Behaviourally modulated hippocampal theta oscillations in the ferret persist during both locomotion and immobility

Theta oscillations are a hallmark of hippocampal activity across mammals and play a critical role in many hippocampal models of memory and spatial navigation. To reconcile the cross-species differences observed in the presence and properties of theta, we recorded hippocampal local field potentials in rats and ferrets during auditory and visual localisation tasks designed to vary locomotion and sensory attention. Here, we show that theta oscillations occur during locomotion in both ferrets and rats, however during periods of immobility, theta oscillations persist in the ferret, contrasting starkly with the switch to large irregular activity (LIA) in the rat. Theta during immobility in the ferret is identified as analogous to Type 2 theta that has been observed in rodents due to its sensitivity to atropine, and is modulated by behavioural state with the strongest theta observed during reward epochs. These results demonstrate that even under similar behavioural conditions, differences exist between species in the relationship between theta and behavioural state

Political Self-characterization of U.S. Medical Students

BACKGROUND: There have been no prior studies of the political self-characterization of U.S. physicians-in-training, and little is known about physicians’ political leanings or the critical relationship between medical issues and political orientations of physicians and physicians-in-training. METHODS: All medical students in the class of 2003 at 16 nationally representative U.S. schools were eligible to complete three questionnaire administrations (at freshman orientation, entrance to wards, and senior year). RESULTS: Among these medical students, 5% self-characterized as politically very conservative, 21% conservative, 33% moderate, 31% liberal, and 9% as very liberal.” Being male, white, Protestant, intending to specialize in Surgery or anesthesiology/pathology/radiology, or currently or previously being married significantly (P ≤ .001) increased the likelihood that a student self-identified as very conservative or conservative. Disagreement or strong disagreement with the statements, “I’m glad I chose to become a physician” and “Access to care is a fundamental human right,” were also both associated with being very conservative or conservative. Being more liberal was reported by blacks and Hispanics; those intending to become ob-gyns, psychiatrists, and pediatric subspecialists; and atheists, Jews, and adherents of eastern religions. CONCLUSIONS: U.S. medical students are considerably more likely to be liberal than conservative and are more likely to be liberal than are other young U.S. adults. Future U.S. physicians may be more receptive to liberal messages than conservative ones, and their political orientation may profoundly affect their health system attitudes

Prescribing practices of primary-care veterinary practitioners in dogs diagnosed with bacterial pyoderma

Concern has been raised regarding the potential contributions of veterinary antimicrobial use to increasing levels of resistance in bacteria critically important to human health. Canine pyoderma is a frequent, often recurrent diagnosis in pet dogs, usually attributable to secondary bacterial infection of the skin. Lesions can range in severity based on the location, total area and depth of tissue affected and antimicrobial therapy is recommended for resolution. This study aimed to describe patient signalment, disease characteristics and treatment prescribed in a large number of UK, primary-care canine pyoderma cases and to estimate pyoderma prevalence in the UK vet-visiting canine population

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE) : study protocol for a randomized controlled trial

Peer reviewedPublisher PD

Relationships between big-five personality factors and Alzheimer\u27s disease pathology in autosomal dominant Alzheimer\u27s disease

Introduction: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer\u27s disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD. Methods: Personality traits measured with the International Personality Item Pool at baseline from DIAN participants were analyzed as a function of estimated years to onset of clinical symptoms and well-established AD biomarkers. Results: Both neuroticism and conscientiousness were correlated with years to symptom onset and markers of tau pathology in the cerebrospinal fluid. Self-reported conscientiousness and both neuroticism and conscientiousness ratings from a collateral source were correlated with longitudinal rates of cognitive decline such that participants who were rated as higher on neuroticism and lower on conscientiousness exhibited accelerated rates of cognitive decline. Discussion: Personality traits are correlated with the accumulation of AD pathology and time to symptom onset, suggesting that AD progression can influence an individual\u27s personality characteristics. Together these findings suggest that measuring neuroticism and conscientiousness may hold utility in tracking disease progression in AD

DNA replication stress restricts ribosomal DNA copy number

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number

Are adolescents with high socioeconomic status more likely to engage in alcohol and illicit drug use in early adulthood?

<p>Abstract</p> <p>Background</p> <p>Previous literature has shown a divergence by age in the relationship between socioeconomic status (SES) and substance use: adolescents with low SES are more likely to engage in substance use, as are adults with high SES. However, there is growing evidence that adolescents with high SES are also at high risk for substance abuse. The objective of this study is to examine this relationship longitudinally, that is, whether wealthier adolescents are more likely than those with lower SES to engage in substance use in early adulthood.</p> <p>Methods</p> <p>The study analyzed data from the National Longitudinal Survey of Adolescent Health (AddHealth), a longitudinal, nationally-representative survey of secondary school students in the United States. Logistic regression models were analyzed examining the relationship between adolescent SES (measured by parental education and income) and substance use in adulthood, controlling for substance use in adolescence and other covariates.</p> <p>Results</p> <p>Higher parental education is associated with higher rates of binge drinking, marijuana and cocaine use in early adulthood. Higher parental income is associated with higher rates of binge drinking and marijuana use. No statistically significant results are found for crystal methamphetamine or other drug use. Results are not sensitive to the inclusion of college attendance by young adulthood as a sensitivity analysis. However, when stratifying by race, results are consistent for white non-Hispanics, but no statistically significant results are found for non-whites. This may be a reflection of the smaller sample size of non-whites, but may also reflect that these trends are driven primarily by white non-Hispanics.</p> <p>Conclusions</p> <p>Previous research shows numerous problems associated with substance use in young adults, including problems in school, decreased employment, increases in convictions of driving under the influence (DUI) and accidental deaths. Much of the previous literature is focused on lower SES populations. Therefore, it is possible that teachers, parents and school administrators in wealthier schools may not perceive as great to address substance abuse treatment in their schools. This study can inform teachers, parents, school administrators and program officials of the need for addressing drug abuse prevention activities to this population of students.</p

PPAR? Downregulation by TGF in Fibroblast and Impaired Expression and Function in Systemic Sclerosis: A Novel Mechanism for Progressive Fibrogenesis

The nuclear orphan receptor peroxisome proliferator-activated receptor-gamma (PPAR-γ) is expressed in multiple cell types in addition to adipocytes. Upon its activation by natural ligands such as fatty acids and eicosanoids, or by synthetic agonists such as rosiglitazone, PPAR-γ regulates adipogenesis, glucose uptake and inflammatory responses. Recent studies establish a novel role for PPAR-γ signaling as an endogenous mechanism for regulating transforming growth factor-ß (TGF-ß)- dependent fibrogenesis. Here, we sought to characterize PPAR-γ function in the prototypic fibrosing disorder systemic sclerosis (SSc), and delineate the factors governing PPAR-γ expression. We report that PPAR-γ levels were markedly diminished in skin and lung biopsies from patients with SSc, and in fibroblasts explanted from the lesional skin. In normal fibroblasts, treatment with TGF-ß resulted in a time- and dose-dependent down-regulation of PPAR-γ expression. Inhibition occurred at the transcriptional level and was mediated via canonical Smad signal transduction. Genome-wide expression profiling of SSc skin biopsies revealed a marked attenuation of PPAR-γ levels and transcriptional activity in a subset of patients with diffuse cutaneous SSc, which was correlated with the presence of a ''TGF-ß responsive gene signature'' in these biopsies. Together, these results demonstrate that the expression and function of PPAR-γ are impaired in SSc, and reveal the existence of a reciprocal inhibitory cross-talk between TGF-ß activation and PPAR-γ signaling in the context of fibrogenesis. In light of the potent anti-fibrotic effects attributed to PPAR-γ, these observations lead us to propose that excessive TGF-ß activity in SSc accounts for impaired PPAR-γ function, which in turn contributes to unchecked fibroblast activation and progressive fibrosis. © 2010 Wei et al

Human papillomavirus prevalence, viral load and pre-cancerous lesions of the cervix in women initiating highly active antiretroviral therapy in South Africa: a cross-sectional study

Background Cervical cancer and infection with human immunodeficiency virus (HIV) are both important public health problems in South Africa (SA). The aim of this study was to determine the prevalence of cervical squamous intraepithelial lesions (SILs), high-risk human papillomavirus (HR-HPV), HPV viral load and HPV genotypes in HIV positive women initiating anti-retroviral (ARV) therapy. Methods A cross-sectional survey was conducted at an anti-retroviral (ARV) treatment clinic in Cape Town, SA in 2007. Cervical specimens were taken for cytological analysis and HPV testing. The Digene Hybrid Capture 2 (HC2) test was used to detect HR-HPV. Relative light units (RLU) were used as a measure of HPV viral load. HPV types were determined using the Roche Linear Array HPV Genotyping test. Crude associations with abnormal cytology were tested and multiple logistic regression was used to determine independent risk factors for abnormal cytology. Results The median age of the 109 participants was 31 years, the median CD4 count was 125/mm3, 66.3% had an abnormal Pap smear, the HR-HPV prevalence was 78.9% (Digene), the median HPV viral load was 181.1 RLU (HC2 positive samples only) and 78.4% had multiple genotypes. Among women with abnormal smears the most prevalent HR-HPV types were HPV types 16, 58 and 51, all with a prevalence of 28.5%. On univariate analysis HR-HPV, multiple HPV types and HPV viral load were significantly associated with the presence of low and high-grade SILs (LSIL/HSIL). The multivariate logistic regression showed that HPV viral load was associated with an increased odds of LSIL/HSIL, odds ratio of 10.7 (95% CI 2.0 – 57.7) for those that were HC2 positive and had a viral load of ≤ 181.1 RLU (the median HPV viral load), and 33.8 (95% CI 6.4 – 178.9) for those that were HC2 positive with a HPV viral load > 181.1 RLU. Conclusion Women initiating ARVs have a high prevalence of abnormal Pap smears and HR-HPV. Our results underscore the need for locally relevant, rigorous screening protocols for the increasing numbers of women accessing ARV therapy so that the benefits of ARVs are not partially offset by an excess risk in cervical cancer