Real-Time Sonoelastography of Salivary Glands for Diagnosis and Functional Assessment of Primary Sjögren’s Syndrome

The purpose of this study was to investigate the value of real-time sonoelastography (RTS) of salivary glands for the diagnosis and assessment of glandular damage in primary Sjögren’s syndrome (pSS). After institutional review board approval, 45 pSS patients, 24 sicca patients and 11 healthy controls were investigated prospectively. Questionnaires were completed and Saxon and Schirmer tests and routine blood tests carried out in all patients. All patients underwent B-mode ultrasonography and RTS of parotid and submandibular glands. Abnormal findings were graded from 0 to 48 and from 0 to 16, respectively. Sialoscintigraphy was done according to a routine protocol; scoring ranged from 0 to 12. Statistical analysis comprised receiver operating characteristic curve and multivariate regression analysis. Patients with pSS had higher B-mode (median score = 25 [range: 2–44] vs. 9 [1–20], p < 0.001) and RTS (6.5 [2–13] versus 4 [1–9], p < 0.001) scores than controls with sicca syndrome, yielding areas under the curve of 0.83 and 0.85 (p < 0.05 each), respectively for pSS diagnosis. In cases with an inconclusive B-mode ultrasonography result, RTS (cutoff score: ≥6) led to a sensitive (66.7%) and specific (85.7%) classification of patients and sicca controls. In multivariate regression analysis, RTS (regression coefficient = –0.48, p = 0.005), but not B-mode ultrasonography, reflected impaired salivary gland function according to the Saxon test, whereas none of the subjective measures of dryness or discomfort were related to ultrasonography results. B-mode and RTS results were both associated with sialoscintigraphy scores (regression coefficient = 0.66, p < 0.001, and regression coefficient = 0.55, p = 0.001, respectively). Reproducibility of B-mode ultrasonography and RTS was good, with intra-class correlation coefficients of 0.93 (95% confidence interval: 0.57–0.98) and 0.93 (95% confidence interval: 0.79–0.98), respectively. In summary, RTS might be a useful adjunct to B-mode ultrasonography for diagnosis and assessment of salivary gland impairment in primary Sjögren’s syndrome.     

Das Modellprojekt ReWiKs

Several studies point to various barriers in achieving sexual self-determination for people with disabilities as well as a high degree of thematic uncertainty among staff in residential homes. In addition, women with disabilities and people in institutions are especially at risk in a particular way, to be victims of sexual violence. The ReWiKs project develops, based on evaluated guidelines for sexual self-determination, materials in order to reflect the institutional handling of the subject. Training modules and recommendations are also developed. In addition, extracts of materials are created in simple language. All materials are evaluated before their publication in an intensive theory-practice dialogue.     

Recommended Immunological Strategies to Screen for Botulinum Neurotoxin-Containing Samples

Botulinum neurotoxins (BoNTs) cause the life-threatening neurological illness botulism in humans and animals and are divided into seven serotypes (BoNT/A–G), of which serotypes A, B, E, and F cause the disease in humans. BoNTs are classified as “category A” bioterrorism threat agents and are relevant in the context of the Biological Weapons Convention. An international proficiency test (PT) was conducted to evaluate detection, quantification and discrimination capabilities of 23 expert laboratories from the health, food and security areas. Here we describe three immunological strategies that proved to be successful for the detection and quantification of BoNT/A, B, and E considering the restricted sample volume (1 mL) distributed. To analyze the samples qualitatively and quantitatively, the first strategy was based on sensitive immunoenzymatic and immunochromatographic assays for fast qualitative and quantitative analyses. In the second approach, a bead-based suspension array was used for screening followed by conventional ELISA for quantification. In the third approach, an ELISA plate format assay was used for serotype specific immunodetection of BoNT-cleaved substrates, detecting the activity of the light chain, rather than the toxin protein. The results provide guidance for further steps in quality assurance and highlight problems to address in the future.     

Flow cytometric analysis of Pig‐a gene mutation and chromosomal damage induced by procarbazine hydrochloride in CD‐1 mice

Procarbazine is a genotoxic carcinogen whose DNA‐damaging activities are not reliably detected in vitro. We evaluated the in vivo genotoxic effects of procarbazine on hematopoietic cells of male CD‐1 mice using a multi‐endpoint study design that scored micronucleated reticulocyte (MN‐RET) frequency and gene mutation at the Pig‐a locus. CD‐1 mice were treated for 3 days with procarbazine, up to 150 mg/kg/day. Blood samples collected on Day 3 exhibited robust induction of MN‐RETs, with the high dose group exhibiting a mean 29‐fold increase. Blood collected 15 and 30 days after treatment began was analyzed for Pig‐a mutation with a dual labeling method that facilitated mutant cell frequency measurements in both total erythrocytes and the reticulocyte subpopulation. Procarbazine significantly increased mutant reticulocyte frequencies by Day 15. Mutant erythrocyte responses were also apparent, with a peak incidence observed for the high dose group on Day 30. These results demonstrate that the complex metabolism and resulting genotoxicity of procarbazine is best evaluated in intact animal models, and show that the flow cytometric methods employed offer a means to efficiently monitor both in vivo chromosomal damage and mutation. Environ. Mol. Mutagen. 54:294–298, 2013. © 2013 Wiley Periodicals, Inc.     

Diet‐induced obesity increases the frequency of Pig‐a mutant erythrocytes in male C57BL/6J mice

Obesity increases the risk of a number of chronic diseases in humans including several cancers. Biological mechanisms responsible for such increased risks are not well understood at present. Increases in systemic inflammation and oxidative stress, endogenous production of mutagenic metabolites, altered signaling in proliferative pathways, and increased sensitivity to exogenous mutagens and carcinogens are some of the potential contributing factors. We hypothesize that obesity creates an endogenously mutagenic environment in addition to increasing the sensitivity to environmental mutagens. To test this hypothesis, we examined two in vivo genotoxicity endpoints. Pig‐a mutant frequencies and micronucleus frequencies were determined in blood cells in two independent experiments in 30‐week old male mice reared on either a high‐fat diet (60% calories from fat) that exhibit an obese phenotype or a normal‐fat diet (10% calories from fat) that do not exhibit an obese phenotype. Mice were assayed again at 52 weeks of age in one of the experiments. N‐ethyl‐N‐nitrosourea (ENU) was used as a positive mutation control in one experiment. ENU induced a robust Pig‐a mutant and micronucleus response in both phenotypes. Obese, otherwise untreated mice, did not differ from non‐obese mice with respect to Pig‐a mutant frequencies in reticulocytes or micronucleus frequencies. However, such mice, had significantly higher and sustained Pig‐a mutant frequencies (increased 2.5‐3.7‐fold, p < 0.02) in erythrocytes as compared to non‐obese mice (based on measurements collected at 30 weeks or 30 and 52 weeks of age). This suggests that obesity, in the absence of exposure to an exogenous mutagen, is itself mutagenic. Environ. Mol. Mutagen. 57:668–677, 2016. © 2016 Wiley Periodicals, Inc.