Optimizing Data for Modeling Neuronal Responses

In this technical note, we address an unresolved challenge in neuroimaging statistics: how to determine which of several datasets is the best for inferring neuronal responses. Comparisons of this kind are important for experimenters when choosing an imaging protocol—and for developers of new acquisition methods. However, the hypothesis that one dataset is better than another cannot be tested using conventional statistics (based on likelihood ratios), as these require the data to be the same under each hypothesis. Here we present Bayesian data comparison (BDC), a principled framework for evaluating the quality of functional imaging data, in terms of the precision with which neuronal connectivity parameters can be estimated and competing models can be disambiguated. For each of several candidate datasets, neuronal responses are modeled using Bayesian (probabilistic) forward models, such as General Linear Models (GLMs) or Dynamic Casual Models (DCMs). Next, the parameters from subject-specific models are summarized at the group level using a Bayesian GLM. A series of measures, which we introduce here, are then used to evaluate each dataset in terms of the precision of (group-level) parameter estimates and the ability of the data to distinguish similar models. To exemplify the approach, we compared four datasets that were acquired in a study evaluating multiband fMRI acquisition schemes, and we used simulations to establish the face validity of the comparison measures. To enable people to reproduce these analyses using their own data and experimental paradigms, we provide general-purpose Matlab code via the SPM software

Adjacent level discitis after anterior cervical discectomy and fusion (ACDF): a case report

This report describes a case of spondylodiscitis occurring adjacent to levels at which anterior cervical discectomy and fusion was performed. The objective is to describe a rare cause of spondylodiscitis and discuss its successful management. Post-operative discitis involving the same level is a known occurrence. We report an interesting case of spondylodiscitis occurring at the adjacent level of fusion, and to our knowledge this is the first such case reported in literature. A two-level decompression and fusion was performed at C5–6 and C6–7 levels with PEEK cages and anterior cervical plating in a middle-aged gentleman for persistent axial neck pain and left-sided radiculopathy involving C6 and C7 distribution. After 6 weeks, the patient presented to us with complaints of mild paresthesia in the abdomen and extremities. Radiological investigations including plain radiographs and MRI revealed a surprising finding of discitis at C4–5 level with an associated epidural abscess. In view of the patient’s myelopathic symptoms, surgical debridement and decompression of the spinal cord was performed. The plate and screws were removed, the cages were left intact, and the C4–5 disc level was reconstructed with tricortical iliac crest autograft. No further instrumentation was performed. The biopsy specimen from the disc at C4–5 level grew Serratia marcescens. It was contemplated that C4–5 discitis was initiated by inoculation of bacteria at the superior endplate of C5 by contaminated vertebral pins/drill-bit or screws. Adjacent level discitis is a rare but potentially serious complication of anterior cervical fusion. A high index of suspicion of infection is necessary if the patient complains of new symptoms after anterior cervical fusion. Thorough assessment and aggressive treatment is necessary for successful management

Hemorrhage-Adjusted Iron Requirements, Hematinics and Hepcidin Define Hereditary Hemorrhagic Telangiectasia as a Model of Hemorrhagic Iron Deficiency

BACKGROUND: Iron deficiency anemia remains a major global health problem. Higher iron demands provide the potential for a targeted preventative approach before anemia develops. The primary study objective was to develop and validate a metric that stratifies recommended dietary iron intake to compensate for patient-specific non-menstrual hemorrhagic losses. The secondary objective was to examine whether iron deficiency can be attributed to under-replacement of epistaxis (nosebleed) hemorrhagic iron losses in hereditary hemorrhagic telangiectasia (HHT). METHODOLOGY/PRINCIPAL FINDINGS: The hemorrhage adjusted iron requirement (HAIR) sums the recommended dietary allowance, and iron required to replace additional quantified hemorrhagic losses, based on the pre-menopausal increment to compensate for menstrual losses (formula provided). In a study population of 50 HHT patients completing concurrent dietary and nosebleed questionnaires, 43/50 (86%) met their recommended dietary allowance, but only 10/50 (20%) met their HAIR. Higher HAIR was a powerful predictor of lower hemoglobin (p = 0.009), lower mean corpuscular hemoglobin content (p<0.001), lower log-transformed serum iron (p = 0.009), and higher log-transformed red cell distribution width (p<0.001). There was no evidence of generalised abnormalities in iron handling Ferritin and ferritin(2) explained 60% of the hepcidin variance (p<0.001), and the mean hepcidinferritin ratio was similar to reported controls. Iron supplement use increased the proportion of individuals meeting their HAIR, and blunted associations between HAIR and hematinic indices. Once adjusted for supplement use however, reciprocal relationships between HAIR and hemoglobin/serum iron persisted. Of 568 individuals using iron tablets, most reported problems completing the course. For patients with hereditary hemorrhagic telangiectasia, persistent anemia was reported three-times more frequently if iron tablets caused diarrhea or needed to be stopped. CONCLUSIONS/SIGNIFICANCE: HAIR values, providing an indication of individuals' iron requirements, may be a useful tool in prevention, assessment and management of iron deficiency. Iron deficiency in HHT can be explained by under-replacement of nosebleed hemorrhagic iron losses

Acyl-Protein Thioesterase 2 Catalizes the Deacylation of Peripheral Membrane-Associated GAP-43

An acylation/deacylation cycle is necessary to maintain the steady-state subcellular distribution and biological activity of S-acylated peripheral proteins. Despite the progress that has been made in identifying and characterizing palmitoyltransferases (PATs), much less is known about the thioesterases involved in protein deacylation. In this work, we investigated the deacylation of growth-associated protein-43 (GAP-43), a dually acylated protein at cysteine residues 3 and 4. Using fluorescent fusion constructs, we measured in vivo the rate of deacylation of GAP-43 and its single acylated mutants in Chinese hamster ovary (CHO)-K1 and human HeLa cells. Biochemical and live cell imaging experiments demonstrated that single acylated mutants were completely deacylated with similar kinetic in both cell types. By RT-PCR we observed that acyl-protein thioesterase 1 (APT-1), the only bona fide thioesterase shown to mediate deacylation in vivo, is expressed in HeLa cells, but not in CHO-K1 cells. However, APT-1 overexpression neither increased the deacylation rate of single acylated GAP-43 nor affected the steady-state subcellular distribution of dually acylated GAP-43 both in CHO-K1 and HeLa cells, indicating that GAP-43 deacylation is not mediated by APT-1. Accordingly, we performed a bioinformatic search to identify putative candidates with acyl-protein thioesterase activity. Among several candidates, we found that APT-2 is expressed both in CHO-K1 and HeLa cells and its overexpression increased the deacylation rate of single acylated GAP-43 and affected the steady-state localization of diacylated GAP-43 and H-Ras. Thus, the results demonstrate that APT-2 is the protein thioesterase involved in the acylation/deacylation cycle operating in GAP-43 subcellular distribution