Fluorescence confocal microscopy for evaluation of fresh surgical specimens and consecutive tumor cell isolation in rare pediatric tumors.

Fluorescence confocal microscopy (FCM) is an optical technique that uses laser light sources of different wavelengths to generate real-time images of fresh, unfixed tissue specimens. FCM allows histological evaluation of fresh tissue samples without the associated cryo artifacts after frozen sectioning. The aim of this study was to prospectively evaluate pediatric tumor specimens and assess their suitability for fresh tumor sampling. In addition, we aimed to determine whether tumor cell isolation for stable cell culture is still feasible after FCM imaging. Pediatric tumor specimens were imaged using FCM. Tumor viability and suitability for tissue sampling were evaluated and compared with H&E staining after paraffin embedding. In addition, FCM-processed and non-FCM-processed tissue samples were sent for tumor cell isolation to evaluate possible effects after FCM processing. When comparing estimated tumor cell viability using FCM and H&E, we found good to excellent correlating estimates (intraclass correlation coefficient = 0.891, p < 0.001), as well as substantial agreement in whether the tissue appeared adequate for fresh tissue collection (κ = 0.762, p < 0.001). After FCM, seven out of eight samples yielded passable cell cultures, compared to eight out of eight for non-FCM processed samples. Our study suggests that the use of FCM in tumor sampling can increase the yield of suitable fresh tumor samples by identifying viable tumor areas and ensuring that sufficient tissue remains for diagnosis. Our study also provides first evidence that the isolation and growth of tumor cells in culture are not compromised by the FCM technique.

[Utilization of video consultation in cardiovascular lipid treatment]. / Anwendung der Videosprechstunde in der kardiovaskulären Lipidbehandlung.

BACKGROUND: Video consultation is a possibility for physician-patient communication independent of the location; however, only limited information is available for the possibility of sole use since 2018. METHODS: After the implementation of video consultation (Viomedi) in lipid consultations at the Medical University Mainz, the patients in the first quarter of 2022 were assessed depending on the possibility, suitability and readiness to participate. Included were patients under lipid management and long COVID patients. After treatment an online survey was carried out on the utilization and appraisal. RESULTS: Of the 134 patients 29.1% were inclusively treated (3 refusals). All subjects (16 replies) reported having managed (very) well. Advantages were seen in counselling and follow-up. Problems were feared with respect to technology and possible disorders. Data protection aspects played a subordinate role. In comparison to telephone calls, a significant improvement in the physician-patient relationship (p-value = 0.00027), the quality of treatment and information (p-value both = 0.00044), the access to care (p-value = 0.0053) and the communication (p-value = 0.021) was assumed. An improvement in access to care (p-value = 0.021) and the quality of information (p-value = 0.034) was seen in comparison to personal contact. The main problems were a lack of experience, technical requirements, technical problems and unpunctuality of the practitioner. The flexibility, low effort and the pleasant consultation were all praised. All subjects wanted to use the video consultation again. CONCLUSION: Video consultation can represent a supplement to treatment of patients under lipid management. The correct use requires exact planning and further research.

Plasma protein signatures for high on-treatment platelet reactivity to aspirin and clopidogrel in peripheral artery disease.

BACKGROUND: A significant proportion of patients with peripheral artery disease (PAD) displays a poor response to aspirin and/or the platelet P2Y12 receptor antagonist clopidogrel. This phenomenon is reflected by high on-treatment platelet reactivity (HTPR) in platelet function assays in vitro and is associated with an increased risk of adverse cardiovascular events. OBJECTIVE: This study aimed to elucidate specific plasma protein signatures associated with HTPR to aspirin and clopidogrel in PAD patients. METHODS AND RESULTS: Based on targeted plasma proteomics, 184 proteins from two cardiovascular Olink panels were measured in 105 PAD patients. VerifyNow ASPI- and P2Y12-test values were transformed to a continuous variable representing HTPR as a spectrum instead of cut-off level-defined HTPR. Using the Boruta random forest algorithm, the importance of 3 plasma proteins for HTPR in the aspirin, six in clopidogrel and 10 in the pooled group (clopidogrel or aspirin) was confirmed. Network analysis demonstrated clusters with CD84, SLAMF7, IL1RN and THBD for clopidogrel and with F2R, SELPLG, HAVCR1, THBD, PECAM1, TNFRSF10B, MERTK and ADM for the pooled group. F2R, TNFRSF10B and ADM were higher expressed in Fontaine III patients compared to Fontaine II, suggesting their relation with PAD severity. CONCLUSIONS: A plasma protein signature, including eight targets involved in proatherogenic dysfunction of blood cell-vasculature interaction, coagulation and cell death, is associated with HTPR (aspirin and/or clopidogrel) in PAD. This may serve as important systems-based determinants of poor platelet responsiveness to aspirin and/or clopidogrel in PAD and other cardiovascular diseases and may contribute to identify novel treatment strategies.

Computed Tomography Radiomics to Differentiate Intrahepatic Cholangiocarcinoma and Hepatocellular Carcinoma.

AIMS: Intrahepatic cholangiocarcinoma (iCCA) and hepatocellular carcinoma (HCC) differ in prognosis and treatment. We aimed to non-invasively differentiate iCCA and HCC by means of radiomics extracted from contrast-enhanced standard-of-care computed tomography (CT). MATERIALS AND METHODS: In total, 94 patients (male, n = 68, mean age 63.3 ± 12.4 years) with histologically confirmed iCCA (n = 47) or HCC (n = 47) who underwent contrast-enhanced abdominal CT between August 2014 and November 2021 were retrospectively included. The enhancing tumour border was manually segmented in a clinically feasible way by defining three three-dimensional volumes of interest per tumour. Radiomics features were extracted. Intraclass correlation analysis and Pearson metrics were used to stratify robust and non-redundant features with further feature reduction by LASSO (least absolute shrinkage and selection operator). Independent training and testing datasets were used to build four different machine learning models. Performance metrics and feature importance values were computed to increase the models' interpretability. RESULTS: The patient population was split into 65 patients for training (iCCA, n = 32) and 29 patients for testing (iCCA, n = 15). A final combined feature set of three radiomics features and the clinical features age and sex revealed a top test model performance of receiver operating characteristic (ROC) area under the curve (AUC) = 0.82 (95% confidence interval =0.66-0.98; train ROC AUC = 0.82) using a logistic regression classifier. The model was well calibrated, and the Youden J Index suggested an optimal cut-off of 0.501 to discriminate between iCCA and HCC with a sensitivity of 0.733 and a specificity of 0.857. CONCLUSIONS: Radiomics-based imaging biomarkers can potentially help to non-invasively discriminate between iCCA and HCC.

The NeuroSAFE frozen section technique during radical prostatectomy - Implementation and optimization of technical aspects in a routine pathology workflow.

BACKGROUND AND AIMS: In prostate cancer patients, application of the NeuroSAFE frozen section technique during radical prostatectomy has been shown to increase the rate of nerve sparing surgery and to improve functional outcome for the patients. The aim of this study is to report on technical and organizational optimization opportunities of the procedure. MATERIAL AND METHODS: All patients submitted to bilateral intraoperative frozen section from January 2018 until December 2020 (n = 452) were retrospectively analyzed and parameters such as turnaround time, staff situation in the laboratory and histologic properties of the tumors were assessed. RESULTS: The median turnaround time per case was 40.3 ( ± 10.5) min. In 2020 the average time needed from accessioning to diagnosis was 38.1 min. Multivariate linear regression suggested that the number of technical assistants/cryotomes (46.1 min vs. 39.13 min; p < 0.001), the place of microscopic examination (43.0 min vs. 38.7 min; p < 0.001) and the presence of a positive margin (38.0 vs. 44.0 min; p < 0.001) were significant influential factors. The turnaround time was independent of the uropathological expertize of the consultant (39.84 min vs. 40.7 min; p = 0.09), the tumor grade (42.3 vs 39.8 min; p = 0.493) and the presence of extraprostatic extension (44.0 vs 39.8 min; p = 0.099). CONCLUSION: The implementation of simple optimization measures in the workflow as well as structured training of all pathology staff involved in the examination leads to a significant increase in the efficiency of the examination while maintaining the same level of resources. The results could thus be a contribution to the broader application of the procedure.

Evolution of the biomechanical dimension of the professional gestures of grinders when using a collaborative robot.

Using a cobot could relieve workers of strenuous and repetitive tasks while preserving their expertise. To understand the consequences of using a cobot on the occurrence of musculoskeletal disorders (MSDs), within a theoretical framework based on activity-centred ergonomics, an example cobot used in grinding activities in a real work situation is studied. This article analyses the evolution of the biomechanical dimension of the professional gestures of grinders when using the cobot. Effort linked to tool carrying and the vibrations perceived were reduced. Repetitiveness decreased but workers did not accomplish the entirety of their task. The work postures did improve for different joints but not for all, which shows the advantage of varying the contexts of using a cobot and taking into account workers' strategy diversity. To investigate other explanatory elements of the effects on MSDs, these results must be linked to the evolution of the other dimensions of professional gestures.

The association of depression and all-cause mortality: Explanatory factors and the influence of gender.

BACKGROUND: The association of depression with mortality and the significance of explanatory factors, in particularly gender, have remained an issue of debate. We therefore aimed to estimate the effect of depression on all-cause mortality, to examine potential explanatory factors and to assess effect modification by gender. METHODS: We used Cox regression models to estimate the effect of depression on mortality based on data from the Gutenberg Health Study, which is a prospective cohort study of the adult population in the districts of Mainz and Mainz-Bingen, Germany. Baseline assessment was between 2007 and 2012. Effect modification by gender was measured on both additive and multiplicative scales. RESULTS: Out of 14,653 participants, 7.7% were depressed according to Patient Health Questionnaire 9 (PHQ-9), and 1,059 (7.2%) died during a median follow-up of 10.7 years. Depression elevated the risk of mortality in men and women in age-adjusted models (HR: 1.41, 95%-CI: 1.03-1.92; resp. HR: 1.96, 95%-CI: 1.43-2.69). Adjustment for social status, physical health and lifestyle covariates attenuated the effect and in the fully-adjusted model the hazard ratio was 0.96 (95%-CI: 0.69-1.33) in men and 1.53 (95%-CI: 1.10-2.12) in women. For effect modification by gender, the measure on multiplicative interaction was 0.68 (95%-CI 0.44-1.07) and on additive interaction was RERI=-0.47 (95%-CI -1.24-0.30). LIMITATIONS: The PHQ-9 is a single self-report measure of depression reflecting symptoms of the past two weeks, limiting a more detailed assessment of depression and course of symptoms, which likely affects the association with mortality. CONCLUSIONS: Depression elevates mortality by multifactorial pathways, which should be taken into account in the biopsychosocially informed treatment of depression. Effect modification by gender was not statistically significant.

The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis

IntroductionPenile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias.Materials and methodsA cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed.ResultsOur study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival.ConclusionPD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

The peri- and intratumoral immune cell infiltrate and PD-L1 status in invasive squamous cell carcinomas of the penis.

INTRODUCTION: Penile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias. MATERIALS AND METHODS: A cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed. RESULTS: Our study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival. CONCLUSION: PD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.

[Localized prostate cancer]. / Das lokalisierte Prostatakarzinom.

Prostate cancer is the most prevalent noncutaneous cancer in men. The Gleason grading is considered to be the strongest prognostic parameter regarding progression-free survival and overall survival. The original grading system has been modified during the last decade resulting in a more precise prognostic tool. The pretreatment Gleason score guides clinical management and is a key component in S3 guidelines for prostate cancer. In addition to Gleason score several other histologic findings in prostate needle biopsy influence patient management. In this second part of our CME series about prostate cancer, we will discuss the diagnosis of prostate cancer and current guidelines for reporting prostate cancer. In addition, we will highlight prostate lesions of urothelial origin and neuroendocrine prostate cancer as well as prognostic biomarkers.

Particle and metal exposure in Parisian subway: Relationship between exposure biomarkers in air, exhaled breath condensate, and urine.

Subway particulate toxicity results from in vitro and in vivo studies diverge and call for applied human research on outcomes from chronic exposures and potential exposure biomarkers. We aimed to (1) quantify airborne particulate matter (PM) concentrations (mass and number) and metal concentrations in exhaled breath condensate (EBC), urine, and PM; (2) investigate their associations (EBC vs. PM vs. urine); and (3) assess the relevance of EBC in biomonitoring. Nine subway workers in three jobs: station agents, locomotive operators and security guards were monitored during their 6-h shifts over two consecutive weeks. Six-hour weighed average mass concentrations expressed as PM10, PM2.5 and their metal concentrations were determined. Urine and EBC samples were collected pre- and post-shift. Ultrafine particle (UFP) number concentrations were quantified in PM and EBC samples. Metal concentrations in urine and EBC were standardized by creatinine and EBC volume, respectively, and log-transformed. Associations were investigated using Pearson correlation and linear mixed regression models, with participant's ID as random effect. PM concentrations were below occupational exposure limits (OEL) and varied significantly between jobs. Locomotive operators had the highest exposure (189 and 137 µg/m3 for PM10 and PM2.5, respectively), while station agents had the highest UFP exposure (1.97 × 104 particles/cm3). Five metals (Al, Fe, Zn, Cu, and Mn) in PM2.5 and three (Al, Fe, and Zn) in PM10 were above the limit of quantification (LOQ). Fe, Cu, Al and Zn were the most abundant by mass fraction in PM. In EBC, the metal concentrations in decreasing order were: Zn > Cu > Ni > Ba > Mn. Security guards had the highest EBC metal concentrations, and in particular Zn and Cu. Urinary metal concentrations in decreasing order were: Si > Zn > Mo > Ti > Cu > Ba ≈ Ni > Co. All urinary metal concentrations from the subway workers were similar to concentrations found in the general population. A statistically significant relationship was found for ultrafine particle number concentrations in PM and in EBC. Zn and Cu concentrations in post-shift EBC were associated with Zn and Cu concentrations in PM10 and with post-shift urinary Zn and Cu concentrations. Therefore, EBC appears a relevant matrix for assessing exposure to UFP in human biomonitoring when inhalation is a primary route of exposure. We found different temporal variation patterns between particle and metal exposures in three matrices (PM, urine, EBC) quantified daily over two full weeks in subway workers. These patterns might be related to metal oxidation, particulates' solubility and size as well as their lung absorption capabilities, which need to be further explored in toxicological research. Further research should also focus on understanding possible influences of low chronic exposures to subway particulates on health in larger cohorts.

Influence of experimental parameters on in vitro human skin permeation of Bisphenol A.

Bisphenol A (BPA) in vitro skin permeation studies have shown inconsistent results, which could be due to experimental conditions. We studied the impact of in vitro parameters on BPA skin permeation using flow-through diffusion cells with ex-vivo human skin (12 donors, 3-12 replicates). We varied skin status (viable or frozen skin) and thickness (200, 400, 800 µm), BPA concentrations (18, 250 mg/l) and vehicle volumes (10, 100 and 1000 µl/cm2). These conditions led to a wide range of BPA absorption (2%-24% after 24 h exposure), peak permeation rates (J = 0.02-1.31 µg/cm2/h), and permeability coefficients (Kp = 1.6-5.2 × 10-3 cm/h). This is the first time steady state conditions were reached for BPA aqueous solutions in vitro (1000 µl/cm2 applied at concentration 250 mg/l). A reduction of the skin thickness from 800 and 400 µm to 200 µm led to a 3-fold increase of J (P < 0.05). A reduction of the vehicle volume from 1000 to 100 led to a 2-fold decrease in J (P > 0.05). Previously frozen skin led to a 3-fold increase in J compared to viable skin (P < 0.001). We found that results from published studies were consistent when adjusting J according to experimental parameters. We propose appropriate J values for different exposure scenarios to calculate BPA internal exposures for use in risk assessment.

Plastic recycling in a circular economy; determining environmental performance through an LCA matrix model approach.

To ensure a circular economy for plastics, insights in the environmental impacts of recycling and optimal recycling choices for specific plastic polymers are crucial. This was obtained by determining the environmental performance of 10 selected recycling technologies with varying TRL levels, using the chemical properties of the top 25 produced polymers in Europe. The results were collected in a life cycle assessment (LCA) 'matrix' model. To simulate realistic plastic recycling challenges, case studies of PE/PP foils from municipal waste and ABS plastic with brominated flame retardants were developed, to be used as an addition to the LCA matrix model results. Potential emission reduction was assessed by combining LCA matrix outcomes with European polymer demand data. The LCA matrix model illustrates that potential environmental performance of recycling technologies varied strongly per polymer type and did not always follow the state-of-the-art recycling hierarchy. Commodity plastics performed well with tertiary recycling technologies, such as gasification and pyrolysis to monomers; secondary mechanical recycling was outperformed. A focus on primary recycling is environmentally beneficial for most engineering and high performance plastics. To enhance the performance of primary recycling technologies, a higher purity and improved sorting is required. As demonstrated in the case studies, low sorting efficiencies due to impurities reduces positive environmental impacts. Hence, optimal environmental performance of recycling is obtained where pre-treatment (sorting, cleaning) is adapted to the recycling technology. According to the model, recycling the 15 most demanded polymers in Europe reduces CO2 emissions from plastics by 73% or 200 Mtonne CO2 eq.

[Movember health care initiative 2019: prostate cancer screening at the University Hospital Frankfurt]. / Urologische Prostatakrebsvorsorge im Rahmen der Movember-Gesundheitsinitiative 2019 am Universitätsklinikum Frankfurt.

BACKGROUND: Men die earlier than women in Germany. Men also have impaired access to cancer screening compared to women. OBJECTIVES: Our Movember campaign 2019 at University Hospital Frankfurt (UKF) aimed at improving health care awareness in the context of prostate cancer checkup. MATERIALS AND METHODS: In November 2019, every male employee of the UKF with a minimum age of 45 yrs (or 40 yrs with a first degree relative with prostate cancer) was offered a free prostate cancer checkup. This checkup contained digital rectal examination (DRE), transrectal ultrasound and PSA (prostata-specific antigen) testing. RESULTS: Overall, 121/840 employees (14.4%) participated in the Movember campaign. A first degree relative with prostate cancer was reported in overall by 14% of the participants (n = 17). At least one prior prostate cancer check up had 33%. A total of 2.5% (n = 3) had one prior negative prostate biopsy. Median age was 54 yrs (interquartile range 50-58). Median PSA level was 0.9 ng/ml and median free-PSA 0.3 ng/ml. A suspicious DRE was found in 5% (n = 6). After stratification according to age (≤ 50 yrs vs. > 50 yrs), participants over 50 yrs had a significantly higher PSA level (1.0 ng/ml vs. 0.7 ng/ml, p < 0.01) and had more frequently at least one prior prostate cancer checkup in the past (42.0 vs. 12.1%, p < 0.01). All suspicious DREs were in the cohort > 50 yrs. Overall, 32.2% (n = 39) had at least a suspicious checkup. A total of 3.3% (n = 4) had suspicious PSA levels. 17.4% (n = 21) of the participants had a suspicious PSA ratio (< 20%) only. During follow-up, 6 prostate biopsies were performed, with the detection of one case of intermediate-risk prostate cancer (Gleason 3 + 4, pT3a, pPn1, pNx, R0). CONCLUSION: Overall, 121 employees participated in our Movember Prostate cancer checkup campaign with measurement of the PSA level. Suspicious results were recorded in 32.2%. One employee was diagnosed and successfully treated with an intermediate-risk prostate cancer.

Frequency of cataract surgery and its impact on visual function-results from the German Gutenberg Health Study.

PURPOSE: To determine the frequency of cataract surgery in Germany and to evaluate its impact on visual function in an adult population. METHODS: The population-based Gutenberg Health Study was conducted in Germany with its baseline examination between 2007 and 2012 and a 5-year follow-up examiantion. An ophthalmological examination including slit-lamp examination, ocular biometry, and Scheimpflug imaging was carried out. Overall and age-specific frequencies of unilateral and bilateral cataract surgery within 5 years were computed including the 95% confidential intervals [95%-CI]. Association analyses were conducted to determine social and ocular associated factors using multivariable logistic regression analysis. Vision-related quality of life was assessed using NEI VFQ-25. RESULTS: A total of 10,544 people aged 35 to 74 years were bilateral phakic at baseline and had information on lens status at the 5-year examination. Of these, 168 had unilateral cataract surgery (1.6% [1.4-1.9%]), and 448 had bilateral cataract surgery (4.2% [3.9-4.7%]) in the following 5 years. The frequency of cataract surgery increased with age: 45-54-year-old subjects had twice as often cataract surgery (in at least on eye: OR = 2.32) than at age 35-44 years. The frequency further strongly increases with age (55-64 years: OR = 10.5; 65-74 years: OR = 43.8, p < 0.001). Subjects with glaucoma were more likely to have cataract surgery (OR = 2.52, p < 0.001). Visual function increased when undergoing bilateral cataract surgery. CONCLUSIONS: The frequency of cataract surgery is low at younger ages and increases up to 26% at age 70-74 years. Persons with glaucoma are more likely to undergo cataract surgery at population-based level in Germany.

Urinary 8-isoprostane as a biomarker for oxidative stress. A systematic review and meta-analysis.

Oxidative stress is defined as an imbalance between the production and elimination of reactive oxygen species (ROS) are associated with various inflammation-related human disease. ROS can oxidize lipids, which subsequently undergo fragmentation to produce F2-isoprostanes (F2-IsoPs). Eight-isoprostane is one of the most extensively studied F2-IsoPs and the most commonly used biomarker for the assessment of oxidative stress in human studies. This urinary biomarker is quantified using either chemical or immunological techniques. A "physiological" range for 8-isoprostanes is needed to use this biomarker as a measure of excess oxidative stress originating from occupational exposures. However, ranges reported in the literature are inconsistent. We designed a standardized protocol of a systematic review and meta-analysis to assess baseline values for 8-isoprostane concentrations in urine of healthy adults and identify determinants of their inter- and intra-individual variability. We searched PubMed from journal inception and up to April 2019, and screened articles for studies containing F2-IsoPs concentrations in urine for healthy adult participants. We grouped studies in three biomarker groups: "8-isoprostane", "Isoprostanes" "15- F2t-Isoprostane". We computed geometric mean (GM) and geometric standard deviation (GSD) as the basis for the meta-analysis. Of the initial 1849 articles retrieved, 63 studies were included and 107 subgroups within these study populations were identified. We stratified the subgroups analyzed with the chemical methods by body mass index (BMI) reported. We provide pooled GM values for urinary 8-isoprostane concentrations in healthy adults, separately for chemical and immunological analysis in this review. The interquartile range (IQR) in subgroups with a mean BMI below 25 measured using chemical methods was 0.18 to 0.40 µg/g creatinine. We show that there is a significant positive association between BMI and urinary 8-isoprostane concentrations. We recommend adjusting urinary 8-isoprostane concentrations in spot urine with creatinine, quantifying 8-isoprostane with chemical analytical methods, and reporting results as median and quartiles. This will help in comparing results across studies.

Reference ranges of oxidative stress biomarkers selected for non-invasive biological surveillance of nanotechnology workers: Study protocol and meta-analysis results for 8-OHdG in exhaled breath condensate.

In the field of engineered nanomaterials (ENMs) and other airborne particulate exposure biomonitoring, circulating oxidative stress biomarkers appear promising. These biomarkers could be monitored in different biological matrices. Exhaled breath condensate (EBC) enables their measurements in the respiratory tract, without affecting airway function or creating inflammation. The 8-hydroxy-2-deoxyguanosine (8-OHdG) was found increased in the EBC of ENM-exposed workers. Our objectives were to assess the reference range of 8-OHdG in the EBC and to identify determinants of its inter- and intra-individual variability. The meta-analysis was stratified by analytical method (chemical versus immunochemical analysis) and resulted in a between-study variability over 99 % of the total variability. The between-study variability completely dominated the within-studies variability. By using a mixed model with study ID as a random effect rather than a meta-regression, only smoking was evidenced as a potential determinant of 8-OHdG inter-individual variability, and only when immunochemical analysis was used. To our knowledge, this is the first meta-analysis aimed at estimating reference values for 8-OHdG in the EBC. The estimated values should be considered preliminary, as they are based on a limited number of studies, mostly of moderate to low quality of evidence. Further research is necessary to standardize EBC sampling, storage and analytical methods. Such a standardization would enable a more accurate estimation of the reference ranges of the 8-OHdG and potentially other biomarkers measurable in the EBC, which are essential for a meaningful interpretation of the biomonitoring results.

Temporal leeway: can it help to reduce biomechanical load for older workers performing repetitive light assembly tasks?

Current industrial production systems allow assembly of customised products which include additional elements distinguishing them from a reference model. This customisation can result in significant additional time constraints which compel workers to complete their tasks faster, which may pose problems for older workers. The objective of this laboratory study was to investigate the impact of restrictive or flexible pacing during assembly of customised products among groups of younger and older participants. The data gathered were used to analyse cycle-time, assembly performance, muscular load, and kinematic adaptations. The flexible pacing condition was found to improve production performance, increasing customised assembly cycle-time and reducing biomechanical load, for both young and older participants. However, as the task required fine manual dexterity, older participants were subjected to a higher biomechanical load, even in the flexible pacing scenario. These results should encourage assembly-line designers to allow flexible time constraints as much as possible and to be particularly attentive to the needs of older workers.

[Status of the availability and use of next generation sequencing (NGS) in bladder cancer-a questionnaire within the uropathology working group]. / Status der Verfügbarkeit und Anwendung von "next generation sequencing" (NGS) beim Harnblasenkarzinom ­ eine Umfrage in der Arbeitsgemeinschaft Uropathologie.

BACKGROUND: Technical advancement and availability of high-throughput analysis has advanced molecular subtyping of most cancers. Thus, new possibilities for precision oncology have emerged. AIM: Therefore, we aimed to collect data regarding availability and use of next generation sequencing (NGS) for urothelial cancer within the uropathology working group of the German Society of Pathology. METHODS: We collected data by questionnaires and additionally asked for sequencing results of bladder cancers in the participating institutions. RESULTS: A total of 13 university-affiliated institutes of pathology took part in the survey. All university institutes offer NGS-based molecular panel diagnostics and provide panels covering between 15 and 170 genes. Altogether, only 20 bladder cancers were sequenced in routine diagnostics and for 10 cancers potential targeted treatment options were available. DISCUSSION: So far, despite availability of NGS diagnostics at university institutes of pathology, only few bladder cancer samples have been sequenced. Based on current data from the molecular subtyping of bladder cancers, we recommend a step-by-step protocol with basic immunohistochemistry analysis and subsequent subtype-dependent analyses, e.g., alterations of the fibroblast growth factor receptors (FGFR) or comprehensive gene panel analyses.

Does exposure to inflammatory particles modify the pattern of anion in exhaled breath condensate?

Exposure to environmental and occupational particulate matter (PM) induces health effects on the cardio-pulmonary system. In addition, associations between exposure to PM and metabolic syndromes like diabetes mellitus or obesity are now emerging in the literature. Collection of exhaled breath condensate (EBC) is an appealing non-invasive technique to sample pulmonary fluids. This hypothesis-generating study aims to (1) validate an ion chromatography method allowing the robust determination of different metabolism-related molecules (lactate, formate, acetate, propionate, butyrate, pyruvate, nitrite, nitrate) in EBC; (2) apply this method to EBC samples collected from workers exposed to quartz (a known inflammatory particle), to soapstone (a less inflammatory particle than quartz), as well as to controls. A multi-compound standard solution was used to determine the linearity range, detection limit, repeatability and bias from spiked EBC. The biological samples were injected without further treatment into an ion chromatograph with a conductivity detector. RTube® were used for field collection of EBC from 11 controls, 55 workers exposed to soapstone and 12 volunteers exposed to quartz dust. The analytical method used proved to be adequate for quantifying eight anions in EBC samples. Its sub-micromolar detection limits and repeatability, combined with a very simple sample preparation, allowed an easy and fast quantification of different glycolysis or nitrosative stress metabolites. Using multivariate discriminant analysis to maximize differences between groups, we observed a different pattern of anions with a higher formate/acetate ratio in the EBC samples for quartz exposed workers compared to the two other groups. We hypothesize that a modification of the metabolic signature could be induced by exposure to inflammatory particles like quartz and might be observed in the EBC via a change in the formate/acetate ratio.