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An exponential increase in the prevalence of neurological disorders requires substantial steps to be taken for their prevention and treatment. Neurodiagnostic biomarkers are gaining momentum presently in order to enhance the diagnostic accuracy of neurodegenerative disorders, to precisely assess their advancement and to monitor the efficiency of therapeutic interventions. Therefore, the primary focus of the present review is the recent development in this field of neurodiagnostic biomarkers, and the current state of biomarker exploration in the context of various neurodegenerative diseases. This review encompasses an updated and detailed account of specific (β-Amyloid, Tau and Phospho-tau 181, Tar-DNA binding protein-43, Progranulin, a-synuclein, Clusterin, etc) and non-specific (genetic, synaptic, inflammatory and coagulation) neurodiagnostic biomarkers and the recent advances in this growing field. This comprehensive review also suggests the utilization of neurodiagnostic markers in network approaches and personalized medication that will eventually improvise the existing diagnostic and therapeutic complexities of neurodiagnostic biomarkers., (© 2019 John Wiley & Sons Australia, Ltd.)

Background: Acne is a common chronic skin disease with a multifactorial aetiology and pathogenesis. Recently, circular RNAs (circRNAs) have been identified as a key factor in regulating gene expression through circRNA-miRNA-mRNA networks in many biological processes and human diseases. However, the circRNAs expression in patients with acne is still unknown., Objective: To investigate circRNA expression profile in severe acne., Methods: The expression profile of circRNAs in three paired lesional skin and adjacent non-lesional skin in severe acne was detected by high-throughput RNA sequencing technology and bioinformatics analysis. The candidate circRNAs were validated by PCR, Sanger sequencing and qRT-PCR in the separate group (n = 4). The circRNA-miRNA-mRNA interaction networks were predicted., Results: A total of 538 circRNAs including 271 up- and 267 downregulated circRNAs were differentially expressed in lesional skin compared with adjacent non-lesional skin in severe acne. Gene Ontology and KEGG pathway enrichment analyses revealed that the aberrantly expressed circRNAs were primarily involved in inflammatory, metabolism and immune responses. Five candidate circRNAs (circRNA_0084927, circRNA_0001073, circRNA_0005941, circRNA_0086376 and circRNA_0018168) were validated to have significant decrease in severe acne by PCR, Sanger sequencing and qRT-PCR, in agreement with the results from RNA-Seq data analysis. The five identified circRNAs were predicted to interact with 213 miRNAs and regulated target gene expression., Conclusion: This study firstly showed that circRNAs were differentially expressed in severe acne and suggested that circRNAs could be used as a potential biomarker for the drug targets of acne., (© 2018 European Academy of Dermatology and Venereology.)

Osteoporosis is a frequent complication in patients with chronic liver disease, especially in end-stages and in chronic cholestasis, in addition to non-alcoholic fatty liver disease, haemochromatosis and alcoholism. Mechanisms underlying osteoporosis are poorly understood, but osteoporosis mainly results from low bone formation. In this setting, sclerostin, a key regulator of the Wnt/β-catenin signalling pathway which regulates bone formation, in addition to the effects of the retained substances of cholestasis such as bilirubin and bile acids on osteoblastic cells, may influence the decreased bone formation in chronic cholestasis. Similarly, the damaging effects of iron and alcohol on osteoblastic cells may partially explain bone disease in haemochromatosis and alcoholism. A role for proinflammatory cytokines has been proposed in different conditions. Increased bone resorption may occur in cholestatic women with advanced disease. Low vitamin D, poor nutrition and hypogonadism, may be contributing factors to the full picture of bone disorders in chronic liver disease., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

This spotlight issue of Microcirculation contains four state-of-the-art review articles on the role of microRNAs (miRNAs), a class of endogenous, highly conserved, small, non-coding RNAs that regulate gene expression at the post transcriptional level, and can act as key regulators of cellular mechanisms within the microcirculation. The expert reviews address issues, such as the role of miRNAs in determining endothelial cell differentiation and lineage commitment, the physiological role of miRNAs as critical modulators of endothelial cell proliferation, apoptosis and in angiogenesis, and their aberrant expression in different vascular disorders. The reviews also explore the prognostic value of miRNAs in cardiovascular disease and how they may serve both as a therapeutic target and clinical biomarker in the future. This cutting edge edition of the journal Microcirculation highlights the progress that has been made in this new and challenging research area., (© 2012 John Wiley & Sons Ltd.)

Pharmacogenetic clinical trials seek to identify genetic modifiers of treatment effects. When a trial has collected data on many potential genetic markers, a first step in analysis is to screen for evidence of pharmacogenetic effects by testing for treatment-by-marker interactions in a statistical model for the outcome of interest. This approach is potentially problematic because (i) individual significance tests can be overly sensitive, particularly when sample sizes are large; and (ii) standard significance tests fail to distinguish between markers that are likely, on biological grounds, to have an effect, and those that are not. One way to address these concerns is to perform Bayesian hypothesis tests [Berger (1985) Statistical decision theory and Bayesian analysis. New York: Springer; Kass and Raftery (1995) J Am Stat Assoc 90:773-795], which are typically more conservative than standard uncorrected frequentist tests, less conservative than multiplicity-corrected tests, and make explicit use of relevant biological information through specification of the prior distribution. In this article we use a Bayesian testing approach to screen a panel of genetic markers recorded in a randomized clinical trial of bupropion versus placebo for smoking cessation. From a panel of 59 single-nucleotide polymorphisms (SNPs) located on 11 candidate genes, we identify four SNPs (one each on CHRNA5 and CHRNA2 and two on CHAT) that appear to have pharmacogenetic relevance. Of these, the SNP on CHRNA5 is most robust to specification of the prior. An unadjusted frequentist test identifies seven SNPs, including these four, none of which remains significant upon correction for multiplicity. In a panel of 43 randomly selected control SNPs, none is significant by either the Bayesian or the corrected frequentist test., (2007 Wiley-Liss, Inc.)

Individuals belonging to six different Amerindian tribes and two African groups of Costa Rica were genotyped for factor V Leiden (FV), factor V haplotype HR2 (FV HR2), Factor II 20210G>A (FII), the methylenetetrahydrofolate reductase (MTHFR), factor VII polymorphisms (FVII IVS7, FVII R353Q), factor XIII (FXIII V34L), and the insertion/deletion (I/D) polymorphism of the gene of angiotensin converting enzyme (ACE). Clear differences in the prevalence were found and are first reported. The prevalence of some of the established genetic risk factors was low in Amerindians of Costa Rica (ACE) or even absent (FVL, FII), and others (MTHFR, FVHR2) had an extremely high prevalence. People of African origin carried very rare FVL or FII polymorphisms, but the DD genotype of ACE is the highest reported. Concerning the protective factors, the QQ genotype of FVII R353Q was absent in Amerindians, but the protective 7/7 genotype of FVII IVS7 frequently found. Novel alleles of FVII IVS7 (4, 8, and 9 monomers) were found. Intertribal heterogeneity was observed that may reflect the evolutionary history of these tribal groups and their admixture with other populations., (Copyright 2003 Wiley-Liss, Inc.)

Background: Discussions between the World Health Organization (WHO) and the International Society on Biomedical Research on Alcoholism (ISBRA) identified the need for a multiple-center international study on state and trait markers of alcohol abuse and alcohol dependence. The reasoning behind the generation of such a project included the need to understand the alcohol use characteristics of diverse populations and the performance of biological markers of alcohol use in a variety of settings throughout the world. A second major reason for initiating this study was to collect DNA for well-structured and stratified association studies between genetic markers and/or "candidate" genes and behavioral/physiological phenotypes of importance to predisposition to alcohol dependence., Methods: An extensive interview instrument was developed with leadership from the U.S. National Institute on Alcohol Abuse and Alcoholism (NIAAA). The instrument was translated from English to Finnish, French, German, Japanese, and Portuguese (Brazilian). One thousand eight hundred sixty-three subjects were recruited at five clinical centers (Montreal, Canada; Helsinki, Finland; Sapporo, Japan; São Paulo, Brazil; and Sydney, Australia). The subjects responded to the structured interview and provided blood and urine samples for biochemical analysis. This article focuses on the demographic characteristics of the study subjects, their drinking habits, alcohol-dependence characteristics, comorbid psychiatric and other drug variables, and predictors for seeking treatment for alcohol dependence. Multiple logistic regression models were constructed and used to explore variables that contribute to various levels of alcohol consumption, to a diagnosis of alcohol dependence, and to seeking treatment for alcohol dependence. ANOVA with post hoc comparisons, chi2, and Pearson moment calculations were used as necessary to assess additional relationships between variables., Results: A number of factors previously noted in disparate studies were confirmed in our analysis. Men consumed more alcohol than women, Asians consumed less alcohol than whites or Blacks, alcohol-dependent subjects consumed more alcohol than nondependent subjects, alcohol consumption increased with age, and an increased level of education (university or postgraduate education) reduced the percentage of such individuals in the category designated as heavy drinkers (>210 g alcohol/week) and in the group who were currently in treatment for dependence. However, our analysis allowed for much more detailed comparisons; for example, although men drank more than women on a g/day basis, the differences were less pronounced on g/kg/day basis, and alcohol-dependent women drank equal amounts of alcohol as alcohol-dependent men on a g/kg/day basis. Antisocial personality characteristics or reports of trouble sleeping when an individual stops drinking were associated with higher alcohol intake. The most important of the tested factors that contributed to a DSM-IV diagnosis of dependence, however, was the report of anxiety if an individual stopped drinking. In terms of the various criteria within the DSM-IV criteria for alcohol dependence, no one criterion seemed to be prominent for individuals who sought alcohol dependence treatment, but the higher the number of criteria met by the individual, the higher was the probability that he or she would be in treatment., Conclusions: This initial report is the beginning of the "data mining" of this rich data set. The cross-national/cross-cultural aspects of this study allowed for multiple comparisons of variables across several ethnic/racial groups and allowed for assessment of biochemical markers for alcohol intake and predisposition to alcohol dependence in diverse settings.

Background: The P300 (P3) component of the event related potential has been established as a sensitive risk marker of vulnerability to alcoholism. Most alcoholism studies have focused on men; recent studies indicate that women are equally vulnerable to developing alcoholism., Methods: Visual P3 recorded from 31 electrode positions was evaluated in 44 alcoholic and 60 control women, 24-50 years of age. P3 amplitudes and latencies of the two groups were statistically compared using Analysis of Variance; source localization of surface amplitude values from each group were plotted using a low-resolution brain electromagnetic tomography., Results: The results indicated that alcoholic women had significantly smaller P3 amplitudes in the frontal and central regions compared with controls. Source localization showed lowered activation in alcoholic women in right dorso-lateral prefrontal cortex and the ventro-medial fronto-central regions., Conclusions: The results suggest that P3 is an equally sensitive endophenotypic marker of vulnerability to alcoholism in women. The findings are discussed in terms of functional and physiologic significance of the P3 amplitude in alcoholic women and its relationship to drinking behaviors.

Objective: To determine whether polymorphism in the manganese superoxide dismutase (MnSOD) gene is associated with susceptibility or disease outcome in rheumatoid arthritis (RA)., Methods: We used a case-control approach with 153 RA patients and 218 control subjects to examine for any associations between MnSOD genotypes and susceptibility to RA. We also investigated the influence of genotypes on radiologic outcome, as measured using the Larsen score for radiographs of the hands and feet, and on functional outcome, as assessed by the Health Assessment Questionnaire. MnSOD typing was carried out using polymerase chain reaction-based methods. Results were analyzed using multiple regression analysis, with adjustment for age, sex, and disease duration. In separate analyses, we corrected for rheumatoid factor (RF) status and/or the presence of the HLA-DRB1 "shared epitope" (SE). We also examined whether radiologic outcome was influenced by interactions between MnSOD and glutathione S-transferase (GST) genes., Results: No association between MnSOD genotype and development of RA was found. The MnSOD VV genotype was associated with a significantly higher (P = 0.04) Larsen score (104.4) than MnSOD AA (83.0), while MnSOD AV was associated with an intermediate score (91.8). Correction for RF status had no significant effect on the results of the analysis, but significance was lost (P = 0.09) after correction for the presence of the SE. There was evidence of interaction between the GSTT1 and MnSOD genotypes, with the MnSOD VV/GSTT1-null combination being associated with the highest Larsen score (142.1; P = 0.007 after correction for the SE)., Conclusion: Polymorphism in the MnSOD gene is not associated with susceptibility to RA. Our data suggest that MnSOD VV is associated with more severe radiologic outcome, although this relationship may not be independent of the effect of the SE. However, interaction between MnSOD and GST genes appears to influence radiologic outcome independently of the SE.

Myostatin belongs to the transforming growth factor-beta superfamily, and is expressed specifically in developing and mature skeletal muscle. Myostatin appears to act as a negative regulator of muscle development, since mice with targeted disruption of this gene display a large increase in muscle mass. In this study, the porcine myostatin gene was mapped to chromosome 15q2.3 by fluorescence in situ hybridization. Myostatin was also positioned within the chromosome 15 linkage group using both a polymorphism located in the second intron and an associated microsatellite. The development of highly polymorphic markers associated with myostatin will support population studies to identify alleles of this gene that affects muscle mass and/or fat deposition in swine.