PM2.5 as a marker of exposure to tobacco smoke and other sources of particulate matter in Cairo, Egypt.

SETTING: Cairo and Giza governorates of Egypt. BACKGROUND: Particulate matter under 2.5 µm in diameter (PM2.5) arises from diverse sources, including tobacco smoke from cigarettes and waterpipes, and is recognized as a cause of acute and chronic morbidity and mortality. OBJECTIVE: To measure PM2.5 in workplaces with different intensities of smoking and varying levels of smoking restrictions. DESIGN: We conducted an air sampling study to measure PM2.5 levels in a convenience sample of indoor and outdoor venues in 2005-2006. RESULTS: Using a calibrated SidePak instrument, 3295 individual measurements were collected at 96 venues. Compared to indoor venues where tobacco smoking was banned (PM2.5 levels 72-81 µg/m(3)), places offering waterpipes to patrons of cafes (478 µg/m(3)) and Ramadan tents (612 µg/m(3)) had much higher concentrations, as did venues such as public buildings with poor enforcement of smoking restrictions (range 171-704 µg/m(3)). Both the number of waterpipe smokers and the number of cigarette smokers observed at each venue contributed significantly to the overall burden of PM2.5. CONCLUSION: Such data will support smoke-free policies and programs aimed specifically at reducing environmental tobacco exposure and improving air quality in general, and will provide a baseline for monitoring the impact of tobacco control policies.

Radical acylation of L-lysine derivatives and L-lysine-containing peptides by peroxynitrite-treated diacetyl and methylglyoxal.

Highly electrophilic α-dicarbonyls such as diacetyl, methylglyoxal, 3-deoxyglucosone, and4,5-dioxovaleric acid have been characterized as secondary catabolites that can aggregate proteins and form DNA nucleobase adducts in several human maladies, including Alzheimer's disease, rheumatoid arthritis, diabetes, sepsis, renal failure, and respiratory distress syndrome. In vitro, diacetyl and methylglyoxal have also been shown to rapidly add up the peroxynitrite anion (k2 ~ 10(4)-10(5) M(-1) s(-1)), a potent biological nucleophile, oxidant and nitrosating agent, followed by carbon chain cleavage to carboxylic acids via acetyl radical intermediate that can modify amino acids. In this study, we used the amino acid derivatives Ac-Lys-OMe and Z-Lys-OMe and synthesized the tetrapeptides H-KALA-OH, Ac-KALA-OH, and H-K(Boc)ALA-OH to reveal the preferential Lys amino group targeted by acyl radical generated by the α-dicarbonyl/peroxynitrite system. The pH profiles of the reactions are bell-shaped, peaking at approximately 7.5; hence, they are close to the pKa values of ONOOH and of the catalytic H2PO4(-) anion. RP-HPLC and ESI-MS analyses of reaction products confirmed (α)N- and (ϵ)N-acetylation of Lys by diacetyl as well as acetylation and formylation by methylglyoxal, with preference for the α-amino group. These data suggest the possibility of radical acylation of proteins in epigenetic processes, where enzymatic acetylation of these biomolecules is a well-documented event, recently reported to be as critical to the cell cycle as phosphorylation. Also noteworthy is the observed formylation of L-Lys containing peptides by methylglyoxal never reported to occur in amino acid residues of peptides and proteins.

[Radiobiological Human Tissue repository: progress and perspectives for solving the problems of radiation safety and health protection of personnel and population].

Radiobiological Human Tissue repository was established in order to obtain and store biological material from Mayak PA workers occupationally exposed to ionizing (α- and/or γ-) radiation in a wide dose range, from the residents exposed to long term radiation due to radiation accidents and transfer of the samples to scientists for the purpose of studying the effects of radiation for people and their offspring. The accumulated biomaterial is the informational and research potential that form the basis for the work of the scientists in different spheres of biology and medicine. The repository comprises 5 sections: tumor and non-tumor tissues obtained in the course of autopsies, biopsies, surgeries, samples of blood and its components, of DNA, induced sputum, saliva, and other from people exposed or unexposed (control) to radiation. The biomaterial is stored in formalin, in paraffin blocks, slides, as well as in the freezers under low temperatures. All the information on the samples and the registrants (medical, dosimetry, demographic, and occupational data) was obtained and entered into the electronic database. A constantly updated website of the repository was developed in order to provide a possibility to get acquainted with the material and proceed with application for biosamples for scientists from Russia and abroad. Some data obtained in the course of scientific research works on the basis of the biomaterial from the Repository are briefly introduced in the review.

Identifying early events of gene expression in breast cancer with systems biology phylogenetics.

Advanced omics technologies such as deep sequencing and spectral karyotyping are revealing more of cancer heterogeneity at the genetic, genomic, gene expression, epigenetic, proteomic, and metabolomic levels. With this increasing body of emerging data, the task of data analysis becomes critical for mining and modeling to better understand the relevant underlying biological processes. However, the multiple levels of heterogeneity evident within and among populations, healthy and diseased, complicate the mining and interpretation of biological data, especially when dealing with hundreds to tens of thousands of variables. Heterogeneity occurs in many diseases, such as cancers, autism, macular degeneration, and others. In cancer, heterogeneity has hampered the search for validated biomarkers for early detection, and it has complicated the task of finding clonal (driver) and nonclonal (nonexpanded or passenger) aberrations. We show that subtyping of cancer (classification of specimens) should be an a priori step to the identification of early events of cancers. Studying early events in oncogenesis can be done on histologically normal tissues from diseased individuals (HNTDI), since they most likely have been exposed to the same mutagenic insults that caused the cancer in their neighboring tissues. Polarity assessment of HNTDI data variables by using healthy specimens as outgroup(s), followed by the application of parsimony phylogenetic analysis, produces a hierarchical classification of specimens that reveals the early events of the disease ontogeny within its subtypes as shared derived changes (abnormal changes) or synapomorphies in phylogenetic terminology.

Assessment of tobacco dependence in waterpipe smokers in Egypt.

SETTING: Waterpipe smoking is increasing worldwide. Nevertheless, little is known about nicotine dependence in tobacco smokers who use waterpipes. OBJECTIVE: To assess evidence of dependence among non-cigarette smoking waterpipe smokers in Egypt. METHODS: A total of 154 male exclusive current waterpipe smokers were enrolled for the present study. We adapted the Fagerström test for nicotine dependence and the Reasons for Smoking (RFS) scales and related these to smoking behavior. RESULTS: The mean age of the subjects was 47 ± 14 years, the mean age at smoking initiation was 22 ± 9 years, and average daily consumption was 4 ± 8 hagars (tobacco units). The time to the first smoke of the day (P < 0.001), smoking even when ill (P = 0.003), time to tobacco craving (P < 0.001), and hating to give up the first smoke of the day (P = 0.033) were each significantly associated with the number of hagars smoked per day. The RFS subscales of addictive smoking, smoking to relieve negative affect, and smoking for stimulation were also associated with these variables. CONCLUSION: The overall findings suggest that waterpipe smokers exhibit many of the same features of nicotine dependency attributed to cigarette smokers.

Peak selection from MALDI-TOF mass spectra using ant colony optimization.

MOTIVATION: Due to the large number of peaks in mass spectra of low-molecular-weight (LMW) enriched sera, a systematic method is needed to select a parsimonious set of peaks to facilitate biomarker identification. We present computational methods for matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) spectral data preprocessing and peak selection. In particular, we propose a novel method that combines ant colony optimization (ACO) with support vector machines (SVM) to select a small set of useful peaks. RESULTS: The proposed hybrid ACO-SVM algorithm selected a panel of eight peaks out of 228 candidate peaks from MALDI-TOF spectra of LMW enriched sera. An SVM classifier built with these peaks achieved 94% sensitivity and 100% specificity in distinguishing hepatocellular carcinoma from cirrhosis in a blind validation set of 69 samples. Area under the receiver operating characteristic (ROC) curve was 0.996. The classification capability of these peaks is compared with those selected by the SVM-recursive feature elimination method. AVAILABILITY: Supplementary material and MATLAB scripts to implement the methods described in this article are available at http://microarray.georgetown.edu/web/files/bioinf.htm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A cluster of hypoplastic left heart malformation in Baltimore, Maryland.

Congenital cardiovascular malformations (CCVMs) of the left side of the heart show familial recurrence of various forms of obstructive malformations, including hypoplastic left heart (HLH), interrupted aortic arch, coarctation of the aorta, and aortic stenosis. In a previous population-based study in the Baltimore-Washington region, these malformations were associated with parental reports of occupational or leisure solvent exposure, overt diabetes, and family history of CCVM in first-degree relatives. Spatial analysis in this well-characterized study population may augment self-reported data by revealing additional associations with potential environmental risk factors. We used spatial analysis to identify clusters of HLH as a group. The study population included all live-born cases of hypoplastic left heart syndrome diagnosed in the first year of life between 1981 and 1989 and a random sample of unaffected infant controls matched by year and hospital of birth. The nested case-control cohort in this spatial analysis included 77 HLH cases and 1894 controls in Maryland and the District of Columbia. Nonparametric and regression analyses included personal variables from the interview data set as well as spatial variables. A region of Baltimore was identified that contained HLH at twice the expected frequency based on the distribution of population younger than 5 years of age. The region included 30 of 77 geocoded cases of HLH in the cohort and is significant by spatial scanning at p = 0.056. Within this region, male cases of HLH were disproportionately present compared to females. This cluster is in a region of Baltimore with industrial release of solvents, dioxin, and polychlorinated biphenyls in air. Outside the cluster, HLH is associated with family history of CCVM in a first-degree relative, maternal exposure to miscellaneous solvents, paternal anesthesia, maternal art painting, aspirin ingestion, and maternal diabetes. Inside the cluster, father's painting and exposure to sympathomimetic drugs were associated risk factors. Spatial analysis of HLH cases delineated an urban region with increased prevalence of this left heart malformation. Within this region, excess male cases of HLH occurred, and industrial release to air of solvents, dioxin, and polychlorinated biphenyl compounds was documented. We propose that both genetic and environmental factors contribute to the phenotype of HLH.

A population-based study of coarctation of the aorta: comparisons of infants with and without associated ventricular septal defect.

BACKGROUND: Coarctation of the aorta (CoA) is a congenital cardiovascular malformation (CCVM) sometimes associated with ventricular septal defect (VSD). Although the phenotypic association is well documented, little research exists on the epidemiological features distinguishing CoA with and without VSD. METHODS: The Baltimore-Washington Infant Study (1981-1989), a population-based study of CCVM, evaluated 126 infants with "pure" CoA (free of associated cardiac defects) and 67 infants with CoA and VSD (COA/VSD) in comparison to 3,572 controls. RESULTS: The proportion of infants with associated extracardiac anomalies was greater among CoA/VSD than among pure CoA (31% versus 11%). Infants with CoA/VSD were twice as likely as those with pure CoA to be born small for gestational age (23% versus 12%, respectively, compared with 6% of controls). All-cause mortality during the first year of life was higher in CoA/VSD than in pure CoA (21% vs. 7%). Multiple logistic regression models revealed that family history of CCVM was associated with pure CoA (adjusted case-control odds ratio [OR] = 4.6; 99% confidence interval [CI] = 1.5-13.9) and with CoA/VSD (OR = 5.9, CI = 1.2-23.5); maternal history of organic solvent exposures early in pregnancy was also associated with pure CoA (OR = 3.2, CI = 1.0-10.2) and with CoA/VSD (OR = 3.7, CI 0.9-14.9). Additional risk factors, including maternal epilepsy (OR = 5.3, CI = 0.9-30.6), and use of macrodantin (OR = 6.7, CI = 1.4-31.8) were associated only with pure CoA. CONCLUSIONS: These findings highlight possible genetic and environmental differences between pure CoA and CoA/VSD and may stimulate further investigations of the etiology of CoA.

Vitamin A and cardiac outflow tract defects.

To assess the relationship between maternal intake of vitamin A and cardiac outflow tract defects, we examined data from a population-based case-control study among liveborn infants born from 1987 through 1989 to mothers residing in the Baltimore-Washington area. Case infants (126) had a nonsyndromic cardiac outflow tract defect. Control infants (679) did not have birth defects and were a stratified random sample of liveborn infants from the same area. The main exposure was average daily maternal intake of retinol and provitamin A carotenoids from foods and supplements during the year before conception. Compared with an average intake of less than 10,000 IU, retinol intake of 10,000 IU or more from supplements was associated with a ninefold increased risk for transposition of the great arteries (odds ratio = 9.2; 95% confidence interval = 4.0-21.2), but not for outflow tract defects with normally related arteries (odds ratio = 0.8; 95% confidence interval = 0.1-6.6). Similar intakes of carotenoids and dietary retinol were not associated with an increased risk for either type of outflow tract defect.

Maternal diabetes: an independent risk factor for major cardiovascular malformations with increased mortality of affected infants.

BACKGROUND: Intensive medical care of women with diabetes has reduced their risks of bearing infants with congenital anomalies. To assess the preventive potential of preconceptional care, the data of a population-based study of cardiovascular malformations (CVM) were analyzed to determine the morphogenetic specificity of maternal diabetes risks, the morbidity and mortality of the infants, and maternal characteristics that might affect these risks. METHODS: The Baltimore-Washington Infant Study was a case-control study (1981-1989) that included all live born infants with confirmed CVM; control infants were a representative sample of the birth cohort. A questionnaire administered in home visits recorded parental information on social, medical, occupational, and environmental factors. For these analyses of preconceptional diabetes risks, the case group excluded chromosomal and mendelian disorders and was divided into 3 developmental categories and 12 diagnostic groups. RESULTS: Preconceptional maternal diabetes was strongly associated with CVM of early embryonic origin (odds ratio [OR] = 4.7, 95% confidence interval [CI] 2.8-7.9) and with cardiomyopathy (OR = 15.1, 95% CI 5.5-41.3), but not with obstructive and shunting defects (OR = 1.4, 95% CI 0.7-3.0). There was heterogeneity within these developmental categories: among laterality defects, diabetes was associated only with cardiovisceral and atrioventricular discordance (OR = 10.0, 95% CI 3.7-27.0); among outflow tract anomalies, the risk was strongly associated with normally related great arteries (OR = 6.6, 95% CI 3.2-13.3) but not with simple transpositions; and among atrioventricular septal defects, diabetes was associated with the complete but not with the partial forms (OR = 22.8, 95% CI 7.4-70.5). The association in early CVM was strongest among infants with multisystem, predominantly VACTERL, anomalies. All-cause mortality of infants with CVM was 39% among those with diabetic mothers and 17.8% in those with nondiabetic mothers. Deceased infants of diabetic mothers were also more likely to have extracardiac anomalies (P = 0.041), to be born prematurely (P = 0.007), and to have low birth weight (P = 0.011). Multivariate analyses of maternal factors revealed no significant confounders of the diabetes associations. CONCLUSIONS: The evidence of diabetes-induced major cardiac defects is of urgent clinical significance. The effectiveness of early preconceptional care in the prevention of congenital anomalies has been demonstrated repeatedly.

Association of transposition of the great arteries in infants with maternal exposures to herbicides and rodenticides.

The Baltimore-Washington Infant Study, a case-control study of congenital heart defects in liveborn infants conducted in 1981--1989, interviewed parents about a wide range of environmental exposures that occurred during and before the pregnancy. In the period 1987--1989, the questionnaire was expanded to include a detailed inquiry about exposures to pesticides. An analysis of these latter data revealed an association of maternal exposure to any pesticides during the first trimester with transposition of the great arteries in their infants (TGA; n = 66 infants), relative to 771 control infants, with an odds ratio of 2.0 (95% confidence interval (CI): 1.2, 3.3). No other heart defects were associated with pesticides. When analyzed by type of pesticide and adjusted for covariates, there were associations of TGA with maternal exposures to herbicides (odds ratio (OR) = 2.8; 95% CI: 1.3, 7.2) and to rodenticidal chemicals (OR = 4.7; 95% CI: 1.4, 12.1) but not to insecticides (OR = 1.5; 95% CI: 0.9, 2.6). No data were collected on specific chemicals or brand names. These results raise new questions about the possible epidemiologic association of TGA with some classes of pesticides and warrant new, carefully targeted investigations.

Atrioventricular septal defects: possible etiologic differences between complete and partial defects.

BACKGROUND: Recent advances in clinical, pathological, and genetic aspects of atrioventricular septal defects (AVSD) have set the stage for epidemiologic investigations into possible risk factors. Previous analyses of the total case group of AVSD included complete and partial subtypes without analysis of the subsets. METHODS: To address the question of possible morphogenetic heterogeneity of AVSD, the Baltimore-Washington Infant Study data on live-born cases and controls (1981-1989) was reanalyzed for potential environmental and genetic risk-factor associations in complete AVSD (n = 213), with separate comparisons to the atrial (n = 75) and the ventricular (n = 32) forms of partial AVSD. RESULTS: Complete and ventricular forms of AVSD had a similar proportion of isolated cases (12.2% and 15.6%, respectively, without associated extracardiac anomalies) and high rates of Down syndrome, whereas the atrial form of partial AVSD included 55% isolated cases. Trisomy 18 occurred in 22% of infants with the ventricular form, compared with <2% in the other AVSD groups. Analysis of potential risk factors revealed further distinctions. Complete AVSD as an isolated cardiac defect was strongly associated with maternal diabetes (odds ratio [OR] = 20.6; 95% confidence interval [CI] =5.6-76.4) and also with antitussive use (OR = 8.8; CI = 1.2-48.2); there were no strong associations other than maternal age among Down syndrome infants with this type of heart defect. Isolated cases with the atrial type of partial AVSD were associated with a family history of heart defects (OR = 6.2; CI = 1.4-24.4) and with paternal occupational exposures to ionizing radiation (OR = 5.1; CI = 1.4-27.4), but no risk factors were associated with Down syndrome. There were no significant associations of any risk factors in the numerically small subsets of isolated and Down syndrome cases with the ventricular form of partial AVSD. CONCLUSIONS: These results indicate a similar risk profile of complete AVSD and the ventricular type of partial AVSD, with a possible subset of the latter due to trisomy 18. Maternal diabetes constituted a potentially preventable risk factor for the most severe, complete form of AVSD.

Interrupted aortic arch: an epidemiologic study.

BACKGROUND: Interruption of the aortic arch (IAA) is a rare but severe anomaly associated with major intracardiac defects and with multisystem noncardiac malformations, recently linked to chromosome deletion of 22q11.2. METHODS: The Baltimore-Washington Infant Study (1981-1989), a population-based epidemiologic study of cardiovascular malformations, evaluated 53 infants with IAA in comparison with 3,572 controls. Risk factors for the anatomic subtypes were evaluated in 14 cases of IAA type A and 32 cases of IAA type B, but no molecular genetic tests were available. The distribution of associated cardiac defects was similar for both types. RESULTS: DiGeorge syndrome (DGS) occurred more frequently in IAA type B. Case-control comparisons demonstrated that infants in both groups were growth retarded at birth. A family history of noncardiac defects occurred only in IAA type B cases and included relatives with cleft lip and/or cleft palate. Candidate risk factors were associated only in type B cases and differed for those with (n = 10) and for those without (n = 19) DGS: a family history of noncardiac defects (odds ratio [OR] = 7.2, 95% confidence interval [CI] = 1.5-39.2) and maternal use of aspirin during the critical period (OR = 4.8, 95% CI = 1.3-25.4) occurred with DGS, while previous stillbirth (OR = 9.4, 95% CI = 1.3-53.1), bleeding during pregnancy (OR = 3.7, 95% CI = 1.4-11.4), and maternal exposure to arts/crafts paints (OR = 4.8, 95% CI = 1.3-17.4) were associated in those without DGS. CONCLUSIONS: These findings confirm the heterogeneity of IAA and of the type B subtype. Risk factors specific for cases with DGS may open a window to further investigations of the etiology of IAA and of the associated molecular genetic abnormalities.

Epidemiology of cardiovascular malformations: prevalence and risk factors.

Epidemiological approaches to the study of cardiovascular malformations (CVMs) face challenges of disease definition, nomenclature, changing diagnostic methodologies, the rarity of the disease in the general population, and the incorporation of current knowledge on genetics and morphogenesis into designing studies to investigate risk factors and implement preventive strategies. Previous studies, especially the population-based Baltimore-Washington Infant Study, have documented variability in the prevalence of specific types of CVM by time, place, and personal characteristics and have highlighted the potential prevention of diabetes-associated heart malformations through timely medical management of pre-conception diabetes. Left-sided obstructive heart defects have been identified as targets for new studies of genetic risk factors. Potential environmental risk factors for CVMs also have been identified, such as organic solvents and pesticides, coincident with the emergence of new strategies to study genetic susceptibility and gene-environment interactions. Increased collaborative, multicenter research on these and other factors, such as nutritional factors in early pregnancy, offers new hope for potentially reducing the burden of CVM in the population.

Failure to diagnose congenital heart disease in infancy.

OBJECTIVE: To identify factors that predict failure to diagnose congenital heart disease in newborns. DESIGN: All fatal cases in the Baltimore-Washington Infant Study were compiled. The Baltimore-Washington Infant Study includes 4390 cases of infants with congenital cardiovascular malformations identified in a population-based study between 1981 and 1989 in the Baltimore-Washington metropolitan area. Death occurred in 800 such infants in the first year of life. In 76 of these infants, death occurred before diagnosis of heart disease. These cases were identified by community search of autopsy records. Their characteristics are compared with those of infants who died after a cardiac diagnosis was made. RESULTS: Infant characteristics (birth weight, gestational age, intrauterine growth retardation, and chromosomal anomaly) are associated with death of infants with congenital cardiovascular malformations and with death of such infants before diagnosis. Diagnoses of coarctation of the aorta, Ebstein's anomaly, atrial septal defect, and truncus arteriosus are overrepresented in infants found by community search, particularly in those infants without associated malformations. Paternal education is associated with failure to diagnose congenital heart disease in life but other sociodemographic characteristics of the infant's family are not. CONCLUSIONS: Diagnosis of congenital cardiovascular malformations requires close observation in the neonatal period. Analysis of age at death of infants with undiagnosed congenital cardiovascular malformation suggests that such infants may be at risk if discharged within the first 2 days of life.

Attributable fraction for cardiac malformations.

To the authors' knowledge, attributable fractions for cardiac malformations have not been reported before. The Baltimore-Washington Infant Study published factors associated with several major cardiac malformations in Maryland, the District of Columbia, and adjacent counties of northern Virginia in 1981-1989. For eight of these malformations, the authors provide attributable fractions of those factors that are potentially causal. Summary attributable fractions range from 13.6% (four factors) for hypoplastic left heart to 30.2% (seven factors) for transposition of great arteries with intact ventricular septum. Extra attributable fraction for factor x, defined as summary attributable fraction for all factors minus that for all but x, is largest for: 1) paternal marijuana use in transposition of great arteries with intact ventricular septum, 7.8%; 2) paternal anesthesia in tetralogy of Fallot, 3.6%; 3) painting in atrioventricular septal defect with Down syndrome, 5.1 %; 4) solvent/degreasing agent exposure in hypoplastic left heart, 4.6%; 5) sympathomimetics in coarctation of aorta, 5.8%; 6) pesticide exposure in isolated membranous ventricular septal defect, 5.5%; 7) hair dye in multiple/multiplex membranous ventricular septal defect, 3.3%; and 8) urinary tract infection in atrial septal defect, 6.4%. Percent-of-cases-exposed dominates relative risk in attributable fraction. If these factors are causal, the larger extra attributable fractions suggest the potential for prevention by specific interventions before/during pregnancy.

Preconceptional folate intake and malformations of the cardiac outflow tract. Baltimore-Washington Infant Study Group.

We compared cases with outflow tract defects (N = 126) with controls representative of the same birth cohort (N = 679). Infants with clinically recognized syndromes were excluded. Daily total maternal folate intake of > or =245 microg was inversely related to risk of cardiac outflow tract defects among those with transposition (odds ratio estimates: 0.65, 0.78, and 0.76 with increasing quartile of daily folate intake), but positively related among those with normally related vessels (corresponding odds ratio estimates: 1.18, 1.59, and 1.68). This difference disappeared when maternal intake of supplemental folic acid of > or =400 microg compared with <400 microg was considered, excluding dietary intake [odds ratio (OR) = 1.04; 95% confidence interval (CI) = 0.5-2.2 for infants with transposition, and OR = 0.91; 95% CI = 0.5-1.8 for those without transposition of the great arteries].