Mean diffusivity: A biomarker for CSF-related disease and genetic liability effects in schizophrenia

Mean diffusivity (MD), the rotationally invariant magnitude of water diffusion that is greater in cerebrospinal fluid (CSF) and smaller in organized brain tissue, has been suggested to reflect schizophrenia-associated cortical atrophy. Regional changes, associations with CSF, and the effects of genetic predisposition towards schizophrenia, however, remain uncertain. Six-direction diffusion tensor imaging DTI and high-resolution structural images were obtained from 26 schizophrenia patients, 36 unaffected first-degree patient relatives, 20 control subjects and 32 control relatives (N = 114). Registration procedures aligned diffusion tensor imaging (DTI) data across imaging modalities. MD was averaged within lobar regions and the cingulate and superior temporal gyri. CSF volume and MD were highly correlated. Significant bilateral temporal, and superior temporal MD increases were observed in schizophrenia compared with unrelated control probands. First-degree relatives of schizophrenia probands showed larger MD measures compared with controls within bilateral superior temporal regions with CSF volume correction. Superior temporal lobe brain tissue deficits and proximal CSF enlargements are widely documented in schizophrenia. Larger MD indices in patients and their relatives may thus reflect similar pathophysiological mechanisms. However, persistence of regional MD effects after controlling for CSF volume, suggests that MD is a sensitive biological marker of disease and genetic liability, characterizing at least partially distinct aspects of brain structural integrity.     

Wide beam reconstruction “quarter-time” gated myocardial perfusion SPECT functional imaging: a comparison to “full-time” ordered subset expectation maximum

Background  

Previously we reported that compared to iterative reconstruction with ordered subset expectation maximum (OSEM), wide beam reconstruction (WBR), which incorporates resolution recovery and controls noise during reconstruction without applying a post-processing filter, allows half-time SPECT acquisition with preserved diagnostic quality. We now postulate that with further Poisson noise treatment, quarter-time acquisition is possible.     

The effect of training status on inter-limb joint stiffness regulation during repeated maximal sprints

The purpose of this study was to examine the effect of anaerobic fatigue and training status on the joint stiffness (JS) regulation of the lower limbs. Twenty-two subjects participated in this study, with a group of athletes (ATH: n = 11, age: 22.1 ± 9.9 yrs, ht: 181.9 ± 6.3 cm, mass: 88.2 ± 12.7 kg) compared to a group of non-athletes (NON: n = 11, age: 20.9 ± 2.3 yrs, ht: 177.8 ± 7.1 cm, mass: 80.9 ± 22.0 kg). A modified phosphate decrement test, which consisted of eight 35 m timed sprints separated by a 30 s active recovery, allowed for inducement of anaerobic fatigue while incorporating measures of sprinting performance and JS. Assessment of JS consisted of a single-legged 2.2 Hz spring-mass hopping protocol, measured for each limb. This test was performed prior to the warm-up and after sprints two, four and six. Data analysis consisted of repeated measures MANOVA comparing groups, limbs and test. Repeated measures ANOVAs were also performed on the sprint times and the magnitude of inter-limb JS difference. For all data analysis the alpha level was set at p < 0.05. Assessment of between limb JS revealed that the ATH group possessed significantly lower inter-limb variation in comparison with the NON group after completion of the first pair of sprints, potentially due to their training status offsetting some of the mechanical and neuromuscular effects of repeated stretch-shortening cycle (SSC) fatigue. This enhanced ability to regulate inter-limb JS, in addition to enhancing performance, may reduce the risk of injury by preserving mechanical efficiency and therefore reducing metabolic cost during SSC contractions.     

Identification and characterization of novel uroporphyrinogen decarboxylase gene mutations in a large series of porphyria cutanea tarda patients and relatives

Porphyria cutanea tarda (PCT) arises from decreased hepatic activity of uroporphyrinogen decarboxylase (UROD). Both genetic and environmental factors interplay in the precipitation of clinically overt PCT, but these factors may vary between different geographic areas. Decreased activity of UROD in erythrocytes was used to identify patients with UROD mutations among a group of 130 Spanish PCT patients. Nineteen patients (14.6%) were found to harbor a mutation in the UROD gene. Eight mutations were novel: M1I, 5del10, A22V, D79N, F84I, Q116X, T141I and Y182C. Five others were previously described: F46L, V134Q, R142Q, P150L and E218G. The new missense mutations and P150L were expressed in Escherichia coli. D79N and P150L resulted in proteins that were localized to inclusion bodies. The other mutations produced recombinant proteins that were purified and showed reduced activity (range: 2.3–73.2% of wild type). These single amino acid changes were predicted to produce complex structural alterations and/or reduced stability of the enzyme. Screening of relatives of the probands showed that 37.5% of mutation carriers demonstrated increased urinary porphyrins. This study emphasizes the role of UROD mutations as a strong risk factor for PCT even in areas where environmental factors (hepatitis C virus) have been shown to be highly associated with the disease.