High-resolution analyses of associations between medications, microbiome, and mortality in cancer patients.

Discerning the effect of pharmacological exposures on intestinal bacterial communities in cancer patients is challenging. Here, we deconvoluted the relationship between drug exposures and changes in microbial composition by developing and applying a new computational method, PARADIGM (parameters associated with dynamics of gut microbiota), to a large set of longitudinal fecal microbiome profiles with detailed medication-administration records from patients undergoing allogeneic hematopoietic cell transplantation. We observed that several non-antibiotic drugs, including laxatives, antiemetics, and opioids, are associated with increased Enterococcus relative abundance and decreased alpha diversity. Shotgun metagenomic sequencing further demonstrated subspecies competition, leading to increased dominant-strain genetic convergence during allo-HCT that is significantly associated with antibiotic exposures. We integrated drug-microbiome associations to predict clinical outcomes in two validation cohorts on the basis of drug exposures alone, suggesting that this approach can generate biologically and clinically relevant insights into how pharmacological exposures can perturb or preserve microbiota composition. The application of a computational method called PARADIGM to a large dataset of cancer patients' longitudinal fecal specimens and detailed daily medication records reveals associations between drug exposures and the intestinal microbiota that recapitulate in vitro findings and are also predictive of clinical outcomes.

ExPRSweb: An online repository with polygenic risk scores for common health-related exposures.

Complex traits are influenced by genetic risk factors, lifestyle, and environmental variables, so-called exposures. Some exposures, e.g., smoking or lipid levels, have common genetic modifiers identified in genome-wide association studies. Because measurements are often unfeasible, exposure polygenic risk scores (ExPRSs) offer an alternative to study the influence of exposures on various phenotypes. Here, we collected publicly available summary statistics for 28 exposures and applied four common PRS methods to generate ExPRSs in two large biobanks: the Michigan Genomics Initiative and the UK Biobank. We established ExPRSs for 27 exposures and demonstrated their applicability in phenome-wide association studies and as predictors for common chronic conditions. Especially the addition of multiple ExPRSs showed, for several chronic conditions, an improvement compared to prediction models that only included traditional, disease-focused PRSs. To facilitate follow-up studies, we share all ExPRS constructs and generated results via an online repository called ExPRSweb.

Identification of differential m6A RNA methylomes and ALKBH5 as a potential prevention target in the developmental neurotoxicity induced by multiple sevoflurane exposures.

Sevoflurane, as a commonly used inhaled anesthetic for pediatric patients, has been reported that multiple sevoflurane exposures are associated with a greater risk of developing neurocognitive disorder. N6-Methyladenosine (m6A), as the most common mRNA modification in eukaryotes, has emerged as a crucial regulator of brain function in processes involving synaptic plasticity, learning and memory, and neurodevelopment. Nevertheless, the relevance of m6A RNA methylation in the multiple sevoflurane exposure-induced developmental neurotoxicity remains mostly elusive. Herein, we evaluated the genome-wide m6A RNA modification and gene expression in hippocampus of mice that received with multiple sevoflurane exposures using m6A-sequencing (m6A-seq) and RNA-sequencing (RNA-seq). We discovered 19 genes with differences in the m6A methylated modification and differential expression in the hippocampus. Among these genes, we determined that a total of nine differential expressed genes may be closely associated with the occurrence of developmental neurotoxicity induced by multiple sevoflurane exposures. We further found that the alkB homolog 5 (ALKBH5), but not methyltransferase-like 3 (METTL3) and Wilms tumor 1-associated protein (WTAP), were increased in the hippocampus of mice that received with multiple sevoflurane exposures. And the IOX1, as an inhibitor of ALKBH5, significantly improved the learning and memory defects and reduced neuronal damage in the hippocampus of mice induced by multiple sevoflurane exposures. The current study revealed the role of m6A methylated modification and m6A-related regulators in sevoflurane-induced cognitive impairment, which might provide a novel insight into identifying biomarkers and therapeutic strategies for inhaled anesthetic-induced developmental neurotoxicity.

Intrauterine exposure to SARS-CoV-2 infection and early newborn brain development.

Epidemiologic studies suggest that prenatal exposures to certain viruses may influence early neurodevelopment, predisposing offspring to neuropsychiatric conditions later in life. The long-term effects of maternal COVID-19 infection in pregnancy on early brain development, however, remain largely unknown. We prospectively enrolled infants in an observational cohort study for a single-site study in the Washington, DC Metropolitan Area from June 2020 to November 2021 and compared these infants to pre-pandemic controls (studied March 2014-February 2020). The primary outcomes are measures of cortical morphometry (tissue-specific volumes), along with global and regional measures of local gyrification index, and sulcal depth. We studied 210 infants (55 infants of COVID-19 unexposed mothers, 47 infants of COVID-19-positive mothers, and 108 pre-pandemic healthy controls). We found increased cortical gray matter volume (182.45 ± 4.81 vs. 167.29 ± 2.92) and accelerated sulcal depth of the frontal lobe (5.01 ± 0.19 vs. 4.40 ± 0.13) in infants of COVID-19-positive mothers compared to controls. We found additional differences in infants of COVID-19 unexposed mothers, suggesting both maternal viral exposures, as well as non-viral stressors associated with the pandemic, may influence early development and warrant ongoing follow-up.

Effect of age and season on respiratory mucosal immune marker profiles.

BACKGROUND: The upper respiratory tract is continuously exposed to microorganisms and noxious elements, leading to local immune responses and the secretion of immune markers. While several studies describe immune marker profiles in respiratory mucosal samples in defined patient cohorts, mucosal immune profiles from the general population during the different seasons are lacking. Such baseline profiles are essential to understand the effect of various exposures to the mucosal immune system throughout life. OBJECTIVE: We sought to establish baseline local upper respiratory mucosal immune profiles in the general population and assess these profiles with regard to age, sex, seasonality, and basic health and lifestyle factors. METHODS: We measured the concentrations of 35 immune markers involved in a broad range of immunological processes at the mucosa in nasopharyngeal swab samples from 951 individuals, aged 0 to 86 years, from a nationwide study. RESULTS: Clustering analysis showed that immune marker profiles clearly reflected immunological functions, such as tissue regeneration and antiviral responses. Immune marker concentrations changed strongly with seasonality and age, with the most profound changes occurring in the first 25 years of life; they were also associated with sex, body mass index, smoking, mild symptoms of airway infection, and chronic asthma and hay fever. CONCLUSION: Immunological analyses of noninvasive mucosal samples provide insight into mucosal immune responses to microbial and noxious element exposure in the general population. These data provide a baseline for future studies on respiratory mucosal immune responses and for the development of mucosal immune-based diagnostics.

Clinical and Molecular Analysis of Longitudinal Rhinitis Phenotypes in an Urban Birth Cohort.

BACKGROUND: Chronic rhinitis symptoms cause significant health burden among children and can have a heterogeneous presentation. Defining phenotypes of childhood chronic rhinitis and associated pathobiology may lead to prevention or improved treatments. OBJECTIVES: To identify longitudinal patterns of rhinitis symptoms in childhood and determine their associations with early life risk factors, allergic comorbidities, and nasal epithelial cell gene expression. METHODS: Chronic rhinitis symptoms were evaluated from ages 1 through 11 years in 485 urban children at high risk for allergic disease in the Urban Environment and Childhood Asthma (URECA) birth cohort. We identified longitudinal rhinitis phenotypes and their relationships to early life exposures, atopic comorbidities, and patterns of nasal epithelial gene expression at age 11 years. RESULTS: Chronic rhinitis symptoms started early in many children and were a risk factor for developing aeroallergen sensitization. We identified four longitudinal rhinitis phenotypes: low/minimal disease, persistent, persistent decreasing, and late increasing. Persistent rhinitis was most closely linked to allergic sensitization and asthma. Risk factors for persistent rhinitis included frequent colds (p<0.001), antibiotic use (p<0.001), and reduced exposure to common indoor aeroallergens (p=0.003). Compared to low/minimal disease, rhinitis phenotypes were associated with increased expression of canonical Type 2 genes and decreased expression of immune response genes. CONCLUSIONS: In urban children, rhinitis symptoms often precede aeroallergen sensitization. Rhinitis phenotypes based on symptoms had distinct risk factors and nasal transcriptome. These results suggest that focusing on early life risk factors and distinct immune mechanisms may be a target to preventing chronic rhinitis in childhood.

Phylogeographic Analysis of Mycobacterium kansasii Isolates from Patients with M. kansasii Lung Disease in Industrialized City, Taiwan.

Little is known about environmental transmission of Mycobacterium kansasii. We retrospectively investigated potential environmental acquisition, primarily water sources, of M. kansasii among 216 patients with pulmonary disease from an industrial city in Taiwan during 2015-2017. We analyzed sputum mycobacterial cultures using whole-genome sequencing and used hierarchical Bayesian spatial network methods to evaluate risk factors for genetic relatedness of M. kansasii strains. The mean age of participants was 67 years; 24.1% had previously had tuberculosis. We found that persons from districts served by 2 water purification plants were at higher risk of being infected with genetically related M. kansasii isolates. The adjusted odds ratios were 1.81 (1.25-2.60) for the Weng Park plant and 1.39 (1.12-1.71) for the Fongshan plant. Those findings unveiled the association between water purification plants and M. kansasii pulmonary disease, highlighting the need for further environmental investigations to evaluate the risk for M. kansasii transmission.

Multigenerational association between smoking and autism spectrum disorder: findings from a nationwide prospective cohort study.

Animal studies have shown that exposure to cigarette smoke during pregnancy can induce neurobehavioral anomalies in multiple subsequent generations. However, little work has examined such effects in humans. We examined the risk of grandchild autism spectrum disorder (ASD) in association with grandmother's smoking during pregnancy, using data from 53 562 mothers and grandmothers and 120 267 grandchildren in Nurses' Health Study II. In 1999, Nurses' Health Study II participants with children reported on their mothers' smoking. Grandchildren's ASD diagnoses were reported by the mothers in 2005 and 2009. Among grandmothers, 13 383 (25.0%) smoked during pregnancy, and 509 (0.4%) grandchildren were diagnosed with ASD. The adjusted odds ratio for ASD for grandmother smoking during pregnancy was 1.52 (95% CI, 1.06-2.20). Results were similar with direct grandmother reporting in 2001 of her smoking during pregnancy from the Nurses' Mothers Cohort Study subgroup (n = 22 167 grandmothers, n = 49 917 grandchildren) and were stronger among grandmothers who smoked ≥15 cigarettes per day during pregnancy (adjusted odds ratio = 1.93 [95% CI, 1.10-3.40]; n = 1895 grandmothers, n = 4212 grandchildren). Results were similar when we adjusted for mother's smoking during pregnancy. There was no association with grandfather's smoking as reported by the grandmother. Our results suggest a potential persistent impact of gestational exposure to environmental insults across 3 generations.

Multiple prenatal exposures and acute-care clinical encounters for asthma among children born to mothers living near a Superfund site.

Prenatal exposures are associated with childhood asthma, and risk may increase with simultaneous exposures. Pregnant women living in lower-income communities tend to have elevated exposures to a range of potential asthma risk factors, which may interact in complex ways. We examined the association between prenatal exposures and the risk of childhood acute-care clinical encounters for asthma (hospitalizations, emergency department visits, observational stays) using conditional logistic regression with a multivariable smoothing term to model the interaction between continuous variables, adjusted for maternal characteristics and stratified by sex. All births near the New Bedford Harbor (NBH) Superfund site (2000-2006) in New Bedford, Massachusetts, were followed through 2011 using the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System to identify children aged 5-11 years with acute-care clinical asthma encounters (265 cases among 7787 children with follow-up). Hazard ratios (HRs) were higher for children living closer to the NBH site with higher umbilical cord blood lead levels than in children living further away from the NBH site with lower lead levels (P <.001). HRs were higher for girls (HR = 4.17; 95% CI, 3.60-4.82) than for boys (HR = 1.72; 95% CI, 1.46-2.02). Our results suggest that prenatal lead exposure in combination with residential proximity to the NBH Superfund site is associated with childhood asthma acute-care clinical encounters. This article is part of a Special Collection on Environmental Epidemiology.

Combined impact of dynamic air pollution and transportation noise on cardiometabolic disorders in San Diego County.

Air pollution and noise exposure may synergistically contribute to increased cardiometabolic disorders; however, few studies have examined this potential interaction nor considered exposures beyond residential location. This study investigates the combined impact of dynamic air pollution and transportation noise on cardiometabolic disorders in San Diego County. Using the Community of Mine Study (2014-2017), 602 ethnically diverse participants were assessed for obesity, dyslipidemia, hypertension, and metabolic syndrome (MetS) using anthropometric measurements and biomarkers from blood samples. Time-weighted measures of exposure to PM2.5, NO2, road and aircraft noise were calculated using global positioning system (GPS) mobility data and Kernel Density Estimation. Generalized estimating equation models were used to analyze associations. Interactions were assessed on the multiplicative and additive scales using relative excess risk due to interaction (RERI). We found that air pollution and noise interact to affect metabolic disorders on both multiplicative and additive scales. The effect of noise on obesity and MetS was higher when air pollution was higher. The RERI of aircraft noise and NO2 on obesity and MetS were 0.13 (95%CI 0.03, 0.22) and 0.13 (95%CI 0.02, 0.25), respectively. This finding suggests that aircraft noise and air pollution may have synergistic effects on obesity and MetS.

Exploring the Landscape of Social Epidemiological Research: A Scoping Review of AJE Publications.

As social epidemiology is a growing interdisciplinary field with a broad scope, this scoping review investigated its current landscape based on articles published in the American Journal of Epidemiology. Among 1,194 extracted records between 2013 and 2022 submitted under the "social" category, we identified 178 accepted articles that had a social factor as a primary exposure. We categorized social exposures into nine major domains, and health outcomes into eight domains. Study design, population, and authorship were also analyzed. Our findings indicate that social epi studies reflect a range of social exposures, including socioeconomic position (37%), neighborhood and built environment (20%), race, racism, and discrimination (16%), and policy and social welfare (12%). The most frequently studied health outcomes were non-communicable diseases and chronic conditions (42%), mental health (14%), and maternal and child health outcomes (11%). Most studies had quantitative observational designs and focused on high-income countries, particularly the U.S. contexts. Most authors appeared only once, suggesting a range of voices as contributors. Findings suggest that, to enhance knowledge, social epi could benefit from a greater representation of social factors beyond tangible resources, a broader range of health outcomes, study designs and populations, and low- and middle-income countries.

Site-specific cancer mortality after low level exposure to ionizing radiation: Findings from an update of the International Nuclear Workers Study (INWORKS).

A major update to the International Nuclear Workers Study was undertaken that allows us to report updated estimates of associations between radiation and site-specific solid cancer mortality. A cohort of 309,932 nuclear workers employed in France, the United Kingdom, and United States were monitored for external radiation exposure and associations with cancer mortality were quantified as the excess relative rate (ERR) per gray (Gy) using a maximum likelihood and a Markov chain Monte Carlo method (to stabilize estimates via a hierarchical regression). The analysis included 28,089 deaths due to solid cancer, the most common being lung, prostate, and colon cancer. Using maximum likelihood, positive estimates of ERR per Gy were obtained for stomach, colon, rectum, pancreas, peritoneum, larynx, lung, pleura/mesothelioma, bone and connective tissue, skin, prostate, testis, bladder, kidney, thyroid, and residual cancers; negative estimates of ERR per Gy were found cancers of oral cavity and pharynx, esophagus, and ovary. A hierarchical model stabilized site-specific estimates of association, including for lung (ERR per Gy=0.65; 95% credible interval [CrI]: 0.24, 1.07), prostate (ERR per Gy=0.44; 95% CrI: -0.06, 0.91), and colon cancer (ERR per Gy=0.53; 95% CrI: -0.07, 1.11). The results contribute evidence regarding associations between low dose radiation and cancer.

Mechanisms linking prenatal environment and linear growth: the case of Ramadan during pregnancy.

Despite established links between prenatal nutritional deprivation and impaired offspring growth, the underlying dynamics and potential moderators remain largely unexplored. This study investigates the dynamics underlying Ramadan during pregnancy and its associations with children's linear growth, using data from the Indonesian Family Life Survey (1993 - 2015). We exploit Ramadan during pregnancy as a natural experiment, separating exposure from maternal background characteristics and season of birth effects. Employing OLS and logistic regressions, we explore two key mechanisms predicted by medical theory. First, the realization of health impairments in response to prenatal shocks is influenced by postnatal circumstances. Our results reveal significant growth impairments primarily in children raised under poor sanitary conditions, which is a risk factor for diminished linear growth by itself. Secondly, we assess whether prenatal Ramadan prompts epigenetic shifts towards earlier reproductive activity, potentially at the expense of height growth. Our data shows that prenatally exposed women tend to have their first childbirth at a younger age, though menarche onset remains unaffected. These results suggest that postnatal environments play a crucial role in mitigating sensitivity to prenatal shocks, highlighting the critical need for favorable living conditions for all children.

Prenatal environmental risk factors for autism spectrum disorder and their potential mechanisms.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder that is globally increasing in prevalence. The rise of ASD can be partially attributed to diagnostic expansion and advocacy efforts; however, the interplay between genetic predisposition and modern environmental exposures is likely driving a true increase in incidence. A range of evidence indicates that prenatal exposures are critical. Infection during pregnancy, gestational diabetes, and maternal obesity are established risk factors for ASD. Emerging areas of research include the effects of maternal use of selective serotonin reuptake inhibitors, antibiotics, and exposure to toxicants during pregnancy on brain development and subsequent ASD. The underlying pathways of these risk factors remain uncertain, with varying levels of evidence implicating immune dysregulation, mitochondrial dysfunction, oxidative stress, gut microbiome alterations, and hormonal disruptions. This narrative review assesses the evidence of contributing prenatal environmental factors for ASD and associated mechanisms as potential targets for novel prevention strategies.

A Screening Approach to the Safe-and-Sustainable-by-Design Development of Advanced Insulation Materials.

Herein, a Safe-and-Sustainable-by-Design (SSbD) screening strategy on four different inorganic aerogel mats and two conventional mineral wools for ranking purposes is demonstrated. Given that they do not consist of particles, the release is first simulated, addressing three occupational exposure scenarios, realistic for their intended use as building insulators. No exposure to consumers nor to the environment is foreseen in the use phase, however, aerosols may be released during mat installation, posing an inhalation risk for workers. All four aerogel mats release more respirable dust than the benchmark materials and 60% thereof deposits in the alveolar region according to modelling tools. The collected aerogel dust allows for subsequent screening of hazard implications via two abiotic assays: 1) surface reactivity in human blood serum; 2) biodissolution kinetics in lung simulant fluids. Both aerogels and conventional insulators show similar surface reactivity. Differences in biodissolution are influenced by the specifically designed organic and inorganic structural modifications. Aerogel mats are better-performing insulators (2-fold lower thermal conductivity than the benchmark) However, this work demonstrates how investment decisions can be balanced with safety and sustainability aspects. Concepts of analogy and similarity thus support easily accessible methods to companies for safe and economically viable innovation with advanced materials.

The Undiagnosed Diseases Network: Characteristics of solvable applicants and diagnostic suggestions for nonaccepted ones.

PURPOSE: Can certain characteristics identify as solvable some undiagnosed patients who seek extensive evaluation and thorough record review, such as by the Undiagnosed Diseases Network (UDN)? METHODS: The UDN is a national research resource to solve medical mysteries through team science. Applicants provide informed consent to access to their medical records. After review, expert panels assess if applicants meet inclusion and exclusion criteria to select participants. When not accepting applicants, UDN experts may offer suggestions for diagnostic efforts. Using minimal information from initial applications, we compare features in applicants who are not accepted with those who are accepted and either solved or still not solved by the UDN. The diagnostic suggestions offered to nonaccepted applicants and their clinicians were tallied. RESULTS: Nonaccepted applicants were more often female, older at first symptoms and application, and longer in review compared with accepted applicants. The accepted and successfully diagnosed applicants were younger, shorter in review time, more often non-White, of Hispanic ethnicity, and presenting with nervous system features. Half of nonaccepted applicants were given suggestions for further local diagnostic evaluation. A few seemed to have 2 major diagnoses or a provocative environmental exposure history. CONCLUSION: Comprehensive UDN record review generates possibly helpful advice.

Employing a Toxic Aging Coin approach to assess hexavalent chromium (Cr[VI])-induced neurotoxic effects on behavior: Heads for age differences.

We are facing a rapidly growing geriatric population (65+) that will live for multiple decades and are challenged with environmental pollution far exceeding that of previous generations. Consequently, we currently have a poor understanding of how environmental pollution will impact geriatric health distinctly from younger populations. Few toxicology studies have considered age differences with geriatric individuals. Critically, all top ten most prevalent age-related diseases are linked to metal exposures. Hexavalent chromium [Cr(VI)] is a metal of major environmental health concern that can induce aging phenotypes and neurotoxicity. However, there are many knowledge gaps for Cr(VI) neurotoxicity, including how Cr(VI) impacts behavior. To address this, we exposed male rats across three ages (3-, 7-, and 18-months old) to Cr(VI) in drinking water (0, 0.05, 0.1 mg/L) for 90 days. These levels reflect the maximum contaminant levels determined by the World Health Organization (WHO) and the U.S. Environmental Protection Agency (US EPA). Here, we report how these Cr(VI) drinking water levels impacted rat behaviors using a battery of behavior tests, including grip strength, open field assay, elevated plus maze, Y-maze, and 3-chamber assay. We observed adult rats were the most affected age group and memory assays (spatial and social) exhibited the most significant effects. Critically, the significant effects were surprising as rats should be particularly resistant to these Cr(VI) drinking water levels due to the adjustments applied in risk assessment from rodent studies to human safety, and because rats endogenously synthesize vitamin C in their livers (vitamin C is a primary reducer of Cr[VI] to Cr[III]). Our results emphasize the need to broaden the scope of toxicology research to consider multiple life stages and suggest the current regulations for Cr(VI) in drinking water need to be revisited.

Maternal inflammation during pregnancy is associated with risk of ADHD in children at age 10.

INTRODUCTION: Maternal inflammation during pregnancy may affect early neurodevelopment in offspring as suggested by preclinical and register data. However, clinical evidence for risk of aberrant neurodevelopment later in childhood is scarce. In the population-based COPSAC2010 mother-child cohort, we investigated associations between maternal inflammation levels during pregnancy and the risk of a diagnosis of ADHD as well as the load of ADHD symptoms in the children at age 10. METHODS: The COPSAC2010 cohort consists of 700 mother-child pairs followed prospectively since pregnancy week 24.Maternal high-sensitivity C-Reactive Protein (hs-CRP) level at week 24 of gestation was investigated in relation to child neurodevelopment by age 10 using logistic and linear regression models with extensive confounder adjustment, including socioeconomic status and maternal polygenic risk of ADHD. The children completed a comprehensive examination of neurodevelopment including categorical (i.e., diagnostic) and dimensional (i.e., symptom load) psychopathology using the Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) and parental rated ADHD-Rating Scale (ADHD-RS). RESULTS: A total of 604 (86 %) of the 700 children in the COPSAC2010 cohort participated in the COPSYCH visit at age 10. Sixty-five (10.8 %) fulfilled a research diagnosis of ADHD (16 girls and 49 boys). Higher maternal hs-CRP level in pregnancy at week 24 (median 5.4 mg/L) was significantly associated with increased risk for a diagnosis of ADHD, adjusted OR 1.40, 95 %CI (1.16-1.70), p = 0.001. Additionally, higher maternal hs-CRP was associated with increased ADHD symptom load in the entire cohort, reflected by ADHD-RS raw scores. DISCUSSION: These clinical data demonstrated a robust association of prenatal maternal inflammation assessed by hs-CRP with a diagnosis of ADHD by age 10. Moreover, maternal inflammation was associated with ADHD symptom load in the complete cohort. Identifying inflammation as an important marker will provide a potential target for future increased awareness and prevention during pregnancy thereby ultimately improving neurodevelopmental outcomes in children.

Compliance of blood donors in Germany with non-sexual deferral criteria.

BACKGROUND AND OBJECTIVES: In addition to mandatory testing of blood donations, the deferral of donors in the case of various sexual and non-sexual risk exposures ensures the safety of blood products in Germany. The study aimed to quantify non-disclosure of non-sexual risk exposures, as no data are available so far. MATERIALS AND METHODS: We conducted an anonymous online survey among whole-blood donors with successful donations between January and March 2020. Data on travel to countries with endemic malaria, recent mild or febrile infections, tattoos or piercings and drug use were collected. We analysed non-compliance in relation to donor demographics by multivariable analyses. RESULTS: Altogether, 5.4% of the donors were non-compliant. Non-disclosure was highest for mild infection with 3.3% of donors, followed by febrile infections (1.4%), travel to malaria endemic countries (0.7%) and body modifications (0.5%). Intravenous drug use was negligible in our study population. Age was a predictor for all investigated risks, with higher prevalence in younger age groups. Prevalence ratios for non-disclosure of body modifications and mild infection were higher in females than males. Donation in blood establishments with mobile services was associated with higher non-disclosure of mild infections. CONCLUSION: The considerable degree of non-compliance in some donor groups reflects the prevalence of risk factors in the underlying population (e.g., body modification) as well as probable tendency to socially desirable responding. Donor education should not focus exclusively on sexual risk behaviour, as undisclosed non-sexual exposures may bear risks for recipients and donors.

Atopic diseases-Diagnostics, mechanisms, and exposures.

Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early-life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early-life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic.