Lytic to temperate switching of viral communities.

Microbial viruses can control host abundances via density-dependent lytic predator-prey dynamics. Less clear is how temperate viruses, which coexist and replicate with their host, influence microbial communities. Here we show that virus-like particles are relatively less abundant at high host densities. This suggests suppressed lysis where established models predict lytic dynamics are favoured. Meta-analysis of published viral and microbial densities showed that this trend was widespread in diverse ecosystems ranging from soil to freshwater to human lungs. Experimental manipulations showed viral densities more consistent with temperate than lytic life cycles at increasing microbial abundance. An analysis of 24 coral reef viromes showed a relative increase in the abundance of hallmark genes encoded by temperate viruses with increased microbial abundance. Based on these four lines of evidence, we propose the Piggyback-the-Winner model wherein temperate dynamics become increasingly important in ecosystems with high microbial densities; thus 'more microbes, fewer viruses'.

Genetic association study of preterm birth and gestational age in a population-based case-control study in Peru.

BACKGROUND: Preterm birth (PTB) affects ∼15 million pregnancies worldwide. Genetic studies have identified several candidate loci for PTB, but results remain inconclusive and limited to European populations. Thus, we conducted a genome-wide association study (GWAS) of PTB and gestational age at delivery (GA) among 2,212 Peruvian women. METHODS: PTB cases delivered≥20 weeks' but < 37 weeks' gestation, while controls delivered at term (≥37 weeks but <42 weeks). Multivariable regressions were used to identify genetic markers for PTB and GA (∼6 million SNPs), adjusting for maternal age and the first two genetic principal components. In silico functional analysis was conducted among top signals detected with an arbitrary P < 1.0×10-5 . We sought to replicate genetic markers for PTB and GA identified in Europeans, and we developed a genetic risk score for GA based on European markers. RESULTS: Mean GA was 30 ± 4 weeks in PTB cases (N = 933) and 39 ± 1 in the controls (N = 1,279). No associatiosn were identified at genome-wide level. Nominal PTB variants were enriched for biological pathways associated with polyketide, progesterone, steroid hormones, and glycosyl metabolism. Nominal GA variants were enriched in intronic regions and cancer pathways. Variants in WNT4 associated with GA in Europeans were replicated in our study. A genetic risk score was associated with a 2-day longer GA (P = 0.002) in our sample. CONCLUSIONS: This study identified various signals suggestively associated with PTB and GA in pregnant Peruvian women. None of these variants overlapped with signals previously identified in Europeans.

Chronic HPA activity in mothers with preterm delivery: A pilot nested case-control study.

BACKGROUND: Chronic hypothalamic-pituitary-adrenal (HPA) axis activity role in the pathogenesis of preterm birth (PTB) remains unclear due to inconsistent measures with limited ability to monitor long-term cortisol concentrations. We explored this relationship using the novel method of assessing cortisol in hair, which is a valid and reliable measure of chronic HPA axis activity. METHODS: 137 participants (40 PTB cases and 97 controls from a birth cohort of pregnant women in Peru) were interviewed and invited to provide a 9-cm hair sample from the posterior vertex position of the scalp (mean = 13 weeks gestation). Hair cortisol concentration (HCC) was determined using luminescence immunoassay and values were natural-log transformed. PTB cases were defined as women who delivered before 37 gestational weeks. Case-control differences were assessed using multivariable linear and logistic regressions. RESULTS: Overall, combined pre-conception and first-trimester HCC was 13% lower among cases as compared with controls (p-value = 0.01). Compared with controls, maternal HCC among PTB cases were 14% (p = 0.11), 10% (p = 0.22) and 14% (p = 0.08) lower for 3-6 months pre-conception, 0-3 months pre-conception, and first trimester, respectively. After adjusting for putative confounders, a 1-unit increase in HCC was associated with 55% reduced odds of PTB (aOR = 0.45; 95% CI: 0.17-1.17). For a 1-unit increase in HCC in the scalp-intermediate and scalp-distal segments (representing HCC concentrations in 0-3 months pre-conception and first trimester), the corresponding odds for PTB were 0.53 (95% CI: 0.19-1.48) and 0.39 (95% CI: 0.13-1.13), respectively. CONCLUSIONS: Women who deliver preterm, as compared with those who deliver at term, have lower preconception and first trimester HCC. Our findings suggest that HPA axis activation, integral to the adaptive stress-response system, may be chronically dysregulated in women at increased risk of PTB.

Oxidized low-density lipoprotein (Oxidized LDL) and the risk of preeclampsia.

Oxidative stress plays an important role in the pathophysiology of preeclampsia. In a case-control study of 99 women with preeclampsia and 99 controls, we assessed maternal plasma oxidized low-density lipoprotein (oxidized LDL) in relation to preeclampsia risk. Logistic regression procedures were used to derive odds ratios (OR) and 95 % confidence intervals (CI). Plasma oxidized LDL was determined using enzyme immunoassay. Maternal plasma oxidized LDL was significantly positively correlated with lipids in both cases and controls. After adjusting for nulliparity, pre-pregnancy body mass index, physical inactivity, family history of chronic hypertension and plasma vitamin C concentrations, women who had elevated oxidized LDL concentrations ( > or = 50 U/l) experienced a 2.9-fold increased risk of preeclampsia when compared with women having lower oxidized LDL concentrations (95 % CI 1.4-5.9). The risk of preeclampsia was markedly increased in women who had both elevated oxidized LDL and elevated triglyceride concentrations (OR=8.9, 95 % CI 3.1-26.2). Women with both elevated oxidized LDL and low vitamin C concentrations experienced a 9.8-fold increased risk of preeclampsia (95 % CI 3.0-32.2). Our results confirm the role of oxidative stress in the pathogenesis of preeclampsia. Prospective studies are needed to determine if elevated oxidized LDL concentrations can predict the occurrence of preeclampsia.

Tumor necrosis factor-alpha soluble receptor p55 (sTNFp55) and risk of preeclampsia in Peruvian women.

We conducted a large case-control study to assess the risk of preeclampsia with elevated sTNFp55 concentrations (markers of excessive TNF-alpha release) in Peruvian women. A total of 125 women with preeclampsia and 179 normotensive women were included in a study conducted during the period, June 1997 through January 1998. Antepartum (third-trimester) plasma sTNFp55 was measured by enzyme linked immunosorbent assay. Mean plasma sTNFp55 concentrations were 32.4% higher among preeclampsia cases (920.1+/-30.4 pg/ml) as compared with controls (694.8+/-15.0 pg/ml, Student's t-test P<0.001). There was a strong linear increase in risk of preeclampsia with increasing concentrations of sTNFp55 (linear trend P-value <0. 001). After adjusting for confounding factors, women in the highest quartile experienced a 10-fold increased risk of preeclampsia as compared with women in the lowest quartile (adjusted odds ratio, 10.3; 95% confidence interval, 4.1-25.9). Compared with women in the highest quartile, women in the second and third quartiles experienced a 3-fold or greater increased risk of preeclampsia (adjusted odds ratios were 3.1 and 3.8, respectively). Excessive TNF-alpha release (as measured by the detection of the soluble receptor sTNFp55 in maternal plasma collected before delivery) is increased in pregnancies complicated by preeclampsia as compared with normotensive pregnancies. These findings are consistent with most previous studies.

The influence of maternal triglyceride levels on infant birth weight in Peruvian women with pre-eclampsia.

OBJECTIVE: Hypertriglyceridemia is an important pathophysiological feature of pre-eclampsia, a complication associated with retarded fetal growth. We studied the relation between third-trimester maternal triglyceride levels and infant birth weight in 113 pre-eclamptic and 150 normotensive women. METHODS: Plasma triglyceride concentrations were determined using enzymatic methods. The relative risk of infant low birth weight (LBW, < 2500 g) was determined using logistic regression to calculate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Approximately 12% of normotensive and 32% of pre-eclamptic mothers delivered LBW infants. After adjusting for maternal age, parity, pre-pregnancy adiposity and gestational age at delivery, pre-eclamptics were 2.3 times more likely to deliver a LBW infant as compared with normotensive mothers (95% CI 1.1-5.0). There was no association between plasma triglyceride level and infant birth weight. Pearson correlation coefficients for birth weight and triglyceride were r = 0.10 (p = 0.24) and r = 0.06 (p = 0.49) for normotensive and pre-eclamptic women, respectively. The OR for LBW associated with high triglyceride level (> or = 233 mg/dl) was 0.8 (95% CI 0.2-3.1) and 0.9 (95% CI 0.4-2.0) for the two groups. Triglyceride levels did not modify the pre-eclampsia and LBW association. Compared to normotensive women with low triglyceride level (< 233 mg/dl), the ORs for LBW were 1.2 (95% CI 0.4-4.0), 3.6 (95% CI 1.0-12.5) and 2.8 (95% CI 1.0-8.0) for normotensive and high triglyceride, pre-eclamptic and low triglyceride, and pre-eclamptic and high triglyceride mothers, respectively. CONCLUSIONS: Hypertriglyceridemia in late pregnancy, considered a maternal adaptation to maintain stable fuel distribution to the fetus, was not related to birth weight.

Methylenetetrahydrofolate reductase 677 C-->T polymorphism and plasma folate in relation to pre-eclampsia risk among Peruvian women.

OBJECTIVES: Pre-eclampsia is an important cause of maternal and fetal morbidity and mortality worldwide. Hyperhomocyst(e)inemia in pregnancy is associated with an increased risk of pre-eclampsia in most studies. Nutritional and genetic factors regulate homocyst(e)ine levels. A missense mutation 677 C-->T in the gene for methylenetetrahydrofolate reductase (MTHFR) has been associated with an increased pre-eclampsia risk in some, although not most, previously studied populations. METHODS: To further understand the role of this polymorphism in the etiology of pre-eclampsia, we genotyped a total of 125 pre-eclamptics and 179 normotensive pregnant Peruvian women. RESULTS: The wild-type allele frequency among cases and controls was 54% and 58%, respectively. Twenty percent of cases and 17% of controls were homozygous for the 677 C-->T MTHFR genotype (T/T). After adjustment for confounding by covariates including maternal age, nulliparity, pre-pregnancy body mass index and use of prenatal vitamins, women homozygous for the 677 C-->T MTHFR genotype (T/T) experienced a modest, statistically non-significant increased risk of pre-eclampsia (adjusted OR 1.6, 95% CI 0.7, 3.8). Maternal folate deficiency was associated with a statistically non-significant doubling in risk of pre-eclampsia in this population (adjusted OR 2.0, 95% CI 0.9, 4.3). CONCLUSIONS: There was no evidence to suggest that pre-eclampsia risk is positively associated with the T/T genotype overall, or in the context of folate deficiency.

Plasma lipid concentrations in pre-eclamptic and normotensive Peruvian women.

OBJECTIVES: Dyslipidemia is thought to be of etiological importance in pre-eclampsia. We studied the relationship between maternal plasma lipid concentrations and risk of pre-eclampsia. METHODS: A total of 125 pre-eclampsia cases and 179 normotensive control subjects were included in this case-control study conducted in Lima, Peru, between August 1997 and January 1998. Postdiagnosis, antepartum plasma lipid profiles were determined by standard enzymatic methods. Logistic regression procedures were used to calculate odds ratios (OR) adjusted for potential confounders. RESULTS: Mean plasma total cholesterol and triglyceride concentrations were, on average, 6% and 21% higher in pre-eclamptics than controls, respectively. High-density lipoprotein (HDL) cholesterol concentrations were, on average, 9% lower in cases than controls. After adjusting for maternal age, prepregnancy body mass index, education, parity and other potential confounders, the risk of pre-eclampsia increased with successively higher quartiles of plasma triglyceride (adjusted OR: 1.00, 1.62, 2.21, 5.00, with the lowest quartile as referent; P-value for trend < 0.001). The association between pre-eclampsia risk and plasma total cholesterol was much less pronounced. In general, there was an inverse association between pre-eclampsia risk and HDL cholesterol concentration (adjusted OR: 1.00, 0.41, 0.50, 0.38, with the first quartile as the referent group; P-value for trend = 0.02). CONCLUSIONS: These findings suggest that high triglyceride and low HDL cholesterol concentrations are important risk factors for pre-eclampsia among Peruvian women.

Waist Circumference, Body Mass Index, and Other Measures of Adiposity in Predicting Cardiovascular Disease Risk Factors among Peruvian Adults.

Objectives. To examine the extent to which measures of adiposity can be used to predict selected components of metabolic syndrome (MetS) and elevated C-reactive protein (CRP). Methods. A total of 1,518 Peruvian adults were included in this study. Waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), waist-height ratio (WHtR), and visceral adiposity index (VAI) were examined. The prevalence of each MetS component was determined according to tertiles of each anthropometric measure. ROC curves were used to evaluate the extent to which measures of adiposity can predict cardiovascular risk. Results. All measures of adiposity had the strongest correlation with triglyceride concentrations (TG). For both genders, as adiposity increased, the prevalence of Mets components increased. Compared to individuals with low-BMI and low-WC, men and women with high-BMI and high- WC had higher odds of elevated fasting glucose, blood pressure, TG, and reduced HDL, while only men in this category had higher odds of elevated CRP. Overall, the ROCs showed VAI, WC, and WHtR to be the best predictors for individual MetS components. Conclusions. The results of our study showed that measures of adiposity are correlated with cardiovascular risk although no single adiposity measure was identified as the best predictor for MetS.

Prevalence and correlates of migraine among women attending a prenatal care clinic in Lima, Peru.

Migraine headaches are among the leading causes of disability in the world. The burden of migraines is highest in women of reproductive age. This cross-sectional study characterized the prevalence, symptoms and correlates of migrainous headaches in 154 pregnant women attending a prenatal care clinic in Lima, Peru. Lifetime prevalence of migraine defined by modified IHS criteria was 9.1% (95% CI 4.6-13.6). When probable migraines were included, the lifetime prevalence of migraine in this population was 29.2% (95% CI 22.0-36.4). Migraine headaches were associated with a maternal history of headache, childhood carsickness, a diagnosis of allergies, and a high frequency of fatigue. Although headache-related disability was low in terms of missed work and recreation, high rates of headache pain and medicinal use reflect the true impact on this population.

Plasma folate, vitamin B(12), and homocyst(e)ine concentrations in preeclamptic and normotensive Peruvian women.

The authors measured maternal third trimester plasma folate, vitamin B(12), and homocyst(e)ine concentrations among 125 women with preeclampsia and 179 normotensive women in Lima, Peru (1997-1998), to determine whether these analytes were associated with the occurrence of preeclampsia. Logistic regression procedures were used to calculate maximum likelihood estimates of odds ratios and 95% confidence intervals. Relative to women in the upper quartile of the control distribution of maternal plasma folate concentrations, women with values in the lowest quartile experienced a 1.6-fold increased risk of preeclampsia (odds ratio = 1.6; 95% confidence interval: 0.8, 3.2). There was no evidence of an increased risk of preeclampsia associated with low plasma vitamin B(12) concentrations. The unadjusted relative risk of preeclampsia increased across successively higher quartiles of plasma homocyst(e)ine level (odds ratios were 1.0, 1.0, 1.5, and 2.9, respectively, with the lowest quartile used as the referent; p for linear trend = 0.0004). After adjustment for maternal age, parity, gestational age, use of prenatal vitamins, whether the pregnancy had been planned, and educational attainment, the relative risk between extreme quartiles was 4.0 (95% confidence interval: 1.8, 8.9). These findings are consistent with earlier reports suggesting that hyperhomocyst(e)inemia in pregnancy may be a risk factor for preeclampsia.

Rapid and inexpensive approaches to managing abnormal vaginal discharge or lower abdominal pain: an evaluation in women attending gynaecology and family planning clinics in Peru.

OBJECTIVES: To assess low abdominal pain, yellow vaginal discharge, other symptoms and signs, and demographic and behavioural variables as predictors for cervical or vaginal infection. METHODS: A cross sectional study of women attending gynaecology and family planning clinics in Lima, Peru was undertaken. 630 consecutive eligible female patients with chief or elicited complaints of yellow vaginal discharge, low abdominal pain, or both were interviewed and examined, together with a comparable reference group without these complaints. Vaginal specimens were tested for trichomoniasis and bacterial vaginosis. Endocervical specimens were tested for Neisseria gonorrhoeae and Chlamydia trachomatis using the ligase chain reaction. RESULTS: Infections found included chlamydial infection in 69 women (10.9%), gonorrhoea in 10 (1.6%), and either infection in 77 (12.2%); trichomoniasis in 46 (7.3%), bacterial vaginosis in 189 (30%), and either infection in 209 (33.2%). Cervical infection with C trachomatis and/or N gonorrhoeae was independently associated with history of a new sex partner within the last 3 months, more than one sex partner within the last year, use of condoms never or in less than 50% of sex acts, history of sex partner with STD within the last year; with symptoms of persistent low abdominal pain and of yellow vaginal discharge; and with signs of profuse and yellow vaginal discharge, cervical ectopy, easily induced endocervical bleeding, or brown cervical secretion. Using these findings, an algorithm was created that had a positive predictive value (PPV) of 36% for cervical infection among women reporting chief or elicited complaint of this abnormal vaginal discharge and a PPV of 25% among those without a complaint. A chief complaint of yellow vaginal discharge had a PPV of 50% for trichomoniasis or bacterial vaginosis. Among women without a chief complaint of yellow vaginal discharge, clinical findings of yellow vaginal discharge had a PPV of 55%. CONCLUSIONS: Where economic and technical constraints preclude testing, clinical findings and risk assessment are helpful in detecting vaginal and cervical infections. Several demographic, behavioural, clinical, and laboratory variables were predictive of infection in this population.

Plasma concentrations of carotenoids, retinol, and tocopherols in preeclamptic and normotensive pregnant women.

This case-control study was conducted in Lima, Peru, from June 1997 through January 1998 to assess whether plasma concentrations of carotenoids (alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin), retinol, and tocopherols (alpha-tocopherol and gamma-tocopherol) are decreased in women with preeclampsia. A total of 125 pregnant women with preeclampsia and 179 normotensive pregnant women were included. Plasma concentrations of antioxidants were determined using high performance liquid chromatography. After adjusting for maternal demographic, behavioral, and reproductive characteristics and total plasma lipid concentrations, the authors found a linear increase in risk of preeclampsia with increasing concentrations of alpha-tocopherol (odds ratio of the highest quartile = 3.13; 95% confidence interval: 1.06, 9.23, with the lowest quartile as the reference group; p value of the test of linear trend = 0.040). The risk of preeclampsia decreased across increasing quartiles of concentrations for retinol (odds ratio of the highest quartile = 0.32; 95% confidence interval: 0.15, 0.69, with the lowest quartile as the reference group; p value of the test of linear trend = 0.001). Some of these results are inconsistent with the prevailing hypothesis that preeclampsia is an antioxidant-deficient state. Preliminary findings confirm an earlier observation of increased plasma concentrations of alpha-tocopherol among women with preeclampsia as compared with normotensive pregnant women.