Angiotensin-Converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism and ACE Inhibitor-Related Cough: A Meta-Analysis

Objective: An insertion/deletion (I/D) variant in the angiotensin-converting enzyme (ACE) gene was associated with ACE inhibitor (ACEI)-related cough in previous studies. However, the results were inconsistent. Our objective was to assess the relationship between the ACE I/D polymorphism and ACEI-related cough by meta-analysis and to summarize all studies that are related to ACE I/D polymorphism and ACEI-cough and make a summary conclusion to provide reference for the researchers who attempt to conduct such a study. Methods: Databases including PubMed, EMbase, Cochrane Library, and China National Knowledge Infrastructure, were searched for genetic association studies. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity. Results: Eleven trials, including 906 cases (ACEI-related cough) and 1,175 controls, were reviewed in the present meta-analysis. The random effects pooled OR was 1.16 (95% CI: 0.78-1.74, p = 0.46) in the dominant model and 1.61 (95% CI: 1.18-2.20, p = 0.003) in the recessive model. Heterogeneity was found among and within studies. Metaregression indicated that the effect size was positively associated with age and negatively associated with follow-up duration of ACEI treatment. Subgroup analysis revealed a significant association between ACE I/D polymorphism and ACEI-related cough in studies with mean age >60 y, but not in studies with mean age 2 mo or in studies in Caucasians. No heterogeneity was detected in these two subgroups. Conclusions: Synthesis of the available evidence supports ACE I/D polymorphism as an age-dependent predictor for risk of ACEI-related cough

Imbalanced functional link between executive control network and reward network explain the online-game seeking behaviors in Internet gaming disorder

Literatures have shown that Internet gaming disorder (IGD) subjects show impaired executive control and enhanced reward sensitivities than healthy controls. However, how these two networks jointly affect the valuation process and drive IGD subjects' online-game-seeking behaviors remains unknown. Thirty-five IGD and 36 healthy controls underwent a resting-states scan in the MRI scanner. Functional connectivity (FC) was examined within control and reward network seeds regions, respectively. Nucleus accumbens (NAcc) was selected as the node to find the interactions between these two networks. IGD subjects show decreased FC in the executive control network and increased FC in the reward network when comparing with the healthy controls. When examining the correlations between the NAcc and the executive control/reward networks, the link between the NAcc - executive control network is negatively related with the link between NAcc - reward network. The changes (decrease/increase) in IGD subjects' brain synchrony in control/reward networks suggest the inefficient/overly processing within neural circuitry underlying these processes. The inverse proportion between control network and reward network in IGD suggest that impairments in executive control lead to inefficient inhibition of enhanced cravings to excessive online game playing. This might shed light on the mechanistic understanding of IGD

Mutation analysis of the MDM4 gene in German breast cancer patients

<p>Abstract</p> <p>Background</p> <p>MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether <it>MDM4 </it>gene alterations play some role in the inherited component of breast cancer susceptibility.</p> <p>Methods</p> <p>We sequenced the whole <it>MDM4 </it>coding region and flanking untranslated regions in genomic DNA samples obtained from 40 German patients with familial breast cancer. Selected variants were subsequently screened by RFLP-based assays in an extended set of breast cancer cases and controls.</p> <p>Results</p> <p>Our resequencing study uncovered two <it>MDM4 </it>coding variants in 4/40 patients. Three patients carried a silent substitution at codon 74 that was linked with another rare variant in the 5'UTR. No association of this allele with breast cancer was found in a subsequent screening of 133 patients with bilateral breast cancer and 136 controls. The fourth patient was heterozygous for the missense substitution D153G which is located in a less conserved region of the MDM4 protein but may affect a predicted phosphorylation site. The D153G substitution only partially segregated with breast cancer in the family and was not identified on additional 680 chromosomes screened.</p> <p>Conclusion</p> <p>This study did not reveal clearly pathogenic mutations although it uncovered two new unclassified variants at a low frequency. We conclude that there is no evidence for a major role of <it>MDM4 </it>coding variants in the inherited susceptibility towards breast cancer in German patients.</p

Cardiovascular risk assessment scores for people with diabetes: a systematic review

People with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Multivariate cardiovascular risk scores have been used in many countries to identify individuals who are at high risk of CVD. These risk scores include those originally developed in individuals with diabetes and those developed in a general population. This article reviews the published evidence for the performance of CVD risk scores in diabetic patients by: (1) examining the overall rationale for using risk scores; (2) systematically reviewing the literature on available scores; and (3) exploring methodological issues surrounding the development, validation and comparison of risk scores. The predictive performance of cardiovascular risk scores varies substantially between different populations. There is little evidence to suggest that risk scores developed in individuals with diabetes estimate cardiovascular risk more accurately than those developed in the general population. The inconsistency in the methods used in evaluation studies makes it difficult to compare and summarise the predictive ability of risk scores. Overall, CVD risk scores rank individuals reasonably accurately and are therefore useful in the management of diabetes with regard to targeting therapy to patients at highest risk. However, due to the uncertainty in estimation of true risk, care is needed when using scores to communicate absolute CVD risk to individuals

Analyses of 32 Loci Clarify Phylogenetic Relationships among Trypanosoma cruzi Lineages and Support a Single Hybridization prior to Human Contact

Trypanosoma cruzi is the protozoan parasite that causes Chagas disease, a major health problem in Latin America. The genetic diversity of this parasite has been traditionally divided in two major groups: T. cruzi I and II, which can be further divided in six major genetic subdivisions (subgroups TcI-TcVI). T. cruzi I and II seem to differ in important biological characteristics, and are thought to represent a natural division relevant for epidemiological studies and development of prophylaxis. Having a correct reconstruction of the evolutionary history of T. cruzi is essential for understanding the potential connection between the genetic and phenotypic variability of T. cruzi with the different manifestations of Chagas disease. Here we present results from a comprehensive phylogenetic analysis of T. cruzi using more than 26 Kb of aligned sequence data. We show strong evidence that T. cruzi II (TcII-VI) is not a natural evolutionary group but a paraphyletic lineage and that all major lineages of T. cruzi evolved recently (<3 million years ago [mya]). Furthermore, the sequence data is consistent with one major hybridization event having occurred in this species recently (< 1 mya) but well before T. cruzi entered in contact with humans in South America

How do parents experience being asked to enter a child in a randomised controlled trial?

<p>Abstract</p> <p>Background</p> <p>As the number of randomised controlled trials of medicines for children increases, it becomes progressively more important to understand the experiences of parents who are asked to enrol their child in a trial. This paper presents a narrative review of research evidence on parents' experiences of trial recruitment focussing on qualitative research, which allows them to articulate their views in their own words.</p> <p>Discussion</p> <p>Parents want to do their best for their children, and socially and legally their role is to care for and protect them yet the complexities of the medical and research context can challenge their fulfilment of this role. Parents are simultaneously responsible for their child and cherish this role yet they are dependent on others when their child becomes sick. They are keen to exercise responsibility for deciding to enter a child in a trial yet can be fearful of making the 'wrong' decision. They make judgements about the threat of the child's condition as well as the risks of the trial yet their interpretations often differ from those of medical and research experts. Individual pants will experience these and other complexities to a greater or lesser degree depending on their personal experiences and values, the medical situation of their child and the nature of the trial. Interactions at the time of trial recruitment offer scope for negotiating these complexities if practitioners have the flexibility to tailor discussions to the needs and situation of individual parents. In this way, parents may be helped to retain a sense that they have acted as good parents to their child whatever decision they make.</p> <p>Summary</p> <p>Discussing randomised controlled trials and gaining and providing informed consent is challenging. The unique position of parents in giving proxy consent for their child adds to this challenge. Recognition of the complexities parents face in making decisions about trials suggests lines for future research on the conduct of trials, and ultimately, may help improve the experience of trial recruitment for all parties.</p

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference