Handheld x-ray fluorescence spectroscopy evaluation of leather chromium and cobalt.

We present a 29-year-old non-atopic male apprentice power lineman and recreational cowboy with a case of allergic contact dermatitis due to both occupational and recreational exposure. He presented with a 4-month history of a pruritic, steroid-responsive, intermittent hand, foot and leg dermatitis. Patch testing was positive for chromium, cobalt and a piece of leather from his cowboy boots. His leather work gloves, inner lining of work harness, work boots and cowboy boots were assessed for chromium and cobalt content with handheld fluorescence x-ray spectrometry. Upon replacement of all leather items including the items tested and his leather cowboy saddle, the rash resolved. This case demonstrates the clinical relevance of using a handheld fluorescence x-ray spectrometer to assess for chromium and leather content.

Mixed occupational and iatrogenic allergic contact dermatitis in a hairdresser.

Allergic contact dermatitis (ACD) is a common occupational disease. Hairdressers and beauticians are at increased risk of occupational chronic hand eczema. We present a case of mixed occupational, non-occupational and iatrogenic ACD in a hairdresser which illustrates that delayed diagnosis can result in high morbidity, and unnecessary treatment and cost. A hairdresser with chronic hand and facial eczema failed medical management with topical steroids and dupilumab. Patch testing revealed contact allergy to multiple occupational exposures, home exposures and topical medicaments.

The clinical spectrum and incidence of anti-MOG-associated acquired demyelinating syndromes in children and adults.

OBJECTIVES: The aim of this study was to assess the Dutch nationwide incidence of myelin oligodendrocyte glycoprotein (MOG)-IgG-associated acquired demyelinating syndromes (ADS) and to describe the clinical and serological characteristics of these patients. METHODS: All serum samples for routine diagnostics from February 2014 to December 2017 were sent to the single central reference laboratory for the full-length MOG-IgG cell-based assay (CBA) in the Netherlands. Clinical data from patients known in our National ADS centre were available. RESULTS: A total of 1414 samples of 1277 patients were received; of these, 92 patients (7%) were MOG-IgG-seropositive. The mean incidence was 0.16/100,000 people, with higher seropositivity in children (0.31/100,000) than in adults (0.13/100,000). In MOG-IgG-positive patients at the National ADS centre (61/92, 66%), the most common presenting phenotype is acute disseminated encephalomyelitis (ADEM, 56%) in children and optic neuritis (ON, 44%) in adults. Relapsing disease occurred in 9/34 (26%) children and 11/27 (41%) adults during median follow-up of 27.5 months. Patients were tested MOG-IgG-positive >200 months after the initial attack, suggesting an extended time to first relapse (TTFR). Longitudinal analysis of MOG-IgG (25/61, 41%) showed that 67% of the monophasic patients remain seropositive and 60% in relapsing patients. Majority of seronegative patients had no relapses (89%). CONCLUSION: This nationwide study shows that the overall incidence of MOG-IgG-seropositive disorders is 0.16 per 100,000 people. The distribution over the clinical phenotypes differs between adults and children. Seropositivity can be maintained over years even without clinical activity, while seronegative patients generally had no relapses.

High voltage fragmentation of composites from secondary raw materials - Potential and limitations.

The comminution of composites for liberation of valuable components is a costly and energy-intensive process within the recycling of spent products. It therefore is continuously studied and optimized. In addition to conventional mechanical comminution innovative new principles for size reduction have been developed. One is the use of high voltage (HV) pulses, which is known to be a technology selectively liberating along phase boundaries. This technology offers the advantage of targeted liberation, preventing overgrinding of the material and thus improving the overall processing as well as product quality. In this study, the high voltage fragmentation of three different non-brittle composites (galvanized plastics, carbon fibre composites, electrode foils from Li-ion batteries) was investigated. The influence of pulse rate, number of pulses and filling level on the liberation and efficiency of comminution is discussed. Using the guideline VDI 2225 HV, fragmentation is compared to conventional mechanical comminution with respect to numerous criteria such as cost, throughput, energy consumption, availability and scalability. It was found that at current state of development, HV fragmentation cannot compete with mechanical comminution beyond laboratory scale.

Comprehensive approach to study complement C4 in systemic lupus erythematosus: Gene polymorphisms, protein levels and functional activity.

Genetic variation of the genes encoding complement component C4 is strongly associated with systemic lupus erythematosus (SLE), a chronic multi-organ auto-immune disease. This study examined C4 and its isotypes on a genetic, protein, and functional level in 140 SLE patients and 104 healthy controls. Gene copy number (GCN) variation, silencing CT-insertion, and the retroviral HERV-K(C4) insertion) were analyzed with multiplex ligation-dependent probe amplification. Increased susceptibility to SLE was found for low GCN (≪2) of C4A. Serositis was the only clinical manifestation associated with low C4A GCN. One additional novel silencing mutation in the C4A gene was found by Sanger sequencing. This mutation causes a premature stop codon in exon 11. Protein concentrations of C4 isoforms C4A and C4B were determined with ELISA and were significantly lower in SLE patients compared to healthy controls. To study C4 isotypes on a functional level, a new C4 assay was developed, which distinguishes C4A from C4B by its binding capacity to amino or hydroxyl groups, respectively. This assay showed high correlation with ELISA and detected crossing over of Rodgers and Chido antigens in 3.2% (8/244) of individuals. The binding capacity of available C4 to its substrates was unaffected in SLE. Our study provides, for the first time, a complete overview of C4 in SLE from genetic variation to binding capacity using a novel test. As this test detects crossing over of Rodgers and Chido antigens, it will allow for more accurate measurement of C4 in future studies.

Reproducibility in density functional theory calculations of solids.

The widespread popularity of density functional theory has given rise to an extensive range of dedicated codes for predicting molecular and crystalline properties. However, each code implements the formalism in a different way, raising questions about the reproducibility of such predictions. We report the results of a community-wide effort that compared 15 solid-state codes, using 40 different potentials or basis set types, to assess the quality of the Perdew-Burke-Ernzerhof equations of state for 71 elemental crystals. We conclude that predictions from recent codes and pseudopotentials agree very well, with pairwise differences that are comparable to those between different high-precision experiments. Older methods, however, have less precise agreement. Our benchmark provides a framework for users and developers to document the precision of new applications and methodological improvements.

Neuromyelitis optica spectrum disorders: comparison of clinical and magnetic resonance imaging characteristics of AQP4-IgG versus MOG-IgG seropositive cases in the Netherlands.

BACKGROUND AND PURPOSE: Neuromyelitis optica spectrum disorders (NMOSDs) are a group of rare inflammatory demyelinating disorders of the central nervous system. The identification of specific antibodies directed to aquaporin 4 (AQP4-IgG) led to the distinction from multiple sclerosis. However, up to 25% of the clinically diagnosed NMO patients are seronegative for AQP4-IgG. A subgroup of these patients might be identified by antibodies directed to myelin oligodendrocyte glycoprotein (MOG-IgG). Our objective was to investigate whether the clinical characteristics of these patients differ. METHODS: Using a cell-based assay, samples of 61 AQP4-IgG seronegative patients and 41 AQP4-IgG seropositive patients with clinically NMOSD were analysed for the presence of MOG-IgG. Clinical characteristics of the AQP4-IgG, MOG-IgG seropositive and double seronegative NMOSD patients were compared. RESULTS: Twenty of the 61 AQP4-IgG seronegative patients tested MOG-IgG seropositive (33%). MOG-IgG seropositive patients were more frequently males in contrast to AQP4-IgG seropositive patients (55% vs. 15%, P < 0.01) and Caucasians (90% vs. 63%, P = 0.03). They more frequently presented with coincident optic neuritis and transverse myelitis (40% vs. 12%, P = 0.02) and had a monophasic disease course (70% vs. 29%, P < 0.01). AQP4-IgG seropositive patients were 2.4 times more likely to suffer from relapses compared with MOG-IgG seropositive patients (relative risk 2.4, 95% confidence interval 1.2-4.7). AQP4-IgG seropositive patients had higher Expanded Disability Status Scale levels at last follow-up (P < 0.01). CONCLUSION: Antibodies directed to MOG identify a subgroup of AQP4-IgG seronegative NMO patients with generally a favourable monophasic disease course.

Concentration variability of potent allergens of p-tert-butylphenol-formaldehyde resin (PTBP-FR) in patch test preparations and commercially available PTBP-FR.

BACKGROUND: p-tert-Butylphenol-formaldehyde resin (PTBP-FR) is a common component of glues used in the manufacturing of many plastic, electronic, rubber, wood and leather products. Two main allergens of PTBP-FR have been described. OBJECTIVES: To determine the concentrations of the two main allergens of PTBP-FR in diagnostic patch testing preparations and PTBP-FR available to glue and adhesive manufacturers. METHODS: Nuclear magnetic resonance spectrometry was used to confirm the identity and determine the purity of reference materials. High-pressure liquid chromatography was used to analyse patch test preparations and commercially available PTBP-FR. RESULTS: In the PTBP-FR in analysed patch test preparations the highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 1·79% and the lowest 0·21%. The highest concentration of the allergenic dimer 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found in PTBP-FR of analysed patch test preparations was 0·50% and the lowest concentration found was 0·04%. In commercially available PTBP-FR the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-3-hydroxymethyl-benzyloxymethyl)-6-hydroxymethylphenol found was 3·7% and the highest concentration of 4-tert-butyl-2-(5-tert-butyl-2-hydroxy-benzyloxymethyl)-6-hydroxymethylphenol found was 1·1%. In three PTBP-FR samples neither allergen could be detected. CONCLUSIONS: Our data suggest that reporting resin concentration in petrolatum is not predictive of a consistent concentration of the two main allergens of PTBP-FR. The 10-fold difference in allergen concentration between different patch test preparations has significant ramifications for maintaining consistent dose of delivered allergen. The results of this study reinforce the need for patch test product standardization in the contact dermatitis community.

Service Desk Calls in a Home-based Clinical Informatics Study: Supporting End Users in the Field.

Home-based clinical informatics technologies are being developed to facilitate health care provision and management. Given the novelty of these technologies, end users such as patients and their formal and informal caregivers may require support during use. This paper presents a case study within the United States of the service desk calls generated over a 31-month period by patients enrolled in a large randomized field experiment, HeartCare II. This case study provides future deployers of home-based clinical information technologies with an understanding of the types of support that may be required during use. Our analysis reveals that calls to the service desk originated as a result of user problems, hardware problems, software problems, and internal communication problems among individuals involved in the delivery and use of the technology. Implications of these needs for support during use are also discussed.

Preferential decrease in IgG4 anti-citrullinated protein antibodies during treatment with tumour necrosis factor blocking agents in patients with rheumatoid arthritis.

OBJECTIVE: To investigate the dynamics of IgG1 and IgG4 anti-citrullinated protein antibody (ACPA) subclasses during anti-tumour necrosis factor (TNF) treatment in patients with rheumatoid arthritis (RA). METHODS: IgG, IgG1 and IgG4 ACPA levels were determined by ELISA on anti-citrullinated fibrinogen (ACF) and IgG1 : IgG4 ACPA ratios were calculated. A pilot study was performed in 28 ACF-positive patients treated with infliximab for one year. Confirmation of the results was obtained using a cohort of 180 consecutive patients treated with adalimumab for 28 weeks. RESULTS: The median reduction in ACF levels was 31% for total IgG, 29% for IgG1, 40% for IgG4 and 22% for the IgG4 : IgG1 ACF ratio in the infliximab cohort. In adalimumab-treated patients, ACF levels declined 14% for total IgG and IgG1, and 36% for IgG4 ACF; the IgG4 : IgG1 ratio was reduced by 24% (all percentage values p<0.05). The decrease in antibody levels was correlated with the clinical response; European League Against Rheumatism good responders had the greatest decline in antibody levels and this effect was most pronounced for IgG4 (48% reduction). The IgG4 : IgG1 ACF ratio preferentially decreased in patients with adequate therapeutic adalimumab levels. CONCLUSION: ACPA subclass distribution is modulated by effective anti-inflammatory treatment. The preferential decline of IgG4 ACPA, reflected by the decreased IgG4 : IgG1 ratio, suggests a beneficial effect of anti-TNF treatment on chronic antigenic stimulation by citrullinated proteins. This effect may be directly anti-TNF mediated or the result of effective dampening of the inflammation in the rheumatoid joint.

Tailored release of TGF-beta1 from porous scaffolds for cartilage tissue engineering.

In view of cartilage tissue engineering, the possibility to prepare porous scaffolds releasing transforming growth factor-beta(1) (TGF-beta(1)) in a well controlled fashion was investigated by means of an emulsion-coating method. Poly(ether-ester) multiblock copolymers were used to prepare emulsions containing TGF-beta(1) which were subsequently applied onto prefabricated scaffolds. This approach resulted in defined porous structures (66%) with interconnected porosity, suitable to allow tissue ingrowth. The scaffolds were effectively associated with TGF-beta(1) and allowed to tailor precisely the release of the growth factor from 12 days to more than 50 days by varying the copolymer composition of the coating. An incomplete release was measured by ELISA, possibly linked to the rapid concentration decrease of the protein in solution. The released growth factor retained its biological activity as was assessed by a cell proliferation assay and by the ability of the released protein to induce chondrogenic differentiation of bone marrow-derived mesenchymal stem cells. However, exact bioactivity quantification was rendered difficult by the protein concentration decrease during storage. Therefore, this study confirms the interest of poly(ether-ester) multiblock copolymers for controlled release of growth factors, and indicates that emulsion-coated scaffolds are promising candidates for cartilage tissue engineering applications requiring precise TGF-beta(1) release rates.

Determinants of CD4 counts among HIV-negative Ethiopians: role of body mass index, gender, cigarette smoking, khat (Catha Edulis) chewing, and possibly altitude?

To study the determinants of CD4% and CD4 counts among HIV-negative Ethiopians, and to identify factors susceptible to explain the low CD4 counts observed among Ethiopian subjects. Cohort studies among factory workers in Akaki and Wonji, Ethiopia. Clinical and laboratory examinations, including determination of HIV serological status and T-cell subsets, were performed during follow-up visits every six months. In addition, micronutrients (retinol, carotenoids, tocopherol, transferrin receptor, and selenium) plasma concentrations were determined in a subset of 38 HIV-positive and 121 HIV-negative participants. HIV-negative participants with at least one CD4 count measurement were 157 females in Akaki, 203 males in Akaki, and 712 males in Wonji. CD4 counts were independently and positively associated with body mass index (through an increase in lymphocyte counts), female gender (through an increase in CD4%), cigarette smoking (through an increase in CD4%), khat chewing (through an increase in both lymphocyte counts and CD4%), and Akaki study site (through a large increase in lymphocyte counts compensating a decrease in CD4%). Intestinal parasitic infections were not associated with CD4% or CD4 counts. Retinol, carotenoids, and alpha-tocopherol plasma concentrations decreased with HIV infection and advancing immunosuppression, but were not associated with CD4 counts among HIV-negative subjects. Low body mass index among Ethiopians may have contributed to their overall low CD4 counts. Other factors remain to be elucidated.

Antibodies to citrullinated human fibrinogen (ACF) have diagnostic and prognostic value in early arthritis.

BACKGROUND: The anti-cyclic citrullinated peptide (CCP) test has a high sensitivity and specificity for rheumatoid arthritis, although CCP is not the physiological target of the autoantibodies. Citrullinated fibrin is abundant in inflamed synovium OBJECTIVE: To assess the diagnostic and prognostic value of antibodies against citrullinated fibrinogen (ACF), a soluble precursor of fibrin, in comparison with IgM-rheumatoid factor (IgM-RF) and the second generation anti-CCP test. METHODS: In 379 patients with early arthritis (258 rheumatoid and 121 undifferentiated), the sensitivity, specificity, and positive predictive value of ACF, anti-CCP, and IgM-RF for diagnosing rheumatoid arthritis were calculated. Multivariate logistic regression analysis was used to assess the diagnostic and prognostic value (radiographic progression after two years) of the tests. RESULTS: The sensitivities of the ACF, anti-CCP, and IgM-RF tests were 55.8%, 57.8%, and 44.6%, with specificities of 92.6%, 94.2%, and 96.7%, respectively. Approximately 30% of the IgM-RF negative patients were positive for ACF or anti-CCP or both. The ACF and anti-CCP test had a high agreement in early arthritis (kappa = 0.84). Of all baseline characteristics, the ACF test and the anti-CCP test were the best predictors for diagnosing rheumatoid arthritis at one year (odds ratio (OR) = 10.3 and 10.6, respectively) and for radiographic progression after two years (OR = 12.1 and 14.8). CONCLUSIONS: ACF is as sensitive as anti-CCP and more sensitive than IgM-RF in diagnosing rheumatoid arthritis in early arthritis. The ACF test is also a good predictor of radiographic progression, with a performance similar to the anti-CCP test. The ACF test and the anti-CCP test are especially valuable in IgM-RF negative arthritis.

Role of incidental and/or cured intestinal parasitic infections on profile of CD4+ and CD8+ T cell subsets and activation status in HIV-1 infected and uninfected adult Ethiopians.

Intestinal parasitic infections have been suggested to cause persistent immune activation leading to an unbalanced immune state. Such a state has been proposed to be a major factor in the pathogenesis of AIDS in an African context. The present study investigated the effect of incidental parasitic infection and treatment on the profile of T cell differentiation and activation markers on CD4+ and CD8+ T cells from HIV-1 infected and uninfected adult Ethiopians. Cryopreserved PBMCs from 64 subjects (41 HIV-negative and 23 HIV-positive) with follow-up visits at 6-monthly intervals were used to compare the effect of incidental intestinal parasites and their treatment upon T cell subset profiles and activation status. The samples were stained with antibodies to various T cell differentiation and activation markers allowing naive, memory, effector, memory/effector, activated and resting CD4+ and CD8+ T cell subsets to be quantified by triple-colour FACScan. Incidental intestinal parasitic infections resulted in a significant increase in memory CD4+ T cell numbers both in HIV-negative and HIV-positive subjects (P < 0.05). There was also a significant increase in the percentage of CD8+ HLA-DR+ T cells (P < 0.05) in HIV-positive subjects co-infected with parasites. In HIV-negative subjects, a significant decline in activated cells and a significant increase in resting CD8+ T cells (P < 0.05) was observed after treatment for parasites. These data suggest that intestinal parasitic infections could result in the alteration of T cell subset counts and also in the up-regulation of T cell activation markers in peripheral blood. Treatment of parasitic infections showed a tendency to reduce the activation suggesting that, together with other community based intervention strategies, such treatment could be used to down-regulate immune activation and hence protect the host from being easily attacked by HIV.

Direct fabrication of large micropatterned single crystals.

Micropatterning of single crystals for technological applications is a complex, multistep process. Nature provides alternative fabrication strategies, when crystals with exquisite micro-ornamentation directly develop within preorganized frameworks. We report a bio-inspired approach to growing large micropatterned single crystals. Micropatterned templates organically modified to induce the formation of metastable amorphous calcium carbonate were imprinted with calcite nucleation sites. The template-directed deposition and crystallization of the amorphous phase resulted in the fabrication of millimeter-sized single calcite crystals with sub-10-micron patterns and controlled crystallographic orientation. We suggest that in addition to regulating the shape, micropatterned frameworks act as sites for stress and impurity release during the amorphous-to-crystalline transition. The proposed mechanisms may have direct biological relevance and broad implications in materials synthesis.

Absolute and approximate calculations of electron-energy-loss spectroscopy edge thresholds.

Systematic studies of binding energies for the electron excitation of core levels for atoms, molecules, and solids have been calculated with various density functional theories. The generalized gradient approximation provides the most accurate description of the absolute binding energies when spin polarization is included. Relative core level shifts can be determined to within 0.5 eV without spin polarization. Core level shifts can be predicted from ground-state eigenvalue differences only when comparing environments of similar electronegativity. Such is the case for the O K edge, but not the Si L edge at Si/SiO(2) interfaces in nanotransistors.

Distribution of lymphocyte subsets in healthy human immunodeficiency virus-negative adult Ethiopians from two geographic locales.

Immunological values for 562 factory workers from Wonji, Ethiopia, a sugar estate 114 km southeast of the capital city, Addis Ababa, Ethiopia, were compared to values for 218 subjects from Akaki, Ethiopia, a suburb of Addis Ababa, for whom partial data were previously published. The following markers were measured: lymphocytes, T cells, B cells, NK cells, CD4(+) T cells, and CD8(+) T cells. A more in depth comparison was also made between Akaki and Wonji subjects. For this purpose, various differentiation and activation marker (CD45RA, CD27, HLA-DR, and CD38) expressions on CD4(+) and CD8(+) T cells were studied in 60 male, human immunodeficiency virus-negative subjects (30 from each site). Data were also compared with Dutch blood donor control values. The results confirmed that Ethiopians have significantly decreased CD4(+) T-cell counts and highly activated immune status, independent of the geographic locale studied. They also showed that male subjects from Akaki have significantly higher CD8(+) T-cell counts, resulting in a proportional increase in each of the CD8(+) T-cell compartments studied: naïve (CD45RA(+)CD27(+)), memory (CD45RA(-)CD27(+)), cytotoxic effector (CD45RA(+)CD27(-)), memory/effector (CD45RA(-)CD27(-)), activated (HLA-DR(+)CD38(+)), and resting (HLA-DR(-)CD38(-)). No expansion of a specific functional subset was observed. Endemic infection or higher immune activation is thus not a likely cause of the higher CD8 counts in the Akaki subjects. The data confirm and extend earlier observations and suggest that, although most lymphocyte subsets are comparable between the two geographical locales, there are also differences. Thus, care should be taken in extrapolating immunological reference values from one population group to another.