Blunted rostral anterior cingulate response during a simplified decoding task of negative emotional facial expressions in alcoholic patients

BACKGROUND: Alcoholism is characterized by deficits in emotional functioning as well as by deficits in cognitive functioning. However, most brain imaging research on alcoholism has focused on cognition rather than emotion. METHOD: We used an event-related functional magnetic imaging approach to examine alcoholics' brain blood oxygenation level dependent (BOLD) response to evaluation of emotional stimuli and to compare their response to that of nonalcoholic controls. The task used was a simplified variant of a facial emotion-decoding task in which subjects determined the intensity level of a target emotion displayed as a facial expression. Facial expressions of happy, sad, anger, disgust, and fear were used as stimuli. RESULTS: Alcoholics and controls did not differ in accurately identifying the intensity level on the simple emotional decoding task but there were significant differences in their BOLD response during evaluation of facial emotion. In general, alcoholics showed less brain activation than nonalcoholic controls. The greatest differences in activation were during decoding of facial expressions of fear and disgust during which alcoholics had significantly less activation than controls in the affective division of the anterior cingulate cortex (ACC). Alcoholics also had significantly less activation than controls in the affective division of the ACC, while viewing sad faces. Only to facial expressions of anger did the alcoholics show significant activation in the affective ACC and in this case, their BOLD response did not significantly differ from that of the controls. CONCLUSION: Alcoholics show a deficit in the function of the affective division of the ACC during evaluation of negative facial emotions that can serve as cues for flight or avoidance. This deficit may underlie some of the behavioral dysfunction in alcoholism.     

Dynamic changes in CREB phosphorylation and neuroadaptive gene expression in area V1 of adult monkeys after monocular enucleation

Our understanding of the molecular events that emerge after change in sensory input remains elusive, especially with regard to mature area V1. Here, we characterized P-CREB expression in area V1 of monkeys at multiple time-points after monocular enucleation (ME) to assess the possible contribution of CREB in visually deprived neocortex. Immunoblot assays and immunostainings showed that P-CREB is dynamically regulated in adult area V1, reaching a peak level between 5 and 30 days after ME, and becoming reduced at the 90-day post-ME time-point. This striking temporal increase in P-CREB level was paralleled by a concomitant increase of two CREB-regulated pro-survival effectors, namely Bcl-2 and Bcl-w. We present our results in the context of recent advances about adult visual neocortex and propose that ME induces a multifaceted CREB-mediated response that favors intrinsic stability of neurons and facilitates mature cortical networks to reorganize over a prolonged period.     

Essential Role of Osteopontin in Smoking-Related Interstitial Lung Diseases

Smoking-related interstitial lung diseases are characterized by the accumulation of macrophages and Langerhans cells, and fibrotic remodeling, which are linked to osteopontin (OPN) expression. Therefore, OPN levels were investigated in bronchoalveolar lavage (BAL) cells in 11 patients with pulmonary Langerhans cell histiocytosis (PLCH), 15 patients with desquamative interstitial pneumonitis (DIP), 10 patients with idiopathic pulmonary fibrosis, 5 patients with sarcoidosis, 13 otherwise healthy smokers, and 19 non-smoking controls. Furthermore, OPN overexpression was examined in rat lungs using adenoviral gene transfer. We found that BAL cells from patients with either PLCH or DIP spontaneously produced abundant amounts of OPN. BAL cells from healthy smokers produced 15-fold less OPN, and those cells from non-smoking healthy volunteers produced no OPN. BAL cells from patients with either idiopathic pulmonary fibrosis or sarcoidosis produced significantly less OPN, as compared with patients with PLCH. These data were confirmed by immunochemistry. Nicotine stimulation increased production of both OPN and granulocyte-macrophage colony stimulating factor by alveolar macrophages from smokers. Nicotinic acetylcholine receptor expression resembled the pattern of spontaneous OPN production and was dramatically increased in both PLCH and DIP. OPN overexpression in rat lungs induced lesions similar to PLCH with marked alveolar and interstitial accumulation of Langerhans cells. Our findings suggest a pathogenetic role of increased OPN production in both PLCH and DIP by promoting the accumulation of macrophages and Langerhans cells.Cigarette smoke is linked to a variety of lung diseases including chronic obstructive pulmonary disease, lung cancer, and interstitial lung diseases. Respiratory bronchiolar interstitial lung disease, desquamative interstitial pneumonitis (DIP), and pulmonary Langerhans cell histiocytosis (PLCH) belong to the group of smoking-related interstitial lung diseases.^1,2,3 Cigarette smoke is a complex mixture of more than 4000 compounds and is known to cause systemic and pulmonary effects.⁴ However, the underlying mechanisms as to how cigarette smoking leads to the changes observed in smoking-related interstitial lung diseases are largely unknown.^1,2,3Cigarette smoke induces inflammation, oxidative stress, and tissue injury, and has an important effect on the number, distribution, and activation state of macrophages and Langerhans cells.^5,6 There is a strong epidemiological link between PLCH and smoking. PLCH is characterized by the accumulation of activated Langerhans cells originating from the distal bronchiole walls.^1,2,3,7 The accumulations of Langerhans cells are poorly demarcated and extend to the adjacent alveoli, which often contain an abundance of pigmented macrophages. These areas show morphological changes similar to DIP.^7,8 In DIP, the predominant feature is the accumulation of alveolar macrophages, densely filling the alveolar lumen, combined with moderate fibrotic interstitial remodeling.^1,2As measured by bronchoalveolar lavage (BAL) in healthy individuals, cigarette smoking induces a 5- to 10-fold increase in alveolar macrophages in a dose-response curve.^9,10,11 It was shown that concentrations of granulocyte-macrophage colony stimulating factor (GMCSF) in patients with PLCH are increased,¹² but the mechanisms that lead to the expansion of the pulmonary macrophage pool and fibrosis in smokers are poorly understood.^1,2,3 Based on the findings of a microarray study, Woodruff et al¹³ have recently proposed that alveolar macrophages from smokers exhibit a distinctive macrophage activation state that is accompanied by increased OPN expression. Osteopontin is a glycoprotein found in the extracellular matrix of bone.¹⁴ However, multiple studies have reported cytokine properties of OPN in cell-mediated immunity.¹⁴ Further, OPN exhibits a strong chemotactic activity for macrophages, monocytes, Langerhans cells, and dendritic cells.^15,16,17In the context of these findings we speculated that OPN might be involved in the pathogenesis of smoking-related lung interstitial diseases. We found abundant OPN production by alveolar macrophages from patients with PLCH and DIP. Alveolar macrophages from both healthy smokers and patients with DIP and PLCH show up-regulated nicotine receptor expression as a sign of chronic nicotine stimulation. Further, nicotine directly induced OPN and GMCSF in alveolar macrophages. Our data provides evidence for a role of osteopontin in the pathogenesis of smoking- related interstitial lung diseases.     

Postpartum Haemorrhage and Eclampsia: Differences in Knowledge and Care-seeking Behaviour in Two Districts of Bangladesh

In high- and low-performing districts of Bangladesh, the study explored the demand-side of maternal healthcare by looking at differences in perceived knowledge and care-seeking behaviours of women in relation to postpartum haemorrhage or eclampsia. Haemorrhage and eclampsia are two major causes of maternal mortality in Bangladesh. The study was conducted during July 2006–December 2007. Both postpartum bleeding and eclampsia were recognized by women of different age-groups as severe and life-threatening obstetric complications. However, a gap existed between perception and actual care-seeking behaviours which could contribute to the high rate of maternal deaths associated with these conditions. There were differences in care-seeking practices among women in the two different areas of Bangladesh, which may reflect sociocultural differences, disparities in economic and educational opportunities, and a discrimination in the availability of care.Key words: Beliefs, Care-seeking behaviour, Maternal mortality, Postpartum haemorrhage, Eclampsia, Qualitative research, Bangladesh     

Pathological features of Gleason score 6 prostate cancers in the low and intermediate range of prostate‐specific antigen level: is there a difference?

OBJECTIVE

To assess the pathological features of Gleason score 6 prostate cancers after radical prostatectomy in the low (<4 ng/mL) and intermediate range of prostate‐specific antigen level (4–10 ng/mL), as such prostate cancers are considered to be well differentiated tumours with a low risk for recurrence after therapy.

PATIENTS AND METHODS

In all, 1354 patients with T1c prostate cancer and PSA levels of <10.0 ng/mL had a radical retropubic prostatectomy. Patients with Gleason score 6 tumours were divided into two groups, those with PSA levels of <4 and 4.0–10.0 ng/mL. Extracapsular extension, positive surgical margins, biochemical recurrence (BCR) and mean time to BCR were evaluated.

RESULTS

Of the 1354 patients, there were 437 (32.3%) with Gleason score 6 prostate cancers. Patients in the low PSA group had less extraprostatic disease than those with a higher level (5.9% vs 14.5%) and both groups had an almost equal proportion of positive surgical margins (9.4% vs 11.0%). In the low PSA group there was statistically significantly shorter BCR than in the high PSA group, with a mean time to BCR of 1.7 vs 3.1 years.

CONCLUSIONS

These results show a statistically significantly higher rate of extraprostatic disease and earlier BCR in men with a high than a low PSA level even in Gleason score 6 prostate cancer. As the rate of BCR and extracapsular extension are significantly related to prostate cancer mortality, these findings further support the concept of screening using low PSA levels.     

Extracting variant and invariant information from faces: the neural substrates of gaze detection and sex categorization

Guided by influential models of face processing, efforts have been expended to uncover the neural substrates subserving the many facets of face perception. Extending this work, the present study used functional brain imaging (fMRI) to explore the relationship between the operations supporting the explicit extraction of sex and gaze-related information from faces. The brain imaging data showed the right superior temporal sulcus to be preferentially involved during assessments of gaze direction and a region of the left fusiform gyrus to be involved during sex categorization. These results provide support for the distributed face-processing model advanced by Haxby and colleagues (2000).     

Therapeutic efficacy of artemether-lumefantrine for the treatment of uncomplicated Plasmodium falciparum malaria in Bangladesh

Bangladesh faces increasing levels of chloroquine resistance, and drug sensitivity to sulfadoxine-pyremethamine is already compromised. Therefore, the Ministry of Health recently changed the national treatment guidelines to artemisinin-based combination therapies. The purpose of this study was to determine the baseline therapeutic efficacy of artemether-lumefantrine used as a six-dose regimen for the treatment of uncomplicated Plasmodium falciparum malaria. Sixty-seven patients were enrolled in the study; the cure rate in a 42-day follow-up after an adjustment by polymerase chain reaction was 94.3%. The treatment led to rapid fever (mean +/- SD = 25.82 +/- 12.14 hours) and parasite (30.36 +/- 19.43 hours) clearance. These data suggest that artemether-lumefantrine is a highly efficacious and well-tolerated treatment for uncomplicated P. falciparum malaria in Bangladesh.