ProCARs: Progressive Reconstruction of Ancestral Gene Orders

International audienceBackground: In the context of ancestral gene order reconstruction from extant genomes, there exist two main computational approaches: rearrangement-based, and homology-based methods. The rearrangement-based methods consist in minimizing a total rearrangement distance on the branches of a species tree. The homology-based methods consist in the detection of a set of potential ancestral contiguity features, followed by the assembling of these features into Contiguous Ancestral Regions (CARs). Results: In this paper, we present a new homology-based method that uses a progressive approach for both the detection and the assembling of ancestral contiguity features into CARs. The method is based on detecting a set of potential ancestral adjacencies iteratively using the current set of CARs at each step, and constructing CARs progressively using a 2-phase assembling method. We show the usefulness of the method through a reconstruction of the boreoeutherian ancestral gene order, and a comparison with three other homology-based methods: AnGeS, InferCARs and GapAdj. The program is written in Python, and the dataset used in this paper are available at http://bioinfo.lifl.fr/procars/

Seroprevalence and risk factors for Neospora caninum in small dairy farms in central Chile

Indexación: Scopus.Objetivos. Proveer información sobre la seroprevalencia y factores de riesgo asociados a la infección por Neospora caninum en bovinos en Chile central. Materiales y métodos. La población estudiada corresponde a pequeñas lecherías que son parte de un programa gubernamental de Asistencia Técnica (SAT), en la región de O´Higgins en Chile central. Muestras de suero fueron recolectadas desde vacas en lactancia y analizadas mediante un kit comercial ELISA. Además, se aplicó un cuestionario a los dueños de los animales para la identificación de factores de riesgo a través de regresión logística. Resultados. Se identificó una prevalencia a nivel de granja del 67%, mientras que dentro de las granjas positivas, esta fue en promedio de 55%. El historial de abortos (p= 0.037, OR=5.09), la fuente de alimentación de perros (p= 0.0429, OR=6), la fuente de agua de bebida de las vacas (p=0.034, OR=4.5) y el manejo de los abortos (p=0.017, OR=7.43) fueron identificados como factores de riesgo para la infección. Conclusiones. Se observa una alta seroprevalencia de N. caninum en pequeños productores lecheros pertenecientes al SAT en Chile central. Los resultados presentados resaltan la necesidad de mejorar las acciones de vigilancia de esta enfermedad y el desarrollo de medidas preventivas para evitar las pérdidas asociadas a esta enfermedad.Objective. To provide information about seroprevalence and risk factors of Neospora caninum infection in bovines of central Chile. Material and Methods. The study population are small dairy farms that are part of a Government Technical Support Service (SAT) in the O'Higgins region in central Chile. Sera samples were collected from milking cows and analyzed by a commercial ELISA kit. Additionally, a questionnaire was applied to farmers to identify risk factors through logistic regression. Results. The farm level prevalence was found to be 67%, and within farms seroprevalence 55%. Abortion history (p= 0.037, OR=5.09), dogs feed source (p= 0.0429, OR=6), cattle drinking water source (p=0.034, OR=4.5) and abortions management (p=0.017, OR=7.43) were found as significant risk factors for infection. Conclusion. There is a high N. caninum seroprevalence in small SAT's dairy farms in O'Higgins region. These results highlight the need of improving N. caninum surveillance, and the development of preventive measures to avoid losses related with this disease.http://revistas.unicordoba.edu.co/index.php/revistamvz/article/view/92

A systematic review and meta-analysis of interventions to induce attempts to quit tobacco among adults not ready to quit

The prevalence of past-year smoking cessation remains below 10% in the U.S. Most who smoke are not ready to quit in the near future. Cessation requires both (a) initiating a quit attempt (QA) and (b) maintaining abstinence. Most research has focused on abstinence among people already motivated to quit. We systematically reviewed interventions to promote QAs among people not motivated to quit tobacco. We searched PubMed, CENTRAL, APA PsycInfo, Embase, and our personal libraries for randomized trials of tobacco interventions that reported QAs as an outcome among adults not ready to quit. We screened studies and extracted data in duplicate. We pooled findings of the 25 included studies using Mantel–Haenszel random effects meta-analyses when ≥ 2 studies tested the same intervention. Most (24) trials addressed cigarettes and one addressed smokeless tobacco. Substantial heterogeneity among trials resulted in a series of small meta-analyses. Findings indicate varenicline may increase QAs more than no varenicline, n = 320; RR = 1.4, 95% CI [1.1, 1.7]; I² = 0%, and nicotine replacement therapy (NRT) may increase QAs more than no NRT, n = 2,568; RR = 1.1, 95% CI [1.02, 1.3]; I² = 0%. Pooled effects for motivational counseling, reduction counseling, and very low nicotine content cigarettes showed no clear evidence of benefit or harm. The evidence was judged to be of medium to very low certainty due to imprecision, inconsistency, and risk of bias, suggesting that further research is likely to change interpretation of our results. Findings demonstrate the need for more high-quality research on interventions to induce QAs among adults not ready to quit tobacco

Predictors of health-related quality of life in patients with colorectal cancer

<p>Abstract</p> <p>Background</p> <p>Most studies that have identified variables associated with the health-related quality of life (HRQL) of patients with colorectal cancer have been cross-sectional or included patients with other diagnoses. The objectives of this study were to identify predictors of HRQL in patients with colorectal cancer and interpret the clinical importance of the results.</p> <p>Methods</p> <p>We conducted a population-based longitudinal study of patients identified through three regions of the California Cancer Registry. Surveys were completed by 568 patients approximately 9 and 19 months post-diagnosis. Three HRQL outcomes from the Functional Assessment of Cancer Therapy – Colorectal (FACT-C) were evaluated: social/family well-being (SWB), emotional well-being (EWB) and the Trial Outcome Index (TOI), which is a colorectal cancer-specific summary measure of physical function and well-being. Sociodemographic, cancer/health, and healthcare variables were assessed in multivariable regression models. We computed the difference in predicted HRQL scores corresponding to a large difference in a predictor variable, defined as a 1 standard deviation difference for interval variables or the difference relative to the reference category for nominal variables. The effect of an explanatory variable on HRQL was considered clinically meaningful if the predicted score difference was at least as large as the minimally important difference.</p> <p>Results</p> <p>Common predictors of better TOI, SWB and EWB were better general health and factors related to better perceived quality of cancer care. Predictor variables in addition to general health and perceived quality of care were identified only for SWB. Being married/living as married was associated with better SWB, whereas being male or of Hispanic ethnicity was associated with worse SWB. Among the sociodemographic, cancer/health, and healthcare variables evaluated, only Hispanic ethnicity had a clinically meaningful effect on an HRQL outcome.</p> <p>Conclusion</p> <p>Our findings, particularly the information on the clinical importance of predictor variables, can help clinicians identify patients who may be at risk for poor future HRQL. Potentially modifiable factors were related to perceived quality of cancer care; thus, future research should evaluate whether improving these factors improves HRQL.</p

VEZF1 elements mediate protection from DNA methylation

There is growing consensus that genome organization and long-range gene regulation involves partitioning of the genome into domains of distinct epigenetic chromatin states. Chromatin insulator or barrier elements are key components of these processes as they can establish boundaries between chromatin states. The ability of elements such as the paradigm &#946;-globin HS4 insulator to block the range of enhancers or the spread of repressive histone modifications is well established. Here we have addressed the hypothesis that a barrier element in vertebrates should be capable of defending a gene from silencing by DNA methylation. Using an established stable reporter gene system, we find that HS4 acts specifically to protect a gene promoter from de novo DNA methylation. Notably, protection from methylation can occur in the absence of histone acetylation or transcription. There is a division of labor at HS4; the sequences that mediate protection from methylation are separable from those that mediate CTCF-dependent enhancer blocking and USF-dependent histone modification recruitment. The zinc finger protein VEZF1 was purified as the factor that specifically interacts with the methylation protection elements. VEZF1 is a candidate CpG island protection factor as the G-rich sequences bound by VEZF1 are frequently found at CpG island promoters. Indeed, we show that VEZF1 elements are sufficient to mediate demethylation and protection of the APRT CpG island promoter from DNA methylation. We propose that many barrier elements in vertebrates will prevent DNA methylation in addition to blocking the propagation of repressive histone modifications, as either process is sufficient to direct the establishment of an epigenetically stable silent chromatin stat

Rapid Heterotrophic Ossification with Cryopreserved Poly(ethylene glycol-) Microencapsulated BMP2-Expressing MSCs

Autologous bone grafting is the most effective treatment for long-bone nonunions, but it poses considerable risks to donors, necessitating the development of alternative therapeutics. Poly(ethylene glycol) (PEG) microencapsulation and BMP2 transgene delivery are being developed together to induce rapid bone formation. However, methods to make these treatments available for clinical applications are presently lacking. In this study we used mesenchymal stem cells (MSCs) due to their ease of harvest, replication potential, and immunomodulatory capabilities. MSCs were from sheep and pig due to their appeal as large animal models for bone nonunion. We demonstrated that cryopreservation of these microencapsulated MSCs did not affect their cell viability, adenoviral BMP2 production, or ability to initiate bone formation. Additionally, microspheres showed no appreciable damage from cryopreservation when examined with light and electron microscopy. These results validate the use of cryopreservation in preserving the viability and functionality of PEG-encapsulated BMP2-transduced MSCs

Experiences, acceptability and feasibility of an isometric exercise intervention for stage 1 hypertension: embedded qualitative study in a randomised controlled feasibility trial.

Background Healthy lifestyle changes for patients with stage 1 hypertension are recommended before antihypertensive medication. Exercise has antihypertensive benefits; however, low adoption and high attrition are common. Patients need easily adoptable, effective and manageable exercise interventions that can be sustained for life. We present participant and stakeholder perceptions of an isometric exercise intervention for stage 1 hypertension delivered in the National Health Service (NHS, UK). Methods An embedded qualitative study within a randomised-controlled feasibility study included intervention arm participants (n = 10), healthcare professionals from participating NHS sites (n = 3) and non-participating NHS sites (n = 5) taking part in semi-structured interviews to explore feasibility of delivering an isometric exercise intervention within the study design and an NHS context. Data was analysed using reflective thematic analysis. Results Three themes were identified: study deliverability; motivators and barriers; support for study participation. Findings indicated that the study was well designed. Health benefits, unwillingness to take medication, altruism and interest in the study helped motivation and adherence. Study support received was good, but healthcare professionals were insecure in intervention delivery with regular training/supervision needed. Perception of health improvement was mixed, but, in some, uptake of wider lifestyle changes resulted from participation. Stakeholders felt that current service challenges/demand would make implementation challenging. Conclusions Despite participant positivity, delivery of an isometric intervention in an NHS setting was considered challenging given the current service demand, although possible with robust effectiveness evidence. Findings support further effectiveness data and implementation development of the isometric exercise intervention. Trial registration ISRCTN, ISRCTN13472393. Registered 18 September 2020

Addressing alcohol and tobacco harms in remote Indigenous communities and rapid responses to mental health crises in regional centres

Alcohol Management Plans (AMPs) were initially designed as part of a wide range of innovative and significant Queensland Government reforms. As well as supply control, these promised to reduce alcohol and substance misuse and violence through demand reduction by addressing key social determinants: economic development; education and training, land and sustainable natural resource management, housing, and health 3, 4. The limited available evidence in the peer-reviewed published literature points to some favourable impacts of restrictions 5, 6, including a reduction in indicators of serious injury in some communities to historically low levels 7. These favourable findings were reflected in an internal Queensland Government review 4. However, the evidence that these initial positive effects were experienced in all communities, or that they have been sustained, particularly after the most recent round of restrictions in 2008, has become equivocal 8. This paper was the first in a unique evaluation research program designed to examine the health and social effects of Queensland�s AMPs 1, 9. It investigates issues surrounding implementation of the designed AMP intervention components, specifically their perceived impacts on alcohol supply and consumption, violence, injury and community health and well-being. Perceptions and experiences are reported of the community leaders, service providers and relevant organisations with a mandate or responsibility for alcohol-related matters in the affected AMP communities and nearby towns.The research reported in this paper is a project of the Australian Primary Health Care Research Institute, which is supported by a grant from the Australian Government Department of Health and Ageing under the Primary Health Care Research, Evaluation and Development Strategy

Maternal postnatal depression and anxiety and their association with child emotional negativity and behavior problems at two years

Postnatal maternal depression is associated with poorer child emotional and behavioral functioning, but it is unclear whether this occurs following brief episodes or only with persistent depression. Little research has examined the relation between postnatal anxiety and child outcomes. The present study examined the role of postnatal major depressive disorder (MDD) and generalized anxiety disorder (GAD) symptom chronicity on children’s emotional and behavioral functioning at 24 months. Following postnatal screening mothers (n = 296) were identified as having MDD, GAD, MDD and GAD, or no disorder at 3 months postnatal; the average age was 32.3 (SD = 5.0), 91.9% self-identified as Caucasian, and 62.2% were married. Maternal disorder symptom severity was assessed by questionnaires and structured interview at 3, 6, 10, 14, and 24 months postpartum. At 24 months, child emotional negativity and behavior were assessed using questionnaires and by direct observation. Latent trait-state-occasion modeling was used to represent maternal disorder symptom chronicity; both stable trait and time-specific occasion portions of maternal symptomatology were examined in relation to child outcomes. Only the stable trait portion of maternal MDD and GAD symptom severity were related to maternal report of child behavior problems and higher levels of emotional negativity. Persistent maternal MDD, but not GAD, symptom severity was related to higher levels of child emotional negativity as measured observationally. These data suggest that children’s behavior problems and emotional negativity are adversely affected by persistent maternal depression, and possibly anxiety. This has implications for interventions to prevent negative effects of postnatal psychopathology on children