Skin cancer risk and shade: comparing the risk of foresters with other outdoor workers.

BACKGROUND: Keratinocyte carcinoma (KC) is an increasingly important public health problem with an especially high prevalence in outdoor workers. In contrast to other occupations, foresters spend most of their outdoor time under the shade of trees. OBJECTIVES: We aimed to compare the unique sun exposure patterns and sun protection behaviour of foresters with those of other outdoor workers and their relation to the KC risk. METHODS: In July 2018, a cross-sectional study was conducted at an international forestry fair using a questionnaire about health awareness and skin cancer screening by dermatologists to assess the prevalence of KC. RESULTS: A total of 591 participants (78.7% male; mean age 46.8 ± 16.2 years) including 193 foresters were enrolled. Of all foresters, 72% experienced sunburns (solar erythema) within the past year and 50% of them experienced the worst sunburn during work. Foresters were most likely to often/always wear protective clothes (29.0%) but were least likely to often/always avoid midday sun (23.8%) and stay in the shade (31.1%). Having an outdoor profession or spending hours outside for leisure was negatively associated with sun protection. Skin examination revealed an overall KC prevalence of 16.7%, with 16.5% of foresters being affected. CONCLUSION: Despite being protected by trees, the risk of KC for foresters is comparable to that of other professional groups. Shade alone may not provide sufficient protection. Additional sun protection measures are necessary.

An approach to the asthma-protective farm effect by geocoding: Good farms and better farms.

BACKGROUND: The highly consistent association of growing up on a farm with a reduced asthma risk has so far been attributed to direct farm exposure. In contrast, geographic determinants of the larger environment have never been assessed. In this study, the effects of proximity to farms and environmental variables in relation to the residential address on asthma and atopy were assessed. METHODS: Addresses of 2265 children of the Bavarian arm of the GABRIELA study were converted into geocodes. Proximity to the nearest cow farm was calculated, and environmental characteristics were derived from satellite data or terrestrial monitoring. Bacterial diversity in mattress dust samples was assessed in 501 children by sequencing of the 16S rRNA amplicons. Logistic regression models were used to calculate associations between outcomes and exposure variables. RESULTS: Asthma and atopy were inversely associated with the presence of a farm within a radius of maximum 100 m. The environmental variables greenness, tree cover, soil sealing, altitude, air pollution differed not only between farm and non-farm children but also between farm children with and without another farm nearby. The latter distinction revealed strong associations with characteristics of traditional farms including a broader diversity of microbial exposure, which mainly contributed to the protective effect on asthma. In non-farm children, the protective effect of a farm nearby was completely explained by consumption of farm milk. CONCLUSIONS: Clustering of farms within a neighborhood of 100 m is strongly associated with the protective effect on asthma and may represent a more traditional style of farming with broader microbial exposure.

Environmental and mucosal microbiota and their role in childhood asthma.

BACKGROUND: High microbial diversity in the environment has been associated with lower asthma risk, particularly in children exposed to farming. It remains unclear whether this effect operates through an altered microbiome of the mucosal surfaces of the airways. METHODS: DNA from mattress dust and nasal samples of 86 school age children was analyzed by 454 pyrosequencing of the 16S rRNA gene fragments. Based on operational taxonomic units (OTUs), bacterial diversity and composition were related to farm exposure and asthma status. RESULTS: Farm exposure was positively associated with bacterial diversity in mattress dust samples as determined by richness (P = 8.1 × 10-6 ) and Shannon index (P = 1.3 × 10-5 ). Despite considerable agreement of richness between mattress and nasal samples, the association of richness with farming in nasal samples was restricted to a high gradient of farm exposure, that is, exposure to cows and straw vs no exposure at all. In mattress dust, the genera Clostridium, Facklamia, an unclassified genus within the family of Ruminococcaceae, and six OTUs were positively associated with farming. Asthma was inversely associated with richness [aOR = 0.48 (0.22-1.02)] and Shannon index [aOR = 0.41 (0.21-0.83)] in mattress dust and to a lower extent in nasal samples [richness aOR 0.63 = (0.38-1.06), Shannon index aOR = 0.66 (0.39-1.12)]. CONCLUSION: The stronger inverse association of asthma with bacterial diversity in mattress dust as compared to nasal samples suggests microbial involvement beyond mere colonization of the upper airways. Whether inhalation of metabolites of environmental bacteria contributes to this phenomenon should be the focus of future research.

Farm-derived Gram-positive bacterium Staphylococcus sciuri W620 prevents asthma phenotype in HDM- and OVA-exposed mice.

BACKGROUND: Farm-derived dust samples have been screened for bacteria with potential allergo-protective properties. Among those was Staphylococcus sciuri W620 (S. sciuri W620), which we tested with regard to its protective capacities in murine models of allergic airway inflammation. METHODS: We employed two protocols of acute airway inflammation in mice administering either ovalbumin (OVA) or house dust mite extract (HDM) for sensitization. Mechanistic studies on the activation of innate immune responses to S. sciuri W620 were carried out using human primary monocytic dendritic cells (moDC) and co-culture with autologous T cells. RESULTS: The allergo-protective properties of S. sciuri W620 were proven in a T(H)2-driven OVA model as well as in a mixed T(H)1/T(H)2 phenotype HDM model as demonstrated by abrogation of eosinophils and neutrophils in the airways after intranasal treatment. In the HDM model, lymph node cell T(H)1/T(H)2 signature cytokines were decreased in parallel. Studies on human moDC revealed an activation of TLR2 and NOD2 receptors and initiation of DC maturation following incubation with S. sciuri W620. Cytokine expression analyses after exposure to S. sciuri W620 showed a lack of IL-12 production in moDC due to missing transcription of the IL-12p35 mRNA. However, such DC selectively supported T(H)1 cytokine release by co-cultured T cells. CONCLUSION AND CLINICAL RELEVANCE: Our proof-of-concept experiments verify the screening system of farm-derived dust samples as suitable to elucidate new candidates for allergo-protection. S. sciuri W620 was shown to possess preventive properties on airway inflammation providing the basis for further mechanistic studies and potential clinical implication.

Environmental bacteria and childhood asthma.

BACKGROUND: We have previously found an inverse association of bacterial diversity with childhood asthma. It remains unclear whether certain bacteria account for the protective effect. METHODS: The high variability of the bacterial 16S rRNA gene allows assessing diversity and specificity of bacterial communities by single-strand configuration polymorphism (SSCP). DNA was extracted from mattress dust samples of 489 school-age children from rural and suburban regions in Germany. A fragment of the bacteria-specific 16S rRNA gene was amplified by PCR, digested to single-strand DNA, and subjected to electrophoresis. The resulting band patterns reflect the underlying DNA sequences. The individual bands were tested for associations with asthma, hay fever, and atopy in quantitative and qualitative multivariable analyses. Significantly associated bands were isolated and sequenced. The sequences were compared to a database, and distinct bacteria were identified. RESULTS: Seven of 76 independent bands were found to be inversely associated with asthma, atopic sensitization, and hay fever with odds ratios ranging from 0.17 to 0.73. The bands contained the sequences of Acinetobacter sp., Lactobacillus spp., Neisseria spp., Staphylococcus sciuri, Jeotgalicoccus sp., Corynebacterium spp., and others. CONCLUSIONS: In a diverse microbial environment, certain bacteria may account for the protective effect on the development of asthma and atopy.

Development and genetic influence of the rectal bacterial flora of newborn calves.

The aim of the study was to investigate a dynamic change in the rectal flora of calves as well as to study a genetic influence on the intestinal microflora of calves. The bacterial community of fecal samples from calves was examined by PCR single strand conformation polymorphism (PCR-SSCP) in two independent studies. In study one 14 newborn calves of the same farm were examined. Sampling was conducted directly after delivery (meconium) and after 6 h, 12 h, 24 h, 48 h, 3 d, 7 d, 14 d and 42 d of life. In study two 6 twin calves and their coresident of the same age and farm were analysed in order to study for the first time whether genetic predisposition of the host may influence the fecal microflora. All calves were weaned directly after delivery and received pumped colostrum without direct contact to other farm animals. After delivery and during the first 12h of life the SSCP profiles were simple, but became more complex since the bacterial diversity increased with time in all calves. It became obvious that the intra-individual band-pattern similarity decreased over time and inter-individual similarity was low. The analysis of fecal samples from twin calves revealed higher similarity in SSCP profiles for twins compared to their coresident indicating that the individual microflora might be genetically or epigenetically influenced. The insight that there are several conformities between intestinal microfloras of healthy calves and that there might be genetic influence on the fecal flora could help to prevent diarrhoeal diseases in the future.

Maternal vitamin D intake during pregnancy increases gene expression of ILT3 and ILT4 in cord blood.

BACKGROUND: Recent studies indicate that prenatal vitamin D intake may protect against the development of atopic diseases in young children. Vitamin D has been shown to induce tolerogenic antigen-presenting cells such as dendritic cells. Whether the allergy-protective potential of prenatal vitamin D is mediated through such mechanisms is, however, unknown. OBJECTIVE: To evaluate the association between prenatal vitamin D supplementation and tolerogenic antigen-presenting cells in cord blood (CB) as determined by mRNA measurement of immunoglobulin-like transcripts (ILT)3 and ILT4. METHODS: A prospective multi-centre birth cohort was established in rural areas of five European countries. Information on maternal exposures including vitamin D intake was collected by questionnaires during pregnancy. The gene expression of ILT3 and ILT4 was analysed by real-time PCR in the CB of 927 children. Maternal vitamin D supplementation was assessed in Finland and France (n=349). RESULTS: Maternal vitamin D supplementation during pregnancy was associated with an increase in the gene expression of ILT3 (P=0.012) and ILT4 (P<0.001). This association remained significant for ILT4 (P=0.020) and showed a positive trend for the gene expression of ILT3 (P=0.059) after multivariate analysis controlling for various confounders. CONCLUSIONS: Vitamin D supplementation during pregnancy may increase the mRNA levels of ILT3 and ILT4 in CB. This finding may point towards an early induction of tolerogenic immune responses by maternal vitamin D intake.

Coincidence of recurrent hemiparesis and detection of ALL in a 4-year-old girl: one or two diseases?

Stroke like symptoms in children such as hemiparesis are often associated with infection, cranial trauma, cardiac anomalies or sickle cell disease. In childhood leukemia, stroke like symptoms at presentation are rare and normally caused by cerebral bleedings. Here we report a patient who presented with classical stroke symptoms and hemiparesis prior to the diagnosis of acute lymphoblastic leukemia without proven CNS infiltration by leukemic cells. In general, acute leukemia or cerebral lymphoma do not lead to extensive defects of brain tissue. This unusual case suggests that acute lymphoblastic leukemia may present with stroke like CNS symptoms including hemiparesis.

Specific IgE to allergens in cord blood is associated with maternal immunity to Toxoplasma gondii and rubella virus.

BACKGROUND: Various studies have found reduced prevalences of atopic sensitization and atopic diseases in children previously exposed to infections or living conditions with a high microbial burden, such as the farming environment. OBJECTIVE: We sought to determine the relationships of cord blood immunoglobulin E (IgE) with maternal health conditions before and during pregnancy. METHODS: Pregnant women living in rural areas in five European countries were recruited in the third trimester of pregnancy. Information on maternal health during pregnancy was collected from maternity records and by questionnaires (n = 497). Specific IgE for inhalant and food allergens was assessed in cord blood and peripheral blood samples of the mothers. RESULTS: Inverse associations of cord blood IgE to seasonal allergens with positive maternal records for Toxoplasma gondii (adjusted odds ratio = 0.37 [0.17-0.81]) and rubella virus (adjusted odds ratio = 0.35 [0.13-0.96]) were found. The previously described effect of prenatal farm exposure on IgE to seasonal allergens was partly confounded by a positive maternal record for T. gondii. The number of maternal siblings, maternal contact to cats during pregnancy or during her first year of life, predicted a positive maternal record for T. gondii. CONCLUSIONS: Maternal immunity to T. gondii and rubella may impact on atopic sensitization in the fetus. A positive T. gondii record explained the previously identified effect of prenatal farm exposure on IgE to seasonal allergens only to a minor extent.

Environmental determinants of atopic eczema phenotypes in relation to asthma and atopic sensitization.

BACKGROUND: There is still uncertainty about the determinants of atopic eczema (AE). To explain the heterogeneity of the disease, different phenotypes of AE have been suggested. METHODS: The cross-sectional PARSIFAL study included 14 893 school-age children of farmers or children attending Steiner schools and their respective reference groups. A detailed questionnaire was completed, and house dust was collected for the measurement of endotoxin and glucans. Atopic sensitization was defined by allergen-specific IgE levels in the serum. RESULTS: In multivariate analyses, helping with haying was the only variable related to a farming environment having a consistent inverse association with both current symptoms and a doctor's diagnosis of AE [aOR = 0.65 (95% CI: 0.46-0.93) and 0.73 (0.51-1.05)], respectively. Severe lower respiratory tract infections (LRTI) in the first 2 years of life and usage of antibiotics ever were found to be positively related only to asthma-associated AE, whereas the effect of LRTI on AE without asthma had an opposite effect. Levels of beta(1-->3)-glucans in mattress dust were inversely related to a doctor's diagnosis of asthma-associated AE [aOR = 0.75 (0.57-0.98)], and endotoxin levels to current symptoms of asthma-associated AE [aOR = 0.73 (0.57-0.94)]. CONCLUSIONS: The analyses of the PARSIFAL study revealed two different phenotypes of AE, depending on the association with asthma and wheezing ever. With regard to the hygiene hypothesis, help with haying, exposure to beta(1-->3)-glucans and endotoxin were found to be inversely associated with the AE phenotype associated with asthma and wheezing.