An EEG Investigation of Sleep Homeostasis in Healthy and CLN5 Batten Disease Affected Sheep.

UNLABELLED: Sheep have large brains with human-like anatomy, making them a useful species for studying brain function. Sleep homeostasis has not been studied in sheep. Here, we establish correlates of sleep homeostasis in sheep through a sleep deprivation experiment. We then use these correlates to elucidate the nature of sleep deficits in a naturally occurring ovine model of neuronal ceroid lipofuscinosis (NCL, Batten disease) caused by a mutation in CLN5 In humans, mutations in this gene lead to cortical atrophy and blindness, as well as sleep abnormalities. We recorded electroencephalograms (EEGs) from unaffected and early stage CLN5(-/-) (homozygous, affected) sheep over 3 consecutive days, the second day being the sleep deprivation day. In unaffected sheep, sleep deprivation led to increased EEG delta (0.5-4 Hz) power during non-rapid eye movement (NREM) sleep, increased time spent in the NREM sleep state, and increased NREM sleep bout length. CLN5(-/-) sheep showed comparable increases in time spent in NREM sleep and NREM sleep bout duration, verifying the presence of increased sleep pressure in both groups. Importantly, CLN5(-/-) sheep did not show the increase in NREM sleep delta power seen in unaffected sheep. This divergent delta power response is consistent with the known cortical degeneration in CLN5(-/-) sheep. We conclude that, whereas sleep homeostasis is present in CLN5(-/-) sheep, underlying CLN5(-/-) disease processes prevent its full expression, even at early stages. Such deficits may contribute to early abnormalities seen in sheep and patients and warrant further study. SIGNIFICANCE STATEMENT: Sleep abnormalities pervade most neurological diseases, including the neuronal ceroid lipofuscinoses (NCLs). Here, we show that, in an ovine model of a variant late-infantile NCL, there is abnormal expression of sleep homeostasis. Whereas some sleep pressure correlates respond to sleep deprivation, the strongest electroencephalogram (EEG) correlate of sleep pressure, non-REM delta power, failed to increase. This highlights the relevance of sleep deficits in this disease, in which the drive for sleep exists but the underlying disease prevents its full expression. Sleep abnormalities could contribute to early disease symptoms such as behavioral disorder and cognitive decline. Our study also shows sleep homeostatic EEG correlates in sheep, opening up new opportunities for studying sleep in a large social mammal with complex human-like brain neuroanatomy.This work was funded by CHDI, Inc.. Founding the sheep flock and costs in New Zealand relating to the rearing and genotyping of the animals were funded by a series of grants from the Neurological Foundation of New Zealand and the Batten Disease Support and Research Association by a grant from CHDI, Inc..This is the final version of the article. It first appeared from the Society for Neuroscience via http://dx.doi.org/10.1523/JNEUROSCI.4295-15.201

Advocacy with gloves on: The "manners" of strategy used by some third sector organizations undertaking advocacy in NSW and Queensland

This article examines the strategies used by some third sector organizations in Australia to advocate. The purpose of this article is to identify the kinds of activities that organizations in New South Wales and Queensland use to promote advocacy, the kinds of language that is used to describe these activities, and the reasons given for the particular strategies adopted. The extent to which the organizations adopt "softer" (that is more institutional forms of advocacy) rather than more openly challenging forms of activism is examined, particularly in light of a neo-liberal political and economic environment. In this analysis emergent strategies are identified that are not easily categorized as either "institutional" or "radical" advocacy. The article presents an exploratory analysis of some of the implications of the strategies adopted, in terms of their democratic effects and potential to strengthen the capacity of third sector organizations. The article is informed by the findings of a qualitative research project involving interviews with 24 organizations in the community services and environmental fields

Detection, Evaluation, and Treatment of Eating Disorders: The Role of the Primary Care Physician

OBJECTIVE: To describe how primary care clinicians can detect an eating disorder and identify and manage the associated medical complications. DESIGN: A review of literature from 1994 to 1999 identified by a medlinesearch on epidemiology, diagnosis, and therapy of eating disorders, including anorexia nervosa and bulimia nervosa. MEASUREMENTS AND MAIN RESULTS: Detection requires awareness of risk factors for, and symptoms and signs of, anorexia nervosa (e.g., participation in activities valuing thinness, family history of an eating disorder, amenorrhea, lanugo hair) and bulimia nervosa (e.g., unsuccessful attempts at weight loss, history of childhood sexual abuse, family history of depression, erosion of tooth enamel from vomiting, partoid gland swelling, and gastroesophageal reflux). Providers must also remain alert for disordered eating in female athletes (the female athlete triad) and disordered eating in diabetics. Treatment requires a multidisciplinary team including a primary care practitioner, nutritionist, and mental health professional. The role of the primary care practitioner is to help determine the need for hospitalization and to manage medical complications (e.g., arrhythmias, refeeding syndrome, osteoporosis, and electrolyte abnormalities such as hypokalemia). CONCLUSION: Primary care providers have an important role in detecting and managing eating disorders

Role of intensive training in the growth and maturation of artistic gymnasts

Short stature and later maturation of youth artistic gymnasts are often attributed to the effects of intensive training from a young age. Given limitations of available data, inadequate specification of training, failure to consider other factors affecting growth and maturation, and failure to address epidemiological criteria for causality, it has not been possible thus far to establish cause–effect relationships between training and the growth and maturation of young artistic gymnasts. In response to this ongoing debate, the Scientific Commission of the International Gymnastics Federation (FIG) convened a committee to review the current literature and address four questions: (1) Is there a negative effect of training on attained adult stature? (2) Is there a negative effect of training on growth of body segments? (3) Does training attenuate pubertal growth and maturation, specifically, the rate of growth and/or the timing and tempo of maturation? (4) Does training negatively influence the endocrine system, specifically hormones related to growth and pubertal maturation? The basic information for the review was derived from the active involvement of committee members in research on normal variation and clinical aspects of growth and maturation, and on the growth and maturation of artistic gymnasts and other youth athletes. The committee was thus thoroughly familiar with the literature on growth and maturation in general and of gymnasts and young athletes. Relevant data were more available for females than males. Youth who persisted in the sport were a highly select sample, who tended to be shorter for chronological age but who had appropriate weight-for-height. Data for secondary sex characteristics, skeletal age and age at peak height velocity indicated later maturation, but the maturity status of gymnasts overlapped the normal range of variability observed in the general population. Gymnasts as a group demonstrated a pattern of growth and maturation similar to that observed among short-, normal-, late-maturing individuals who were not athletes. Evidence for endocrine changes in gymnasts was inadequate for inferences relative to potential training effects. Allowing for noted limitations, the following conclusions were deemed acceptable: (1) Adult height or near adult height of female and male artistic gymnasts is not compromised by intensive gymnastics training. (2) Gymnastics training does not appear to attenuate growth of upper (sitting height) or lower (legs) body segment lengths. (3) Gymnastics training does not appear to attenuate pubertal growth and maturation, neither rate of growth nor the timing and tempo of the growth spurt. (4) Available data are inadequate to address the issue of intensive gymnastics training and alterations within the endocrine system