Genomic dissection of behavioral maturation in the honey bee

Honey bees undergo an age-related, socially regulated transition from working in the hive to foraging that has been previously associated with changes in the expression of thousands of genes in the brain. To understand the meaning of these changes, we conducted microarray analyses to examine the following: (i) the ontogeny of gene expression preceding the onset of foraging, (ii) the effects of physiological and genetic factors that influence this behavioral transition, and (iii) the effects of foraging experience. Although >85% of approximately 5,500 genes showed brain differences, principal component analysis revealed discrete influences of age, behavior, genotype, environment, and experience. Young bees not yet competent to forage showed extensive, age-related expression changes, essentially complete by 8 days of age, coinciding with previously described structural brain changes. Subsequent changes were not age-related but were largely related to effects of juvenile hormone (JH), suggesting that the increase in JH that influences the hive bee-forager transition may cause many of these changes. Other treatments that also influence the onset age of foraging induced many changes but with little overlap, suggesting that multiple pathways affect behavioral maturation. Subspecies differences in onset age of foraging were correlated with differences in JH and JH-target gene expression, suggesting that this endocrine system mediates the genetic differences. We also used this multifactorial approach to identify candidate genes for behavioral maturation. This successful dissection of gene expression indicates that, for social behavior, gene expression in the brain can provide a robust indicator of the interaction between hereditary and environmental information.     

Sub-acute neuropathy in patients with African tick bite fever

African tick bite fever (ATBF) caused by Rickettsia africae is an emerging health problem in travellers to sub-Saharan Africa. We here present 6 patients with evidence of long-lasting sub-acute neuropathy following ATBF contracted during safari trips to southern Africa. Three patients developed radiating pain, paresthaesia and/or motor weakness of extremities, 2 had hemi-facial pain and paresthaesia, and 1 developed unilateral sensorineural hearing loss. When evaluated 3-26 months after symptom onset, cerebrospinal fluid samples from 5 patients were negative for R. africae PCR and serology, but revealed elevated protein content in 3 and mild pleocytosis in 1 case. Despite extensive investigations, no plausible alternative causes of neuropathy could be identified. Treatment with doxycycline in 2 patients had no clinical effect. Given the current increase of international safari tourism to sub-Saharan Africa, more cases of sub-acute neuropathy following ATBF may well be encountered in Europe and elsewhere in the y to come.     

Place of residence and distance to medical care influence the diagnosis of hepatitis C: a population-based study

BACKGROUND/AIMS: In France, geographic access to medical care may affect the diagnosis of hepatitis C. The aims of this study were to compare the detection rates of hepatitis C in urban and rural areas after adjusting for distance to medical care, and evaluating the impact of the place of residence on patients' clinical characteristics. METHODS: Between 1994 and 2001, 1938 newly detected cases were recorded in a French population of 1,005,817 inhabitants. Age and sex-adjusted detection rates for 10(5) inhabitants were estimated for urban and rural areas and for classes of distance to the nearest practitioner. RESULTS: Detection rates were lower in rural than in urban areas [14.1, (95CI: 12.5-15.7) versus 24.7, (95CI: 23.5-26.0)] and decreased as the distance to the general practitioner increased [27.0, (95CI: 25.5-28.4) versus 13.7, (95CI: 12.1-15.3) for a cutoff value of 1.5 km]. In multivariate analyses, detection rates were only influenced by the distance to general practitioner. Hepatocellular carcinoma at diagnosis was more frequent among rural than among urban patients (adjusted OR = 2.28, 95CI: 0.97-5.39, P = 0.059). CONCLUSIONS: A poorer geographic access to care explained the lower detection of hepatitis C in rural areas. Hepatocellular carcinoma was more frequent in rural patients. It may result from later detection and/or involvement of environmental factors on hepatocarcinogenesis.     

The diagnostic value of biomarkers (AshTest) for the prediction of alcoholic steato-hepatitis in patients with chronic alcoholic liver disease

BACKGROUND/AIMS: The aim was to identify a panel of biomarkers (AshTest) for the diagnosis of alcoholic steato-hepatitis (ASH), in patients with chronic alcoholic liver disease. METHODS: Biomarkers were assessed in patients with an alcohol intake>50 g/d, in a training group, and in two validation groups. Diagnosis of ASH (polymorphonuclear infiltrate and hepatocellular necrosis) and its histological severity (four classes: none, mild, moderate and severe) were assessed blindly. RESULTS: Two hundred and twenty-five patients were included, 70 in the training group, 155 in the validation groups, and 299 controls. AshTest was constructed using a combination of the six components of FibroTest-ActiTest plus aspartate aminotransferase. The AshTest area under the ROC curves for moderate-severe ASH was 0.90 in the training group, 0.88 and 0.89 in the validation groups. The median AshTest value was 0.005 in controls, 0.05 in patients without or with mild ASH, 0.64 in moderate, and 0.84 in severe ASH grade 3, (P<0.05 between all groups). At a 0.50 cut-off, the sensitivity of AshTest was 0.80 and the specificity was 0.84. CONCLUSIONS: In heavy drinkers, AshTest is a simple and non-invasive quantitative estimate of alcoholic hepatitis. The use of AshTest may reduce the need for liver biopsy, and therefore allow an earlier treatment of alcoholic hepatitis.     

High Maintenance Dosage of Clopidogrel is Associated with a Reduced Risk of Stent Thrombosis in Clopidogrel-Resistant Patients

Background

Stent thrombosis remains an important complication after stent implantation, despite the use of dual antiplatelet therapy with aspirin (acetylsalicylic acid) and clopidogrel. Several studies have shown an increased risk of thrombotic events in patients with resistance to clopidogrel. Some recent studies have suggested that a higher clopidogrel maintenance dosage could enhance ex vivo platelet inhibition and thereby overcome resistance to clopidogrel.

Objectives

To investigate whether a higher clopidogrel maintenance dosage is associated with a reduced risk of stent thrombosis after percutaneous coronary intervention (PCI) in clopidogrel-resistant patients and to evaluate the frequency of hemorrhagic accidents that could be associated with a high clopidogrel maintenance dosage.

Methods

An observational study was performed in 52 consecutive clopidogrel-resistant patients (resistance defined according to adenosine diphosphate-induced platelet aggregation assessment) who underwent a PCI with stenting at a tertiary referral center (Toulouse University Hospital, France). All patients received a clopidogrel loading dose of 300 mg, then 32 patients received a clopidogrel maintenance dosage of 75 mg/day (patients admitted between 2004 and 2005) and 20 patients received 150 mg/day (patients admitted in 2006). We compared the occurrence of definite stent thrombosis and hemorrhagic accidents between these two groups, using a regression model.

Results

Among the patients treated with clopidogrel 75 mg/day, 26 (81.3%) had definite stent thrombosis versus seven (35.0%) treated with 150 mg/day (adjusted relative risk [RR] 2.46; 95% CI 1.63, 2.76; p = 0.002). The risk of major adverse cardiac events (MACE) was also significantly lower in patients treated with 150 mg/day (adjusted RR 2.63; 95% CI 1.82, 2.82; p = 0.001). There was no significant difference between the two groups regarding hemorrhagic accidents.

Conclusion

Our data suggest that a high maintenance dosage of clopidogrel (150 mg/day) is associated with a reduced risk of definite stent thrombosis and MACE compared with a maintenance dosage of 75 mg/day. The frequency of hemorrhagic accidents was similar between the two groups, underlining a positive benefit-risk ratio of this strategy in clopidogrel-resistant patients. These findings deserve confirmation in a prospective, well conducted study.     

Rationale for a model of human systems integration: the need of a theoretical framework

Human systems integration (HSI) involves augmented human design with the objectives of augmenting human capabilities and improving human performance using behavioral technologies. The fundamental matter of human systems integration and augmented human design is the organization and the nature of interactions that couple physiological systems, humans- and engineered systems, artifacts. By this definition, augmented human consists of interactive artefacts linked to physiological systems. This paper focuses on the rationale of a HSI model based on specific experiments (comparison of dynamical sensorimotor integration and motor performances in real and virtual environments) that confirm the hypothesis of functional interaction in the framework of Chauvet's mathematical theory of integrative physiology (MTIP). Epistemological constraints for HSI and the role of MTIP are briefly discussed in this context.     

Ontogeny of the somatostatin variant [Pro2,Met13]somatostatin-14 in the brain, pituitary, and sensory organs of the frog Rana esculenta

Two forms of somatostatin are expressed in the frog brain, i.e., somatostatin-14 (SS1) and the [Pro(2), Met(13)]somatostatin-14 variant (SS2). We have previously described the ontogeny of SS1-immunoreactive cells in the brain of Rana esculenta. In the present study, we have investigated the distribution of prepro-SS2 (PSS2)-expressing neurons in the brain of the same species during development by using antibodies directed against the N-flanking region of SS2 (PSS2(54-66)). Immunoreactive perikarya first appeared in the ventral hypothalamus at stages IV-VII. Subsequently, positive neurons were seen in the nucleus of the diagonal band of Broca, the anterior preoptic area, the posterior tuberculum (stages VIII-XII), as well as the dorsal (stages XIII-XV) and medial (stages XIX-XX) periventricular preoptic nucleus. At metamorphic climax and in newly metamorphosed frogs, positive perikarya were found in the striatum and in the interpeduncular nucleus. PSS2(54-66)-immunoreactive fibers were already widely distributed during the first stages of development, indicating that SS2 may act as a neuromodulator and/or neurotransmitter during ontogeny. The presence of PSS2(54-66)-positive nerve fibers in olfactory structures suggests that, in tadpoles, SS2 may be involved in the processing of olfactory information. The occurrence of PSS2(54-66)-like immunoreactivity in taste buds, and in the olfactory and vomeronasal organs indicates that SS2 may mediate the unconditioned and reinforcing properties of natural chemicals. Finally, the intenseexpression of PSS2(54-66)-like immunoreactivity in melanotrope cells of the pituitary suggests that SS2 may diffuse toward the pars distalis to regulate the activity of adenohypophysial cells during tadpole development.