41295496
Therapy for HDV!
Hepatitis delta virus (HDV) can dramatically worsen liver disease in patients coinfected with hepatitis B virus (HBV). No effective medical therapy exists for HDV. The HDV envelope requires HBV surface antigen proteins provided by HBV. Once inside a cell, however, HDV can replicate its genome in the absence of any HBV gene products. In vitro, HDV virion assembly is critically dependent on prenyl lipid modification, or prenylation, of its nucleocapsid-like protein large delta antigen. To overcome limitations of current animal models and to test the hypothesis that pharmacologic prenylation inhibition can prevent the production of HDV virions in vivo, we established a convenient mouse-based model of HDV infection capable of yielding viremia. Such mice were then treated with the prenylation inhibitors FTI-277 and FTI-2153. Both agents were highly effective at clearing HDV viremia. As expected, HDV inhibition exhibited duration-of-treatment dependence. These results provide the first preclinical data supporting the in vivo efficacy of prenylation inhibition as a novel antiviral therapy with potential application to HDV and a wide variety of other viruses.
11606238
Hepatitis delta virus.
Hepatitis delta virus (HDV) is a sub-viral agent that is dependent for its life cycle on hepatitis B virus (HBV). The help it obtains from HBV is limited to the sharing of envelope proteins. These proteins are needed to facilitate the assembly of the HDV genome into new virus particles, and in turn, to allow the attachment and entry of HDV into new host cells. In other respects, the replication of the small single-stranded circular RNA genome of HDV is independent of HBV. HDV genome replication produces two forms of a RNA-binding protein known as the long and small delta antigens (Ag). All other proteins needed for HDV genome replication, especially the RNA-directed RNA polymerase activity, are provided by the host cell. This mini-review article is a mixture of personal perspective and speculations about the future of HDV research. It starts with a brief overview of HDV and its replication, notes some of the major unresolved questions, and directs the interested reader to more detailed reviews.
28296194
Retrovirus Genome Replication: Priming Specificities of Plus-Strand DNA Synthesis
SUMMARY The retroviral reverse transcriptase is a multifunctional protein. Not only does it contain both RNA- and DNA-directed DNA synthesis activities but also it contains an endonuclease activity necessary for the integration of viral RNA and a RNase H. This latter activity can reduce to oligoribonucleotides viral RNA that has been reverse transcribed into minus-strand DNA. However, during avian retrovirus genome replication it does this in a highly specific manner so as to generate a specific 12-base primer for plus-strand DNA synthesis. Even though many other oligoribonucleotides are also made there is an efficient selection of the specific primer followed by its efficient utilization in plus-strand DNA synthesis, and subsequent removal. We have used a reconstructed system to gain an understanding of the factors that contribute towards these observed specificities.
12985098
A note on the incorporation of amino acids by hamster embryo cells in monolayer culture.
33501684
Tumor virus ribonucleic acid directed deoxyribonucleic acid synthesis: nucleotide sequence at the 5' terminus of nascent deoxyribonucleic acid.
27724235
Avian RNA tumor virus DNA before and after integration into the host genome.
22359555
Dental hygiene student experiences in external placements in Australia.
While placements in external locations are being increasingly used in dental education globally, few studies have explored the student learning experience at such placements. The purpose of this study was to investigate student experiences while on external placement in a baccalaureate dental hygiene program. A self-reporting questionnaire was distributed to final-year dental hygiene students (n=77) at the University of Newcastle, Australia, in 2010. The questionnaire included questions regarding the type of placement, experiences offered, supervision, resources available, and lasting impressions. Responding students were generally positive about their external placement experience and indicated that the majority of facilities provided them with the opportunity to provide direct patient care and perform clinical tasks typical of a practicing hygienist. However, there was a statistically significant difference in their opinions about discipline-focused and community placements. Students indicated that their external placement experience provided opportunities to learn more about time and patient management, including hands-on experience with specific clinical tasks. Ongoing evaluations are necessary to ensure that external placements meet both student needs and intended learning outcomes within dental hygiene programs.
207262196
Cough and cold medication use in young children: Pharmacist reaction to changes in Canada.
OBJECTIVE
To gauge how community pharmacists will approach questions from the public after Canada begins requiring product labels to state that cough and cold medications should not be used in children younger than 6 years of age.


DESIGN
Cross-sectional study.


SETTING
Province of Saskatchewan, Canada, in February 2009.


PARTICIPANTS
143 community pharmacists.


INTERVENTION
Questionnaire was faxed to target group.


MAIN OUTCOME MEASURES
Estimates of product use in children aged 2 years to younger than 6 years, pharmacist satisfaction with the new guidelines, and potential plans when the new labels reach the market.


RESULTS
143 pharmacists returned a completed questionnaire by fax. Pharmacists currently recommend products for head colds for children aged 2 years to younger than 6 years more often than antitussives for coughs. More pharmacists were dissatisfied with the new ruling compared with those who were satisfied, with a main concern being that it went too far. Respondents indicated that when the new labels are implemented, they would be more likely to recommend use of the products among close family members than among the public.


CONCLUSION
These results suggest some support for product efficacy but possible concern over potential liability. Pharmacists are also concerned that removing dosing guidelines from packaging may not fully deter parental use of such products.
25161978
A meta-analysis of the effects of psychotherapy with adults sexually abused in childhood.
This paper presents the results of a meta-analysis of the treatment outcome studies of different types of psychotherapeutic approaches for adults sexually abused as children. There were 44 studies included comprising 59 treatment conditions, and most of the studies aimed to treat the psychological effects of childhood sexual abuse. Separate meta-analyses were conducted according to study design and outcome domain, in keeping with meta-analytic conventions. For most outcome domains, there was remarkable consistency in overall effect sizes across study design. Effect sizes were predominantly of moderate magnitude for post-traumatic stress disorder or trauma symptoms (g=0.72-0.77), internalizing symptoms (g=0.68-0.72), externalizing symptoms (g=0.41-0.53), self-esteem (g=0.56-0.58), and global functioning or symptoms (g=0.57-0.60). Studies measuring interpersonal functioning outcomes had inconsistent effect sizes across study design. Effects were largely maintained at follow-up, although relatively few studies provided follow-up data. A number of moderating variables were examined given the inherent heterogeneity of the studies. Moderator analysis revealed a variety of variables, particularly treatment characteristics, that were associated with better outcomes. However, different variables were identified for the diverse outcomes that were measured, emphasizing the importance of moderator analysis in looking beyond overall treatment effects to ascertain specific elements that confer additional benefit in therapy for the diverse psychological effects of child sexual abuse.
43587475
Development of substance dependence in two delinquency subgroups and nondelinquents from a male twin sample.
OBJECTIVE
The effect of delinquency subtype on the development of substance dependence symptoms was examined. It was proposed that early-onset delinquents possess characteristics that increase their likelihood of developing substance dependence problems earlier and more rapidly than late-onset delinquents and nondelinquents.


METHOD
The development of alcohol, nicotine, and cannabis dependence symptoms (DSM-III-R) was examined over a 6-year period of adolescence (age 11-17) among 36 early-onset delinquent, 86 late-onset delinquent, and 25 nondelinquent boys from a large epidemiological twin sample. Multilevel/random coefficients models were used to compare groups on the rate of growth in number of symptoms over time.


RESULTS
As expected, early-onset delinquents showed an earlier onset and a faster rate of increase in the number of cannabis and nicotine dependence symptoms than late-onset delinquents and controls. Both delinquent groups had a more rapid increase in alcohol dependence symptoms than controls.


CONCLUSIONS
The data showed that early-onset delinquency is associated with earlier onset of substance use disorder symptoms and more rapid acceleration of problems with drugs than late-onset delinquency. Treatments for boys with early-onset delinquency should account for their increased risk for drug use problems in adolescence and the potential effects of those problems on the course of antisocial behavior.
13468480
ESPERR: learning strong and weak signals in genomic sequence alignments to identify functional elements.
Genomic sequence signals - such as base composition, presence of particular motifs, or evolutionary constraint - have been used effectively to identify functional elements. However, approaches based only on specific signals known to correlate with function can be quite limiting. When training data are available, application of computational learning algorithms to multispecies alignments has the potential to capture broader and more informative sequence and evolutionary patterns that better characterize a class of elements. However, effective exploitation of patterns in multispecies alignments is impeded by the vast number of possible alignment columns and by a limited understanding of which particular strings of columns may characterize a given class. We have developed a computational method, called ESPERR (evolutionary and sequence pattern extraction through reduced representations), which uses training examples to learn encodings of multispecies alignments into reduced forms tailored for the prediction of chosen classes of functional elements. ESPERR produces a greatly improved Regulatory Potential score, which can discriminate regulatory regions from neutral sites with excellent accuracy ( approximately 94%). This score captures strong signals (GC content and conservation), as well as subtler signals (with small contributions from many different alignment patterns) that characterize the regulatory elements in our training set. ESPERR is also effective for predicting other classes of functional elements, as we show for DNaseI hypersensitive sites and highly conserved regions with developmental enhancer activity. Our software, training data, and genome-wide predictions are available from our Web site (http://www.bx.psu.edu/projects/esperr).