Association of birth mode of delivery with infant faecal microbiota, potential pathobionts, and short chain fatty acids: a longitudinal study over the first year of life.

OBJECTIVE: Caesarean section (CS) interrupts mother-to-newborn microbial transfer at birth. Beyond the neonatal period, the impact of CS on offspring gut microbiota and their short-chain fatty acids (SCFAs) remains unclear. Here, we examine birth delivery mode (CS versus vaginal delivery) with the infant gut microbiota and faecal SCFAs measured 3 and 12 months after birth. DESIGN: Longitudinal study. SETTING: North Carolina. POPULATION: In 2013-15, we enrolled pregnant women and followed up their offspring for 12 months. We asked a subset of participants, enrolled over a 3-month period, to provide faecal samples at the 3- and 12-month follow-up visits. METHODS AND MAIN OUTCOMES: We sequenced the 16S rRNA V4 region with Illumina MiSeq and quantified SCFA concentrations using gas chromatography. We examined delivery mode with differential abundance of microbiota amplicon sequence variants (ASVs) using beta-binomial regression and faecal SCFAs using linear regression. We adjusted models for confounders. RESULTS: Of the 70 infants in our sample, 25 (36%) were delivered by CS. Compared with vaginal delivery, CS was associated with differential abundance of 14 infant bacterial ASVs at 3 months and 13 ASVs at 12 months (all FDR P < 0.05). Of note, CS infants had a higher abundance of the potential pathobionts Clostridium neonatale (P = 0.04) and Clostridium perfringens (P = 0.04) and a lower abundance of potentially beneficial Bifidobacterium and Bacteroides spp. (both P < 0.05) at 3 months. Other ASVs were differentially abundant at 12 months. Infants delivered by CS also had higher faecal butyrate concentration at 3 months (P < 0.005) but not at 12 months. CONCLUSIONS: Caesarean section was associated with increased butyrate excretion, decreased Bifidobacterium and Bacteroides spp., and more colonisation of the infant gut by pathobionts at 3 months of age. CS was also associated with altered gut microbiota composition, but not faecal SCFAs, at 12 months. TWEETABLE ABSTRACT: Caesarean section delivery was associated with increased butyrate excretion, decreased Bifidobacterium, and increased colonisation of the infant gut by pathobionts at 3 months of age.

Elevated metabolites of acetaminophen in cord blood of children with obesity.

BACKGROUND: High-throughput metabolomics has been used cross-sectionally to evaluate differential metabolic profiles associated with human obesity. OBJECTIVES: This study longitudinally assessed the cord blood metabolome to explore if metabolic signatures of obesity at age 3-5 are apparent at birth. METHODS: In a nested case-control design, metabolomics analysis was performed on umbilical cord blood of 25 children who developed obesity by age 3-5 years, compared with 25 sex-matched non-obese children enrolled as part of an ongoing birth cohort. Logistic regression models were used to identify significant metabolites, adjusting for maternal pre-pregnancy obesity. RESULTS: Children who had obesity by age 3-5 years had elevated levels of medium and long chain fatty acids including stearate, oleate and palmitate at birth. Children with obesity were also more likely to have elevated levels of acetaminophen metabolites at birth, specifically: 3-(N-acetyl-L-cystein-S-yl) acetaminophen, 2-hydroxyacetaminophen sulfate, 2-methoxyacetaminophen glucuronide and p-acetamidophenyl glucuronide. CONCLUSION: Although the observed increases in lipids are consistent with previous metabolomic studies of obesity, this study is the first to report associations between acetaminophen metabolites and obesity in children; however, we lack mechanistic insights for this link. Larger human studies with longer follow-up and laboratory-controlled animal experiments are needed to clarify associations.

Associations between imprinted gene differentially methylated regions, appetitive traits and body mass index in children.

BACKGROUND: Knowledge regarding genetic influences on eating behaviours is expanding; yet less is known regarding contributions of epigenetic variation to appetitive traits and body mass index (BMI) in children. OBJECTIVE: The purpose of this study was to explore relationships between methylation at differentially methylated regions (DMRs) of imprinted genes (insulin-like growth factor 2/H19 and Delta-like, Drosophila, homolog 1/maternally expressed gene 3) using DNA extracted from umbilical cord blood leucocytes, two genetically influenced appetitive traits (food responsiveness and satiety responsiveness) and BMI. METHODS: Data were obtained from participants (N = 317; mean age = 3.6 years; SD = 1.8 years) from the Newborn Epigenetic STudy. Conditional process models were implemented to investigate the associations between DMRs of imprinted genes and BMI, and test whether this association was mediated by appetitive traits and birthweight and moderated by sex. RESULTS: Appetitive traits and birthweight did not mediate the relationship between methylation at DMRs. Increased insulin-like growth factor 2 DMR methylation was associated with higher satiety responsiveness. Higher satiety responsiveness was associated with lower BMI. Associations between methylation at DMRs, appetitive traits and BMI differed by sex. CONCLUSIONS: This is one of the first studies to demonstrate associations between epigenetic variation established prior to birth with appetitive traits and BMI in children, providing support for the need to uncover genetic and epigenetic mechanisms for appetitive traits predisposing some individuals to obesity.

Maternal vitamin D, DNA methylation at imprint regulatory regions and offspring weight at birth, 1 year and 3 years.

BACKGROUND/OBJECTIVE: Vitamin D deficiency during pregnancy is associated with poor birth outcomes in some studies, but few have examined weight beyond birth. In addition, little is known about how vitamin D influences DNA methylation of regulatory regions known to be involved in growth, as possible mediators to weight status in offspring. SUBJECTS/METHODS: We conducted linear regressions to assess maternal plasma 25-hydroxyvitamin D (25(OH)D) by quartile and birth weight for gestational age z-score, 1-year weight-for-length z-score and 3-year body mass index (BMI) z-score among 476 mother/infant dyads from a prospective cohort. We assessed maternal 25(OH)D and infant DNA methylation at nine differentially methylated regions (DMRs) of genomically imprinted genes with known functions in fetal growth, including H19, IGF2, MEG3, MEG3-IG, MEST, NNAT, PEG3, PLAGL1 and SGCE/PEG10. RESULTS: Mean (standard deviation, s.d.) maternal 25(OH)D was 41.1 (14.2) nmol l-m at a mean (s.d.) of 13.2 (5.5) weeks gestation. After adjustment for potential confounders, the first (Q1) and second (Q2) quartiles of 25(OH)D, compared to the fourth (Q4), were associated with lower birth weight for gestational age z-scores (-0.43 units; CI: -0.79, -0.07; P=0.02 for Q1 and -0.56 units; CI: -0.89, -0.23; P=0.001 for Q2). Q1 compared to Q4 was associated with higher 1-year weight-for-length z-scores (0.78 units; 0.08, 1.54; P=0.04) and higher 3-year BMI z-scores (0.83 units; 0.11, 0.93; P=0.02). We did not observe associations between maternal 25(OH)D and methylation for any of the nine DMRs after correcting for multiple testing. CONCLUSIONS: Reduced maternal 25(OH)D was associated with lower birth weight for gestational age z-scores but higher 1-year weight-for-length and 3-year BMI z-scores in offspring. However, 25(OH)D does not appear to be operating through the regulatory sequences of the genomically imprinted genes we examined.

Disparities in Cervical Cancer Incidence and Mortality: Can Epigenetics Contribute to Eliminating Disparities?

Screening for uterine cervical intraepithelial neoplasia (CIN) followed by aggressive treatment has reduced invasive cervical cancer (ICC) incidence and mortality. However, ICC cases and carcinoma in situ (CIS) continue to be diagnosed annually in the United States, with minorities bearing the brunt of this burden. Because ICC peak incidence and mortality are 10-15 years earlier than other solid cancers, the number of potential years of life lost to this cancer is substantial. Screening for early signs of CIN is still the mainstay of many cervical cancer control programs. However, the accuracy of existing screening tests remains suboptimal. Changes in epigenetic patterns that occur as a result of human papillomavirus infection contribute to CIN progression to cancer, and can be harnessed to improve existing screening tests. However, this requires a concerted effort to identify the epigenomic landscape that is reliably altered by HPV infection specific to ICC, distinct from transient changes.

Newborns of obese parents have altered DNA methylation patterns at imprinted genes.

BACKGROUND: Several epidemiologic studies have demonstrated associations between periconceptional environmental exposures and health status of the offspring in later life. Although these environmentally related effects have been attributed to epigenetic changes, such as DNA methylation shifts at imprinted genes, little is known about the potential effects of maternal and paternal preconceptional overnutrition or obesity. OBJECTIVE: We examined parental preconceptional obesity in relation to DNA methylation profiles at multiple human imprinted genes important in normal growth and development, such as: maternally expressed gene 3 (MEG3), mesoderm-specific transcript (MEST), paternally expressed gene 3 (PEG3), pleiomorphic adenoma gene-like 1 (PLAGL1), epsilon sarcoglycan and paternally expressed gene 10 (SGCE/PEG10) and neuronatin (NNAT). METHODS: We measured methylation percentages at the differentially methylated regions (DMRs) by bisulfite pyrosequencing in DNA extracted from umbilical cord blood leukocytes of 92 newborns. Preconceptional obesity, defined as BMI ⩾30 kg m(-2), was ascertained through standardized questionnaires. RESULTS: After adjusting for potential confounders and cluster effects, paternal obesity was significantly associated with lower methylation levels at the MEST (ß=-2.57; s.e.=0.95; P=0.008), PEG3 (ß=-1.71; s.e.=0.61; P=0.005) and NNAT (ß=-3.59; s.e.=1.76; P=0.04) DMRs. Changes related to maternal obesity detected at other loci were as follows: ß-coefficient was +2.58 (s.e.=1.00; P=0.01) at the PLAGL1 DMR and -3.42 (s.e.=1.69; P=0.04) at the MEG3 DMR. CONCLUSION: We found altered methylation outcomes at multiple imprint regulatory regions in children born to obese parents, compared with children born to non-obese parents. In spite of the small sample size, our data suggest a preconceptional influence of parental life-style or overnutrition on the (re)programming of imprint marks during gametogenesis and early development. More specifically, the significant and independent association between paternal obesity and the offspring's methylation status suggests the susceptibility of the developing sperm for environmental insults. The acquired imprint instability may be carried onto the next generation and increase the risk for chronic diseases in adulthood.

PEG1/MEST and IGF2 DNA methylation un CIN and in cervical cancer

INTRODUCTION: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. MATERIALS AND METHODS: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. RESULTS: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. CONCLUSIONS: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk (AU)

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PEG1/MEST and IGF2 DNA methylation in CIN and in cervical cancer.

INTRODUCTION: Although most invasive cervical cancer (ICC) harbor <20 human papillomavirus (HPV) genotypes, use of HPV screening to predict ICC from HPV has low specificity, resulting in multiple and costly follow-up visits and overtreatment. We examined DNA methylation at regulatory regions of imprinted genes in relation to ICC and its precursor lesions to determine if methylation profiles are associated with progression of HPV-positive lesions to ICC. MATERIALS AND METHODS: We enrolled 148 controls, 38 CIN and 48 ICC cases at Kilimanjaro Christian Medical Centre from 2008 to 2009. HPV was genotyped by linear array and HIV-1 serostatus was tested by two rapid HIV tests. DNA methylation was measured by bisulfite pyrosequencing at regions regulating eight imprinted domains. Logistic regression models were used to estimate odd ratios. RESULTS: After adjusting for age, HPV infection, parity, hormonal contraceptive use, and HIV-1 serostatus, a 10 % decrease in methylation levels at an intragenic region of IGF2 was associated with higher risk of ICC (OR 2.00, 95 % CI 1.14-3.44) and cervical intraepithelial neoplasia (CIN) (OR 1.51, 95 % CI 1.00-2.50). Methylation levels at the H19 DMR and PEG1/MEST were also associated with ICC risk (OR 1.51, 95 % CI 0.90-2.53, and OR 1.44, 95 % CI 0.90-2.35, respectively). Restricting analyses to women >30 years further strengthened these associations. CONCLUSIONS: While the small sample size limits inference, these findings show that altered DNA methylation at imprinted domains including IGF2/H19 and PEG1/MEST may mediate the association between HPV and ICC risk.

Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring.

OBJECTIVES: Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations. METHODS: Between 2009-2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions. RESULTS: After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (ß-coefficient=-132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (ß-coefficient=-135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight. CONCLUSION: We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.

Improving the gas-solids contact efficiency in a fluidized bed of CO2 adsorbent fine particles.

A modified CO(2) adsorbent is obtained by dry mixing of a Ca(OH)(2) fine powder as received with a commercial silica nanopowder. Silica nanoparticles form light agglomerates of size of the order of tens of microns, which are uniformly fluidizable. These agglomerates act as dispersants of the Ca(OH)(2) fine particles, which coat the nanoparticle agglomerates likely due to contact charging. Ca(OH)(2) particles (CO(2) adsorbent) are thus provided with a vehicle for uniform fluidization. In this way, the contact efficiency between the CO(2) adsorbent and CO(2) in the fluidized bed is greatly enhanced. Experimental results show that the improvement of Ca(OH)(2) fluidizability serves to enhance the carbonation reaction in the fluidized bed.

The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring.

In utero exposures to environmental factors may result in persistent epigenetic modifications affecting normal development and susceptibility to chronic diseases in later life. We explored the relationship between exposure of the growing fetus to maternal depression or antidepressants and DNA methylation at two differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene. Aberrant DNA methylation at the IGF2 and neighboring H19 DMRs has been associated with deregulated IGF2 expression, childhood cancers and several chronic diseases during adulthood. Our study population is comprised of pregnant mothers and their newborns (n = 436), as part of the Newborn Epigenetics Study (NEST). A standardized questionnaire was completed and medical record data were abstracted to ascertain maternal depression and antidepressive drug use. DMR methylation levels in umbilical cord blood leukocytes were quantified using pyrosequencing. From the 436 newborns, laboratory data were obtained for 356 individuals at the IGF2 DMRs, and for 411 individuals at the H19 DMRs; about half of each group was African American or Caucasian. While overall no association between depression and methylation profiles was found, we observed a significant hypermethylation of the H19 DMRs in newborns of African American (n = 177) but not Caucasian (n = 168) mothers who reported the use of antidepressive drugs during pregnancy (ß = +6.89, p = 0.01). Of note, our data reveal a race-independent association between smoking during pregnancy and methylation at the IGF2 DMR (+3.05%, p = 0.01). In conclusion, our findings suggest a race-dependent response related to maternal use of antidepressants at one of the IGF2 DMRs in the offspring.

Factors associated with African Americans' enrollment in a national cancer genetics registry.

This study explored whether reactions to the Cancer Genetics Network (CGN) or CGN enrollment differed by receipt of a standard informational brochure versus a targeted version addressing factors previously associated with African Americans' health behavior decisions and research participation. The 262 participants, identified through tumor registries or clinic contacts, were mailed brochures and completed phone interviews. When asked whether - based on the brochure - they were or were not 'leaning toward' CGN enrollment, about 75% of both standard and targeted groups reported leaning toward. When given the opportunity at the end of the interview, 68% enrolled in the CGN. Trust was strongly related to enrollment. Less education, less satisfaction with cancer care, and individualistic rather than collective orientation were associated with lower trust. Education was also bivariately associated with enrollment, but mediation analysis indicated that the operational mechanism of education's influence on enrollment was through trust.

Influence of clay mineral structure and surfactant nature on the adsorption capacity of surfactants by clays.

Adsorption of three surfactants of different nature, Triton X-100 (TX100) (non-ionic), sodium dodecylsulphate (SDS) (anionic) and octadecyltrimethylammonium bromide (ODTMA) (cationic) by four layered (montmorillonite, illite, muscovite and kaolinite) and two non-layered (sepiolite and palygorskite) clay minerals was studied. The objective was to improve the understanding of surfactant behaviour in soils for the possible use of these compounds in remediation technologies of contaminated soils by toxic organic compounds. Adsorption isotherms were obtained using surfactant concentrations higher and lower than the critical micelle concentration (cmc). These isotherms showed different adsorption stages of the surfactants by the clay minerals, and were classified in different subgroups of the L-, S- or H-types. An increase in the adsorption of SDS and ODTMA by all clay minerals is observed up to the cmc of the surfactant in the equilibrium solution is reached. However, there was further TX100 adsorption when the equilibrium concentration was well above the cmc. Adsorption constants from Langmuir and Freundlich equations (TX100 and ODTMA) or Freundlich equation (SDS) were used to compare adsorption of different surfactants by clay minerals studied. These constants indicated the surfactant adsorption by clay minerals followed this order ODTMA>TX100>>SDS. The adsorption of TX100 and ODTMA was higher by montmorillonite and illite, and the adsorption of SDS was found to be higher by kaolinite and sepiolite. Results obtained show the influence of clay mineral structure and surfactant nature on the adsorption capacity of surfactants by clays, and they indicate the interest to consider the soil mineralogical composition when one surfactant have to be selected in order to establish more efficient strategies for the remediation of soils and water contaminated by toxic organic pollutants.

Novel instrument to characterize dry granular materials at low consolidations.

The performance of traditional instruments for measuring the flow properties of dry granular materials at small consolidation stresses is not fully satisfactory. Generally, commercial quick tests, as, for example, the angle repose method, do not yield intrinsic material properties. This difficulty is solved in currently available ring shear testers, in which the externally applied torque necessary for shearing the sample is measured as a function of the normal stress previously applied through an annular lid. In this article we show a novel device in which the shear stress is caused by the action of a centrifugal force on a vertical layer of unconsolidated material, which is rotated around its vertical axis. At a critical point the shear stress is large enough to drive material avalanches. From a theoretical analysis of these avalanches based on Coulomb's method of wedges, we derive the angle of internal friction and cohesion of the granular material. To illustrate the functioning of the instrument, measurements on steel, ferrite, and magnetite beads of different particle size are presented. The data obtained are used to analyze the gravity-driven avalanches of these materials in a slowly rotated drum.

Fear of sexually transmitted infections among women with male migrant partners -- relationship to oscillatory migration pattern and risk-avoidance behaviour.

BACKGROUND: In South Africa, former apartheid laws encouraged rural males seeking employment to migrate to urban areas, moving weekly, monthly or annually between their rural families and urban workplaces. The combination of the migrant labour system and long family separations caused an explosion of serious health consequences, among others sexually transmitted infections (STIs) in the migrant population. OBJECTIVE: To describe some correlates of male migration patterns for the rural women left behind, especially the fear of STIs that this engendered in them and their risk-avoidance behaviour. Setting and subjects. In KwaZulu-Natal, 208 prenatal patients who were partners of oscillating male migrant workers were interviewed to determine their demographic and behavioural characteristics, and their fear of STIs. RESULTS: Thirty-six per cent of the rural women said that they were afraid of contracting STIs from their returning migrant partners. Women who saw their partners infrequently were more fearful of STI transmission, and were less able to have sexual communication. However, almost none of the women protected themselves, while only 8% used condoms, primarily for contraceptive purposes. CONCLUSIONS: These results reflect the gender-based power relationships of South African male migrants and their rural partners, the social and economic dependency of the women on their migrant partners, and the women's social responsibility to bear children. The results point to the need to go beyond interventions that simply seek to modify behaviour without altering the forces that promote risk taking and discourage risk reduction, and the need to develop appropriate interventions to curb STIs and decrease HIV.

Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under

Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95 CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95 CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95 CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95 CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95 CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95 CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95 CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study

Depo medroxyprogesterone acetate (DMPA) and combined oral contraceptives and cervical carcinoma in-situ in women aged 50 years and under.

Most low-resource settings depend on hormonal contraceptives for their family planning programmes and cervical cancer occurs in higher frequency in these populations. To determine whether hormonal contraception use increases cervical carcinoma in-situ (CIS) risk, a case-control study was conducted in the Kingston and St Andrew Corporate area of Jamaica, using 119 cases from the Jamaica Tumour Registry and 304 population controls matched on year of Papanicolaou (Pap) smear and clinic where Pap smear was obtained. While CIS cases were more likely to have 'ever used' combined oral contraceptives (COC) (OR = 1.4, 95% CI: 0.8, 2.5), depo-medroxyprogesterone acetate (DMPA) use was similar. Compared to women who never used hormonal contraceptives, the risk of CIS was elevated in: women who had used COCs five years or more (OR = 2.1, 95% CI: 1.0, 4.6), women who first used COC for less than 10 years prior to the interview (OR = 1.8, 95% CI: 0.9, 3.7) and women who were 18 to 24 years old when they first used COCs (OR = 1.8, 95% CI: 0.9, 3.4). Similarly, compared to women who never used DMPA, the risk of CIS was elevated in: women using DMPA five years or more (OR = 1.9, 95% CI: 0.7, 4.8), women reporting use within a year prior to interview (OR = 2.8, 95% CI: 0.7, 10.7) and women who initiated use of DMPA when they were 20 and 24 years old (OR = 1.4, 95% CI: 0.7, 3.1). These results suggest that if hormonal contraceptive use confers any risk of CIS, it is confined to long-term users. Increased risk in some groups, however, warrant further study.

Selective screening for cervical neoplasia: an approach for resource-poor settings.

BACKGROUND: Cervical malignancies are the leading cause of cancer-related morbidity and mortality among women in developing countries. Although early detection programmes using cytological methods, followed by aggressive treatment of precursor lesions are accepted as the main disease control strategy, fiscal limitations make this strategy unfeasible in many countries. METHODS: To screen selectively, we developed two risk scores using data from a population-based case-control study in Jamaica with 202 cases and 363 controls. Independent risk factors for cervical neoplasia were determined using logistic regression. An unweighted risk score for each subject was developed by a simple count of risk factors present and a weighted risk score was calculated by summing regression coefficients for each risk factor. RESULTS: Four patient characteristics were independently predictive of cervical neoplasia, older age (OR = 3.4, 95% CI : 1.8-6.7), > or = 4 pregnancies (OR = 5.6, 95% CI : 1.2-18.7), poverty (OR = 2.1, 95% CI : 1.3-3.3) and cigarette smoking (OR = 1.9, 95% CI : 1.2-3.2). Using cut-off points of > or = 20 for the weighted scores and > 3 for unweighted scores, the sensitivity and specificity were 65% and 69% for the unweighted score and 75% and 61%, respectively, for the weighted score. Areas under the receiver operating characteristic (ROC) curves for the weighted versus the unweighted scores were similar, suggesting similar overall accuracy. CONCLUSION: Selective screening using risk assessment strategies is potentially useful, particularly in resource-poor settings. However, whether weighting factors is essential is dependent on prevalence of factors in a given setting. Although this approach needs validation in other populations, women at highest risk for cervical neoplasia can be identified using demographic factors available during a regular clinic visit.

Digestive haemorrhage in patients with anti-Anisakis antibodies.

OBJECTIVE: Anisakis simplex parasite causes anisakidosis, a disease that often mimics other gastrointestinal diseases such as peritonitis, appendicitis, Crohn's disease, ulcer, etc. Patients with digestive haemorrhage caused by ulcers, varices or Mallory syndrome were analysed for antibodies to the worm A. simplex. METHODS: Antibody detection was carried out by enzyme-linked immunosorbent assay (ELISA) and immunoblot using crude extracts of antigen and excretory/secretory products. Total immunoglobulin (Ig), IgG, IgM, IgA and IgE were studied. RESULTS: Eighty-seven patients were studied. The following prevalence rates were found with crude antigen: total Ig 30% (95% confidence interval 21-40), with values for IgG, IgM, IgA and IgE of 22 (CI 14-31), 17 (CI 10-26), 37 (CI 27-47) and 12% (CI 6-20), respectively. Twenty-four positive sera for total Ig response and crude products were selected for determination of specific antibodies with excretory/secretory antigens. We obtained 8, 13, 3 and 16 positive cases for total Ig, IgG, IgM and IgA respectively. The percentages of positivity within the varices and Mallory groups of patients were higher although differences were not significant (35 and 50% respectively). In a healthy population, the prevalence for total Ig is much lower (6%). Twenty-five positive sera for total Ig response were tested by means of immunoblot analysis against crude larval antigen. Concerning total Ig antibody response, 12 of the sera showed an immuno-recognition pattern concordant with the human anisakidosis reference serum (E17). Specific IgG bands were visualized in 30 sera; specific IgM and IgA in 6 and 12, respectively. Different clinical variables of these patients were studied: leucocytes, eosinophils, haemoglobin, prothrombin activity, thromboplastin time, fibrinogen, platelets and erythrocyte sedimentation rate. There were a few significant differences: for total Ig in prothrombin activity and platelets, and for IgM in eosinophils. CONCLUSIONS: The prevalence of detectable antibodies against A. simplex is higher in patients with digestive haemorrhage than in the healthy population.