Abnormal prenatal brain development in Chiari II malformation.

Introduction: The Chiari II is a relatively common birth defect that is associated with open spinal abnormalities and is characterized by caudal migration of the posterior fossa contents through the foramen magnum. The pathophysiology of Chiari II is not entirely known, and the neurobiological substrate beyond posterior fossa findings remains unexplored. We aimed to identify brain regions altered in Chiari II fetuses between 17 and 26 GW. Methods: We used in vivo structural T2-weighted MRIs of 31 fetuses (6 controls and 25 cases with Chiari II). Results: The results of our study indicated altered development of diencephalon and proliferative zones (ventricular and subventricular zones) in fetuses with a Chiari II malformation compared to controls. Specifically, fetuses with Chiari II showed significantly smaller volumes of the diencephalon and significantly larger volumes of lateral ventricles and proliferative zones. Discussion: We conclude that regional brain development should be taken into consideration when evaluating prenatal brain development in fetuses with Chiari II.

The reliability and validity of the Timed Up and Go as a clinical tool in individuals with and without disabilities across a lifespan: a systematic review.

PURPOSE: To summarize the available literature related to reliability and validity of the Timed Up and Go in typical adults and children, and individuals diagnosed with the following pathologies: Huntington's disease, stroke, multiple sclerosis, Parkinson's disease, spinal cord injury, Down syndrome, or cerebral palsy. MATERIALS AND METHODS: A search was conducted using MeSH terms and keywords through a variety of databases. Data regarding reliability and validity were synthesized. RESULTS: This review included 77 articles. Results were variable depending on the studied population. The Timed Up and Go showed excellent reliability in typical adults, in individuals with cerebral palsy, in individuals with multiple sclerosis, in individuals with Huntington's disease, individuals with a stroke, and individuals with a spinal cord injury. The TUG demonstrated strong concurrent validity for individuals with stroke and spinal cord injury. Predictive validity data was limited. CONCLUSIONS: Based on the literature assessed, the Timed Up and Go is clinically applicable and reliable across multiple populations. The Timed Up and Go has a wide variety of clinical use making it a diverse measure that should be considered when choosing an outcome an activity based outcome measure. However, there are some limitations in the validity of the utilization of the Timed Up and Go to some populations due to a lack of data and/or poor choice of comparison outcome measures when assessing validity. Additional research is needed for young to middle aged adults.IMPLICATIONS FOR REHABILITATIONOutcome measures are a vital component of clinical practice across all populations.The Timed Up and Go is a highly studied outcome measure in the geriatric population, but lacks research of its applicability to other populations.This study was able to highlight the clinical utility of the Timed Up and Go in populations that under utilize this outcome measure.

Ghrelin stimulates fatty acid oxidation and inhibits lipolysis in isolated muscle from male rats.

Ghrelin is classically known as a central appetite-stimulating hormone but has recently been recognized to have a significant role in peripheral tissue energy metabolism. However, the direct effects of ghrelin on skeletal muscle, a major site for glucose and lipid disposal, remain understudied. We found that the two major ghrelin isoforms, acylated and unacylated ghrelin, were able to significantly increase skeletal muscle fatty acid oxidation (~20%) while incorporation of fatty acids into major lipid pools remained unchanged. The increase in fatty acid oxidation was accompanied by increases in acetyl-CoA carboxylase phosphorylation, a downstream target of AMPK. Ghrelin isoforms had no independent effect on lipolysis under unstimulated conditions, but nearly completely abolished epinephrine-stimulated lipolysis. This effect was generally, but not consistently related to a blunting in the phosphorylation of HSL activation sites, Ser660 and 563. Taken together, these findings suggest that ghrelin isoforms have a direct, acute effect on fatty acid oxidation and lipolysis.

Acylated and unacylated ghrelin directly regulate ß-3 stimulated lipid turnover in rodent subcutaneous and visceral adipose tissue ex vivo but not in vivo.

Ghrelin has garnered interest as a gut-derived regulator of lipid metabolism, beyond its classical roles in driving appetite and growth hormone release. Ghrelin's circulating concentrations follow an ultradian rhythm, peak immediately before a meal and point towards a potential metabolic role in reducing the mobilization of fatty acid stores in preparation for the storage of ingested food. Here, we demonstrate that both acylated and unacylated ghrelin have physiological roles in attenuating lipolysis in mature subcutaneous and visceral adipose tissue depots of rats. Ghrelin blunted the ß3-induction (CL 316, 243) of glycerol release (index of lipolysis) which coincided with a reduced activation of the key lipid hydrolase HSL at two of its serine residues (Ser563/660). Furthermore, ghrelin appeared to inhibit fatty acid reesterification in the presence of CL such that fatty acid concentrations in the surrounding media were maintained in spite of a reduction in lipolysis. Importantly, these aforementioned effects were not observed following ghrelin injection in vivo, as there was no attenuation of CL-induced glycerol release. This highlights the importance of exercising caution when interpreting the effects of administering ghrelin in vivo, and the necessity for uncovering the elusive mechanisms by which ghrelin regulates lipolysis and fatty acid reesterification. We conclude that both acylated and unacylated ghrelin can exert direct inhibitory effects on lipolysis and fatty acid reesterification in adipose tissue from rats. However, these effects are not observed in vivo and outline the complexity of studying ghrelin's effects on fatty acid metabolism in the living animal.

Associations between hippocampal morphometry and neuropathologic markers of Alzheimer's disease using 7 T MRI.

Hippocampal atrophy, amyloid plaques, and neurofibrillary tangles are established pathologic markers of Alzheimer's disease. We analyzed the temporal lobes of 9 Alzheimer's dementia (AD) and 7 cognitively normal (NC) subjects. Brains were scanned post-mortem at 7 Tesla. We extracted hippocampal volumes and radial distances using automated segmentation techniques. Hippocampal slices were stained for amyloid beta (Aß), tau, and cresyl violet to evaluate neuronal counts. The hippocampal subfields, CA1, CA2, CA3, CA4, and subiculum were manually traced so that the neuronal counts, Aß, and tau burden could be obtained for each region. We used linear regression to detect associations between hippocampal atrophy in 3D, clinical diagnosis and total as well as subfield pathology burden measures. As expected, we found significant correlations between hippocampal radial distance and mean neuronal count, as well as diagnosis. There were subfield specific associations between hippocampal radial distance and tau in CA2, and cresyl violet neuronal counts in CA1 and subiculum. These results provide further validation for the European Alzheimer's Disease Consortium Alzheimer's Disease Neuroimaging Initiative Center Harmonized Hippocampal Segmentation Protocol (HarP).

On-site treatment of exertional heat stroke.

BACKGROUND: Exertional heat stroke is a devastating condition that can cause significant morbidity and mortality. Rapid cooling is the most effective means of treating heat stroke, but little is published on the safety and logistics of cooling patients on site at a major sporting event. PURPOSE: To describe an on-site exertional heat stroke treatment protocol and to compare the outcomes of patients treated on site to those transferred to hospitals. STUDY DESIGN: Descriptive epidemiological study. METHODS: Using race-day medical records and ambulance run sheets, patients who developed exertional heat stroke at the Indianapolis half-marathon from 2005 to 2012 were identified. Exertional heat stroke was defined as runners with a core temperature measured with a rectal thermometer greater than 102° F and altered mental status. Clinical information and patient outcomes were abstracted from the race medical tent and hospital charts by 3 separate trained reviewers using structured methods and a data collection form. Two reviewers, using a RedCAP database and dual-data entry, abstracted records for each patient. A third arbitrated all discrepancies between reviewers. Clinical signs, treatments, and outcomes were calculated using descriptive statistics, and data were grouped and compared for patients treated on site or transferred to local hospitals for treatment. RESULTS: Over 235,000 athletes participated in the event over the 8-year period, with 696 seeking medical care. A total of 32 heat stroke victims were identified during the study period; of these, 22 were treated on site. Of these, 68% were treated with cold-water immersion and 59% were discharged home from the race. Ten exertional heat stroke patients were transported from the race course to local hospitals. None of them underwent cold-water immersion, and 40% of them were subsequently discharged home. No patients in the study died. CONCLUSION: On-site treatment of athletes who develop exertional heat stroke appears to be both safe and effective. On-site treatment may decrease the local burden of critically ill patients to emergency departments during large athletic events.