Direct and indirect effects of screening for Chlamydia trachomatis on the prevention of pelvic inflammatory disease: a mathematical modeling study

BACKGROUND Pelvic inflammatory disease (PID) results from the ascending spread of microorganisms, including Chlamydia trachomatis, to the upper genital tract. Screening could improve outcomes by identifying and treating chlamydial infections before they progress to PID (direct effect) or by reducing chlamydia transmission (indirect effect). METHODS We developed a compartmental model that represents a hypothetical heterosexual population and explicitly incorporates progression from chlamydia to clinical PID. Chlamydia screening was introduced, with coverage increasing each year for 10 years. We estimated the separate contributions of the direct and indirect effects of screening on PID cases prevented per 100,000 women. We explored the influence of varying the time point at which clinical PID could occur and of increasing the risk of PID after repeated chlamydial infections. RESULTS The probability of PID at baseline was 3.1% by age 25 years. After 5 years, the intervention scenario had prevented 187 PID cases per 100,000 women and after 10 years 956 PID cases per 100,000 women. At the start of screening, most PID cases were prevented by the direct effect. The indirect effect produced a small net increase in PID cases, which was outweighed by the effect of reduced chlamydia transmission after 2.2 years. The later that progression to PID occurs, the greater the contribution of the direct effect. Increasing the risk of PID with repeated chlamydial infection increases the number of PID cases prevented by screening. CONCLUSIONS This study shows the separate roles of direct and indirect PID prevention and potential harms, which cannot be demonstrated in observational studies.

About DNA databasing and investigative genetic analysis of externally visible characteristics: A public survey.

During the last decade, DNA profiling and the use of DNA databases have become two of the most employed instruments of police investigations. This very rapid establishment of forensic genetics is yet far from being complete. In the last few years novel types of analyses have been presented to describe phenotypically a possible perpetrator. We conducted the present study among German speaking Swiss residents for two main reasons: firstly, we aimed at getting an impression of the public awareness and acceptance of the Swiss DNA database and the perception of a hypothetical DNA database containing all Swiss residents. Secondly, we wanted to get a broader picture of how people that are not working in the field of forensic genetics think about legal permission to establish phenotypic descriptions of alleged criminals by genetic means. Even though a significant number of study participants did not even know about the existence of the Swiss DNA database, its acceptance appears to be very high. Generally our results suggest that the current forensic use of DNA profiling is considered highly trustworthy. However, the acceptance of a hypothetical universal database would be only as low as about 30% among the 284 respondents to our study, mostly because people are concerned about the security of their genetic data, their privacy or a possible risk of abuse of such a database. Concerning the genetic analysis of externally visible characteristics and biogeographical ancestry, we discover a high degree of acceptance. The acceptance decreases slightly when precise characteristics are presented to the participants in detail. About half of the respondents would be in favor of the moderate use of physical traits analyses only for serious crimes threatening life, health or sexual integrity. The possible risk of discrimination and reinforcement of racism, as discussed by scholars from anthropology, bioethics, law, philosophy and sociology, is mentioned less frequently by the study participants than we would have expected. A national DNA database and the widespread use of DNA analyses for police and justice have an impact on the entire society. Therefore the concerns of lay persons from the respective population should be heard and considered. The aims of this study were to draw a broader picture of the public opinion on DNA databasing and to contribute to the debate about the possible future use of genetics to reveal phenotypic characteristics. Our data might provide an additional perspective for experts involved in regulatory or legislative processes.

Simultaneous analysis of nuclear and mitochondrial DNA, mRNA and miRNA from backspatter from inside parts of firearms generated by shots at "triple contrast" doped ballistic models

When a firearm projectile hits a biological target a spray of biological material (e.g., blood and tissue fragments) can be propelled from the entrance wound back towards the firearm. This phenomenon has become known as "backspatter" and if caused by contact shots or shots from short distances traces of backspatter may reach, consolidate on, and be recovered from, the inside surfaces of the firearm. Thus, a comprehensive investigation of firearm-related crimes must not only comprise of wound ballistic assessment but also backspatter analysis, and may even take into account potential correlations between these emergences. The aim of the present study was to evaluate and expand the applicability of the "triple contrast" method by probing its compatibility with forensic analysis of nuclear and mitochondrial DNA and the simultaneous investigation of co-extracted mRNA and miRNA from backspatter collected from internal components of different types of firearms after experimental shootings. We demonstrate that "triple contrast" stained biological samples collected from the inside surfaces of firearms are amenable to forensic co-analysis of DNA and RNA and permit sequence analysis of the entire mtDNA displacement-loop, even for "low template" DNA amounts that preclude standard short tandem repeat DNA analysis. Our findings underscore the "triple contrast" method's usefulness as a research tool in experimental forensic ballistics.

Home-based versus clinic-based specimen collection in the management of Chlamydia trachomatis and Neisseria gonorrhoeae infections

BACKGROUND Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) are the most frequent causes of bacterial sexually transmitted infections (STIs). Management strategies that reduce losses in the clinical pathway from infection to cure might improve STI control and reduce complications resulting from lack of, or inadequate, treatment. OBJECTIVES To assess the effectiveness and safety of home-based specimen collection as part of the management strategy for Chlamydia trachomatis and Neisseria gonorrhoeae infections compared with clinic-based specimen collection in sexually-active people. SEARCH METHODS We searched the Cochrane Sexually Transmitted Infections Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and LILACS on 27 May 2015, together with the World Health Organization International Clinical Trials Registry (ICTRP) and ClinicalTrials.gov. We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. SELECTION CRITERIA Randomized controlled trials (RCTs) of home-based compared with clinic-based specimen collection in the management of C. trachomatis and N. gonorrhoeae infections. DATA COLLECTION AND ANALYSIS Three review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. We contacted study authors for additional information. We resolved any disagreements through consensus. We used standard methodological procedures recommended by Cochrane. The primary outcome was index case management, defined as the number of participants tested, diagnosed and treated, if test positive. MAIN RESULTS Ten trials involving 10,479 participants were included. There was inconclusive evidence of an effect on the proportion of participants with index case management (defined as individuals tested, diagnosed and treated for CT or NG, or both) in the group with home-based (45/778, 5.8%) compared with clinic-based (51/788, 6.5%) specimen collection (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.60 to 1.29; 3 trials, I² = 0%, 1566 participants, moderate quality). Harms of home-based specimen collection were not evaluated in any trial. All 10 trials compared the proportions of individuals tested. The results for the proportion of participants completing testing had high heterogeneity (I² = 100%) and were not pooled. We could not combine data from individual studies looking at the number of participants tested because the proportions varied widely across the studies, ranging from 30% to 96% in home group and 6% to 97% in clinic group (low-quality evidence). The number of participants with positive test was lower in the home-based specimen collection group (240/2074, 11.6%) compared with the clinic-based group (179/967, 18.5%) (RR 0.72, 95% CI 0.61 to 0.86; 9 trials, I² = 0%, 3041 participants, moderate quality). AUTHORS' CONCLUSIONS Home-based specimen collection could result in similar levels of index case management for CT or NG infection when compared with clinic-based specimen collection. Increases in the proportion of individuals tested as a result of home-based, compared with clinic-based, specimen collection are offset by a lower proportion of positive results. The harms of home-based specimen collection compared with clinic-based specimen collection have not been evaluated. Future RCTs to assess the effectiveness of home-based specimen collection should be designed to measure biological outcomes of STI case management, such as proportion of participants with negative tests for the relevant STI at follow-up.

Punitive reactions to completed crimes versus accidentally uncompleted crimes

Previous studies have shown that the harm caused by crime affects punitive reactions even if differences in the degree of harm are merely accidental. However, it remains unclear whether the effect is direct or whether it is mediated by attributed responsibility or blame. Participants were 303 university students who listened to 4 case vignettes (between-subjects design). Half received information about a completed crime and half about an accidentally uncompleted crime. Crime type was either fraud or rape. The results suggest that individuals consider the actual harm to a significantly greater extent than attribution theory would predict. Moreover, the link between harm and punishment was virtually not mediated by attributed blame and not moderated by individual differences in morality. Future studies should investigate whether the harm-punishment link is a result of an automatic act of retaliation or a desire to compensate for the harm done to the victim (restorative justice).

ICAM1 depletion reduces spinal metastasis formation in vivo and improves neurological outcome

INTRODUCTION Clinical treatment of spinal metastasis is gaining in complexity while the underlying biology remains unknown. Insufficient biological understanding is due to a lack of suitable experimental animal models. Intercellular adhesion molecule-1 (ICAM1) has been implicated in metastasis formation. Its role in spinal metastasis remains unclear. It was the aim to generate a reliable spinal metastasis model in mice and to investigate metastasis formation under ICAM1 depletion. MATERIAL AND METHODS B16 melanoma cells were infected with a lentivirus containing firefly luciferase (B16-luc). Stable cell clones (B16-luc) were injected retrogradely into the distal aortic arch. Spinal metastasis formation was monitored using in vivo bioluminescence imaging/MRI. Neurological deficits were monitored daily. In vivo selected, metastasized tumor cells were isolated (mB16-luc) and reinjected intraarterially. mB16-luc cells were injected intraarterially in ICAM1 KO mice. Metastasis distribution was analyzed using organ-specific fluorescence analysis. RESULTS Intraarterial injection of B16-luc and metastatic mB16-luc reliably induced spinal metastasis formation with neurological deficits (B16-luc:26.5, mB16-luc:21 days, p<0.05). In vivo selection increased the metastatic aggressiveness and led to a bone specific homing phenotype. Thus, mB16-luc cells demonstrated higher number (B16-luc: 1.2±0.447, mB16-luc:3.2±1.643) and increased total metastasis volume (B16-luc:2.87±2.453 mm3, mB16-luc:11.19±3.898 mm3, p<0.05) in the spine. ICAM1 depletion leads to a significantly reduced number of spinal metastasis (mB16-luc:1.2±0.84) with improved neurological outcome (29 days). General metastatic burden was significantly reduced under ICAM1 depletion (control: 3.47×10(7)±1.66×10(7); ICAM-1-/-: 5.20×10(4)±4.44×10(4), p<0.05 vs. control) CONCLUSION Applying a reliable animal model for spinal metastasis, ICAM1 depletion reduces spinal metastasis formation due to an organ-unspecific reduction of metastasis development.

Expression of a bacterial serine acetyltransferase in transgenic potato plants leads to increased levels of cysteine and glutathione

The coding sequence of the wild-type, cys-sensitive, cysE gene from Escherichia coli, which encodes an enzyme of the cysteine biosynthetic pathway, namely serine acetyltransferase (SAT, EC 2.3.1.30), was introduced into the genome of potato plants under the control of the cauliflower mosaic virus 35S promoter. In order to target the protein into the chloroplast, cysE was translationally fused to the 5′-signal sequence of rbcS from Arabidopsis thaliana. Transgenic plants showed a high accumulation of the cysE mRNA. The chloroplastic localisation of the E. coli SAT protein was demonstrated by determination of enzymatic activities in enriched organelle fractions. Crude leaf extracts of these plants exhibited up to 20-fold higher SAT activity than those prepared from wild-type plants. The transgenic potato plants expressing the E. coli gene showed not only increased levels of enzyme activity but also exhibited elevated levels of cysteine and glutathione in leaves. Both were up to twofold higher than in control plants. However, the thiol content in tubers of transgenic lines was unaffected. The alterations observed in leaf tissue had no effect on the expression of O-acetylserine(thiol)-lyase, the enzyme which converts O-acetylserine, the product of SAT, to cysteine. Only a minor effect on its enzymatic activity was observed. In conclusion, the results presented here demonstrate the importance of SAT in plant cysteine biosynthesis and show that production of cysteine and related sulfur-containing compounds can be enhanced by metabolic engineering.