Special vulnerability of children to environmental exposures

Fetal life and childhood are the periods most vulnerable to the harmful effects of exposure to environmental insults. This is because, during these periods, there is rapid cell division, organs are being formed, and growth is rapid. Thus, disruption of these processes may result in life-long abnormalities. Of particular concern are exposures that alter cognitive function and behavior, but exposures that alter growth, development, and reproductive and immune system function and that may increase risk of development of diseases like cancer later in life are also especially important. Exposure to environmental chemicals as well as infectious agents occurs via air, food, water, and absorption through the skin. Therefore, the environment in which fetal and childhood development occurs is very important. Unfortunately, poverty is a major risk factor for both exposures and childhood and later-life disease resulting from exposures to both environmental chemicals and infectious agents. It is very important to protect children because they are the future generation

Changes in Youth Cigarette Use Following the Dismantling of an Antitobacco Media Campaign in Florida

We examined the association of the termination of a successful youth-targeted antitobacco media campaign ("truth") and changes in smoking rates among youths aged 12-17 years in Florida. Six telephone-based surveys were completed during the active media campaign (1998-2001), and 2 postcampaign surveys were completed in 2004 and 2006 (each n ~1,800). Prevalence of current smoking among youth observed during the campaign continued to decrease in the first postcampaign survey; however, by the second follow-up survey, youth smoking rates had increased significantly for youth aged 16 years or older. Our findings support the need for consistent antitobacco messaging to reduce the prevalence of youth smoking

The Value of Inherited Deficiencies of Human Carbonic Anhydrase Isozymes in Understanding Their Cellular Roles a

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73265/1/j.1749-6632.1984.tb12346.x.pd

The Taste of Carbonation

Carbonated beverages are commonly available and immensely popular, but little is known about the cellular and molecular mechanisms underlying the perception of carbonation in the mouth. In mammals, carbonation elicits both somatosensory and chemosensory responses, including activation of taste neurons. We have identified the cellular and molecular substrates for the taste of carbonation. By targeted genetic ablation and the silencing of synapses in defined populations of taste receptor cells, we demonstrated that the sour-sensing cells act as the taste sensors for carbonation, and showed that carbonic anhydrase 4, a glycosylphosphatidylinositol-anchored enzyme, functions as the principal CO_2 taste sensor. Together, these studies reveal the basis of the taste of carbonation as well as the contribution of taste cells in the orosensory response to CO_2

Lipopolysaccharide-induced interferon response networks at birth are predictive of severe viral lower respiratory infections in the first year of life

Appropriate innate immune function is essential to limit pathogenesis and severity of severe lower respiratory infections (sLRI) during infancy, a leading cause of hospitalization and risk factor for subsequent asthma in this age group. Employing a systems biology approach to analysis of multi-omic profiles generated from a high-risk cohort (n = 50), we found that the intensity of activation of an LPS-induced interferon gene network at birth was predictive of sLRI risk in infancy (AUC = 0.724). Connectivity patterns within this network were stronger among susceptible individuals, and a systems biology approach identified IRF1 as a putative master regulator of this response. These findings were specific to the LPS-induced interferon response and were not observed following activation of viral nucleic acid sensing pathways. Comparison of responses at birth versus age 5 demonstrated that LPS-induced interferon responses but not responses triggered by viral nucleic acid sensing pathways may be subject to strong developmental regulation. These data suggest that the risk of sLRI in early life is in part already determined at birth, and additionally that the developmental status of LPS-induced interferon responses may be a key determinant of susceptibility. Our findings provide a rationale for the identification of at-risk infants for early intervention aimed at sLRI prevention and identifies targets which may be relevant for drug development

Environmental threats to children's health in Southeast Asia and the Western Pacific.

The Southeast Asia and Western Pacific regions contain half of the world's children and are among the most rapidly industrializing regions of the globe. Environmental threats to children's health are widespread and are multiplying as nations in the area undergo industrial development and pass through the epidemiologic transition. These environmental hazards range from traditional threats such as bacterial contamination of drinking water and wood smoke in poorly ventilated dwellings to more recently introduced chemical threats such as asbestos construction materials; arsenic in groundwater; methyl isocyanate in Bhopal, India; untreated manufacturing wastes released to landfills; chlorinated hydrocarbon and organophosphorous pesticides; and atmospheric lead emissions from the combustion of leaded gasoline. To address these problems, pediatricians, environmental health scientists, and public health workers throughout Southeast Asia and the Western Pacific have begun to build local and national research and prevention programs in children's environmental health. Successes have been achieved as a result of these efforts: A cost-effective system for producing safe drinking water at the village level has been devised in India; many nations have launched aggressive antismoking campaigns; and Thailand, the Philippines, India, and Pakistan have all begun to reduce their use of lead in gasoline, with resultant declines in children's blood lead levels. The International Conference on Environmental Threats to the Health of Children, held in Bangkok, Thailand, in March 2002, brought together more than 300 representatives from 35 countries and organizations to increase awareness on environmental health hazards affecting children in these regions and throughout the world. The conference, a direct result of the Environmental Threats to the Health of Children meeting held in Manila in April 2000, provided participants with the latest scientific data on children's vulnerability to environmental hazards and models for future policy and public health discussions on ways to improve children's health. The Bangkok Statement, a pledge resulting from the conference proceedings, is an important first step in creating a global alliance committed to developing active and innovative national and international networks to promote and protect children's environmental health

Exposure to adversity and inflammatory outcomes in mid and late childhood

Background We aimed to estimate the association between exposure to adversity and inflammatory markers in mid (4 years) and late (11-12 years) childhood, and whether effects differ by type and timing of exposure. Methods Data sources: Barwon Infant Study (BIS; N = 510 analyzed) and Longitudinal Study of Australian Children (LSAC; N = 1156 analyzed). Exposures: Adversity indicators assessed from 0 to 4 (BIS) and 0-11 years (LSAC): parent legal problems, mental illness and substance abuse, anger in parenting responses, separation/divorce, unsafe neighborhood, and family member death; a count of adversities; and, in LSAC only, early (0-3), middle (4-7), or later (10-11) initial exposure. Outcomes: Inflammation quantified by high sensitivity C-reactive protein (hsCRP, Log (ug/ml)) and glycoprotein acetyls (GlycA, Log (umol/L)). Analyses: Linear regression was used to estimate relative change in inflammatory markers, adjusted for sociodemographic characteristics, with exposure to adversity. Outcomes were log-transformed. Results Evidence of an association between adversity and hsCRP was weak and inconsistent (e.g., 3+ versus no adversity: BIS: 12% higher, 95%CI -49.4, 147.8; LSAC 4.6% lower, 95%CI: −36.6, 48.3). A small positive association between adversity and GlycA levels was observed at both 4 years (e.g., 3+ versus no adversity: 3.3% higher, 95%CI -3.0, 9.9) and 11-12 years (3.2% higher, 95%CI 0.8, 5.8). In LSAC, we did not find evidence that inflammatory outcomes differed by initial timing of adversity exposure. Conclusions Small positive associations between adversity and inflammation were consistently observed for GlycA, across two cohorts with differing ages. Further work is needed to understand mechanisms, clinical relevance, and to identify opportunities for early intervention.Meredith O'Connor and Sarah Arnup were supported by the Melbourne Children's LifeCourse initiative, funded by a Royal Children's Hospital Foundation Grant (2018-984). Anne-Louise Ponsonby is supported by a National Health and Medical Research Council (NHMRC) Fellowship (1110200). Peter Sly is sup- ported by an NHMRC Fellowship (APP1102590). Naomi Priest is sup- ported by an NHMRC Career Development Fellowship (APP1123677). Kate Lycett is supported by an NHMRC Early Career Fellowship (APP1091124) and Honorary National Heart Foundation Postdoctoral Fellowship (101239). Sharon Goldfeld is supported by an NHMRC Career Development Fellowship (1082922). David Burgner is supported by an NHMRC Investigator Grant (1175744)

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves.Peer reviewe

Ancestral SARS-CoV-2, but not Omicron, replicates less efficiently in primary pediatric nasal epithelial cells

Children typically experience more mild symptoms of Coronavirus Disease 2019 (COVID-19) when compared to adults. There is a strong body of evidence that children are also less susceptible to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection with the ancestral viral isolate. However, the emergence of SARS-CoV-2 variants of concern (VOCs) has been associated with an increased number of pediatric infections. Whether this is the result of widespread adult vaccination or fundamental changes in the biology of SARS-CoV-2 remain to be determined. Here, we use primary nasal epithelial cells (NECs) from children and adults, differentiated at an air-liquid interface to show that the ancestral SARS-CoV-2 replicates to significantly lower titers in the NECs of children compared to those of adults. This was associated with a heightened antiviral response to SARS-CoV-2 in the NECs of children. Importantly, the Delta variant also replicated to significantly lower titers in the NECs of children. This trend was markedly less pronounced in the case of Omicron. It is also striking to note that, at least in terms of viral RNA, Omicron replicated better in pediatric NECs compared to both Delta and the ancestral virus. Taken together, these data show that the nasal epithelium of children supports lower infection and replication of ancestral SARS-CoV-2, although this may be changing as the virus evolves

Advance Access published March 30

Summary The modern environment is associated with an increasing burden of non-communicable diseases (NCDs). Mounting evidence implicates environmental exposures, experienced early in life (including in utero), in the aetiology of many NCDs, though the cellular/molecular mechanism(s) underlying this elevated risk across the life course remain unclear. Epigenetic variation has emerged as a candidate mediator of such effects. The Barwon Infant Study (BIS) is a population-derived birth cohort study (n ¼ 1074 infants) with antenatal recruitment, conducted in the south-east of Australia (Victoria). BIS has been designed to facilitate a detailed mechanistic investigation of development within an epidemiological framework. The broad objectives are to investigate the role of specific environmental factors, gut microbiota and epigenetic variation in early-life development, and subsequent immune, allergic, cardiovascular, respiratory and neurodevelopmental outcomes. Participants have been reviewed at birth and at 1, 6, 9 and 12 months, with 2-and 4-year reviews under way. Biological samples and measures include: maternal blood, faeces and urine during pregnancy; infant urine, faeces and blood at regular intervals during the first 4 years; lung function at 1 month and 4 years; cardiovascular assessment at 1 month and 4 years; skin-prick allergy testing and food challenge at 1 year; and neurodevelopmental assessment at 9 months, 2 and 4 years. Data access enquiries can be made at [www.barwoninfantstudy.org.au] or via [[email protected]]