Curriculum topics in radiology education

There is a need for a standardized curriculum for medical school instruction in diagnostic radiology. A survey of clinicians, recent medical school graduates, and educators in radiology resulted in remarkable agreement as to the clinical curriculum topics considered important in a medical school course in diagnostic radiology. This report outlines these topics and discusses both their commonality and their differences.     

Double- and monofunctional CD4⁺ and CD8⁺ T-cell responses to Mycobacterium tuberculosis DosR antigens and peptides in long-term latently infected individuals

More than 2 billion individuals are latently infected with Mycobacterium tuberculosis (Mtb). Knowledge of the key Mtb antigens and responding T-cell subsets mediating protection against Mtb is critical for developing improved tuberculosis (TB) vaccines. We previously reported that Mtb DosR-regulon-encoded antigens are recognized well by human T cells in association with control of Mtb infection. The characteristics of the responding T-cell subsets, however, remained unidentified. We have therefore studied the cytokine production and memory phenotypes of Mtb DosR-regulon-encoded antigen-specific T cells from individuals who had been infected with Mtb decades ago, yet never developed TB (long-term latent Mtb-infected individuals). Using multi-parameter flow cytometry and intracellular cytokine staining for IFN-γ, TNF-α and IL-2, we found double and single cytokine-producing CD4(+) as well as CD8(+) T cells to be the most prominent subsets, particularly IFN-γ(+) TNF-α(+) CD8(+) T cells. The majority of these T cells comprised effector memory and effector T cells. Furthermore, CFSE labeling revealed strong CD4(+) and CD8(+) T-cell proliferative responses induced by several "immunodominant" Mtb DosR antigens and their specific peptide epitopes. These findings demonstrate the prominent presence of double- and monofunctional CD4(+) and CD8(+) T-cell responses in naturally protected individuals and support the possibility of designing Mtb DosR antigen-based TB vaccines.     

Alcohol selectively reduces brain activity during the affective processing of negative information

BACKGROUND: Although it has frequently been suggested that alcohol influences emotions such as anxiety and fear through the modulation of affective information processing, few studies addressed this topic using objective measures. OBJECTIVES: The acute effects of alcohol on affective processing of pictorial stimuli were investigated using electrophysiological measures. METHODS: Event-related brain potentials (ERP) resulting from watching pleasant, unpleasant, and neutral pictures were investigated in a group of participants receiving a beverage containing a moderate dose of alcohol (n=26) and a group of participants receiving a nonalcoholic placebo beverage (n=24). Both early [early posterior negativity (EPN)] and late [late positive potential (LPP)] ERP components were employed as index of emotional processing. RESULTS: The results show that alcohol reduced brain activity during watching unpleasant information in a late stage (700-1000 ms). This suggests that alcohol selectively influences the processing of unpleasant information. CONCLUSIONS: The findings are in concordance with theories linking alcohol administration to decreased processing of affective information. The results are discussed in the context of the role of the effect of alcohol on affective information processing, and its relevance to alcoholism.     

Genomic and proteomic approaches towards an understanding of sleep

The basic functions of sleep are still unclear, however, recent advances in genomics and proteomics have begun to contribute to our understanding of both normal and pathological sleep. In this review, we focus primarily on normal sleep and wake that have been studied in model organisms such as mice. Mice have been especially valuable since many different inbred strains exist that differ in sleep-related traits, and genes can be altered by either mutagenesis or targeted approaches. Advances in QTL (Quantitative Trait Loci) analysis have also helped to identify important sleep related genes, and several other QTLs have been mapped as a first step toward finding the genes that underlie basic sleep traits. In addition to more traditional genetic approaches, the abundance of different mRNAs across sleep and wake can now be studied and compared in different brain regions much more thoroughly using microarray methods. Progress at the protein level has been more difficult, but a few studies have begun to investigate changes in proteins during sleep and wake, and we present some of our own preliminary data in this area. A knowledge of which genes and proteins control or respond to changes in sleep will not only help answer fundamental questions, but may also suggest novel drug targets for improving multiple aspects of sleep and wake.     

123I-2-iodo-tyrosine, a new tumour imaging agent: human biodistribution, dosimetry and initial clinical evaluation in glioma patients

Purpose ¹²³I-2-iodo-tyrosine (¹²³I-2IT) has been identified as a promising new amino acid tracer in animals. Uptake is mediated by LAT1 transport, which is increased in tumour cells. In this study we present the human biodistribution and first clinical results in glioma patients. Methods For the biodistribution study, six male volunteers received 60–95 MBq ¹²³I-2IT. Whole-body scans and blood and urine samples were obtained up to 24 h after injection; dosimetry was calculated using OLINDA 1.0 software. Initial clinical evaluation of ¹²³I-2IT SPECT was performed in 35 patients with suspected or known glioma, either as primary diagnosis or for detection of recurrence. Tumour-to-background (T/B) ratios were calculated for semi-quantitative analysis. The results were correlated with clinical and MRI follow-up data or histology. Results ¹²³I-2IT showed both renal and intestinal clearance. Bladder (0.12 mGy/MBq) and small intestine (0.03 mGy/MBq) received the highest absorbed doses. The effective dose equivalent and effective dose were estimated at 0.020 and 0.016 mSv/MBq, respectively. In patients, ¹²³I-2IT SPECT did not differentiate between neoplastic and non-neoplastic lesions after an indeterminate MRI. In follow-up of known glioma, 13/15 patients with disease recurrence had increased T/B values (range 1.39–3.91). Out of seven recurrence-negative patients, two showed an important increase in T/B, in one case due to radionecrosis (T/B 1.59) and in the other probably due to residual but stable disease (T/B 2.07). Conclusion ¹²³I-2IT has a favourable biodistribution for a tumour imaging agent. It shows increased uptake in central nervous system glioma and is potentially useful in the follow-up of glioma patients. M. Keyaerts is an “aspirant” of the FWO-Vlaanderen.     

The functions of sleep

Here we report on The Satellite Symposium on Sleep Function that was held in Lausanne during 6^th FENS forum and brought together neuroscientists from basic and clinical sleep research. We illustrate the principal questions that arose during this interdisciplinary gathering and introduce the contents of nine review articles on aspects of sleep that are contained in this Special Issue of the European Journal of Neuroscience.     

Identification of citrullinated vimentin peptides as T cell epitopes in HLA–DR4–positive patients with rheumatoid arthritis

Objective

Antibodies directed against citrullinated proteins (ACPAs) are highly specific for rheumatoid arthritis (RA). The production of ACPAs is most likely dependent on the presence of T cells, since ACPAs undergo isotype switching and are associated with the shared epitope (SE)–containing HLA–DRB1 alleles. Vimentin is a likely candidate protein for T cell recognition, since >90% of patients positive for ACPAs that are reactive with (peptides derived from) citrullinated vimentin carry SE‐containing HLA–DRB1 alleles. The aim of this study was to identify citrullinated vimentin peptides that are presented to HLA–DRB1*0401–restricted T cells.

Methods

HLA–DR4–transgenic mice were immunized with all possible citrulline‐containing peptides derived from vimentin, and T cell reactivity was analyzed. Peptides recognized in a citrulline‐specific manner by T cells were selected and analyzed for their ability to be processed from the entire vimentin protein. A first inventory of the selected epitopes recognized by T cells was performed using peripheral blood mononuclear cells (PBMCs) from ACPA+, HLA–DR4+ patients with RA.

Results

A citrulline‐specific response was observed for 2 of the peptides analyzed in DR4‐transgenic mice. These peptides were found to be naturally processed from the vimentin protein, since citrullinated vimentin was recognized by peptide‐specific T cells. T cell reactivity against these peptides was also observed in cultures of PBMCs from RA patients.

Conclusion

This study identifies, for the first time, 2 naturally processed peptides from vimentin that are recognized by HLA–DRB1*0401–restricted T cells in a citrulline‐specific manner. These peptides can be recognized by T cells in ACPA+, HLA–DR4+ patients with RA, as shown in a first inventory.

     

Impulsivity is associated with behavioral decision-making deficits

Impaired decision-making is a key-feature of many neuropsychiatric disorders. In the present study, we examined task performance in a healthy population consisting of those whose scores indicated high and low impulsivity on several behavioral decision-making tasks reflecting orbitofrontal functioning. The measures included tasks that assess decision-making with and without a learning component and choice flexibility. The results show that subjects high on impulsivity display an overall deficit in their decision-making performance as compared with subjects low on impulsivity. More specifically, subjects with high impulsivity show weaknesses in learning of reward and punishment associations in order to make appropriate decisions (reversal-learning task and Iowa Gambling Task), and impaired adaptation of choice behavior according to changes in stimulus-reward contingencies (reversal-learning task). Simple, non-learning, components of reward- and punishment-based decision-making (Rogers Decision-Making Task) seem to be relatively unaffected. Above all, the results indicate that impulsivity is associated with a decreased ability to alter choice behavior in response to fluctuations in reward contingency. The findings add further evidence to the notion that trait impulsivity is associated with decision-making, a function of the orbitofrontal cortex.     

Effects of single and repeated shock on perceived pain and startle response in healthy volunteers

Contingent shock (CS) has been used in a number of studies to suppress health-threatening self-injurious behavior of individuals with mental retardation and autism. As sustained suppression is an issue of concern, research into procedural variables of CS is needed. In this study, clinical evidence was used to infer a variable that might be of relevance for the application of clinical contingent shock, that is, to assess the effect of single versus repeated shock at a specific location on the body. With pain intensity and startle response as dependent variables, shocks were administered to 48 healthy volunteers. Electric shocks were identical to those that used in clinical practice. The second shock in succession to the same location of the body produced higher pain intensity ratings than the first shock and that the third shock in succession to the same location of the body produced higher pain intensity ratings than the second shock in succession. Startle responses, however, failed to be affected in this direction. The latter result is consistent with a previous study. Our data suggest that repeated shock to the same location is likely to be more effective to establish suppression than repeated shock to different locations.