Distinct resistance mutation and polymorphism acquisition in HIV-1 protease of subtypes B and F1 from children and adult patients under virological failure

The goal of this work was to compare the differences between human immunodeficiency Virus type 1 (HIV-1) of B and F1 Subtypes in the acquisition of major and rninot- protease inhibitor (P1)-associated resistance mutations and of other polymorphisms at the protease (PR) gene, through a cross sectional Study. PR sequences from subtypes B and F1 isolates matched according to P1 exposure time from Brazilian patients were included in this study. Sequences were separated in four groups: 24 and 90 from children and 141 and 99 from adults infected with isolates of subtypes F1 and B, respectively. For comparison, 211 subype B and 79 subtype F1 PR sequences from drug-naive individuals Were included. Demographic and clinical data were similar among B- and F1-infected patients. In untreated patients, Mutations L1OV, K20R, and M361 were more frequent in subtype F1, while L63P, A7IT, and V771 were more prevalent in Subtype B. In treated patients, K20M, D30N, G73S, 184V, and L90M, were More prevalent in subtype B, and K20T and N88S Were more prevalent in Subtype F1. A higher proportion of subtype F1 than Of subtype B Strains Containing other polymorphisms was observed. V82L mutation was Present With increased frequency in isolates from children compared to isolates from adults infected with both subtypes. We could observe a faster resistance emergence in children than in adults, during treatment with protease inhibitors. This data provided evidence that, although rates of overall drug resistance do not differ between subtypes B and F1, the former accumulates resistance at higher proportion in specific amino acid positions of protease when compared to the latter. (c) 2008 Elsevier B.V. All rights reserved.

Evaluation of anti-inflammatory activity of derivatives from aerial parts of Baccharis uncinella

Context: Species of Baccharis exhibit antibiotic, antiseptic, and wound-healing properties, and have been used in the traditional medicine of South America for the treatment of inflammation, headaches, diabetes, and hepatobiliary disorders. Objective: To investigate the anti-inflammatory activity of organic phases from EtOH extract of the aerial parts of Baccharis uncinella DC (Asteraceae). Materials and methods: The crude EtOH extract from the aerial parts of B. uncinella was subjected to partition procedures and the corresponding CH(2)Cl(2) and EtOAc phases were subjected to several chromatographic separation procedures. Thus, these phases and their purified compounds were assayed for evaluation of anti-inflammatory activity. Results: The CH(2)Cl(2) phase from EtOH extract from B. uncinella contained two triterpenoids (oleanolic and ursolic acids) and one flavonoid (pectolinaringenin), whereas the respective EtOAc phase showed to be composed mainly by two phenylpropanoid derivatives (caffeic and ferulic acids). The CH(2)Cl(2) and EtOAc phases as well as their isolated compounds exhibited anti-inflammatory effects against inflammatory reactions induced by phospholipase A2 (from Crotalus durissus terrificus venom) and by carrageenan. Discussion and conclusion: The results suggested that the components obtained from partition phases of EtOH extract of B. uncinella could represent lead molecules for the development of anti-inflammatory agents. Additionally, the results confirmed the use of Baccharis genus in the traditional medicine of South America for the treatment of inflammation and other heath disorders. To date, the present work describes for the first time the anti-inflammatory effects of compounds isolated from B. uncinella.

Nomenclature for congenital and paediatric cardiac disease: Historical perspectives and The International Pediatric and Congenital Cardiac Code

Clinicians working in the field of congenital and paediatric cardiology have long felt the need for a common diagnostic and therapeutic nomenclature and coding system with which to classify patients of all ages with congenital and acquired cardiac disease. A cohesive and comprehensive system of nomenclature, suitable for setting a global standard for multicentric analysis of outcomes and stratification of risk, has only recently emerged, namely, The International Paediatric and Congenital Cardiac Code. This review, will give an historical perspective on the development of systems of nomenclature in general, and specifically with respect to the diagnosis and treatment of patients with paediatric and congenital cardiac disease. Finally, current and future efforts to merge such systems into the paperless environment of the electronic health or patient record on a global scale are briefly explored. On October 6, 2000, The International Nomenclature Committee for Pediatric and Congenital Heart Disease was established. In January, 2005, the International Nomenclature Committee was constituted in Canada as The International Society for Nomenclature of Paediatric and Congenital Heart Disease. This International Society now has three working groups. The Nomenclature Working Group developed The International Paediatric and Congenital Cardiac Code and will continue to maintain, expand, update, and preserve this International Code. It will also provide ready access to the International Code for the global paediatric and congenital cardiology and cardiac surgery communities, related disciplines, the healthcare industry, and governmental agencies, both electronically and in published form. The Definitions Working Group will write definitions for the terms in the International Paediatric and Congenital Cardiac Code, building on the previously published definitions from the Nomenclature Working Group. The Archiving Working Group, also known as The Congenital Heart Archiving Research Team, will link images and videos to the International Paediatric and Congenital Cardiac Code. The images and videos will be acquired from cardiac morphologic specimens and imaging modalities such as echocardiography, angiography, computerized axial tomography and magnetic resonance imaging, as well as intraoperative images and videos. Efforts are ongoing to expand the usage of The International Paediatric and Congenital Cardiac Code to other areas of global healthcare. Collaborative efforts are under-way involving the leadership of The International Nomenclature Committee for Pediatric and Congenital Heart Disease and the representatives of the steering group responsible for the creation of the 11th revision of the International Classification of Diseases, administered by the World Health Organisation. Similar collaborative efforts are underway involving the leadership of The International Nomenclature Committee for Pediatric and Congenital Heart Disease and the International Health Terminology Standards Development Organisation, who are the owners of the Systematized Nomenclature of Medicine or ""SNOMED"". The International Paediatric and Congenital Cardiac Code was created by specialists in the field to name and classify paediatric and congenital cardiac disease and its treatment. It is a comprehensive code that can be freely downloaded from the internet (http://www.IPCCC.net) and is already in use worldwide, particularly for international comparisons of outcomes. The goal of this effort is to create strategies for stratification of risk and to improve healthcare for the individual patient. The collaboration with the World Heath Organization, the International Health Terminology Standards Development Organisation, and the healthcare Industry, will lead to further enhancement of the International Code, and to Its more universal use.

Isolation and partial characterization of Brazilian samples of feline immunodeficiency virus

Feline immunodeficiency virus (FIV) causes a slow progressive degeneration of the immune system which eventually leads to a disease comparable to acquired immune deficiency syndrome (AIDS) in humans. FIV has extensive sequence variation, a typical feature of lentiviruses. Sequence analysis showed that diversity was not evenly distributed throughout the genome, but was greatest in the envelope gene, env. The virus enters host cells via a sequential interaction, initiated by the envelope glycoprotein (env) binding the primary receptor molecule CD134 and followed by a subsequent interaction with chemokine co-receptor CXCR4. The purpose of this study was to isolate and characterize isolates of FIV from an open shelter in Sao Paulo, Brazil. The separated PBMC from 11 positive cats were co-cultured with MYA-1 cells. Full-length viral env glycoprotein genes were amplified and determined. Chimeric feline x human CD134 receptors were used to investigate the receptor utilization of 17 clones from Brazilian isolates of Fly. Analyses of the sequence present of molecular clones showed that all clones grouped within subtype B. In contrast to the virulent primary isolate FIV-GL8, expression of the first cysteine-rich domain (CRD1) of feline CD134 in the context of human CD134 was sufficient for optimal receptor function for all Brazilian FIV isolates tested. (C) 2011 Elsevier B.V. All rights reserved.

Height discordance in monozygotic females is not attributable to discordant inactivation of X-linked stature determining genes

We tested the hypothesis that X-linked genes determining stature which are subject to skewed or non-random X-inactivation can account for discordance in height in monozygotic female twins. Height discordant female monozygotic adult twins (20 pairs) were identified from the Australian Twin Registry, employing the selection criteria of proven monozygosity and a measured height discordance of at least 5 cm. Differential X-inactivation was examined in genomic DNA extracted from peripheral lymphocytes by estimating differential methylation of alleles at the polymorphic CAG triplet repeat of the Androgen receptor gene (XAR). There were 17/20 MZ pairs heterozygous at this locus and informative for analysis. Of these, 10/17 both had random X-inactivation, 5/17 showed identical X-inactivation patterns of non random inactivation and 2/17 (12%) showed discordant X-inactivation. There was no relationship between inactivation patterns and self-report chorionicity. We conclude that non-random X-inactivation does not appear to be a major contributor to intra-pair height discordance in female MZ twins.

Phenotypic and genetic analyses of a short measure of psychosis-proneness in a large-scale Australian twin study

Previous genetic analyses of psychosis proneness have been limited by their small sample size. For the purposes of large-scale screening, a 12-item questionnaire was developed through a two-stage process of reduction from the full Chapman and Chapman scales. 3685 individuals (including 1438 complete twin pairs) aged 18–25 years and enrolled in the volunteer Australian Twin Registry returned a mail questionnaire which included this psychosis proneness scale and the Eysenck Personality Questionnaire. Despite the brevity of the questionnaire, item and factor analysis identified four unambiguous and essentially uncorrelated scales. There were (1) Perceptual Aberration – Magical Ideation; (2) Hypomania – Impulsivity/Nonconformity; (3) Social Anhedonia and (4) Physical Anhedonia. Model-fitting analyses showed additive genetic and specific environmental factors were sufficient for three of the four scales, with the Social Anhedonia scale requiring also a parameter for genetic dominance. There was no evidence for the previously hypothesised sex differences in the genetic determination of psychosis-proneness. The potential value of multivariate genetic analysis to examine the relationship between these four scales and dimensions of personality is discussed. The growing body of longitudinal evidence on psychosis-proneness suggests the value of incorporating this brief measure into developmental twin studies.

Natural selection and quantitative genetics of life-history traits in Western women: A twin study

Whether contemporary human populations are still evolving as a result of natural selection has been hotly debated. For natural selection to cause evolutionary change in a trait, variation in the trait must be correlated with fitness and be genetically heritable and there must be no genetic constraints to evolution. These conditions have rarely been tested in human populations. In this study, data from a large twin cohort were used to assess whether selection Will cause a change among women in contemporary Western population for three life-history traits: age at menarche, age at first reproduction, and age at menopause. We control for temporal variation in fecundity (the baby boom phenomenon) and differences between women in educational background and religious affiliation. University-educated women have 35% lower fitness than those with less than seven years education, and Roman Catholic women have about 20% higher fitness than those of other religions. Although these differences were significant, education and religion only accounted for 2% and 1% of variance in fitness, respectively. Using structural equation modeling, we reveal significant genetic influences for all three life-history traits, with heritability estimates of 0.50, 0.23, and 0.45, respectively. However, strong genetic covariation with reproductive fitness could only be demonstrated for age at first reproduction, with much weaker covariation for age at menopause and no significant covariation for age at menarche. Selection may, therefore, lead to the evolution of earlier age at first reproduction in this population. We also estimate substantial heritable variation in fitness itself, with approximately 39% of the variance attributable to additive genetic effects, the remainder consisting of unique environmental effects and small effects from education and religion. We discuss mechanisms that could be maintaining such a high heritability for fitness. Most likely is that selection is now acting on different traits from which it did in pre-industrial human populations.

Genetic and environmental contributions to educational attainment in Australia

The genetic and environmental contributions to educational attainment in Australia are examined using a multiple regression model drawn from the medical research literature. Data from a large sample of Australian twins are analysed. The findings indicate that at least as much as 50 percent and perhaps as much as 65 percent of the variance in educational attainments can be attributed to genetic endowments. It is suggested that only around 25 percent of the variance in educational attainments may be due to environmental factors, though this contribution is shown to be around 40 percent when adjustments for measurement error and assortative mating are made. The high fraction of the observed variation in educational attainments due to genetic differences is consistent with results reported by Heath et al. (Heath, A.C., Berg, K., Eaves, L.J., Solaas, M.H., Corey, L.A., Sundet, J., Magnus, P., Nance, W.E., 1985. Education policy and the heritability of educational attainment. Nature 314(6013), 734-736.), Tambs et al. (Tambs, K., Sundet, J.M., Magnus, P., Berg, K., 1989. Genetic and environmental contributions to the covariance between occupational status, educational attainment and IQ: a study of twins. Behavior Genetics 19(2), 209-222.), Vogler and Fulker (Vogler, G.P., Fulker, D.W., 1983. Familial resemblance for educational attainment. Behavior Generics 13(4), 341-354.) and Behrman and Taubman (Behrman, J., Taubman, P., 1989. Is schooling mostly in the genes? Nature-nurture decomposition using data on relatives. Journal of Political Economy 97(6), 1425-1446.), suggesting that the finding is robust. (C) 2001 Elsevier Science Ltd. All rights reserved.

Towards a molecular epidemiology of alcohol dependence analysing the interplay of genetic and environmental risk factors

Background Progress in identifying genetic factors protective against alcohol dependence (AlcD) requires a paradigm shift in psychiatric epidemiology. Aims To integrate analysis of research into the genetics of alcoholism. Method Data from prospective questionnaire and interview surveys of the Australian twin panel, and from a subsample who underwent alcohol challenge, were analysed. Results In men, effects of alcohol dehydrogenase ADH2*1/*2 genotype or high alcohol sensitivity (risk-decreasing), and of history of childhood conduct disorder, or having monozygotic co-twin or twin sister with AlcD (risk-increasing) were significant and comparable in magnitude. Religious affiliation (Anglican versus other) was associated with the ADH2 genotype, but did not explain the associations with AlcD symptoms. No protective effect of the ADH2*1/*2 genotype was observed in women. Conclusions The early onset and strong familial aggregation of AlcD, and opportunity for within-family tests of genetic association to avoid confounding effects, make epidemiological family studies of adolescents and young adults and their families a priority.

An integrative approach for studying the etiology of alcoholism and other addictions

Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.

The influence of genetic and environmental factors in estimations of current body size, desired body size, and body dissatisfaction

The objective was to investigate the genetic epidemiology of figural stimuli. Standard figural stimuli were available from 5,325 complete twin pairs: 1,751 (32.9%) were monozygotic females, 1,068 (20.1%) were dizygotic females, 752 (14.1%) were monozygotic males, 495 (9.3%) were dizygotic males, and 1,259 (23.6%) were dizygotic male-female pairs. Univariate twin analyses were used to examine the influences on the individual variation in current body size and ideal body size. These data were analysed separately for men and women in each of five age groups. A factorial analysis of variance, with polychoric correlations between twin pairs as the dependent variable, and age, sex, zygosity, and the three interaction terms (age x sex, age x zygosity, sex x zygosity) as independent variables, was used to examine trends across the whole data set. Results showed genetic influences had the largest impact on the individual variation in current body size measures, whereas non-shared environmental influences were associated with the majority of individual variation in ideal body size. There was a significant main effect of zygosity (heritability) in predicting polychoric correlations for current body size and body dissatisfaction. There was a significant main effect of gender and zygosity in predicting ideal body size, with a gender x zygosity interaction. In common with BMI, heritability is important in influencing the estimation of current body size. Selection of desired body size for both men and women is more strongly influenced by environmental factors.

The genetic and environmental relationship between the interpersonal sensitivity measure (IPSM) and the personality dimensions of Eysenck and Cloninger

A shortened version of the Interpersonal Sensitivity Measure (IPSM) developed to predict depression prone personalities was administered in a self-report questionnaire to a community-based sample of 3269 Australian twin pairs aged 18-28 years, along with Eysenck's EPQ and Cloninger's TPQ. The IPSM included four sub-scales: Separation Anxiety (SEP); Interpersonal Sensitivity (INT); Fragile Inner-Self (FIS); and Timidity (TIM). Univariate analysis revealed that individual differences in the IPSM sub-scale scores were best explained by additive genetic and specific environmental effects. Confirming previous research findings, familial aggregation for the EPQ and TPQ personality dimensions was entirely due to additive genetic effects. In the multivariate case, a model comprising additive genetic and specific environmental effects best explained the covariation between the latent factors for male and female twin pairs alike. The EPQ and TPQ dimensions accounted for moderate to large proportions of the genetic variance (40-76%) in the IPSM sub-scales, while most of the non-shared environment variance was unique to the IPSM sub-scales. (C) 2001 Elsevier Science Ltd. All rights reserved.

Variation in Alcohol Pharmacokinetics as a Risk Factor for Alcohol Dependence

Background: The significant association between alcohol dehydrogenase (ADH)-2 genotype and alcohol-dependence risk, demonstrated in both Asian and non-Asian populations, suggests a link between the metabolism of alcohol (ethanol) and individual differences in susceptibility to dependence. Methods: We tested this hypothesis by following up on subjects who took part in the Alcohol Challenge Twin Study conducted in 1979-1981 and comparing the blood and breath alcohol results in that study between subjects who subsequently did or did not meet diagnostic criteria for lifetime alcohol dependence in 1992-1993. Results: Subjects who met DSM-III-R criteria for lifetime alcohol dependence at follow-up had higher blood and breath alcohol values after alcohol challenge than never-dependent subjects. Multivariate analysis showed independent effects of susceptibility to alcohol dependence and smoking status on blood alcohol concentrations, whereas habitual alcohol intake at the time of the initial study had marginally significant effects. The risk of alcohol dependence was 2-fold higher in men and 3-fold higher in women with blood or breath alcohol concentrations in the highest quartile than in the lowest quartile. Conclusions: In view of this association and the known genetic influences on both alcohol pharmacokinetics and alcohol dependence, it is probable that part of the heritability of dependence is mediated by genes (other than the known ADH2 and ADH3 polymorphisms) affecting alcohol metabolism.