronal axons following central nervous system damage contributes to nerve dysfunction and clinical decline in various neurological conditions, for which there is an unmet therapeutic demand. Here, we show that interaction between glial cells - astrocytes and mature myelin-forming oligodendrocytes - is a determinant of remyelination. Using in vivo/ ex vivo/ in vitro rodent models, unbiased RNA sequencing, functional manipulation, and human brain lesion analyses, we discover that astrocytes support the survival of regenerating oligodendrocytes, via downregulation of the Nrf2 pathway associated with increased astrocytic cholesterol biosynthesis pathway activation.

Good, bad, and neglectful: Astrocyte changes in neurodegenerative disease.

Astrocytes play key roles in CNS development as well as well as neuro-supportive roles in the mature brain including ionic, bioenergetic and redox homeostasis. Astrocytes undergo rapid changes following acute CNS insults such as stroke or traumatic brain injury, but are also profoundly altered in chronic neurodegenerative conditions such as Alzheimer's disease. While disease-altered astrocytes are often referred to as reactive, this does not represent a single cellular state or group of states, but a shift in astrocyte properties that is determined by the type of insult as well as spatio-temporal factors.

Author Correction: Neurons and neuronal activity control gene expression in astrocytes to regulate their development and metabolism.

This corrects the article DOI: 10.1038/ncomms15132.

Leukoreduced blood transfusion does not increase circulating soluble markers of inflammation: a randomized controlled trial.

Background: Transfused blood may have immunomodulatory and proinflammatory effects. We report the first randomized study exploring whether leukoreduced red blood cell (RBC) transfusion increases circulating proinflammatory mediators, markers of neutrophil activation, and the acute-phase response in critically ill adults.

Study Design And Methods: Eighty-four patients were recruited from six general intensive care units in the United Kingdom as part of a laboratory study nested within a parallel-group randomized trial comparing restrictive and liberal leukoreduced RBC transfusion strategies in critically ill patients aged more than 55 years with measured hemoglobin concentrations of not more than 90 g/L (ClinicalTrials.

Emergency department management of early sepsis: a national survey of emergency medicine and intensive care consultants.

Objectives: Early goal-directed therapy (EGDT) is recommended for sepsis management in current guidelines, but the underpinning evidence is controversial. Clinician beliefs and the capacity to implement all recommended elements of EGDT in emergency departments (EDs) are uncertain. Our study aimed to explore self-reported management of early sepsis by Scottish emergency medicine (EM) and intensive care medicine (ICM) consultants, delineate important differences and determine the guideline recommendations rated most important and deliverable within the ED.

Advanced Cardiac Resuscitation Evaluation (ACRE): a randomised single-blind controlled trial of peer-led vs. expert-led advanced resuscitation training.

Background: Advanced resuscitation skills training is an important and enjoyable part of medical training, but requires small group instruction to ensure active participation of all students. Increases in student numbers have made this increasingly difficult to achieve.

Methods: A single-blind randomised controlled trial of peer-led vs.

Hearing impairment in Tanzanians with albinism.

Community-based studies have suggested that those affected with albinism, an important condition in East Africa, may be at a greater risk of developing hearing problems. This study shows that the prevalence of hearing loss is increased in Tanzanians with albinism and that hearing loss is associated with fewer years in education. 64 participants with albinism and 90 controls without were recruited from clinics held in the Western Kilimanjaro area.