Short communication: Variation in the composition and properties of Swedish raw milk for ultra-high-temperature processing.

The composition and properties of raw milk are of great importance for the quality and shelf life of the final dairy product, especially in products with a long shelf life [e.g., ultra-high-temperature (UHT)-treated milk]. The objective of this study was to investigate the compositional variation in raw milk samples before processing at the dairy plant. Moreover, we wanted to investigate the effect of the UHT process on this variation (i.e., if the same variation could be observed in the corresponding UHT milk). The quality traits analyzed included detailed milk composition, counts of total and psychrotrophic bacteria, proteolytic activity, and color, as well as predictive measures of stability (i.e., ethanol stability and heat coagulating time). Samples of raw milk and the corresponding produced UHT milk were collected and analyzed on a monthly basis during 1 yr. Principal component analysis was used to identify months showing similarities and differences with respect to total variation. In contrast to previous studies, we observed only small variations between months and no clear effect of season for the raw milk. For the UHT milk, July and the winter months (December, January, and February) tended to separate from the other months. Quality traits showing significant variation were only to some extent identical in raw milk and UHT-processed milk. A better understanding of the natural variation in raw milk quality will provide opportunities to improve the shelf life of UHT-treated milk products.

Multidisciplinary Management of Mastocytosis: Nordic Expert Group Consensus.

Mastocytosis is a heterogeneous group of diseases defined by an increased number and accumulation of mast cells, and often also by signs and symptoms of mast cell activation. Disease subtypes range from indolent to rare aggressive forms. Mastocytosis affects people of all ages and has been considered rare; however, it is probably underdiagnosed with potential severe implications. Diagnosis can be challenging and symptoms may be complex and involve multiple organ-systems. In general it is advised that patients should be referred to centres with experience in the disease offering an individualized, multidisciplinary approach. We present here consensus recommendations from a Nordic expert group for the diagnosis and general management of patients with mastocytosis.

Changes in body-site distribution of common melanocytic naevi among 7-year-old Swedish children between 2002 and 2007.

An observational population-based study conducted among 2 sets of 7-year-old children in Sweden in 2002 and 2007 revealed evidence of improved sun protection, also reflected in a significant reduction in the total number of melanocytic naevi. Based on these data-sets, the aim of the current study was to determine whether the overall reduction in naevi had impacted differently on body sites based on their main pattern of sun exposure. In 2002, median naevi counts/m2 were highest on intermittently sun-exposed sites: 13.8 (95% CI 8.0-22.7) compared with chronically sun-exposed sites: 11.0 (95% CI 0.0-20.5). In 2007, median naevi counts/m2 on intermittently sun-exposed body sites were significantly lower: 8.7 (95% CI 4.7-15.2), p < 0.0001, while on chronically exposed sites median naevi counts/m2 were unaltered: 10.3 (95% CI 0.0-14.4), p = 0.9313. Changes were most evident among boys. Future research can evaluate whether this shift in naevi distribution in Swedish children translates into a reduction in cutaneous melanomas on intermittently sun-exposed body sites.

Mobile teledermatology is a valid method to estimate prevalence of melanocytic naevi in children.

The prevalence of melanocytic naevi in children correlates with sun exposure and may serve as an objective population risk indicator of future melanoma incidence. The aim was to investigate if mobile teledermatology could offer a valid methodology compared with standard manual, face-to-face counting of naevi on the back of children. Ninety-seven children aged 7-16 years were enrolled. One dermatologist performed manual naevi counting and imaging of the child's back using an iPhone 4S comprising a safe-coded mobile application. Two other dermatologists independently counted naevi from the images. Cohen's weighted kappa (κw) coefficient demonstrated substantial agreement for both dermatologists: κw = 0.69 (0.57-0.81 [95% confidence intervals]) and κw = 0.78 (0.70-0.86), compared with the manual assessment. Inter-rater reliability was also substantial (κw = 0.80 [0.73-0.87]). Use of mobile teledermatology proved valid for estimating naevi prevalence on the back and could provide a more feasible methodology following trends in sun exposure in children.

IL-18 skews the invariant NKT-cell population via autoreactive activation in atopic eczema.

Atopic eczema (AE) is a chronic relapsing inflammatory skin disease where the commensal yeast Malassezia can act as a microbial trigger factor. Malassezia activates human DC to produce IL-18, an innate cytokine that is elevated in serum of AE patients; however, the precise role of IL-18 in human AE etiology is unknown. Herein, we investigated the effect of IL-18 on the human invariant NKT (iNKT) cell compartment in AE. We found that IL-18 was a potent activator of human iNKT-cells and promoted a pro-inflammatory CD1d-dependent response, even in the absence of exogenous ligands. Chronic activation via IL-18 on the other hand was inhibitory and skewed the iNKT-cell pool by selectively suppressing CD4(+) iNKT-cells. This was mimicked in AE patients where the proportion of CD4(+) iNKT-cells was reduced in peripheral blood and coincided with elevated plasma levels of IL-18. Furthermore, a reduced CD4(+) iNKT-cell pool was associated with elevated IgE levels in plasma, and the plasma levels of IL-18 correlated with both total IgE and disease severity in the AE patients. Based on these findings, we propose that IL-18-mediated activation and subsequent dysregulation of the CD1d-restricted iNKT-cells plays a role in the pathogenesis of human AE.

Elevated peripheral allergen-specific T cell response is crucial for a positive atopy patch test reaction.

BACKGROUND: Atopic eczema is a chronic inflammatory skin disease in which several subgroups of cases can be identified. Atopy patch testing (APT) reveals allergen sensitization also in atopic eczema patients devoid of detectable allergen-specific IgE, suggesting the importance of factors other than IgE in the reaction. Here we investigate the relationship between APT reactions and allergen-specific peripheral IgE and T cell reactivity in atopic eczema patients. METHODS: Adult patients with atopic eczema (n = 64) and healthy controls (n = 24) were analyzed for reactivity to Malassezia sympodialis extract by APT, measurement of specific plasma IgE and in vitro determination of the frequency of allergen-reactive peripheral blood mononuclear cells producing interleukin-4 and interleukin-5 using the ELISpot method. RESULTS: When combining the results of the APT, IgE measurements and the ELISpot analyses, reactivity to M. sympodialis was found in a majority of the atopic eczema patients (69%), whereas the healthy controls were negative throughout. T cell reactivity to M. sympodialis, manifested by production of both interleukins 4 and 5, was highly predictive for a positive APT reaction and displayed a strongly positive correlation with the APT score. In contrast, the allergen-specific IgE levels did not predict the APT outcome, and no correlation could be found between the IgE levels and the APT score. CONCLUSION: Peripheral allergen-specific T helper 2 cell-mediated reactivity appears to be required for a positive APT reaction to M. sympodialis. The diagnostic potential of measuring peripheral allergen-specific T cell responses should be considered in atopic eczema.

The Effect of Calcium, Citrate, and Urea on the Stability of Ultra-High Temperature Treated Milk: A Full Factorial Designed Study.

The composition of raw milk is important for the stability of dairy products with a long shelf-life. Based on known historical changes in raw milk composition, the aim of this study was to get a better understanding of how possible future variations in milk composition may affect the stability of dairy products. The effects of elevated calcium, citrate, and urea levels on the stability of ultra-high temperature (UHT) treated milk stored for 52 weeks at 4, 20, 30, and 37 °C were investigated by a two-level full factorial designed study with fat separation, fat adhesion, sedimentation, color, pH, ethanol stability, and heat coagulation time as response variables. The results showed that elevated level of calcium lowered the pH, resulting in sedimentation and significantly decreased stability. Elevated level of citrate was associated with color, but the stability was not improved compared to the reference UHT milk. Elevated levels of urea or interaction terms had little effect on the stability of UHT milk. Storage conditions significantly affected the stability. In conclusion, to continue produce dairy products with high stability, the dairy industry should make sure the calcium content of raw milk is not too high and that storage of the final product is appropriate.

Changes in stability and shelf-life of ultra-high temperature treated milk during long term storage at different temperatures.

In the ultra-high temperature (UHT) process, milk is subject to temperatures above 135 °C for few seconds giving a product with a shelf-life of several months. The raw milk quality, UHT process and storage conditions affect the stability. In this study, the stability of UHT milk produced in an indirect system was evaluated by studying changes in taste, colour, fat separation, fat adhesion to the package, sedimentation, gelation, heat coagulation time, pH and ethanol stability during storage for up to one year at different temperatures. UHT milk stored at 4 and 20 °C had the longest shelf-life of 34-36 weeks, limited by sediment formation. Storage at 30 and 37 °C considerably decreased the shelf-life of UHT milk to 16-20 weeks, whereby changes in sediment formation, taste and colour were the limiting factors. Our results suggest that the changes observed at the different storage temperatures can be explained by different known mechanisms.

Similar anatomical distributions of childhood naevi and cutaneous melanoma in young adults residing in northern and southern Sweden.

BACKGROUND: Common melanocytic naevi are considered early biomarkers associated with risk of cutaneous malignant melanoma. We sought to investigate if residing at different latitudes in Sweden influences the population's anatomical distribution of naevi in children and melanoma in adults. METHODS: The nationwide Swedish Cancer Registry 1990-2012 gave cumulative number of invasive melanomas per body site, stratified by sex and age in northern (62-69 °N) (n=2823) and southern (55-58 °N) Sweden (n=24,115). A population-based cross-sectional study conducted in 2002 provided the allocation of naevi among 7-year-olds in northern (5695 naevi in 679 children) and southern Sweden (8392 naevi in 681 children). RESULTS: In 2012, northern Sweden had a two-fold lower melanoma incidence: 19.8/100.000 age-standardised population compared with 41.0/100.000 in the south. Similarly, a lower mean naevi density in children was demonstrated: 7.3 (standard deviation (SD) 5.4) in boys and 7.0 (4.7) in girls in the north versus 13.3 (8.4) in boys and 11.9 (8.5) in girls in the south. Across latitudes of residing, gender profiles and proportional body-site distributions of melanoma and naevi, respectively, were largely homogenous, but in southern Sweden slightly higher on the trunk; a body site associated with intermittent sun exposure. Childhood naevi distributions matched with melanomas in young and middle-aged adults. CONCLUSION: This large population-based study demonstrated that latitude of residing similarly affects the number and anatomical distribution of naevi in children and melanoma in adults. It supports a role of childhood naevi as predictors of overall and subsite risk of melanoma among young adults.

The expression of BAFF, APRIL and TWEAK is altered in eczema skin but not in the circulation of atopic and seborrheic eczema patients.

The TNF family cytokines BAFF (B-cell activating factor of the TNF family) and APRIL (a proliferation-inducing ligand) are crucial survival factors for B-cell development and activation. B-cell directed treatments have been shown to improve atopic eczema (AE), suggesting the involvement of these cytokines in the pathogenesis of AE. We therefore analyzed the expression of these TNF cytokines in AE, seborrheic eczema (SE) and healthy controls (HC). The serum/plasma concentration of BAFF, APRIL and a close TNF member TWEAK (TNF-like weak inducer of apoptosis) was measured by ELISA. The expression of these cytokines and their receptors in skin was analyzed by quantitative RT-PCR and immunofluorescence. Unlike other inflammatory diseases including autoimmune diseases and asthma, the circulating levels of BAFF, APRIL and TWEAK were not elevated in AE or SE patients compared with HCs and did not correlate with the disease severity or systemic IgE levels in AE patients. Interestingly, we found that the expression of these cytokines and their receptors was altered in positive atopy patch test reactions in AE patients (APT-AE) and in lesional skin of AE and SE patients. The expression of APRIL was decreased and the expression of BAFF was increased in eczema skin of AE and SE, which could contribute to a reduced negative regulatory input on B-cells. This was found to be more pronounced in APT-AE, the initiating acute stage of AE, which may result in dysregulation of over-activated B-cells. Furthermore, the expression levels of TWEAK and its receptor positively correlated to each other in SE lesions, but inversely correlated in AE lesions. These results shed light on potential pathogenic roles of these TNF factors in AE and SE, and pinpoint a potential of tailored treatments towards these factors in AE and SE.