Simple sequence repeats in prokaryotic genomes

Simple sequence repeats (SSRs) in DNA sequences are composed of tandem iterations of short oligonucleotides and may have functional and/or structural properties that distinguish them from general DNA sequences. They are variable in length because of slip-strand mutations and may also affect local structure of the DNA molecule or the encoded proteins. Long SSRs (LSSRs) are common in eukaryotes but rare in most prokaryotes. In pathogens, SSRs can enhance antigenic variance of the pathogen population in a strategy that counteracts the host immune response. We analyze representations of SSRs in >300 prokaryotic genomes and report significant differences among different prokaryotes as well as among different types of SSRs. LSSRs composed of short oligonucleotides (1-4 bp length, designated LSSR(1-4)) are often found in host-adapted pathogens with reduced genomes that are not known to readily survive in a natural environment outside the host. In contrast, LSSRs composed of longer oligonucleotides (5-11 bp length, designated LSSR(5-11)) are found mostly in nonpathogens and opportunistic pathogens with large genomes. Comparisons among SSRs of different lengths suggest that LSSR(1-4) are likely maintained by selection. This is consistent with the established role of some LSSR(1-4) in enhancing antigenic variance. By contrast, abundance of LSSR(5-11) in some genomes may reflect the SSRs' general tendency to expand rather than their specific role in the organisms' physiology. Differences among genomes in terms of SSR representations and their possible interpretations are discussed.     

Performance of an oral fluid rapid HIV-1/2 test: experience from four CDC studies

OBJECTIVE: To evaluate the performance of a rapid HIV antibody test used with whole blood and oral fluid in settings where the test is likely to be used. DESIGN: In four separate studies, we compared the accuracy of the rapid test performed on whole blood and oral fluid specimens with the results of conventional HIV tests. METHODS: Oral fluid and whole blood from persons of unknown HIV status recruited from clinics, labor and delivery units, and outreach venues were tested with the OraQuick Advance rapid HIV-1/2 antibody test. Sensitivity and specificity were compared with results of the enzyme immunoassay (EIA) and Western blot algorithm used by the study sites. RESULTS: OraQuick sensitivity was 99.7% with whole blood and 99.1% with oral fluid from 327 persons who were HIV antibody positive by the conventional algorithm. OraQuick specificity was 99.9% with whole blood and 99.6% with oral fluid from 12 010 HIV-negative persons; EIA specificity was 99.7%. A cluster of 16 false-positive oral fluid tests occurred in one study, in which specificity was lower (99.0%) than in the other three studies (99.6-99.8%). CONCLUSIONS: In diverse settings in four studies, the OraQuick test showed high sensitivity and specificity for HIV antibody in whole blood and oral fluid specimens. Slightly more false-positive and false-negative results occurred with oral fluid than with whole blood, but performance with both specimen types was similar to, or better than, that of conventional EIAs.     

Effectiveness of various irrigant activation techniques on the penetration of sodium hypochlorite into lateral canals of mature permanent teeth: A systematic review and meta-analysis

ObjectiveThis review aimed to systematically review the effectiveness of various irrigant activation techniques (IATs) on the penetration of sodium hypochlorite (NaOCl) into the lateral canals of mature permanent teeth.MethodsElectronic databases including MEDLINE (via PubMed), Scopus, ProQuest, and Cochrane Library were searched to identify laboratory studies evaluating the penetration of NaOCl into lateral canals following the use of apical negative pressure irrigation (ANP), passive ultrasonic irrigation (PUI), sonic irrigation (SI), and/or manual dynamic activation (MDA) techniques. Meta-analysis was performed for individual IATs in comparison with CNI into the lateral canals of both straight and curved root canals. On the basis of the previous literature and parameters, the risk of bias of the selected studies was evaluated with the help of a customized tool.ResultsOf the 983 records screened, 12 studies were selected to include in the systematic review, and 10 studies were selected for the meta-analysis. The total quality assessment across the included studies indicated a high quality (83.3%). Overall, the meta-analysis demonstrated IATs had significant improvement in the penetration of NaOCl into the lateral canals of straight canals (34.3%) over CNI. The subgroup analysis of individual IATs demonstrated PUI (60.9%) to be superior in the penetration into lateral canals of straight canals.ConclusionsIATs improved the irrigant penetration into lateral canals and therefore their use during routine endodontic practice is recommended. In straight canals, PUI is the most effective IAT followed by ANP, SI, and MDA techniques.     

Multiple traumatic experiences,post‐traumatic stress disorder and offending behaviour in female prisoners

Background

Although it is well established that prisoners commonly have histories of childhood trauma, little is known about mediators between exposure to trauma and criminal behaviour.

Hypotheses

We hypothesised that the experience of trauma in adulthood, post‐traumatic stress disorder (PTSD) and emotional dysregulation would mediate the relationship between childhood traumatic events and later criminal behaviour.

Methods

Eighty‐nine female prisoners were interviewed using standardised scales, in a cross‐sectional study design. History of traumatic events, DSM‐5 PTSD and emotional regulation were assessed, along with offending and demographic information. A series of regression and mediation analyses were undertaken on the data.

Results

Almost all (91%) of the 89 women reported both childhood and adulthood trauma. Over half (58%) met the criteria for DSM‐5 PTSD. Multiple traumas were significantly associated with seriousness of offence, as indicated by sentence length. Adult experience of trauma was the only significant mediator between childhood trauma and subsequent offending.

Conclusions/implications for practice

Women who have experienced multiple traumatic events may be more likely to commit serious offences, so it is very important to assess and meet their trauma‐related needs. While prisons should never be used as substitutes for healthcare facilities, when women or girls are sent to prison, the opportunity for constructive interventions must be seized. Copyright © 2017 John Wiley & Sons, Ltd.     

Novel kinase inhibitors in renal cell carcinoma: Progressive development of static agents

The rapidly expanding knowledge regarding neoplastic diseases is providing a plethora of new targets for drug discovery and development as exemplified by recent data in renal cell carcinoma. The initial experience with molecularly “targeted” agents has demonstrated that development of the newer non-cytotoxic agents will provide unique challenges requiring modification of many traditional drug development concepts and methods. We discuss recently reported data from a few renal cell carcinoma trials with putative cytostatic agents and highlight issues that need to be addressed for efficient development of cytostatic agents during various phases of clinical development.