Double dissociated effects of the functional TNF-α -308G/A polymorphism on processes of cognitive control

Neuroimmunological factors may modulate brain functions and are important to understand the molecular basis of cognition. The tumor necrosis factor alpha (TNF-α) is known to induce neurodegenerative changes in the basal ganglia, but the cognitive effects of these changes are not understood. Since the basal ganglia are neurobiologically heterogeneous, different cognitive functions mediated by basal ganglia-prefrontal loops (response inhibition and error processing) may not necessarily be uniformly affected. Response inhibition and error processing functions were examined using event-related potentials (ERPs) and subjects (N = 71) were genotyped for the functional TNF-α -308G→A polymorphism. We show a double-dissociated effect of the functional TNF-α -308G→A polymorphism on response inhibition and error processing. While response inhibition functions were more effective in the AA/AG genotype group, error monitoring functions are adversely affected in this genotype group. In the GG genotype group, the pattern of results was vice versa. The results refine the view of the effects of TNF-α on cognitive functions.     

Rs710521[A] on chromosome 3q28 close to TP63 is associated with increased urinary bladder cancer risk

Single nucleotide polymorphism (SNP) rs710521[A], located near TP63 on chromosome 3q28, was identified to be significantly associated with increased bladder cancer risk. To investigate the association of rs710521[A] and bladder cancer by new data and by meta-analysis including all published data, rs710521 was studied in 1,425 bladder cancer cases and 1,740 controls that had not been included in previous studies. Blood samples were collected from 1995 to 2010 in Germany (n?=?948/1,258), Hungary (n?=?262/65), Venezuela (n?=?112/190) and Pakistan (n?=?103/227) supplemented by a meta-analysis of 5,695 cases and 40,187 controls. Detection of a A/G substitution (rs710521) on chromosome 3q28, position 191128627 was done via fast real-time polymerase chain reaction (rt-PCR). Rs710521[A] is associated with increased risk in the unadjusted analysis (OR?=?1.21; 95% Cl?=?1.04-1.40; P?=?0.011) and in the recessive model adjusted for age, gender, smoking habits and ethnicity (OR?=?1.23; 95% Cl?=?1.05-1.44; P?=?0.010). No difference between individuals occupationally exposed versus not occupationally exposed to urinary bladder carcinogens was observed concerning the relevance of rs710521[A]. Similarly, rs710521[A] did not confer different susceptibility in smokers and non-smokers. Performing a meta-analysis of 5,695 cases and 40,187 controls including all published studies on rs710521, a convincing association with bladder cancer risk was obtained (OR?=?1.18; 95% Cl?=?1.12-1.25; P?相似文献   

The relationship between poor sleep and inhibitory functions indicated by event-related potentials

The present study focused on the relationship between normal variations of sleep and inhibitory functions as reflected in event-related potentials. For this reason one night of 21 healthy participants was analysed. After waking up all participants completed a visual Go/Nogo task. On the basis of a sleep disturbance index (SDI) the participants were separated into 8 SDI-good and 13 SDI-poor sleepers using a cluster analysis. The results showed that Nogo-N2 amplitude was smaller and Nogo-P3 latency longer in SDI-poor sleepers. Moreover, Go-P3 amplitude was smaller in SDI-poor sleepers. Performance parameters were not influenced by poor sleep. We concluded that poor sleep specifically affects the intensity of pre-motor inhibitory processes (Nogo-N2 amplitude), the speed to inhibit a motor response (Nogo-P3 latency) and the intensity of task-relevant information processing (Go-P3 amplitude). In further studies, it should be explored under which conditions such subliminal deficits also become relevant for overt behaviour.

Effects of Working Memory Load on Performance and Cardiovascular Activity in Younger and Older Workers

Background

Working memory (WM) declines with ageing, and this may cause problems in older workers who have to do complex work requiring WM.

Purpose

We tested the assumption that an increase in WM load negatively affects performance and results in impaired cardiovascular adaptation to changing task demands in older workers relative to younger ones.

Method

Thirty-three younger (29?±?3?years) and 32 older (55?±?3?years) workers had to perform a visual 0-back (low WM load) and 2-back (high WM load) task. Heart rate (HR), heart rate variability (HRV), beat-to-beat blood pressure (BP) and baroreflex were registered.

Results

In the high WM load condition, older adults responded more slowly and less accurately than younger adults, while no age effects in the low WM load condition were found. Older workers showed a higher systolic blood pressure (SBP) reactivity to high WM load as well as a diminished post-task recovery of SBP and HRV than younger workers. Factor analysis demonstrated a close relationship between HR, baroreflex and HRV and their modulation by a common factor (??vagal tone??) in the younger group. By contrast, HR was more related to the ??sympathetic?? factor in the older group.

Conclusion

The data suggest that older workers as compared with younger ones are impaired in tasks requiring WM, which is accompanied by enhanced cardiovascular ??costs?? in terms of increased SBP and reduced vagal control over HR.     

Risk factors for recurrent bleeding and mortality in human immunodeficiency virus–infected patients with acute lower GI hemorrhage

BACKGROUND: Little is known about lower gastrointestinal (GI) hemorrhage in the human immunodeficiency virus (HIV) infected population. Our aim was to determine the underlying causes, the clinical outcome, and the risk factors for recurrent bleeding and mortality in HIV-infected patients with acute LGIH. METHODS: We reviewed the medical records of consecutive HIV-infected patients with acute lower GI hemorrhage who were evaluated with endoscopy from January 1992 through January 1997 at Bellevue Hospital Center. RESULTS: During the 5-year study period, 312 patients with acute lower GI hemorrhage underwent colonoscopy (n = 233) or flexible sigmoidoscopy (n = 79). Cytomegalovirus colitis (25.3%), lymphoma (12.2%), and idiopathic colitis (12.2%) were the most common causes identified. Within 30 days of presentation, recurrent bleeding occurred in 17.6% of patients. Independent predictors of recurrent bleeding included the presence of at least one comorbid illness, a hemoglobin level of less than 8 gm/dL, a platelet count of less than 100,000/mm3, and major stigmata of hemorrhage. The 30-day mortality from lower GI hemorrhage was 14.4%, and the presence of comorbid disease, recurrence of bleeding, and surgical intervention were found to be the only independent predictors of mortality in this patient population. CONCLUSIONS: Acute lower GI hemorrhage in HIV-infected patients is most commonly caused by cytomegalovirus colitis and is associated with a high short-term morbidity and mortality.