Crohn's Disease and Early Exposure to Domestic Refrigeration

Background

Environmental risk factors playing a causative role in Crohn''s Disease (CD) remain largely unknown. Recently, it has been suggested that refrigerated food could be involved in disease development. We thus conducted a pilot case control study to explore the association of CD with the exposure to domestic refrigeration in childhood.

Methodology/Principal Findings

Using a standard questionnaire we interviewed 199 CD cases and 207 age-matched patients with irritable bowel syndrome (IBS) as controls. Cases and controls were followed by the same gastroenterologists of tertiary referral clinics in Tehran, Iran. The questionnaire focused on the date of the first acquisition of home refrigerator and freezer. Data were analysed by a multivariate logistic model. The current age was in average 34 years in CD cases and the percentage of females in the case and control groups were respectively 48.3% and 63.7%. Patients were exposed earlier than controls to the refrigerator (X2 = 9.9, df = 3, P = 0.04) and refrigerator exposure at birth was found to be a risk factor for CD (OR = 2.08 (95% CI: 1.01–4.29), P = 0.05). Comparable results were obtained looking for the exposure to freezer at home. Finally, among the other recorded items reflecting the hygiene and comfort at home, we also found personal television, car and washing machine associated with CD.

Conclusion

This study supports the opinion that CD is associated with exposure to domestic refrigeration, among other household factors, during childhood.     

Regulation of TB Vaccine-Induced Airway Luminal T Cells by Respiratory Exposure to Endotoxin

Tuberculosis (TB) vaccine-induced airway luminal T cells (ALT) have recently been shown to be critical to host defense against pulmonary TB. However, the mechanisms that maintain memory ALT remain poorly understood. In particular, whether respiratory mucosal exposure to environmental agents such as endotoxin may regulate the size of vaccine-induced ALT population is still unclear. Using a murine model of respiratory genetic TB vaccination and respiratory LPS exposure, we have addressed this issue in the current study. We have found that single or repeated LPS exposure increases the number of antigen-specific ALT which are capable of robust secondary responses to pulmonary mycobacterial challenge. To investigate the potential mechanisms by which LPS exposure modulates the ALT population, we have examined the role of ALT proliferation and peripheral T cell recruitment. We have found that LPS exposure-increased ALT is not dependent on increased ALT proliferation as respiratory LPS exposure does not significantly increase the rate of proliferation of ALT. But rather, we find it to be dependent upon the recruitment of peripheral T cells into the airway lumen as blockade of peripheral T cell supplies markedly reduces the initially increased ALT. Thus, our data suggest that environmental exposure to airborne agents such as endotoxin has a profound modulatory effect on TB vaccine-elicited T cells within the respiratory tract. Our study provides a new, M.tb antigen-independent mechanism by which the respiratory mucosal anti-TB memory T cells may be maintained.     

Systemic Respiratory Adaptations to Air Exposure in Intertidal Decapod Crustaceans

SYNOPSIS: The responses of intertidal decapods to emersion areclosely related to the particular conditions of emersion, yetall members of this group of animals face the problems of watershortage and internal hypoxia during air exposure. Several speciesexhibit modification of normal ventilatory activity and thisresponse seems to enable these crabs to take up seawater fromthe substrate. Other crabs have specific morphological adaptationspermitting recirculation of water from the exhalent aperturesback into the gill chamber. The hemocyanin of some species hasa higher affinity for oxygen, and this difference may be moreprevalent in tropical animals. The higher oxygen affinity undoubtedlycompensates in part for the lower internal oxygen tensions duringair exposure. Structural specialization of the branchial apparatusmay prevent the gill lamellae from adhering together, a processwhich reduces the surface available for gas exchange. Thereis a wide range of responses to emersion and yet relativelyfew specific adaptations. Some species are able to merely tolerateair exposure, while others are able to more fully exploit thehabitat.     

Prenatal Exposure to Cadmium,Placental Permeability and Birth Outcomes in Coastal Populations of South Africa

Background

The impact of prenatal exposure to cadmium (Cd) on birth outcomes is an area of concern. This study aimed to assess an impact of prenatal Cd exposure on birth outcomes in distinct coastal populations of South Africa.

Methods

Cadmium was measured in maternal blood (CdB) (n = 641), cord blood and in maternal urine (n = 317). This investigation assessed the associations between CdB (non-transformed) and birth outcomes across the 25^th, 50th, and 75th percentile for birth weight, birth length and head circumference, to test for a linear trend. Associations between natural log-transformed maternal CdB, size at birth and other factors were further evaluated using linear mixed-effects modelling with random intercepts.

Results

The average gestational age in the total sample was 38 weeks; 47% of neonates were female, average birth weight was 3065 g and 11% were of low birth weight (< 2500 g). The geometric mean (GM) of the maternal CdB level was 0.25 μg/L (n = 641; 95% CI, 0.23–0.27). The cord blood Cd level was 0.27 μg/L (n = 317; 95% CI, 0.26–0.29) and urine (creatinine-corrected) Cd level was 0.27 μg/L (n = 318; 95% CI, 0.24–0.29). The CdB cord:maternal ratio in the sub-cohort was 1, suggesting that the placenta offers no protective mechanism to the foetus. An inverse association was found between CdB and the lower birth weight percentile in female neonates only (β = - 0.13, p = 0.047). Mothers who reported eating vine vegetables daily had lower levels of CdB (β = - 0.55, p = 0.025). Maternal smoking was associated with an elevation in natural log-transformed CdB levels in both male and female cohorts.

Discussion

Significant inverse associations between prenatal Cd exposure and birth anthropometry were found in female neonates but not in male neonates, suggesting potential sex differences in the toxico-kinetics and toxico-dynamics of Cd.     

Early Response of Willow to Increasing Silver Concentration Exposure

This is a preliminary hydroponic study to test willow sensitivity to silver nitrate, a highly toxic chemical compound. We grew willow cuttings for a period of three weeks in the presence of increasing AgNO₃ concentrations and assessed the response in terms of growth and physiology. We found that AgNO₃ is generally extremely harmful to willow. AgNO₃ concentration as high as 0.027 μM may result in a significant reduction of biomass productivity and a decrease in stomatal conductance over the first week of exposure. However, willows seem able to adapt to high AgNO₃ concentrations on a longer timeline.     

Nicotine Exposure Does not Alter Plasma to Brain Choline Transfer

Acute and chronic nicotine exposure in rats is associated with an increase in brain acetylcholine (ACh) transmission. The acquisition of choline for neuronal ACh synthesis occurs primarily via two pathways; first, free choline is transported from the blood across the blood-brain barrier (BBB) and/or second, from synaptic choline generated by either hydrolysis of non-bound ACh or membrane phosphatidylcholine catabolism. To determine if nicotine-induced cholinergic demand is associated with increased choline transport rates into brain, we measured BBB choline transport in naïve and S-(−) nicotine exposed rats (acute and chronic, 4.5 mg/kg/d for 1, 14, 21 and 28 d; osmotic minipumps) using the in situ rat brain perfusion technique. No significant changes in choline uptake after acute or chronic nicotine exposure were observed in whole brain or cortex. Of considerable interest was a significant decrease in regional brain choline uptake measured in the hippocampus after chronic nicotine exposure (28 d). Our data suggest that the increased ACh transmission observed after nicotine exposure does not correlate with increased blood-to-brain transfer of choline. Considering these data and previous literature reports, we propose that the additional free choline required under conditions of nicotine exposure (for ACh synthesis) is primarily recruited from membrane phospholipid metabolism.     

Myelin Deficits Produced by Early Postnatal Exposure to Inorganic Lead or Triethyltin Are Persistent

Abstract: Long-Evans rat pups were exposed to either inorganic lead (400 mg Pb as lead acetate/kg body weight/day) or triethyltin sulfate (1.0 mg/kg body weight/day), by gastric intubation, from 2 days through 29 days of age. The rats were then weaned and placed on standard lab chow ad libitum. At 30 days of age, leadtreated rats exhibited statistically significant decreases in body and brain weights (22% and 17%, respectively), and the concentration of forebrain myelin was significantly reduced, by 21% relative to the 4.9 mg myelin protein/g brain in control rats. Although these animals recovered from the body weight deficits after several months, the deficits in brain weight and myelin concentration were still present at 120 days of age. This suggests that the lead-induced myelin deficits were permanent. Lead levels in brain, which were maximal at 30 days of age when the treatment was terminated, decreased more slowly than in other organs and were still 30% of maximal levels at 120 days of age. Triethyltin-treated animals also had significantly decreased body and brain weights (20% and 11%, respectively) at 30 days of age, and an even more severe reduction in forebrain myelin concentration (33%). These animals also regained a normal body weight by 120 days of age, but again the deficits in brain weight and myelin concentration persisted. Tin levels in brain and other organs had decreased to control levels by 60 days of age. Animals malnourished by maternal deprivation to match the body weights of the treated animals had myelin deficits that were less severe than those in the treated animals at 30 days of age (approximately 11% less than controls); however, these myelin deficits also persisted throughout the subsequent 90-day recovery period examined. The apparent lack of recovery from CNS myelin deficits produced by neonatal exposure to different heavy metals or to malnutrition reemphasizes the vulnerability of the developing nervous system to a wide range of metabolic insults.     

Sensitization to Food and Inhalant Allergens in Relation to Atopic Diseases in Early Childhood: A Birth Cohort Study

Objectives

A correct interpretation of sensitization to common allergens is critical in determining susceptibility to allergic diseases. The aim of this study was to investigate the patterns of sensitization to food and inhalant allergens, and their relation to the development of atopic diseases in early childhood.

Methods

Children aged 0 through 4 years from a birth cohort in the Prediction of Allergies in Taiwanese Children (PATCH) study were enrolled. Specific IgE antibody against food and inhalant allergens were measured and their association between total serum IgE levels and atopic diseases were assessed.

Results

A total of 182 children were regular followed up at clinics for a four-year follow-up period. The prevalence of food allergen sensitization increased markedly after 6 months of age, reaching up to 47% at 1.5 years of age and then declined significantly to 10% in parallel with a considerable increase in the prevalence of sensitization to inhalant allergens up to 25% at age 4. Food allergen sensitization appeared to be mainly associated with the elevation of serum total IgE levels before age 2. A combined sensitization to food and inhalant allergens had an additive effect on serum IgE levels after age 2, and was significantly associated with the risk of developing atopic diseases at age 4.

Conclusions

Sensitization to food occurs early in life, in parallel with the rising prevalence of sensitization to inhalant allergens at older age. A combined sensitization to food and inhalant allergens not only has an additive increase in serum IgE antibody production but also increases the risk of developing allergic respiratory diseases in early childhood.     

甲氨蝶呤对早期神经胚基因表达的影响

目的:利用甲氨蝶呤(methotrexate,MTX)干预孕鼠,探讨MTX对早期神经胚基因表达的影响。方法:用MTX(4.5 mg/kg体重)干预孕鼠,通过NimbleGene表达谱芯片、Real time-PCR及免疫组化等方法进行差异表达基因的筛选和验证。结果:MTX处理后神经管畸形(NTDs)发生率为32.1%。表达谱芯片筛选出166个差异表达基因,其中4个凋亡相关基因(Endog,Trp53,Casp3,Bax)均表现为上调(fold change1.5,P0.05),3个增殖相关基因(Ptch1,Pla2g4a,Foxg1)均表现为下调(fold change0.67,P0.05);NTDs胚胎神经上皮Caspase-3表达显著升高(P0.05),phospho-histone H3(pH3)表达显著降低(P0.05)。结论:MTX影响了早期神经胚的基因表达,尤其是引起了凋亡、增殖相关基因表达的异常,这可能在叶酸缺乏引起NTDs发生的相关机制之一。     

Mercury Transfer During Pregnancy and Breastfeeding: Hair Mercury Concentrations as Biomarker

Hair mercury (HHg) concentration is a biomarker of exposure that is widely used to assess environmental contamination by fish methylmercury and neurodevelopment in children. In the Rio Madeira basin (Brazilian Amazon), total HHg concentrations in 649 mother–infant pairs were measured at birth (prenatal exposure) and after 6 months of exclusive breastfeeding; these mother–infant pairs were from high fish-eating communities (urban, n?=?232; rural, n?=?35; and Riverine, n?=?262) and low fish-eating tin-miner settlers (n?=?120). Differences in kinetics were seen between Hg exposure from fish consumption and environmental exposure to a tin-ore mining environment. Overall maternal HHg concentrations (at childbirth and after 6 months of lactation) were higher than those of infant HHg. However, the relative change in HHg after 6 months of lactation showed that mothers decreased HHg while infants increased HHg. The relative change showed a consistently higher increase for girls than boys with a statistical significance only in high fish-eating mothers. The correlation coefficients between maternal and newborn hair were high and statistically significant for mothers living in urban (r?=?0.66, p?<?0.001), rural (r?=?0.89, p?<?0.001), and Riverine (r?=?0.89, p?<?0.001) communities not for tin miner settlers (r?=?0.07, p?=?0.427). After 6 months of exclusive breastfeeding, correlation coefficients showed high correlation coefficients and statistical significance for all groups (urban, r?=?0.73, p?<?0.001; rural, r?=?0.88, p?<?0.001; Riverine, r?=?0.91, p?<?0.001) except for Tin miners (r?=??0.07, p?=?0.428). A linear model analysis was used to assess the longitudinal associations of maternal total HHg and total HHg at birth (0 days) and 6 months of age in exclusively breastfed infants. Regression analysis significantly predicted HHg in newborn from maternal HHg for high fish-eating maternal-infant pairs. Conclusion: The concentration of mercury accumulated in newborn tissues (in utero and during breastfeeding) relevant to both, maternal sources and infant exposure, can be reliably assessed from maternal hair.     

High Uptake of Exclusive Breastfeeding and Reduced Early Post-Natal HIV Transmission

Background

Empirical data showing the clear benefits of exclusive breastfeeding (EBF) for HIV prevention are needed to encourage implementation of lactation support programs for HIV-infected women in low resource settings among whom replacement feeding is unsafe. We conducted a prospective, observational study in Lusaka, Zambia, to test the hypothesis that EBF is associated with a lower risk of postnatal HIV transmission than non-EBF.

Methods and Results

As part of a randomized trial of early weaning, 958 HIV-infected women and their infants were recruited and all were encouraged to breastfeed exclusively to 4 months. Single-dose nevirapine was provided to prevent transmission. Regular samples were collected from infants to 24 months of age and tested by PCR. Detailed measurements of actual feeding behaviors were collected to examine, in an observational analysis, associations between feeding practices and postnatal HIV transmission. Uptake of EBF was high with 84% of women reporting only EBF cumulatively to 4 months. Post-natal HIV transmission before 4 months was significantly lower (p = 0.004) among EBF (0.040 95% CI: 0.024–0.055) than non-EBF infants (0.102 95% CI: 0.047–0.157); time-dependent Relative Hazard (RH) of transmission due to non-EBF = 3.48 (95% CI: 1.71–7.08). There were no significant differences in the severity of disease between EBF and non-EBF mothers and the association remained significant (RH = 2.68 95% CI: 1.28–5.62) after adjusting for maternal CD4 count, plasma viral load, syphilis screening results and low birth weight.

Conclusions

Non-EBF more than doubles the risk of early postnatal HIV transmission. Programs to support EBF should be expanded universally in low resource settings. EBF is an affordable, feasible, acceptable, safe and sustainable practice that also reduces HIV transmission providing HIV-infected women with a means to protect their children''s lives.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00310726","term_id":"NCT00310726"}}NCT00310726     

Medically Complex Pregnancies and Early Breastfeeding Behaviors: A Retrospective Analysis

Background

Breastfeeding is beneficial for women and infants, and medical contraindications are rare. Prenatal and labor-related complications may hinder breastfeeding, but supportive hospital practices may encourage women who intend to breastfeed. We measured the relationship between having a complex pregnancy (entering pregnancy with hypertension, diabetes, or obesity) and early infant feeding, accounting for breastfeeding intentions and supportive hospital practices.

Methods

We performed a retrospective analysis of data from a nationally-representative survey of women who gave birth in 2011–2012 in a US hospital (N = 2400). We used logistic regression to examine the relationship between pregnancy complexity and breastfeeding. Self-reported prepregnancy diabetes or hypertension, gestational diabetes, or obesity indicated a complex pregnancy. The outcome was feeding status 1 week postpartum; any breastfeeding was evaluated among women intending to breastfeed (N = 1990), and exclusive breastfeeding among women who intended to exclusively breastfeed (N = 1418). We also tested whether breastfeeding intentions or supportive hospital practices mediated the relationship between pregnancy complexity and infant feeding status.

Results

More than 33% of women had a complex pregnancy; these women had 30% lower odds of intending to breastfeed (AOR = 0.71; 95% CI, 0.52–0.98). Rates of intention to exclusively breastfeed were similar for women with and without complex pregnancies. Women who intended to breastfeed had similar rates of any breastfeeding 1 week postpartum regardless of pregnancy complexity, but complexity was associated with >30% lower odds of exclusive breastfeeding 1 week among women who intended to exclusively breastfeed (AOR = 0.68; 95% CI, 0.47–0.98). Supportive hospital practices were strongly associated with higher odds of any or exclusive breastfeeding 1 week postpartum (AOR = 4.03; 95% CI, 1.81–8.94; and AOR = 2.68; 95% CI, 1.70–4.23, respectively).

Conclusions

Improving clinical and hospital support for women with complex pregnancies may increase breastfeeding rates and the benefits of breastfeeding for women and infants.     

Existence and Functions of Neurotens in Human Early Placental Villi

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Distribution and Speciation of Arsenic by Transplacental and Early Life Exposure to Inorganic Arsenic in Offspring Rats

The amount of arsenic compounds was determined in the liver and brain of pups and in breast milk in the pup's stomach in relation to the route of exposure: transplacental, breast milk, or drinking water. Forty-eight pregnant rats were randomly divided into four groups, each group was given free access to drinking water that contained 0, 10, 50, and 100 mg/L NaAsO₂ from gestation day 6 (GD 6) until postnatal day 42 (PND 42). Once pups were weaned, they started to drink the same arsenic-containing water as the dams. Contents of inorganic arsenic (iAs), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and trimethylarsenic acid (TMA) in livers and brains of the pups on PND 0, 15, 28, and 42 and breast milk taken from the pup's stomach on PND 0 and 15 were detected using the hydride generation atomic absorption spectroscopy method. Concentrations of iAs, MMA, and DMA in the breast milk, the brain, and the liver of the pups increased with the concentration of arsenic in drinking water on PND 0, 15, 28, and 42. Compared to the liver or brain, breast milk had the lowest arsenic concentrations. There was a significant decrease in the levels of arsenic species on PND 15 compared to PND 0, 28, or 42. It was confirmed that arsenic species can pass through the placental barrier from dams to offspring and across the blood–brain barrier in the pups, and breast milk from dams exposed to arsenic in drinking water contains less arsenic than the liver and brain of pups.     

Abnormal Placental Development and Early Embryonic Lethality in EpCAM-Null Mice

Background

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells.

Methodology/Principal Findings

To gain insights into EpCAM function in vivo, we generated EpCAM −/− mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to βgeo. EpCAM +/− mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/− embryos revealed that βgeo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM −/− mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM −/− embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM −/− placentas.

Conclusion

EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.     

Mitochondrial Respiratory Dysfunction and Oxidative Stress after Chronic Malathion Exposure

Malathion is a pesticide used on a large scale and with high potential risk for human exposure. However, it is reasonable to hypothesize that while the malathion is metabolizing reactive oxygen species (ROS) can be generated and subsequently there is onset of an oxidative stress in central nervous system (CNS) structures: hippocampus, cortex, striatum and cerebellum of intoxicated rats due to mitochondrial respiratory chain disfunctions. The present study was therefore undertaken to evaluate malathion-induced lipid peroxidation (LPO), superoxide production from sub-mitochondrial particles and the activity of complexes II and IV of the mitochondrial respiratory chain. Malathion was administered in doses of 25, 50, 100 and 150 mg malathion/kg. After malathion administration LPO increased in hippocampus and striatum. This was accompanied by an increase in the formation of superoxide in submitochondrial particles in the hippocampus. Complex IV suffered significant inhibition of its activity. We could demonstrate in this study that malathion induces oxidative stress and it could be due to inactivation of mitochondrial respiratory complexes.     

Early Exposure to Volatile Anesthetics Impairs Long-Term Associative Learning and Recognition Memory

Background

Anesthetic exposure early in life affects neural development and long-term cognitive function, but our understanding of the types of memory that are altered is incomplete. Specific cognitive tests in rodents that isolate different memory processes provide a useful approach for gaining insight into this issue.

Methods

Postnatal day 7 (P7) rats were exposed to either desflurane or isoflurane at 1 Minimum Alveolar Concentration for 4 h. Acute neuronal death was assessed 12 h later in the thalamus, CA1-3 regions of hippocampus, and dentate gyrus. In separate behavioral experiments, beginning at P48, subjects were evaluated in a series of object recognition tests relying on associative learning, as well as social recognition.

Results

Exposure to either anesthetic led to a significant increase in neuroapoptosis in each brain region. The extent of neuronal death did not differ between groups. Subjects were unaffected in simple tasks of novel object and object-location recognition. However, anesthetized animals from both groups were impaired in allocentric object-location memory and a more complex task requiring subjects to associate an object with its location and contextual setting. Isoflurane exposure led to additional impairment in object-context association and social memory.

Conclusion

Isoflurane and desflurane exposure during development result in deficits in tasks relying on associative learning and recognition memory. Isoflurane may potentially cause worse impairment than desflurane.     

Human Exposure to Early Morning Anopheles funestus Biting Behavior and Personal Protection Provided by Long-Lasting Insecticidal Nets

A shift towards early morning biting behavior of the major malaria vector Anopheles funestus have been observed in two villages in south Benin following distribution of long-lasting insecticidal nets (LLINs), but the impact of these changes on the personal protection efficacy of LLINs was not evaluated. Data from human and An. funestus behavioral surveys were used to measure the human exposure to An. funestus bites through previously described mathematical models. We estimated the personal protection efficacy provided by LLINs and the proportions of exposure to bite occurring indoors and/or in the early morning. Average personal protection provided by using of LLIN was high (≥80% of the total exposure to bite), but for LLIN users, a large part of remaining exposure occurred outdoors (45.1% in Tokoli-V and 68.7% in Lokohoué) and/or in the early morning (38.5% in Tokoli-V and 69.4% in Lokohoué). This study highlights the crucial role of LLIN use and the possible need to develop new vector control strategies targeting malaria vectors with outdoor and early morning biting behavior. This multidisciplinary approach that supplements entomology with social science and mathematical modeling illustrates just how important it is to assess where and when humans are actually exposed to malaria vectors before vector control program managers, policy-makers and funders conclude what entomological observations imply.