Human epididymis protein 4 (HE4) levels inversely correlate with lung function improvement (delta FEV1) in cystic fibrosis patients receiving ivacaftor treatment

Background

We have recently shown that human epididymis protein 4 (HE4) levels correlate with the severity of cystic fibrosis (CF) lung disease. However, there are no data on how HE4 levels alter in patients receiving CFTR modulating therapy.

Fast CT-PRESS-based spiral chemical shift imaging at 3 Tesla.

A new sequence is presented that combines constant-time point-resolved spectroscopy (CT-PRESS) with fast spiral chemical shift imaging. It allows the acquisition of multivoxel spectra without line splitting with a minimum total measurement time of less than 5 min for a field of view of 24 cm and a nominal 1.5x1.5-cm2 in-plane resolution. Measurements were performed with 17 CS encoding steps in t1 (Deltat1=12.8 ms) and an average echo time of 151 ms, which was determined by simulating the CT-PRESS experiment for the spin systems of glutamate (Glu) and myo-inositol (mI). Signals from N-acetyl-aspartate, total creatine, choline-containing compounds (Cho), Glu, and mI were detected in a healthy volunteer with no or only minor baseline distortions within 14 min on a 3 T MR scanner.     

Bayesian inference of hemodynamic changes in functional arterial spin labeling data.

The study of brain function using MRI relies on acquisition techniques that are sensitive to different aspects of the hemodynamic response contiguous to areas of neuronal activity. For this purpose different contrasts such as arterial spin labeling (ASL) and blood oxygenation level dependent (BOLD) functional MRI techniques have been developed to investigate cerebral blood flow (CBF) and blood oxygenation, respectively. Analysis of such data typically proceeds by separate, linear modeling of the appropriate CBF or BOLD time courses. In this work an approach is developed that provides simultaneous inference on hemodynamic changes via a nonlinear physiological model of ASL data acquired at multiple echo times. Importantly, this includes a significant contribution by changes in the static magnetization, M, to the ASL signal. Inference is carried out in a Bayesian framework. This is able to extract, from dual-echo ASL data, probabilistic estimates of percentage changes of CBF, R(2) (*), and the static magnetization, M. This approach provides increased sensitivity in inferring CBF changes and reduced contamination in inferring BOLD changes when compared with general linear model approaches on single-echo ASL data. We also consider how the static magnetization, M, might be related to changes in CBV by assuming the same mechanism for water exchange as in vascular space occupancy.     

The Neurosteroid Allopregnanolone Is Reduced in Prefrontal Cortex in Alzheimer’s Disease

BACKGROUND: Few data are currently available investigating neurosteroids (NS) in Alzheimer's disease (AD). The NS allopregnanolone may be decreased in serum and plasma in patients with AD, but it is unclear if allopregnanolone is also reduced in brain. Because a number of NS exhibit neuroprotective effects and impact cognitive performance in rodent models, these molecules may be relevant to the pathophysiology of neurodegenerative disorders. We therefore investigated prefrontal cortex (PFC) NS levels in AD. METHODS: Neurosteroid levels (allopregnanolone, pregnenolone, dehydroepiandrosterone [DHEA]) were determined in postmortem PFC in 14 male subjects with AD and 15 cognitively intact male control subjects by gas chromatography/mass spectrometry preceded by high-performance liquid chromatography purification. RESULTS: Subjects with AD exhibit significant reductions in allopregnanolone compared with cognitively intact control subjects (median levels = 2.50 ng/g vs. 5.59 ng/g, respectively; p = .02). Allopregnanolone levels are inversely correlated with neuropathological disease stage (Braak), r = -.49, p = .007. Median DHEA levels are elevated in subjects with AD (p = .01). CONCLUSIONS: Subjects with AD demonstrate significant reductions in PFC allopregnanolone levels, a finding that may be relevant to neuropathological disease stage severity. Neurosteroids may have utility as candidate biomarkers in AD.     

Learning a high-precision locomotor task in patients with Parkinson's disease.

We evaluated the acquisition and performance of a high-precision locomotor task in patients with Parkinson's disease (PD) and healthy subjects. All subjects walked on a treadmill and had to step repetitively as low as possible over an obstacle without touching it. During blocks 1 and 2, the subjects had full vision and received additional acoustic warning and feedback signals. During block 3, vision became restricted. Changes in foot clearance and the number of obstacle hits were evaluated. Initially, PD patients performed poorer and improved foot clearance slower. After task repetition, the groups performed similarly. Restricting vision deteriorated performance in both groups. The similar performance of PD patients after task repetition might indicate that adequate training could improve adaptive locomotor behavior in PD patients.     

Pulsatile Perfusion Reduces the Incidence of Delayed Graft Function in Expanded Criteria Donor Kidney Transplantation

The use of expanded criteria donors (ECD) has been proposed to help combat the discrepancy between organ availability and need. ECD kidneys are associated with delayed graft function (DGF) and worse long-term survival. The aim of this study is to evaluate the impact of pulsatile perfusion (PP) on DGF and graft survival in transplanted ECD kidneys. From January 2000 to December 2003, 4618 ECD kidney-alone transplants were reported to the United Network for Organ Sharing. PP was performed on 912 renal allografts. The prognostic factors of DGF were analyzed using multivariate logistic regression analysis. Risk factors for reduced allograft viability were greater in donors and recipients of PP kidneys. Three-year graft survival of ECD kidneys preserved with PP was similar to cold storage (CS) kidneys. The incidence of DGF in PP kidneys was significantly lower than CS kidneys (26% vs. 36%, p < 0.001). Despite having a greater number of risk factors for reduced graft viability, the ECD-PP kidneys had similar graft survival compared to ECD-CS kidneys. The use of PP, by decreasing the incidence of DGF, may possibly lead to lower overall costs and increased utilization of donor kidneys.     

Proceedings of the 2006 annual meeting of the Fetal Alcohol Spectrum Disorders Study Group.

This article describes the proceedings of the 2006 Annual Meeting of the Fetal Alcohol Spectrum Disorders Study Group (FASDSG), which was held in Baltimore, Maryland on June 24, 2006. The meeting was held in conjunction with the annual meeting of the Research Society on Alcoholism and was supported by a grant from the National Institute on Alcohol Abuse and Alcoholism. The 2005-2006 FASDSG officers, Daniel J. Bonthius (President), Heather Carmichael Olson (Vice-President), and Jennifer Thomas (Secretary-Treasurer), organized the meeting. Nationally prominent speakers delivered plenary lectures on topics of newborn screening, ethics, and neuroscience. Selected members of the FASDSG provided brief scientific data (FASt) reports, describing new research findings. Representatives from national agencies involved in fetal alcohol syndrome (FAS) research, treatment, and prevention provided updates regarding priorities, funding, and agency activities. Presentations were also made by the 2006 Student Merit Award recipient and by the 2006 Rosett Award recipient. The meeting served as a forum for clinicians, neuroscientists, psychologists, social scientists, and other professionals to discuss recent advances in FAS research and to identify the most important gaps in the understanding of alcohol-induced teratology.