Risk of advanced colorectal neoplasia according to age and gender.

Colorectal cancer (CRC) is one of the leading causes of cancer related morbidity and death. Despite the fact that the mean age at diagnosis of CRC is lower in men, screening by colonoscopy or fecal occult blood test (FOBT) is initiated at same age in both genders. The prevalence of the common CRC precursor lesion, advanced adenoma, is well documented only in the screening population. The purpose of this study was to assess the risk of advanced adenoma at ages below screening age. We analyzed data from a census of 625,918 outpatient colonoscopies performed in adults in Bavaria between 2006 and 2008. A logistic regression model to determine gender- and age-specific risk of advanced neoplasia was developed. Advanced neoplasia was found in 16,740 women (4.6%) and 22,684 men (8.6%). Male sex was associated with an overall increased risk of advanced neoplasia (odds ratio 1.95; 95% confidence interval, CI, 1.91 to 2.00). At any age and in any indication group, more colonoscopies were needed in women than in men to detect advanced adenoma or cancer. At age 75 14.8 (95% CI, 14.4-15.2) screening, 18.2 (95% CI, 17.7-18.7) diagnostic, and 7.9 (95% CI, 7.6-8.2) colonoscopies to follow up on a positive FOBT (FOBT colonoscopies) were needed to find advanced adenoma in women. At age 50 39.0 (95% CI, 38.0-40.0) diagnostic, and 16.3 (95% CI, 15.7-16.9) FOBT colonoscopies were needed. Comparable numbers were reached 20 and 10 years earlier in men than in women, respectively. At any age and independent of the indication for colonoscopy, men are at higher risk of having advanced neoplasia diagnosed upon colonoscopy than women. This suggests that starting screening earlier in life in men than in women might result in a relevant increase in the detection of asymptomatic preneoplastic and neoplastic colonic lesions

Human Immunodeficiency Virus Type 1 Nef protein modulates the lipid composition of virions and host cell membrane microdomains

BACKGROUND: The Nef protein of Human Immunodeficiency Viruses optimizes viral spread in the infected host by manipulating cellular transport and signal transduction machineries. Nef also boosts the infectivity of HIV particles by an unknown mechanism. Recent studies suggested a correlation between the association of Nef with lipid raft microdomains and its positive effects on virion infectivity. Furthermore, the lipidome analysis of HIV-1 particles revealed a marked enrichment of classical raft lipids and thus identified HIV-1 virions as an example for naturally occurring membrane microdomains. Since Nef modulates the protein composition and function of membrane microdomains we tested here if Nef also has the propensity to alter microdomain lipid composition. RESULTS: Quantitative mass spectrometric lipidome analysis of highly purified HIV-1 particles revealed that the presence of Nef during virus production from T lymphocytes enforced their raft character via a significant reduction of polyunsaturated phosphatidylcholine species and a specific enrichment of sphingomyelin. In contrast, Nef did not significantly affect virion levels of phosphoglycerolipids or cholesterol. The observed alterations in virion lipid composition were insufficient to mediate Nef's effect on particle infectivity and Nef augmented virion infectivity independently of whether virus entry was targeted to or excluded from membrane microdomains. However, altered lipid compositions similar to those observed in virions were also detected in detergent-resistant membrane preparations of virus producing cells. CONCLUSION: Nef alters not only the proteome but also the lipid composition of host cell microdomains. This novel activity represents a previously unrecognized mechanism by which Nef could manipulate HIV-1 target cells to facilitate virus propagation in vivo

Compensatory premotor activity during affective face processing in subclinical carriers of a single mutant Parkin allele

Patients with Parkinson's disease suffer from significant motor impairments and accompanying cognitive and affective dysfunction due to progressive disturbances of basal ganglia–cortical gating loops. Parkinson's disease has a long presymptomatic stage, which indicates a substantial capacity of the human brain to compensate for dopaminergic nerve degeneration before clinical manifestation of the disease. Neuroimaging studies provide evidence that increased motor-related cortical activity can compensate for progressive dopaminergic nerve degeneration in carriers of a single mutant Parkin or PINK1 gene, who show a mild but significant reduction of dopamine metabolism in the basal ganglia in the complete absence of clinical motor signs. However, it is currently unknown whether similar compensatory mechanisms are effective in non-motor basal ganglia–cortical gating loops. Here, we ask whether asymptomatic Parkin mutation carriers show altered patterns of brain activity during processing of facial gestures, and whether this might compensate for latent facial emotion recognition deficits. Current theories in social neuroscience assume that execution and perception of facial gestures are linked by a special class of visuomotor neurons (‘mirror neurons’) in the ventrolateral premotor cortex/pars opercularis of the inferior frontal gyrus (Brodmann area 44/6). We hypothesized that asymptomatic Parkin mutation carriers would show increased activity in this area during processing of affective facial gestures, replicating the compensatory motor effects that have previously been observed in these individuals. Additionally, Parkin mutation carriers might show altered activity in other basal ganglia–cortical gating loops. Eight asymptomatic heterozygous Parkin mutation carriers and eight matched controls underwent functional magnetic resonance imaging and a subsequent facial emotion recognition task. As predicted, Parkin mutation carriers showed significantly stronger activity in the right ventrolateral premotor cortex during execution and perception of affective facial gestures than healthy controls. Furthermore, Parkin mutation carriers showed a slightly reduced ability to recognize facial emotions that was least severe in individuals who showed the strongest increase of ventrolateral premotor activity. In addition, Parkin mutation carriers showed a significantly weaker than normal increase of activity in the left lateral orbitofrontal cortex (inferior frontal gyrus pars orbitalis, Brodmann area 47), which was unrelated to facial emotion recognition ability. These findings are consistent with the hypothesis that compensatory activity in the ventrolateral premotor cortex during processing of affective facial gestures can reduce impairments in facial emotion recognition in subclinical Parkin mutation carriers. A breakdown of this compensatory mechanism might lead to the impairment of facial expressivity and facial emotion recognition observed in manifest Parkinson's disease

Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects

Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding, while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. Insulin/insulin oligomer μM dissociation constants were determined. Compatible with these findings, type 1 diabetic patients receiving insulin and C-peptide developed 66% more stimulation of glucose metabolism than when given insulin alone. A role of C-peptide in promoting insulin disaggregation may be important physiologically during exocytosis of pancreatic β-cell secretory granulae and pharmacologically at insulin injection sites. It is compatible with the normal co-release of C-peptide and insulin and may contribute to the beneficial effect of C-peptide and insulin replacement in type 1 diabetics

Internal and external information in error processing

<p>Abstract</p> <p>Background</p> <p>The use of self-generated and externally provided information in performance monitoring is reflected by the appearance of error-related and feedback-related negativities (ERN and FRN), respectively. Several authors proposed that ERN and FRN are supported by similar neural mechanisms residing in the anterior cingulate cortex (ACC) and the mesolimbic dopaminergic system. The present study is aimed to test the functional relationship between ERN and FRN. Using an Eriksen-Flanker task with a moving response deadline we tested 17 young healthy subjects. Subjects received feedback with respect to their response accuracy and response speed. To fulfill both requirements of the task, they had to press the correct button and had to respond in time to give a valid response.</p> <p>Results</p> <p>When performance monitoring based on self-generated information was sufficient to detect a criterion violation an ERN was released, while the subsequent feedback became redundant and therefore failed to trigger an FRN. In contrast, an FRN was released if the feedback contained information which was not available before and action monitoring processes based on self-generated information failed to detect an error.</p> <p>Conclusion</p> <p>The described pattern of results indicates a functional interrelationship of response and feedback related negativities in performance monitoring.</p

Deep Brain Stimulation of Nucleus Accumbens Region in Alcoholism Affects Reward Processing

The influence of bilateral deep brain stimulation (DBS) of the nucleus nucleus (NAcc) on the processing of reward in a gambling paradigm was investigated using H2[15O]-PET (positron emission tomography) in a 38-year-old man treated for severe alcohol addiction. Behavioral data analysis revealed a less risky, more careful choice behavior under active DBS compared to DBS switched off. PET showed win- and loss-related activations in the paracingulate cortex, temporal poles, precuneus and hippocampus under active DBS, brain areas that have been implicated in action monitoring and behavioral control. Except for the temporal pole these activations were not seen when DBS was deactivated. These findings suggest that DBS of the NAcc may act partially by improving behavioral control

When Music and Long-Term Memory Interact: Effects of Musical Expertise on Functional and Structural Plasticity in the Hippocampus

The development of musical skills by musicians results in specific structural and functional modifications in the brain. Surprisingly, no functional magnetic resonance imaging (fMRI) study has investigated the impact of musical training on brain function during long-term memory retrieval, a faculty particularly important in music. Thus, using fMRI, we examined for the first time this process during a musical familiarity task (i.e., semantic memory for music). Musical expertise induced supplementary activations in the hippocampus, medial frontal gyrus, and superior temporal areas on both sides, suggesting a constant interaction between episodic and semantic memory during this task in musicians. In addition, a voxel-based morphometry (VBM) investigation was performed within these areas and revealed that gray matter density of the hippocampus was higher in musicians than in nonmusicians. Our data indicate that musical expertise critically modifies long-term memory processes and induces structural and functional plasticity in the hippocampus

Emotional Cues during Simultaneous Face and Voice Processing: Electrophysiological Insights

Both facial expression and tone of voice represent key signals of emotional communication but their brain processing correlates remain unclear. Accordingly, we constructed a novel implicit emotion recognition task consisting of simultaneously presented human faces and voices with neutral, happy, and angry valence, within the context of recognizing monkey faces and voices task. To investigate the temporal unfolding of the processing of affective information from human face-voice pairings, we recorded event-related potentials (ERPs) to these audiovisual test stimuli in 18 normal healthy subjects; N100, P200, N250, P300 components were observed at electrodes in the frontal-central region, while P100, N170, P270 were observed at electrodes in the parietal-occipital region. Results indicated a significant audiovisual stimulus effect on the amplitudes and latencies of components in frontal-central (P200, P300, and N250) but not the parietal occipital region (P100, N170 and P270). Specifically, P200 and P300 amplitudes were more positive for emotional relative to neutral audiovisual stimuli, irrespective of valence, whereas N250 amplitude was more negative for neutral relative to emotional stimuli. No differentiation was observed between angry and happy conditions. The results suggest that the general effect of emotion on audiovisual processing can emerge as early as 200 msec (P200 peak latency) post stimulus onset, in spite of implicit affective processing task demands, and that such effect is mainly distributed in the frontal-central region