Evaluation of the mutagenic potential of urban air pollution in São Paulo, Southeastern Brazil, using the Tradescantia stamen-hair assay

We used a short‐term bioassay—the Tradescantia stamen‐hair assay (TSH)—to evaluate the toxicity of ambient particles with an aerodynamic diameter less than 10 μm sampled in the metropolitan region of São Paulo, Brazil. Two exposure locations were selected: downtown São Paulo and Caucaia do Alto (mean PM₁₀ levels of 64 and 14 μg/m³, respectively). The experiment was conducted July 11–August 15, 2002, and toxicity was assessed with the Tradescantia stamen‐hair assay (TSH) employing clone KU‐20 of Tradescantia. Four experimental groups were defined: inflorescences collected from plants cultivated in Caucaia, inflorescences collected from plants cultivated in São Paulo (to establish the baseline level of mutations in stamen hairs at both sites), inflorescences collected from plants cultivated in Caucaia and brought to São Paulo and maintained in chambers that received ambient air, and inflorescences collected from plants cultivated in Caucaia and brought to São Paulo and maintained in chambers that received air passed through a particle filter. The frequency of mutations observed in Caucaia was significantly lower than that in the remaining groups. Flower cuttings brought from Caucaia and receiving ambient air of São Paulo showed a rate of mutations similar to that of plants cultivated in São Paulo. Filtering particles from the air reduced the rate of mutation but not sufficiently to reach the level of that in Caucaia. The frequency of mutations observed in São Paulo was significantly associated with PM₁₀ levels on the fifth day before the opening of the flowers (r = 0.47, p = 0.025). Our results indicate that urban particles play a significant role in the development of pollution‐dependent mutations. © 2004 Wiley Periodicals, Inc. Environ Toxicol 19: 578–584, 2004.     

Dietary Patterns and Weight Status in Italian Preschoolers with Autism Spectrum Disorder and Typically Developing Children

Atypical eating habits are more common in children with autism spectrum disorders (ASD) than typically developing (TD) peers. Feeding problems may lead to the double burden of specific nutrient deficiencies and excessive weight gain, with a consequent increase in obesity prevalence. The dietary intake of Italian preschoolers with ASD compared to their TD peers and the impact of their dietary choices on their weight status and relationship to food selectivity (FS) were investigated. Dietary patterns and their associations with body mass index (BMI) were evaluated in 65 children with ASD and 82 peers with TD aged 1.3–6.4 years. Eating habits were assessed with a modified version of a parent-rated semi-quantitative Food Frequency Questionnaire. Moreover, the prevalence of FS and possible links with dietary patterns and BMI were investigated in the ASD group. Children with ASD consumed significantly higher amounts of simple sugars, processed and ultra-processed carbohydrates, both low- and high-fat animal proteins, and lower amounts of vegetables and fruits compared to peers with TD. The obesity rate was 1.5% in children with TD and more than fourfold (6.2%) in children with ASD, although the difference between groups was not statistically significant. FS was significantly more frequent in children with ASD than in peers with TD. Children with ASD and FS showed significantly lower annual intakes of vegetable proteins and fiber (considered essential nutrients for a healthy diet) than children with ASD without FS. Our results showed that children with ASD showed different dietary habits than those with TD, with the higher consumption of energy-dense foods and lower amounts of food-sourced fibers, which could place them at increased risk to develop overweight, obesity, and micronutrient deficiencies later in life.     

Anticipation and consumption of food each increase the concentration of neuroactive steroids in rat brain and plasma

Stressful stimuli and anxiogenic drugs increase the plasma and brain concentrations of neuroactive steroids. Moreover, in rats trained to consume their daily meal during a fixed period, the anticipation of food is associated with changes in the function of various neurotransmitter systems. We have now evaluated the effects of anticipation and consumption of food in such trained rats on the plasma and brain concentrations of 3alpha-hydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH PROG) and 3alpha,21-dihydroxy-5alpha-pregnan-20-one (3alpha,5alpha-TH DOC), two potent endogenous positive modulators of type A receptors for gamma-aminobutyric acid (GABA). The abundance of these neuroactive steroids was increased in both the cerebral cortex and plasma of the rats during both food anticipation and consumption. In contrast, the concentration of their precursor, progesterone, was increased in the brain only during food consumption, whereas it was increased in plasma only during food anticipation. Intraperitoneal administration of the selective agonist abecarnil (0.1 mg/kg) 40 min before food presentation prevented the increase in the brain levels of 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC during food anticipation but not that associated with consumption. The change in emotional state associated with food anticipation may thus result in an increase in the plasma and brain levels of 3alpha,5alpha-TH PROG and 3alpha,5alpha-TH DOC in a manner sensitive to the activation of GABA(A) receptor-mediated neurotransmission. A different mechanism, insensitive to activation of such transmission, may underlie the changes in the concentrations of these neuroactive steroids during food consumption.     

The associations of parity and maternal age with small-for-gestational-age,preterm, and neonatal and infant mortality: a meta-analysis

Background

Previous studies have reported on adverse neonatal outcomes associated with parity and maternal age. Many of these studies have relied on cross-sectional data, from which drawing causal inference is complex. We explore the associations between parity/maternal age and adverse neonatal outcomes using data from cohort studies conducted in low- and middle-income countries (LMIC).

Methods

Data from 14 cohort studies were included. Parity (nulliparous, parity 1-2, parity ≥3) and maternal age (<18 years, 18-<35 years, ≥35 years) categories were matched with each other to create exposure categories, with those who are parity 1-2 and age 18-<35 years as the reference. Outcomes included small-for-gestational-age (SGA), preterm, neonatal and infant mortality. Adjusted odds ratios (aOR) were calculated per study and meta-analyzed.

Results

Nulliparous, age <18 year women, compared with women who were parity 1-2 and age 18-<35 years had the highest odds of SGA (pooled adjusted OR: 1.80), preterm (pooled aOR: 1.52), neonatal mortality (pooled aOR: 2.07), and infant mortality (pooled aOR: 1.49). Increased odds were also noted for SGA and neonatal mortality for nulliparous/age 18-<35 years, preterm, neonatal, and infant mortality for parity ≥3/age 18-<35 years, and preterm and neonatal mortality for parity ≥3/≥35 years.

Conclusions

Nulliparous women <18 years of age have the highest odds of adverse neonatal outcomes. Family planning has traditionally been the least successful in addressing young age as a risk factor; a renewed focus must be placed on finding effective interventions that delay age at first birth. Higher odds of adverse outcomes are also seen among parity ≥3 / age ≥35 mothers, suggesting that reproductive health interventions need to address the entirety of a woman’s reproductive period.

Funding

Funding was provided by the Bill & Melinda Gates Foundation (810-2054) by a grant to the US Fund for UNICEF to support the activities of the Child Health Epidemiology Reference Group.

     

Estimates of the US health impact of influenza.

OBJECTIVES. Data from the Tecumseh Community Health Study were used to estimate excess morbidity owing to influenza, and results were compared with estimates made previously using different methodology for an Institute of Medicine report. METHODS. Study participants from Tecumseh, Michigan, were classified as infected or noninfected based on laboratory results. The excess numbers of respiratory illnesses, respiratory illness days, and bed and restricted activity days experienced by the infected compared with the noninfected were estimated. RESULTS. The number of excess influenza-related respiratory illnesses was lower than that estimated in the Institute of Medicine report, in which all illnesses of certain characteristics occurring during an influenza season were attributed to influenza. It is now estimated that the US population under 20 years of age experiences a yearly average of 13.8 to 16.0 million influenza-related excess respiratory illnesses; for older individuals, the yearly estimate is 4.1 to 4.4 million excess illnesses. CONCLUSIONS. For public health purposes, estimates of excess morbidity as well as of total morbidity associated with influenza should be used in setting health priorities.     

Embryotoxic effects of 2,3,7,8 tetrachlorodibenzo-p-dioxin administered to female rats before mating

2,3,7,8-Tetrachlorodibenzo-p-dioxin was administered to female rats by gavage for 2 consecutive weeks at daily doses of 0, 0.125, 0.5, and 2 μg/kg. After treatment females were caged with untreated males. All dams were killed on Day 21 of gestation. Their reproductive statuses were recorded and live fetuses were examined for external, visceral, and skeletal malformations. At 0.125 μg/kg no effects were observed on both maternal and fetal toxicity; 0.5 μg/kg reduced maternal weight gain and increased postimplantation loss. At 2 μg/kg the following features became evident: reduction of both maternal weight gain and ovulation rate, increase of pre- and postimplantation loss, and fetal growth retardation. Also, malformed fetuses were observed at this dose level.     

Measures of the effects of vaccination in a randomly mixing population

Vaccine efficacy in the field is often derived from the relative attack rates in the vaccinated and unvaccinated after an outbreak. In this paper, vaccine efficacy is defined in terms of the probability that the infectious agent is transmitted from an infected to a susceptible person, and a method for estimating it from the usual attack rate data is given. We explore two mechanisms of vaccine action defined by Smith et al, but include an underlying dynamic epidemic model of an acute directly transmitted disease. We show analytically that under the model in which the vaccine mechanism reduces the probability of infection given a certain exposure, vaccine efficacy based on the relative attack rates underestimates the protective effect of the vaccine based on the relative transmission probabilities. Under the other model in which the vaccine mechanism offers complete protection to a certain proportion of those vaccinated, and no protection to the other vaccinated proportion, the vaccine efficacy based on the relative attack rates will equal that based on the transmission probabilities. Parameters for the effectiveness of a vaccination programme are defined in terms of the direct and indirect benefit to a single person as well as the total and average benefit to the entire population, and derived from the dynamic model for an outbreak of an acute directly transmitted disease. These effects can also be estimated without an actual separate unvaccinated population, independent of assumptions about the vaccine mechanism. The variation of these measures as functions of the fraction of vaccinated people in the population is explored numerically.     

Subtype-specific transmission probabilities for human immunodeficiency virus type 1 among injecting drug users in Bangkok, Thailand.

The Bangkok (Thailand) Metropolitan Administration cohort of injecting drug users (IDUs) consisted of 1,209 IDUs initially seronegative for human immunodeficiency virus (HIV) who were followed from 1995 to 1998 at 15 Administration drug treatment clinics. At enrollment and approximately every 4 months thereafter, participants were assessed for HIV seropositivity. As of December 1998, there were 133 HIV type 1 seroconversions and approximately 2,300 person-years of follow-up. Of the 133 observed seroconversions, specimens from 126 persons were available for subtyping (27 subtype B, 99 subtype E). In this analysis, the authors assessed differences in subtype-specific transmission while controlling for important risk factors. The methodology used accounts for left truncation, interval censoring, and competing risks as well as for time-varying covariates such as each IDU's history of reported frequency of injection and of incarceration. Using plausible epidemiologic assumptions and controlling for behavioral risks, the authors found that a significantly higher transmission probability was associated with subtype E compared with subtype B in this population. Since many epidemiologic, virologic, and host factors can influence HIV transmission, it was difficult to conclude whether these differences in transmission probabilities were due to biologic properties associated with subtype.     

Semi-parametric models for mismeasured exposure information in vaccine trials

Exposure to infection information is important for estimating vaccine efficacy, but it is difficult to collect and inherently prone to missingness and mismeasurement. It is, therefore, generally not feasible to collect good exposure information on all participants in a large vaccine trial. We discuss study designs that collect detailed exposure information for only a small subset of trial participants, while collecting crude exposure information on all participants, and treat estimation of vaccine efficacy in the missing data/measurement error framework. We demonstrate with the example of an HIV vaccine trial the improvements in bias and efficiency when we combine the different levels of exposure information to estimate vaccine efficacy for reducing both susceptibility and infectiousness. We compare the performance of recently developed semi-parametric missing data methods of Pepe and Fleming and Carroll and Wand, Robins, Hsieh and Newey, and Reilly and Pepe. © 1998 John Wiley & Sons, Ltd.