Penalized regression models to select biomarkers of environmental enteric dysfunction associated with linear growth acquisition in a Peruvian birth cohort.

Environmental enteric dysfunction (EED) is associated with chronic undernutrition. Efforts to identify minimally invasive biomarkers of EED reveal an expanding number of candidate analytes. An analytic strategy is reported to select among candidate biomarkers and systematically express the strength of each marker's association with linear growth in infancy and early childhood. 180 analytes were quantified in fecal, urine and plasma samples taken at 7, 15 and 24 months of age from 258 subjects in a birth cohort in Peru. Treating the subjects' length-for-age Z-score (LAZ-score) over a 2-month lag as the outcome, penalized linear regression models with different shrinkage methods were fitted to determine the best-fitting subset. These were then included with covariates in linear regression models to obtain estimates of each biomarker's adjusted effect on growth. Transferrin had the largest and most statistically significant adjusted effect on short-term linear growth as measured by LAZ-score-a coefficient value of 0.50 (0.24, 0.75) for each log2 increase in plasma transferrin concentration. Other biomarkers with large effect size estimates included adiponectin, arginine, growth hormone, proline and serum amyloid P-component. The selected subset explained up to 23.0% of the variability in LAZ-score. Penalized regression modeling approaches can be used to select subsets from large panels of candidate biomarkers of EED. There is a need to systematically express the strength of association of biomarkers with linear growth or other outcomes to compare results across studies.

Animal models of endocrine disruption.

Endocrine disrupting chemicals (EDCs) are compounds that alter the structure and function of the endocrine system and may be contributing to disorders of the reproductive, metabolic, neuroendocrine and other complex systems. Typically, these outcomes cannot be modeled in cell-based or other simple systems necessitating the use of animal testing. Appropriate animal model selection is required to effectively recapitulate the human experience, including relevant dosing and windows of exposure, and ensure translational utility and reproducibility. While classical toxicology heavily relies on inbred rats and mice, and focuses on apical endpoints such as tumor formation or birth defects, EDC researchers have used a greater diversity of species to effectively model more subtle but significant outcomes such as changes in pubertal timing, mammary gland development, and social behaviors. Advances in genomics, neuroimaging and other tools are making a wider range of animal models more widely available to EDC researchers.

Method to characterize inorganic particulates in lung tissue biopsies using field emission scanning electron microscopy.

Humans accumulate large numbers of inorganic particles in their lungs over a lifetime. Whether this causes or contributes to debilitating disease over a normal lifespan depends on the type and concentration of the particles. We developed and tested a protocol for in situ characterization of the types and distribution of inorganic particles in biopsied lung tissue from three human groups using field emission scanning electron microscopy (FE-SEM) combined with energy dispersive spectroscopy (EDS). Many distinct particle types were recognized among the 13 000 particles analyzed. Silica, feldspars, clays, titanium dioxides, iron oxides and phosphates were the most common constituents in all samples. Particles were classified into three general groups: endogenous, which form naturally in the body; exogenic particles, natural earth materials; and anthropogenic particles, attributed to industrial sources. These in situ results were compared with those using conventional sodium hypochlorite tissue digestion and particle filtration. With the exception of clays and phosphates, the relative abundances of most common particle types were similar in both approaches. Nonetheless, the digestion/filtration method was determined to alter the texture and relative abundances of some particle types. SEM/EDS analysis of digestion filters could be automated in contrast to the more time intensive in situ analyses.

[The content of protein regulators of apoptosis Bcl-2 and bad in regional lymph nodes of the liver under the influence of 50 Hz a magnetic field].

There was investigated the expression of molecular and cellular regulators of apoptosis Bcl-2 and Bad in the regional lymph nodes of the liver in rats exposed to the magnetic field of 50 Hz during 14 days. There was revealed a reduction in the protein expression of regulators of apoptosis Bcl-2 in the cortical area of the regional lymph nodes of the liver in animals exposed to the magnetic field.

[Features of apoptosis in conditions of the exposure to organochlorine compounds and vanadium].

The cell structures involved into the apoptotic mechanism is an ideal object for the study of toxic effects produced by low-molecular-weight compounds on the immune system. Organic chlorine compounds and heavy metals were tested for their effects in the in vitro system. The experiments show that organic chlorine compounds inhibit apoptotic cell death. An assessment of their results has demonstrated that vanadium promotes activation-induced lymphocyte death. Thus, there are multidirectional immune responses upon exposure to organic chlorine compounds and heavy metals.

[Effect of domestic gas on morphological and functional state of parenchymatous organs in rats].

The work is devoted to a study of morphological and functional changes in liver and kidneys in the simulation of subacute toxic exposure of rats to domestic gas in the experiment. In the course of studies found that the subacute intoxication by domestic gas and its metabolites were shown to causes profound structural and metabolic lesions of the liver and kidneys that can progress to develop the chronic liver and kidney insufficiency.

[Microelemental and cytologic state of children in urban areas].

Microelemental and cytomorphologic studies among preschoolers living in East Kazakhstan revealed accumulation of toxic metals (lead, mercury, cadmium) in hair and lower essential microelements (copper, selenium) in urine, increased number of cells with vacuole dystrophy, phagocyted, apoptotic (residual bodies) and degenerated cells, mastocytes, acaryotes in nasal and buccal epithelium. Noninvasive studies (of hair, urine, nasal and buccal epithelium) are sensitive, informative and prognostically valuable tests for diagnosis of ecologically dependent disorders.

[Impact of ambient air pollution by a pulp-and-paper mill on the cytological status of the nasal and oral mucosa in children].

The cytological state of nasal and oral mucosae in the children and adolescents living in the town of Koryazhma was evaluated at the schools located differently from the Kotlas pulp-and-paper mill (PPM). All the Kozyazhma children under examination were found to have an increased epithelocytic alteration index, which is likely to suggest cytotoxic exposure, which was shown to a greater extent with the duration of residence at the school more adjacent to the PPM. The first-form pupils from the school locates more closely to the PPM were found to showed a higher index of natural microflora colonization with buccal epitheliocytes and a trend for an increase in the epitheliocytic differentiation coefficient characterizing the high incidence of diseases.

[Effect of toxins of cyanobacteria of the Microcystis genus from the Shershnevo Reservoir on DNA, cell cycle, and apoptosis of bone marrow cells in CBA mice].

The effect of toxins of a Cyanobacterium sample of the Shershnevo Reservoir on DNA, which was presented by cyanobacteria of the Microcystis genera, on the bone marrow of male CBA mice (whose age was 3 months and weight 24 g) was evaluated. With intraperitoneal administration, LD50 and LD16 of this sample for male CBA mice were 48.4 and 42.1 mg/kg, respectively. Administration of Microcystis cyanobacterial sample from the Shershnevo Reservoir in doses of 1/10 of LD16 and 1/2 of LD16, and LD16 was found to cause a dose-dependent reduction in the number of bone marrow nucleated cells, a dose-dependent increase in the rate of cell apoptotic death, a reduction in the duration of a cell cycle (within the first 12 hours), which gave way to an increase in the duration of the cycle 24 hours after administration, a dose-dependent increase in the frequency of micronuclei in the murine bone marrow eryphrocytes, and a dose-dependent decrease in the polychromatophil/normochromatophil ratio in the murine bone marrow.

Neuronal correlates of symptom formation in functional somatic syndromes: a fMRI study.

Functional somatic syndromes are characterized by high morbidity due to various, fluctuating symptoms without objective somatic findings. There is increasing evidence for the contribution of emotional and cognitive functions to symptom formation, which has been well established in the perception of pain. In addition to their involvement in various other cognitive and emotional processes, the anterior cingulate and insular cortex are thought to contribute to the so-called "pain neuromatrix". Recent data suggest that these areas appear also to be involved in symptom manifestation in multiple chemical sensitivity. Here we used functional Magnetic Resonance Imaging (fMRI) to test whether this network is also involved in the induction of unpleasant perceptions by sham mobile phone radiation in subjectively electrosensitive patients. This design enabled us to completely dissociate the unpleasant subjective perception from any real physical stimulus. Fifteen subjectively electrosensitive patients and 15 age- and gender-matched healthy controls were exposed to sham mobile phone radiation and heat as a control condition. The perceived stimulus intensities were rated on a five-point scale. During anticipation of and exposure to sham mobile phone radiation increased activations in anterior cingulate and insular cortex as well as fusiform gyrus were seen in the electrosensitive group compared to controls, while heat stimulation led to similar activations in both groups. Symptom manifestation during sham exposure to mobile phone radiation was accompanied by specific alterations of cortical activity in anterior cingulate and insular cortex in subjectively electrosensitive patients further supporting the involvement of these areas in the perception of unpleasantness and generation of functional somatic syndromes.

[Cytogenetic and other cariological parameters of exfoliative buccal cells in Vietnamese children from areas where dioxin-containing herbicides were applied].

In a cohort of 69 South Vietnam children, full cariological analysis of buccal epithelial cells was performed. In order to evaluate the significance of cariological changes, all the parameters under study were divided into three groups: cytogenetic indices, apoptotic indices, and indirect indices of proliferation; integral indexes in each group were determined and the relations between them were found while assessing the effects of environment pollution on public health. The number of cells with cytogenetic alterations (micronuclei and protrusions) was increased, the process of tissue proliferation was intensified, and the apoptotic process was decelerated in children li-ing in areas polluted with Agent Orange/dioxins, which evidenced that the complex of environmental factors these superecotoxicants were part of had a harmful effect on the population. The parameters studied did not depend on age and sex of the children; the number of congenital morphogenetic variants per one child significantly correlated with the sum of cells with cytogenetic alterations.

[Changes of human immunophenotype during adaptation to environmental factors, in different forms of pathology and their specific treatment].

The aim of the study was to elucidate mechanisms underlying variations of human immune phenotype in the course of adaptation to environmental factors, development of different forms of pathology and their specific treatment from dynamics of expression of surface CD-molecules in lymphocyte plasmolemma and immunoglobulin A, M, G levels in blood plasma. 253 assumingly healthy volunteers residing in the Moscow Megapolis exhibited a tendency toward enhanced lymphocyte apoptosis and reduced efficiency of their co-stimulation and cooperative interaction. Pathologies of different etiology were associated with the imbalance of specific and non-specific reactions of immune and biological control. Specifically, expression of CD 95 (Fas/APO-1) molecules triggering apoptosis increased in all patients with postmenopausal osteoporosis, pneumonia, and bronchial asthma but decreased in patients with rheumatic fever, erosive and ulcerative lesions in the digestive tract. Expression of surface receptors by the cells involved in "processing" of unshared antigens, their presentation by T-lymphocytes, inactivation and destruction of pathogens was enhanced only in patients with erosive and ulcerative lesions in the digestive tract. It decreased in rheumatic fever, postmenopausal osteoporosis, pneumonia, and bronchial asthma. Effective specific treatment leading to the normalization of (or tending to normalize) expression of CD molecules in lymphocytes and prevented changes in the immune and biological control system.

[Cyto- and histological criteria for a risk of environment-induced diseases].

The author proposes morphological criteria determining the risk of environment-induced diseases. The experimental studies analyzing 23 indices of the development of reparative regeneration in the liver of rats exposed to environmental factors have revealed that a significant change in the ratio of uni- and binuclear tetraploid hepatocytes is a criterion for the risk of hepatotoxic effect. Evaluation of the cytological status of nasal and oral mucosae, by using 21 indices has indicated that a significant reduction in the proportion of individuals with the normal cytological status is a criterion for the risk of environment-induced diseases.

[The effects of fungous semination of dwelling environment on the cytological status of human mucosal membranes].

High level of fungous semination of dwelling environment is shown to have a destructive effect on mucosal membranes, which is manifested by their inflammation and allergic condition. The study of the cytological status of the nasal and oral mucosa proved its high sensitivity and significance when studying the influence of fungous semination of dwelling environment on the human organism.

Risk perception, somatization, and self report of complaints related to electromagnetic fields--a randomized survey study.

Exposure to electromagnetic fields (EMF) as well as EMF-related complaints has increased over the past decades. However, it is unclear whether these complaints are related to the electromagnetic or other physical properties of these fields per se, to salience of EMF in media, or to both. What is the prevalence of EMF-related complaints in the general population? What are the influencing factors on this prevalence? Does reporting of EMF-related symptoms depend on cognitive factors? To answer these questions, a survey with random variation of three cognitive factors was performed. As expected, EMF-related complaints were reported more by females and people with higher somatization tendency. Age had no significant linear effect on EMF-related complaints. The cognitive condition of threat produced a significant contrast effect among people with high somatization tendency on EMF-related complaints. Cognition can influence reporting of EMF-related effects. Thus, in future research of such effects, psychologically influencing factors should be included. Also risk communication should incorporate knowledge about social cognition.

[Connection between changes in the nasal and mouth mucosa with immune status under the effect of environmental factors]. / Sviaz' izmenenii slizistykh obolochek nosa i rta s imunnym statusom pri vozdeistvii faktorov okruzhaiushchei sredy.

The paper summarizes the results of determination of the cytological status of nasal and oral mucosae in 789 preschool and school children from different cities and towns of the Russian Federation: Moscow, Klimovsk, Yaroslavl. A relationship between the mucosae, immunity, and morbidity, and environmental pollution is shown in the town of Klimovsk as an example.