A nurse-delivered, clinic-based intervention to address intimate partner violence among low-income women in Mexico City : findings from a cluster randomized controlled trial

Background: Rigorous evaluations of health sector interventions addressing intimate partner violence (IPV) in low- and middle-income countries are lacking. We aimed to assess whether an enhanced nurse-delivered intervention would reduce IPV and improve levels of safety planning behaviors, use of community resources, reproductive coercion, and mental quality of life. Methods: We randomized 42 public health clinics in Mexico City to treatment or control arms. In treatment clinics, women received the nurse-delivered session (IPV screening, supportive referrals, health/safety risk assessments) at baseline (T1), and a booster counselling session after 3 months (T2). In control clinics, women received screening and a referral card from nurses. Surveys were conducted at T1, T2, and T3 (15 months from baseline). Our main outcome was past-year physical and sexual IPV. Intent-to-treat analyses were conducted via three-level random intercepts models to evaluate the interaction term for treatment status by time. Results: Between April and October 2013, 950 women (480 in control clinics, 470 in treatment clinics) with recent IPV experiences enrolled in the study. While reductions in IPV were observed for both women enrolled in treatment (OR, 0.40; 95% CI, 0.28-0.55; P < 0.01) and control (OR, 0.51; 95% CI, 0.36-0.72; P < 0.01) clinics at T3 (July to December 2014), no significant treatment effects were observed (OR, 0.78; 95% CI, 0.49-1.24; P = 0.30). At T2 (July to December 2013), women in treatment clinics reported significant improvements, compared to women in control clinics, in mental quality of life (β, 1.45; 95% CI, 0.14-2.75; P = 0.03) and safety planning behaviors (β, 0.41; 95% CI, 0.02-0.79; P = 0.04). Conclusion: While reductions in IPV levels were seen among women in both treatment and control clinics, the enhanced nurse intervention was no more effective in reducing IPV. The enhanced nursing intervention may offer short-term improvements in addressing safety planning and mental quality of life. Nurses can play a supportive role in assisting women with IPV experiences

Interplay of DNA supercoiling and catenation during the segregation of sister duplexes

The discrete regulation of supercoiling, catenation and knotting by DNA topoisomerases is well documented both in vivo and in vitro, but the interplay between them is still poorly understood. Here we studied DNA catenanes of bacterial plasmids arising as a result of DNA replication in Escherichia coli cells whose topoisomerase IV activity was inhibited. We combined high-resolution two-dimensional agarose gel electrophoresis with numerical simulations in order to better understand the relationship between the negative supercoiling of DNA generated by DNA gyrase and the DNA interlinking resulting from replication of circular DNA molecules. We showed that in those replication intermediates formed in vivo, catenation and negative supercoiling compete with each other. In interlinked molecules with high catenation numbers negative supercoiling is greatly limited. However, when interlinking decreases, as required for the segregation of newly replicated sister duplexes, their negative supercoiling increases. This observation indicates that negative supercoiling plays an active role during progressive decatenation of newly replicated DNA molecules in vivo

Conditional genome engineering reveals canonical and divergent roles for the Hus1 component of the 9-1-1 complex in the maintenance of the plastic genome of Leishmania.

Leishmania species are protozoan parasites whose remarkably plastic genome limits the establishment of effective genetic manipulation and leishmaniasis treatment. The strategies used by Leishmania to maintain its genome while allowing variability are not fully understood. Here, we used DiCre-mediated conditional gene deletion to show that HUS1, a component of the 9-1-1 (RAD9- RAD1-HUS1) complex, is essential and is required for a G2/M checkpoint. By analyzing genome wide instability in HUS1 ablated cells, HUS1 is shown to have a conserved role, by which it preserves genome stability, and also a divergent role, by which it promotes genome variability. These roles of HUS1 are related to distinct patterns of formation and resolution of single-stranded DNA and γH2A, throughout the cell cycle. Our findings suggest that Leishmania 9-1-1 subunits have evolved to co-opt canonical genomic maintenance and genomic variation functions. Hence, this study reveals a pivotal function of HUS1 in balancing genome stability and transmission in Leishmania. These findings may be relevant to understanding the evolution of genome maintenance and plasticity in other pathogens and eukaryote

Co-directional replication-transcription conflicts lead to replication restart

August 24, 2011Head-on encounters between the replication and transcription machineries on the lagging DNA strand can lead to replication fork arrest and genomic instability1, 2. To avoid head-on encounters, most genes, especially essential and highly transcribed genes, are encoded on the leading strand such that transcription and replication are co-directional. Virtually all bacteria have the highly expressed ribosomal RNA genes co-directional with replication3. In bacteria, co-directional encounters seem inevitable because the rate of replication is about 10–20-fold greater than the rate of transcription. However, these encounters are generally thought to be benign2, 4, 5, 6, 7, 8, 9. Biochemical analyses indicate that head-on encounters10 are more deleterious than co-directional encounters8 and that in both situations, replication resumes without the need for any auxiliary restart proteins, at least in vitro. Here we show that in vivo, co-directional transcription can disrupt replication, leading to the involvement of replication restart proteins. We found that highly transcribed rRNA genes are hotspots for co-directional conflicts between replication and transcription in rapidly growing Bacillus subtilis cells. We observed a transcription-dependent increase in association of the replicative helicase and replication restart proteins where head-on and co-directional conflicts occur. Our results indicate that there are co-directional conflicts between replication and transcription in vivo. Furthermore, in contrast to the findings in vitro, the replication restart machinery is involved in vivo in resolving potentially deleterious encounters due to head-on and co-directional conflicts. These conflicts probably occur in many organisms and at many chromosomal locations and help to explain the presence of important auxiliary proteins involved in replication restart and in helping to clear a path along the DNA for the replisome.Biotechnology and Biological Sciences Research Council (Great Britain) (Grant BB/E006450/1)Wellcome Trust (London, England) (Grant 091968/Z/10/Z)National Institutes of Health (U.S.) (Grant GM41934)National Institutes of Health (U.S.) (Postdoctoral Fellowship GM093408)Biotechnology and Biological Sciences Research Council (Great Britain) (Sabbatical Visit

Partner notification for sexually transmitted infections in developing countries: a systematic review

<p>Abstract</p> <p>Background</p> <p>The feasibility and acceptability of partner notification (PN) for sexually transmitted infections (STIs) in developing countries was assessed through a comprehensive literature review, to help identify future intervention needs.</p> <p>Methods</p> <p>The Medline, Embase, and Google Scholar databases were searched to identify studies published between January 1995 and December 2007 on STI PN in developing countries. A systematic review of the research extracted information on: (1) willingness of index patients to notify partners; (2) the proportion of partners notified or referred; (3) client-reported barriers in notifying partners; (4) infrastructure barriers in notifying partners; and (5) PN approaches that were evaluated in developing countries.</p> <p>Results</p> <p>Out of 609 screened articles, 39 met our criteria. PN outcome varied widely and was implemented more often for spousal partners than for casual or commercial partners. Reported barriers included sociocultural factors such as stigma, fear of abuse for having an STI, and infrastructural factors related to the limited number of STD clinics, and trained providers and reliable diagnostic methods. Client-oriented counselling was found to be effective in improving partner referral outcomes.</p> <p>Conclusions</p> <p>STD clinics can improve PN with client-oriented counselling, which should help clients to overcome perceived barriers. The authors speculate that well-designed PN interventions to evaluate the impact on STI prevalence and incidence along with cost-effectiveness components will motivate policy makers in developing countries to allocate more resources towards STI management.</p

Co-Orientation of Replication and Transcription Preserves Genome Integrity

In many bacteria, there is a genome-wide bias towards co-orientation of replication and transcription, with essential and/or highly-expressed genes further enriched co-directionally. We previously found that reversing this bias in the bacterium Bacillus subtilis slows replication elongation, and we proposed that this effect contributes to the evolutionary pressure selecting the transcription-replication co-orientation bias. This selection might have been based purely on selection for speedy replication; alternatively, the slowed replication might actually represent an average of individual replication-disruption events, each of which is counter-selected independently because genome integrity is selected. To differentiate these possibilities and define the precise forces driving this aspect of genome organization, we generated new strains with inversions either over ∼1/4 of the chromosome or at ribosomal RNA (rRNA) operons. Applying mathematical analysis to genomic microarray snapshots, we found that replication rates vary dramatically within the inverted genome. Replication is moderately impeded throughout the inverted region, which results in a small but significant competitive disadvantage in minimal medium. Importantly, replication is strongly obstructed at inverted rRNA loci in rich medium. This obstruction results in disruption of DNA replication, activation of DNA damage responses, loss of genome integrity, and cell death. Our results strongly suggest that preservation of genome integrity drives the evolution of co-orientation of replication and transcription, a conserved feature of genome organization

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

MicroMotility: State of the art, recent accomplishments and perspectives on the mathematical modeling of bio-motility at microscopic scales

Mathematical modeling and quantitative study of biological motility (in particular, of motility at microscopic scales) is producing new biophysical insight and is offering opportunities for new discoveries at the level of both fundamental science and technology. These range from the explanation of how complex behavior at the level of a single organism emerges from body architecture, to the understanding of collective phenomena in groups of organisms and tissues, and of how these forms of swarm intelligence can be controlled and harnessed in engineering applications, to the elucidation of processes of fundamental biological relevance at the cellular and sub-cellular level. In this paper, some of the most exciting new developments in the fields of locomotion of unicellular organisms, of soft adhesive locomotion across scales, of the study of pore translocation properties of knotted DNA, of the development of synthetic active solid sheets, of the mechanics of the unjamming transition in dense cell collectives, of the mechanics of cell sheet folding in volvocalean algae, and of the self-propulsion of topological defects in active matter are discussed. For each of these topics, we provide a brief state of the art, an example of recent achievements, and some directions for future research