Object and spatial relational memory in adult rhesus monkeys is impaired by neonatal lesions of the hippocampal formation but not the amygdaloid complex

Adult rhesus monkeys with neonatal aspiration lesions of the hippocampal formation or the amygdaloid complex (including their respective subjacent cortices) and their age-matched controls were tested on the transverse patterning problem (A+ vs. B-, B+ vs. C- and C+ vs. A-) and a spatial version of the delayed nonmatching-to-sample (DNMS) task with delays of 10 s to 30 s, 60 s, 120 s, and 600 s. Monkeys with neonatal damage to the amygdaloid complex learned both tasks and did not differ from controls at any delay of the spatial DNMS task. Monkeys with neonatal hippocampal damage, however, were unable to learn transverse patterning, though they easily transferred to a linear series (A+ vs. B-, B+ vs. C-, and C+ vs. X-). Three of the four were also unable to reach criterion on the spatial DNMS task within the limits of testing, and the performance of all four monkeys deteriorated with increasing choice delays. The data suggest a role of the primate hippocampal region in both object and spatial relational learning.     

Determinants of discontinuation of new courses of antihypertensive medications

Discontinuation of medication use constitutes a major barrier to adequate control of high blood pressure. We examined the effect of an array of potential predisposing, enabling and reinforcing factors on the discontinuation of newly prescribed antihypertensive medications. We conducted a prospective cohort study through a network of 173 pharmacies across Canada where were identified individuals newly prescribed an antihypertensive monotherapy. We interviewed participants by telephone four times to obtain information for a minimum duration of 18 months after entry into the cohort. We analyzed data using a multivariate proportional hazard model. Of 682 eligible participants, 43.3% had discontinued their initial medication at the end of the observation period. Individuals more likely to discontinue their initial medication were those who perceived side effects from this medication [Hazard Ratio (HR) = 1.91; 95% Confidence Interval (CI) 1.47-2.47). Individuals with medication insurance coverage were less likely to discontinue (HR = 0.74; 95% CI 0.55-0.99). Persistence with newly prescribed medications could be improved by selecting antihypertensive medications containing fewer side effects and by lifting economic barriers to drug treatment.     

Carcinogenesis and translational controls: TACC1 is down-regulated in human cancers and associates with mRNA regulators

The three human TACC genes encode a family of proteins that are suspected to play a role in carcinogenesis. Their function is not precisely known; a Xenopus TACC protein called Maskin is involved in translational control, while the Drosophila D-TACC associates with microtubules and centrosomes. We have characterized the human TACC1 gene and its products. The TACC1 gene is located in region p12 of chromosome 8; its mRNA is ubiquitously expressed and encodes a protein with an apparent molecular mass of 125 kDa, which is cytoplasmic and mainly perinuclear. We show that TACC1 mRNA gene expression is down-regulated in various types of tumors. Using immunohistochemistry of tumor tissue-microarrays and sections, we confirm that the level of TACC1 protein is down-regulated in breast cancer. Finally, using the two-hybrid screen in yeast, GST pull-downs and co-immunoprecipitations, we identified two potential binding partners for TACC1, LSM7 and SmG. They constitute a conserved subfamily of Sm-like small proteins that associate with U6 snRNPs and play a role in several aspects of mRNA processing. We speculate that down-regulation of TACC1 may alter the control of mRNA homeostasis in polarized cells and participates in the oncogenic processes.     

Assessment of locus and extent of neurotoxic lesions in monkeys using neuroimaging techniques: a replication

Foot-shock is used in a variety of behavioral tasks either as a motivational stimulus, a way to characterize different rodents, or to test various pharmacological agents for their antinociceptive or analgesic effects. All these procedures need to assess foot-shock sensitivity either to rule out possible differences (when the shock is used as a motivational stimulus) or to use the differences to compare animals or treatments. In addition, many of the procedures that utilize foot-shock as a motivational stimulus evaluate freezing as an index of anxiety or fear. In the present study, data obtained by an automated computer system was compared with data obtained by human observers to validate the automated system for examining foot-shock sensitivity in mice. The different computer measures obtained for foot-shock sensitivity exhibited high correlations with human scoring at shock levels as low as 0.2 mA. The computer controlled analysis provided a non-subjective, quantifiable measurement of the foot-shock-induced response as well as freezing behavior. Automated data collection is an improvement over the methods of human visual observation in that the data collection is more standardized, efficient and consistent.     

The effect of in-utero undernutrition on the insulin resistance syndrome

The metabolic and cardiovascular complications associated with in-utero undernutrition have been identified during the past 10 years. Reduced fetal growth is independently associated with an increased risk for the development of cardiovascular diseases, the insulin resistance syndrome and its components: hypertension, dyslipidemia, impaired glucose tolerance, and type 2 diabetes. All appear to result from the initial development of insulin resistance that seems to be a key component underlying this association. Several hypotheses have been proposed over the past 10 years to understand this unexpected association. Each of them points to either a detrimental fetal environment or genetic susceptibilities or interactions between these two components as playing a critical role in this context. The hypothesis that this association could be the consequence of genetic/environmental interactions remains at the moment the most attractive. Although the mechanism remains unclear, there is also some evidence that adipose tissue plays a role in the emergence of insulin resistance associated with in-utero undernutrition.     

Causes and consequences of elderly's agitated and aggressive behavior

Agitation and aggressiveness are frequent in the elderly and often related to dementia. As a result of the ageing of the general population this is becoming a major public health concern. No or little epidemiological data, during primary health care, about symptoms, co-morbidity, nor medical and social consequences of elderlys' disruptive behavior have been gathered or published in the French literature. Thus, in order to describe these disorders, a survey in cooperation with general practitioners (GP) was conducted. A representative sample of 212 French GP's, all with preferential geriatric activity were asked to conduct a study by including retrospectively their two most recent patients older than 65, who had exhibited agitation and/or aggressiveness. From this cross sectional study, 410 patients (female: 61%, male: 39%) were included. The mean age was 81 years (sd: 7.65). The patients suffered from change in verbal behavior (80%), verbal aggressiveness (71%), physical agitation (60%), wandering (48%), and/or physical aggressiveness (31%). The average of disruptive behavior symptoms per patient was 2.9. The symptoms appeared progressively in 81% of patients, the mean duration was two years and it was the first episode in 40% of patients. Disruptive behaviors may be explained in view of organic illness in 62% of patients (cardiovascular disease: 37%, neurologic: 12%, diabetes: 7%, dehydratation: 5%), dementia (Alzheimer disease: 20%, vascular dementia: 18%, mixed dementia: 14%). In 54% of patients disruptive behavior may be explained in view of depression: 34%, and anxiety disorder: 31%. A triggering factor was observed in 57% of cases (psychosocial stress: 39%). Somatic consequences of the symptoms were frequently identified: decrease of alimentary intake: 39%, weight loss: 27%, dehydratation: 11%, falls: 32%, and irregular medication intake: 31%. Limitation of daily life activities: 85%, and family life: 97% were also noted. Acceptability of patient's symptoms by the family was good (no discomfort or transitory and mild irritability) in 61% of cases, and very bad (reactions of exhaustion, hospitalization requirement) in 13%. This study carried out during primary care, showed that the elderly's disruptive behaviors cause severe medical consequences and familial and social distress.