Childhood atopic dermatitis is associated with cardiovascular risk factors in young adulthood-A population-based cohort study.

BACKGROUND: Studies have indicated that atopic dermatitis (AD) is associated with an increased risk of cardiovascular disease (CVD). However, data are conflicting. Furthermore, the longitudinal effect of childhood AD on cardiovascular risk factors in young adulthood is less investigated. OBJECTIVES: To assess associations between AD in childhood and CVD risk factors in young adulthood. METHODS: The study encompasses longitudinal data from a population-based birth cohort. Participants with data up to age 24 years were included (n = 2270). The primary outcomes were body mass index (BMI), waist circumference (WC), body fat per cent (BF%) and blood pressure (BP) at 24 years. The secondary outcome was blood lipids. Severe AD was defined as AD in combination with sleep disturbance due to itching. RESULTS: In total, 18.6% (n = 420) had AD at 24 years. Males with AD had higher BMI (ßAdj. 0.81, 95% CI 0.15-1.47), BF% (ßAdj. 1.19, 95% CI 0.09-2.29), systolic BP (ßAdj. 1.92, 95% CI 0.02-3.82), total cholesterol (ßAdj. 0.14, 95% CI 0.00-0.28) and LDL cholesterol (ßAdj. 0.15, 95% CI 0.02-0.27) compared with males without AD. No associations were seen in females. Current AD with prepubertal onset was associated with increased BMI in both males (ßAdj. 0.89, 95% CI 0.11-1.67) and females (ßAdj. 0.72, 95% CI 0.11-1.33). At 24 years, 23.1% (n = 97) of all with AD, had severe disease, which was significantly associated with overweight in both sexes, with BMI (ßAdj. 1.83, 95% CI 0.72-2.94), WC (ßAdj. 4.03, 95% CI 1.54-6.52) and BF% (ßAdj. 2.49, 95% CI 0.60-4.39) in females and with BF% (ßAdj. 2.96, 95% CI 0.23-5.69) in males, compared with peers with mild to moderate AD. CONCLUSION: AD in males appears to be associated with CVD risk factors in young adulthood. The duration and severity of AD seem to be of importance in both sexes.

Validation of automated whole-body analysis of metabolic and morphological parameters from an integrated FDG-PET/MRI acquisition.

Automated quantification of tissue morphology and tracer uptake in PET/MR images could streamline the analysis compared to traditional manual methods. To validate a single atlas image segmentation approach for automated assessment of tissue volume, fat content (FF) and glucose uptake (GU) from whole-body [18F]FDG-PET/MR images. Twelve subjects underwent whole-body [18F]FDG-PET/MRI during hyperinsulinemic-euglycemic clamp. Automated analysis of tissue volumes, FF and GU were achieved using image registration to a single atlas image with reference segmentations of 18 volume of interests (VOIs). Manual segmentations by an experienced radiologist were used as reference. Quantification accuracy was assessed with Dice scores, group comparisons and correlations. VOI Dice scores ranged from 0.93 to 0.32. Muscles, brain, VAT and liver showed the highest scores. Pancreas, large and small intestines demonstrated lower segmentation accuracy and poor correlations. Estimated tissue volumes differed significantly in 8 cases. Tissue FFs were often slightly but significantly overestimated. Satisfactory agreements were observed in most tissue GUs. Automated tissue identification and characterization using a single atlas segmentation performs well compared to manual segmentation in most tissues and will be valuable in future studies. In certain tissues, alternative quantification methods or improvements to the current approach is needed.

Maternal body mass index in early pregnancy and offspring asthma, rhinitis and eczema up to 16 years of age.

BACKGROUND: Maternal obesity has been linked to offspring asthma; however, other allergy-related diseases, as well as the association beyond early school age, are largely unstudied. OBJECTIVE: To examine the associations between maternal body mass index (BMI) in pregnancy and offspring asthma, rhinitis, eczema and sensitization up to 16 years of age. METHODS: A total of 3294 children from the Swedish birth cohort BAMSE were included in the analyses. Maternal BMI was assessed around week 10 in pregnancy. Information on asthma, rhinitis, eczema, lifestyle factors and environmental exposures was obtained by parental questionnaires at 1, 2, 4, 8, 12 and 16 years. Sensitization was defined from IgE levels of inhalant allergens at 4, 8 and 16 years in a subsample of 2850 children. Generalized estimated equation models were used to analyse the associations between maternal BMI and the outcomes at 1-16 years. RESULTS: Maternal BMI was positively associated with overall risk of asthma up to age of 16 years (adj OR per 5 kg/m(2) increase: 1.23; 95% CI 1.07-1.40 for prevalent asthma) excluding underweight mothers. In contrast, no significant associations were found for rhinitis, eczema or sensitization. The association with asthma was restricted to obese, rather than overweight mothers, but was attenuated when adjusting for overweight in the offspring. A causal inference test at 16 years further indicated that the child's own overweight is a mediator in the suggested association between maternal BMI and offspring asthma at 16 years. CONCLUSIONS AND CLINICAL RELEVANCE: Maternal BMI is associated with an increased risk of asthma, but not rhinitis, eczema or sensitization; however, overweight in the offspring seems to have a mediating role. Prevention strategies of maternal pre-pregnancy and childhood obesity might be important to reduce the prevalence of childhood asthma.

Experience from start-ups of the first ANITA Mox plants.

ANITA™ Mox is a new one-stage deammonification Moving-Bed Biofilm Reactor (MBBR) developed for partial nitrification to nitrite and autotrophic N-removal from N-rich effluents. This deammonification process offers many advantages such as dramatically reduced oxygen requirements, no chemical oxygen demand requirement, lower sludge production, no pre-treatment or requirement of chemicals and thereby being an energy and cost efficient nitrogen removal process. An innovative seeding strategy, the 'BioFarm concept', has been developed in order to decrease the start-up time of new ANITA Mox installations. New ANITA Mox installations are started with typically 3-15% of the added carriers being from the 'BioFarm', with already established anammox biofilm, the rest being new carriers. The first ANITA Mox plant, started up in 2010 at Sjölunda wastewater treatment plant (WWTP) in Malmö, Sweden, proved this seeding concept, reaching an ammonium removal rate of 1.2 kgN/m³ d and approximately 90% ammonia removal within 4 months from start-up. This first ANITA Mox plant is also the BioFarm used for forthcoming installations. Typical features of this first installation were low energy consumption, 1.5 kW/NH4-N-removed, low N2O emissions, <1% of the reduced nitrogen and a very stable and robust process towards variations in loads and process conditions. The second ANITA Mox plant, started up at Sundets WWTP in Växjö, Sweden, reached full capacity with more than 90% ammonia removal within 2 months from start-up. By applying a nitrogen loading strategy to the reactor that matches the capacity of the seeding carriers, more than 80% nitrogen removal could be obtained throughout the start-up period.

Disposable polymeric high-density nanovial arrays for matrix assisted laser desorption/ionization-time of flight-mass spectrometry: II. Biological applications.

A novel disposable high-density matrix assisted laser desorption/ionization (MALDI) target plate made either from polymethylmethacrylate (PMMA) or polycarbonate (PC) is presented where thousands (1,200-1,600) of samples can be deposited and subsequently analyzed by MALDI-time of flight (TOF) mass spectrometry. Good reproducibility was obtained across the plate regardless of position on the target plate with a relative standard deviation (RSD) on the peak intensity of typically 30% calculated from data generated by analysis of a 10 nm peptide mixture of angiotensin I, II, III and bradykinin. The nanovial array format combined with microdispensing technology makes it possible to carry out in-vial chemistry on deposited samples. This is demonstrated by the analysis of peptides from beta-casein and subsequent in-vial dephosphorylation of its phosphopeptides at 10 fmol levels by microdispensing of alkaline phosphatase, into the nanovial. The mass spectra obtained from these polymeric targets provides can also be used in high sensitivity applications as shown by peptide mass fingerprinting of human fibroblast proteins separated by two-dimensional gel electrophoresis.

Disposable polymeric high-density nanovial arrays for matrix assisted laser desorption/ionization-time of flight-mass spectrometry: I. Microstructure development and manufacturing.

In order to meet the expected enormous demand for mass spectrometry (MS) throughput as a result of the current efforts to completely map the human proteome, this paper presents a new concept for low-cost high-throughput protein identification by matrix assisted laser desorption/ionization-time of flight-(MALDI-TOF)-MS peptide mapping using disposable polymeric high-density nanovial MALDI target plates. By means of microfabrication technology precision engineered nanovial arrays are fabricated in polymer substrates such as polymethylmethacrylate (PMMA) and polycarbonate (PC). The target plate fabrication processes investigated were precision micromilling, cold embossing and injection moulding (work in progress). Nanovial dimensions were 300, 400 or 500 microm. Typical array densities were 165 nanovials/cm2, which corresponds to 3,300 vials on a full Applied Biosystems MALDI target plate. Obtained MALDI data displayed equal mass resolution, accuracy, signal intensity for peptide standards as compared to high-density silicon nanovial arrays previously reported by our group [7], as well as conventional stainless steel or gold targets.

Protein chips based on recombinant antibody fragments: a highly sensitive approach as detected by mass spectrometry.

With the human genome in a first sequence draft and several other genomes being finished this year, the existing information gap between genomics and proteomics is becoming increasingly evident. The analysis of the proteome is, however, much more complicated because the synthesis and structural requirements of functional proteins are different from the easily handled oligonucleotides, for which a first analytical breakthrough already has come in the use of DNA chips. In comparison with the DNA microarrays, the protein arrays, or protein chips, offer the distinct possibility of developing a rapid global analysis of the entire proteome. Thus, the concept of comparing proteomic maps of healthy and diseased cells may allow us to understand cell signaling and metabolic pathways and will form a novel base for pharmaceutical companies to develop future therapeutics much more rapidly. This report demonstrates the possibilities of designing protein chips based on specially constructed, small recombinant antibody fragments using nano-structure surfaces with biocompatible characteristics, resulting in sensitive detection in the 600-amol range. The assay readout allows the determination of single or multiple antigen-antibody interactions. Mass identity of the antigens, currently with a resolution of 8000, enables the detection of structural modifications of single proteins.

Signal amplification using "spot-on-a-chip" technology for the identification of proteins via MALDI-TOF MS.

The presented "spot-on-a-chip" technology enables easy enrichment of samples in the low nanomolar (1-5 nM) range and provides a fast and reliable automated sample preparation method for performing matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis with high sensitivity and throughput. Through microdispensing, which allows accurate deposition of 60-pL droplets, dilute samples were enriched by making multiple droplet depositions in nanovials. The sample was confined to a defined spot area (300 x 300 microm), and multiple depositions increase the surface density of analyte in the nanovial, thereby providing detection of low attomole levels. The impact of the nanovial geometry with respect to the MALDI-TOF MS resolution for peptides deposited in the microfabricated silicon vials was investigated and the optimal geometry and size were determined. The spot-on-a-chip technology, that is, the combination of microdispensing, micromachined silicon nanovials and on-spot enrichment provides a signal amplification of at least 10-50 times as compared to an ordinary sample preparation. The linearity of the enrichment effect is shown by the analysis of a peptide mixture at the 5 nM level. The signal amplification provided by the spot-on-a-chip enrichment is demonstrated by the analysis of relevant biological samples, interleukin-8 from a spiked cell supernatant, and by successful protein identification of an excised spot from a high-sensitivity silver-stained two-dimensional electrophoresis gel separation.

Microfluidic components for protein characterization.

The use of microfluidic components to create an analytical toolbox for the very rapidly growing field of proteomics is described. This toolbox provides novel generic analytical solutions that are highly adaptable for analysis of various biomolecules, ranging from high to low abundant. The components are fabricated using silicon micromachining and consist of a microchip immobilised enzyme reactor (microIMER), a piezoelectric microdispenser and high-density nanovial target plates. This microtechnology based platform interfaces matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI TOF-MS) to a wide range of upstream sample handling and/or analytical techniques. Examples of applications such as rapid on-line digestion (12 s) and sample preparation of proteins, interfacing to capillary liquid chromatography (100 attomol sensitivity), and in-vial chemistry on femtomol amounts of sample are presented.

Downsizing proteolytic digestion and analysis using dispenser-aided sample handling and nanovial matrix-assisted laser/desorption ionization-target arrays.

An efficient technique for enzymatic digestion of proteins in nanovial arrays and identification by peptide mass fingerprinting using matrix-assisted laser desorption/ionization (MALDI-MS) is presented in this work. Through dispensing of a protein solution with simultaneous evaporation the protein (substrate) is concentrated up to 300 times in-vial. At higher substrate concentrations the catalytic turnover numbers increase according to the Michaelis-Menten kinetics. Therefore, the dispenser-aided nanodigestion is valuable for identification of low-level proteins (10 nM-500 nM) as well as for automatic high efficiency digestions performed in 0.2-10 min. As an example of low-level protein identification, a 10 nM solution of lysozyme C was unambiguously identified after 5 min of nanodigestion. Moreover, only 30 s nanodigestion was sufficient to identify hemoglobin (10 microM), exemplifying the fast catalysis of the nanodigestion technique. The developed silicon flow-through piezoelectric dispenser is adapted for low-volume and preconcentrated samples in the nL-microL range and provides fast, accurate and contact-free sample positioning into the nanovials. In this work, the properties of the nanodigestion concept regarding proteins of different characteristics are explored. Furthermore, the potential of automated protein identification using precoated proteolytic nanovial-arrays is demonstrated.

Integrated microanalytical technology enabling rapid and automated protein identification.

Protein identification through peptide mass mapping by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) has become a standard technique, used in many laboratories around the world. The traditional methodology often includes long incubations (6-24 h) and extensive manual steps. In an effort to address this, an integrated microanalytical platform has been developed for automated identification of proteins. The silicon micromachined analytical tools, i.e., the microchip immobilized enzyme reactor (mu-chip IMER), the piezoelectric microdispenser, and the high-density nanovial target plates, are the cornerstones in the system. The mu-chip IMER provides on-line enzymatic digestion of protein samples (1 microL) within 1-3 min, and the microdispenser enables subsequent on-line picoliter sample preparation in a high-density format. Interfaced to automated MALDI-TOF MS, these tools compose a highly efficient platform that can analyze 100 protein samples in 3.5 h. Kinetic studies on the microreactors are reported as well as the operation of this microanalytical platform for protein identification, wherein lysozyme, myoglobin, ribonuclease A, and cytochrome c have been identified with a high sequence coverage (50-100%).

Homogeneous sample preparation for automated high throughput analysis with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry.

This work presents a simple method for obtaining homogeneous sample surfaces in matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS) for the automated analysis of peptides and proteins. The sample preparation method is based on applying the sample/matrix mixture onto a pre-deposited highly diluted matrix spot. The pre-deposited crystals act as seeds for the new sample containing crystals which become much smaller in size and more evenly distributed than with conventional methods. This 'seed-layer' method was developed, optimised and compared with the dried-droplet method using peptides and proteins in the 1000-20,000 Da range. The seed-layer method increases the surface homogeneity, spot to spot reproducibility and sample washability as compared with the commonly used dried-droplet method. This methodology is applicable to alpha-cyanohydroxycinnamic acid, sinapinic acid and ferulic acid, which all form homogeneous crystal surfaces. Within-spot variation and between-spot variation was investigated using statistics at a 95% confidence level (n = 36). The statistical values were generated from more than 5000 data points collected from 500 spectra. More than 90% of the sample locations results in high intensity spectra with relatively low standard deviations (RSDs). Typically obtained data showed an RSD of 19-35% within a sample spot as well as in-between spots for proteins, and an RSD of < or = 50% for peptides. Linear calibration curves were obtained within one order of magnitude using internal calibration with a point-RSD of 3% (n = 10). The sample homogeneity allows mass spectra (average of 16 laser shots) to be obtained on each individual sample within 15 sec, whereby a 100 spot target plate can be run in 25 min. High density target plates using the seed-layer method were prepared by spotting approximately 100 picoliter droplets onto the target, resulting in sample spots < or = 500 microns in diameter using a flow-through piezo-electric micro-dispenser. By using this automated sample preparation step lower standard deviations are obtained in comparison to manually prepared samples.

A psychoeducational approach to educating chronic mental patients for community living.

The psychoeducational approach to psychiatric illness addresses the need for better information about mental illness and its treatment for the patient and family. Most programs focus on the family and its involvement with the patient; in a social rehabilitation program in Sacramento, California, the staff use psychoeducational techniques with chronic psychiatric patients living in the community apart from their families. Educational approaches are employed in all aspects of the program but are most extensively used in the transitional employment service, through work readiness seminars and a graduated continuum of volunteer service, training, and employment; in the adult basic education program; and in the medication education project, which includes weekly seminars for patients and a variety of written materials.