Benzo[a]pyrene diol epoxide-induced 9p21 aberrations associated with genetic predisposition to bladder cancer

CDKN2A, 9p21, encodes two alternatively spiked, functionally distinct, tumor-suppressor proteins, P16INK4A and P14ARF, which play active roles in the RB1 and TP53 pathways, respectively. Deletion of 9p is one of the most frequent genomic alterations in bladder cancer. In addition, alterations of 9p21 and P16 are frequently seen in the epithelial cells of chronic smokers. This pilot study evaluated whether 9p21 aberrations induced by exposure in vitro to benzo[a]pyrene diol epoxide (BPDE), the metabolic product of benzo[a]pyrene, a constituent of tobacco smoke, were more common in the peripheral blood lymphocytes of 61 bladder cancer patients compared to 64 matched controls. Our hypothesis was that 9p21 sensitivity to BPDE reflects the susceptibility of a specific locus to damage from carcinogens in tobacco smoke. We found that BPDE-induced chromosome band 9p21 aberrations were significantly higher in lymphocytes of bladder cancer cases (24.97 +/- 5.26 per 1,000) than in controls (20.72 +/- 4.51 per 1,000; P < 0.0001). However, no difference was observed for CEP9, a control locus. After adjustment for age, sex, ethnicity, and smoking status, 9p BPDE sensitivity had an odds ratio (OR) of 9.01 [95% confidence interval (95% CI) 3.75, 21.67] for bladder cancer. We further observed a gradient of elevated bladder cancer risk associated with increasing chromosomal damage. The adjusted ORs for subjects in the second, third, and highest quartiles of BPDE-induced 9p21 aberrations relative to the first quartile were 0.48 (0.04, 5.69), 5.14 (1.12, 23.59), and 21.51 (4.75, 97.34), respectively, providing increasing dose-response evidence of the locus-specific alterations. Thus, 9p21 may be a molecular target for BPDE-induced damage in bladder cancer cases.     

Attachment in infancy and preschool in low socioeconomic status rural Appalachian children: stability and change and relations to preschool and kindergarten competence

Attachment classifications were obtained from the Strange Situation at 15 months and at 4 years for a sample of 82 low socioeconomic status rural Appalachian children. The rate of secure attachment in infancy was 50.5%, and the majority of insecure infants were disorganized. At 4 years of age 61.2% of children were secure; early secure relationships were likely to be maintained, and about half of the insecure infants changed to a secure classification by 4 years. Overall, there was low but significant stability in attachment at the level of secure/insecure. Comparisons of (a) children who changed from insecure to secure with those who were stable insecure and (b) stable secure children with those who changed from secure to insecure identified contextual, child, and maternal interaction factors associated with attaining secure attachment. Assessments of cognitive and socioemotional competence at 4 years and kindergarten age suggested a protective effect of secure infant attachment but little benefit from secure preschool attachment.     

Antibody response of wild birds to natural infection with alphaviruses

From 1986 to 1990, we conducted our second longitudinal study in the central (upstate) New York (CNY) area on the wild avian hosts of eastern equine encephalomyelitis (EEE) virus. Field-collecting methods mirrored a study conducted from 1978 to 1980 at the same endemic focus. Over the 5-yr study period, we captured 6,296 birds representing 99 species and took 4,174 blood samples from representatives of 83 species. Gray catbirds, song sparrows, and veerys were the three dominant species captured and bled, accounting for 40 and 55% of birds captured and bled. Blood clots were assayed for virus and sera tested for hemagglutination-inhibition (HI) antibodies to EEE and Highlands J virus. Virus isolations from birds defined two epiornitics of EEE virus in 1988 and 1990, and an epiornitic of HJ virus in 1986. Infected birds responded with the production of HI antibodies with titers indicative of recent infection (HI > or = 1:160), and titers of sera positive during the epiornitics were significantly higher than positive sera during nonepiornitics. The 1990 EEE epiornitic extended from mid-July to the end of September, providing data to compare infection rates among species, habitats, and combinations of species with habitats. Few significant differences were found. The HJ epiornitic was only the second time this virus has occurred in CNY. Song sparrows were identified as the primary amplifying avian host of both viruses, although our capture and serological data would suggest a role for gray catbirds as the species most likely involved in yearly virus reintroduction. However, the cryptic nature of enzootic virus maintenance remains unresolved for the CNY virus foci. The appearances of HJ and EEE viruses were not epidemiologically linked, and there were no virus isolations from adults returning on site or virus isolations without concurrent isolations from mosquito vectors. Whether EEE and/or HJ virus are consistently present in or sporadically introduced into the inland foci of CNY area still has not been determined.     

Screening for Escherichia coli O157:H7 in Illinois

Objective: To determine the incidence of infection with Escherichia coli O157:H7 in a tertiary referral center in Chicago, where a similar study had been performed in 1984, to evaluate cases of disease reported to the Illinois Department of Public Health (IDPH) in 1993, and to determine laboratory practices used to detect this infection throughout the state.
Methods: During a 6-month period in 1993, all stool specimens at Rush-Presbyterian-St Luke's Medical Center (RPSLMC) were tested for E. coli O157:H7. Reports of diagnosed E. coli O157:H7 cases investigated by IDPH were also reviewed. A survey of 73 hospitals in the Chicago area was performed to determine routine culturing practices, specifically, the selection of stool specimens for evaluation for this pathogen.
Results: In the RPSLMC survey, two cases were identified among 1985 samples (incidence 0.1%), similar to the 0.08% incidence detected in a similar study conducted at the same institution in 1984. Through passive surveillance, the IDPH received 44 reports of E. coli O157:H7 in 1993. The hospital survey revealed that, in the seven labs testing all stool specimens for E. coli O157:H7, an incidence of 16/8137 specimens (0.2%) was determined.
Conclusions: These data suggest that sporadic E. coli O157:H7 remains uncommon in Illinois and that the incidence may not have changed over a 9-year period. The low yield and substantial cost of culturing all stools suggest that only specimens from patients with bloody diarrhea should be evaluated routinely in areas of low endemicity.     

Rats exhibit aldosterone-dependent sodium appetite during 24 h hindlimb unloading

Hindlimb unloading (HU) is an animal model of microgravity and bed rest. In these studies, we examined the role of ingestive behaviours in regulating body fluid balance during 24 h HU. In the first experiment, all rats were given distilled water to drink while two groups were also given access to a sodium chloride solution (0.9% or 1.8%). Water and saline intakes were measured before, during and after 24 h of HU. Rats reduced water intake during 24 h HU in all conditions. During HU, rats increased their intakes of both saline solutions (0.9% NaCl ( n = 11): control 7.8 ± 3 ml; HU 18.2 ± 4 ml; recovery 8.9 ± 2.5 ml; 1.8% NaCl ( n = 7): control 1.0 ± 0.4 ml; HU 3.8 ± 0.3 ml; recovery 1.2 ± 0.5 ml). Although water intake decreased there was no reduction in total fluid intake when saline was available. Plasma volumes were reduced during HU compared to rats in a normal posture when only water was available to drink (control ( n = 11) versus HU ( n = 11): 4.0 ± 0.2 versus 3.4 ± 0.2 ml (100 g body weight)⁻¹). When 0.9% saline was available in addition to water, plasma volumes after 24 h HU were not different from rats in a normal posture (control ( n = 11) versus HU ( n = 12): 4.3 ± 0.4 versus 4.3 ± 0.1 ml (100 g body weight)⁻¹). Plasma aldosterone but not plasma renin activity was significantly elevated after 24 h HU. Central infusions of spironolactone blocked the increased intake of 1.8% saline that was associated with 24 h HU. Thus, HU results in an aldosterone-dependent sodium appetite and the ingestion of sodium may help maintain plasma volume.     

Memory and event-related potentials for rapidly presented emotional pictures

Dense array event-related potentials (ERPs) and memory performance were assessed following rapid serial visual presentation (RSVP) of emotional and neutral pictures. Despite the extremely brief presentation, emotionally arousing pictures prompted an enhanced negative voltage over occipital sensors, compared to neutral pictures, replicating previous encoding effects. Emotionally arousing pictures were also remembered better in a subsequent recognition test, with higher hit rates and better discrimination performance. ERPs measured during the recognition test showed both an early (250–350 ms) frontally distributed difference between hits and correct rejections, and a later (400–500 ms), more centrally distributed difference, consistent with effects of recognition on ERPs typically found using slower presentation rates. The data are consistent with the hypothesis that features of affective pictures pop out during rapid serial visual presentation, prompting better memory performance.     

The impact of limited English proficiency and physician language concordance on reports of clinical interactions among patients with diabetes: The DISTANCE study

Objective

To assess the association of limited English proficiency (LEP) and physician language concordance with patient reports of clinical interactions.

Methods

Cross-sectional survey of 8638 Kaiser Permanente Northern California patients with diabetes. Patient responses were used to define English proficiency and physician language concordance. Quality of clinical interactions was based on 5 questions drawn from validated scales on communication, 2 on trust, and 3 on discrimination.

Results

Respondents included 8116 English-proficient and 522 LEP patients. Among LEP patients, 210 were language concordant and 153 were language discordant. In fully adjusted models, LEP patients were more likely than English-proficient patients to report suboptimal interactions on 3 out of 10 outcomes, including 1 communication and 2 discrimination items. In separate analyses, LEP-discordant patients were more likely than English-proficient patients to report suboptimal clinician-patient interactions on 7 out of 10 outcomes, including 2 communication, 2 trust, and 3 discrimination items. In contrast, LEP-concordant patients reported similar interactions to English-proficient patients.

Conclusions

Reports of suboptimal interactions among patients with LEP were more common among those with language-discordant physicians.

Practice implications

Expanding access to language concordant physicians may improve clinical interactions among patients with LEP. Quality and performance assessments should consider physician-patient language concordance.     

Evidence against a role for rare ADAM10 mutations in sporadic Alzheimer Disease

The Alzheimer amyloid protein precursor (APP) is subject to proteolysis by ADAM10 and ADAM17, precluding the formation of Aβ. Recently, coding variations in ADAM10 resulting in altered function have been reported in familial Alzheimer disease (AD). The authors carried out a large-scale (n = 576: Controls, 271; AD, 305) resequencing study of ADAM10 in sporadic AD. The results do not support a significant role for ADAM10 mutations in AD. The results also make it clear that the careful examination of ancestry required in any case-control comparison is especially true with rare variations, where even a very small number of variations might form the basis of scientific conclusions.