The Mechanism of Rh(I)-Catalyzed Coupling of Benzotriazoles and Allenes Revisited: Substrate Inhibition, Proton Shuttling, and the Role of Cationic vs Neutral Species.

Direct coupling of benzotriazole to unsaturated substrates such as allenes represents an atom-efficient method for the construction of biologically and pharmaceutically interesting functional structures. In this work, the mechanism of the N2-selective Rh complex-catalyzed coupling of benzotriazoles to allenes was investigated in depth using a combination of experimental and theoretical techniques. Substrate coordination, inhibition, and catalyst deactivation was probed in reactions of the neutral and cationic catalyst precursors [Rh(µ-Cl)(DPEPhos)]2 and [Rh(DPEPhos)(MeOH)2]+ with benzotriazole and allene, giving coordination, or coupling of the substrates. Formation of a rhodacycle, formed by unprecedented 1,2-coupling of allenes, is responsible for catalyst deactivation. Experimental and computational data suggest that cationic species, formed either by abstraction of the chloride ligand or used directly, are relevant for catalysis. Isomerization of benzotriazole and cleavage of its N-H bond are suggested to occur by counteranion-assisted proton shuttling. This contrasts with a previously proposed scenario in which oxidative N-H addition at Rh is one of the key steps. Based on the mechanistic analysis, the catalytic coupling reaction could be optimized, leading to lower reaction temperature and shorter reaction times compared to the literature.

[Economic Relevance of Preventable Prohibitions of Employment in Bavarian Schools]. / Ökonomische Relevanz vermeidbarer Beschäftigungsverbote an Schulen in Bayern.

INTRODUCTION: According to the Maternity Protection Act, an occupational risk of infection (e. g. in childcare) - combined with individual immunity gaps - can result in an irresponsible risk for pregnant women in the workplace. If this risk cannot be eliminated by any other means, the employer must impose a prohibition of employment (PE) for the pregnant woman concerned. We classified PE as preventable if the underlying immunity gaps could have been closed by immunisation prior to pregnancy. METHODS: From 01.09.2016 to 25.03.2020, 1922 pregnant employees of Bavarian state schools obtained medical counselling on their occupational risk of infection as part of a research project. If the individual combination of occupational-risk profile and immunity status resulted in an irresponsible risk for the pregnancy, a PE was recommended by the attending physician. We determined the proportion of PE that would have theoretically been preventable by full immunisation prior to pregnancy and approximated the resulting - theoretically preventable - loss of working hours and personnel costs. RESULTS: In 425 cases (22%), a PE was deemed necessary by the attending physician, whereby 193 (45%) were retrospectively classified as theoretically preventable. Of these cases, 53 PE (27%) were temporary (valid until the 20th week of pregnancy) and 140 were long-term (valid for the complete duration of the pregnancy). Based on these results, we approximated a loss of 2,746 working weeks for our collective, which entails theoretically preventable personnel costs totalling 5,763,305 € for the observation period of our study (3.6 years). We then extrapolated estimates for all employees of Bavarian state schools and found a loss of 4,260 working weeks and theoretically preventable personnel costs amounting to almost 8,941,000 € per year during our observation period. CONCLUSION: Theoretically preventable PE caused by immunity gaps can entail a considerable loss of working hours and high personnel costs. Therefore, we should step up measures aimed at improving vaccination rates in women and increasing their willingness to be vaccinated. In view of the changes in legal and regulatory conditions in Germany since 2020, new investigations should be made as soon as there is sufficient data after the general employment prohibitions due to the SARS-CoV-2-pandemic have been lifted.

[Environmental risks and health literacy: a systematic review]. / Umweltrisiken und Gesundheitskompetenz: Eine systematische Übersichtsarbeit.

BACKGROUND: Environmental factors can play an important role in pathogenesis. However, the understanding of the relationship between environmental risks and health in the general population appears to be poor. The aim of this systematic review is to describe the state of research on the relationship between health literacy (HL) or environmental health literacy (EHL) and environmental risks differentiated by the researched environmental risks, the affected population, the measurement and level of HL or EHL, and their interaction with other variables. METHODS: A systematic literature search was conducted using the Pubmed, Scopus, and LIVIVO databases. Original studies in German or English that investigated HL or EHL in the context of an environmental risk or pollutant in a population were included. The Navigation Guide was used to assess the methodological quality of the studies. RESULTS: Twenty-four studies were included in the qualitative analysis. The operationalization of HL or EHL was heterogeneous in 22 studies. Nine studies referred to environmental issues in general, and 15 studies analyzed individual environmental risks. Eleven studies referred to the general population, 12 to specified target groups, and 1 study examined both. The level of HL or EHL proved to be in need of improvement in all populations. Interventions such as trainings were able to increase HL or EHL. DISCUSSION: The heterogeneous operationalizations impede the comparability of the studies. Future work should target the standardization of methodological aspects. Overall, it appears that interventions such as trainings were conducive to improving HL or EHL. In practice, this should therefore be given greater focus in order to increase HL or EHL.

Health-oriented leadership, gender-differences and job satisfaction: results from a representative population-based study in Germany.

BACKGROUND: In recent years, the topic of health-oriented leadership (HoL) has often been investigated with health-related outcomes like general health, strain, depression, and anxiety symptoms. In contrast, research which considers the gender of leaders and employees in connection to HoL as well as studies on relationships between HoL and job satisfaction, are scarce. The aim of this paper is to explore the relationships between HoL and health status assessed by employees and leaders, to analyse the relationships between HoL and job satisfaction as a non-health-related outcome for employees and leaders and to examine differences in the assessment of HoL between men and women in a representative dataset of the working population in Germany. METHODS: Data were collected via an access panel as a cross-sectional survey. The quota sample included 643 German workers (managers and employees). We focused on staff-care as a core component of HoL. Statistical analyses were performed using Pearson correlations and regression analyses as well as t-tests and Mann-Whitney-U-Tests. RESULTS: The results showed no significant differences between male and female employees or leaders in assessing HoL. Regarding HoL we found relationships between self-rated health status or job satisfaction, both for the self-rated assessment of leaders and employees. CONCLUSIONS: Our findings indicate relationships between HoL and well-being as well as job satisfaction at the workplace. For interventions of any kind, the lack of gender effects leaves a wide scope for the implementation of health-promoting measures. In particular, the findings on the relationship between HoL and job satisfaction through leaders' self-assessment could be used for salutogenic approaches to strengthen resources in leadership trainings.

Setting-based skin cancer prevention at the workplace: A survey among German outdoor workers.

BACKGROUND: Outdoor workers are at increased risk of developing skin cancer. Setting-based prevention at the workplace can reduce the UV exposure of outdoor workers through appropriate technical or organizational measures. We explored the implementation of setting-based UV protection at the workplace in Germany from the perspective of outdoor workers. METHODS: A Germany-wide sample of 319 outdoor workers from different employment sectors (64.3% male) was surveyed via telephone on different technical and organizational measures for UV protection at the workplace. Bivariate analyses were performed to explore associations with job-related characteristics. RESULTS: In general, 28.0% were rarely or never provided with a place in the shade during working hours, and 27.4% rarely or never provided with a shaded place during breaks. One-third had rarely or never the opportunity to work in the shade on hot summer days. Overall, 51.9% reported receiving protective clothing from their employer, 45.5% were provided with headgear, and 25.1% with sunscreen. About one-third had often or always the option of starting work earlier in the morning on hot summer days to work less in the sun, while 18.6% had to work overtime on such days. One-third (35.4%) had been educated at work about risks of solar radiation and sun protection measures. CONCLUSIONS: Our study is among the first to present findings on the implementation of different setting-based UV protection measures at the workplace and provides starting points for employers and policy makers to improve UV protection at the workplace.

[Vaccination Gaps of Employees in Institutions of Preschool Childcare before Introduction of the Measles Protection Act]. / Impflücken bei Beschäftigten in Einrichtungen der vorschulischen Kinderbetreuung vor Einführung des Masernschutzgesetzes.

AIM OF THE STUDY: The measles protection act and the updated recommendations of the permanent commission of vaccination (STIKO) include the obligatory proof of a double vaccination against measles for employees (born after 1970) in childcare. In addition, the standard and professional recommendations for vaccinations should be respected. A retrolective evaluation of vaccination gaps of employees in institutions for preschool childcare was performed. METHODS: The database of 2018 and 2019 of the B·A·D-Health center Erlangen have 1300 recorded cases of occupational medical consultations in preschool childcare. Double consultations and consultations with insufficient data were excluded. 1016 contacts were analyzed with regard to vaccination gaps of measles, mumps, rubella, varicella, pertussis, hepatitis A+B and early summer meningoencephalitis. The evaluation was primarily based on the employees' vaccination cards. Vaccination gaps were assumed in case of missing, commenced or incomplete vaccination protection. RESULTS: In this cohort of 1016 employees, the vaccination gap for measles increased from 16.2% to 20.6%, when applying the updated STIKO recommendation and the resulting change of definition of complete vaccination protection from measles. Further gaps were 22.7% for mumps, 18.9% for rubella, 2.3% for varicella, 27.8% for pertussis, 61.1% for hepatitis A and 60.5% and tick-borne encephalitis. The age group <30 years showed less vaccination gaps than the age group ≥30 years. CONCLUSION: The evaluation of the health center in Erlangen showed considerable age-dependent vaccination gaps in the cohort of employees of preschool childcare. The measles protection act that makes vaccination against measles mandatory contributes to closing this gap. There is room for counselling as well as for action regarding vaccine-preventable diseases in occupational medicine.

[Occupational obstructive airway diseases: How can early diagnosis be made to avoid chronic courses?] / Obstruktive Atemwegserkrankungen im Beruf: Wie gelingt eine frühe Diagnostik zur Vermeidung chronischer Verläufe?

Since abolishing the obligation to terminate the harmful professional activity from January 1st, 2021 onwards for some occupational diseases including obstructive respiratory diseases in Germany, the recognition of occupational diseases coded under 4301, 4302 and 1315 according the Occupational Diseases Ordinance has increased significantly. By the time these diseasese are recognized, they are usually already at an advanced stage. Therefore, early detection will play a greater role in the future, as the statutory accident insurance can offer individual preventive measures in order to minimize the consequences of illness and thus also the socio-economic burden. However, precursors of such obstructive airway diseases are often overlooked. For optimizing early detection, the statutory accident insurance worked out an early notification procedure for the respiratory tract - comparable to the already well-established dermatological procedure. "Early cases" from the pilot regions can be reported there; to qualify for being reported as early cases, patients must persue insured professional activity with potential effects on the respiratory tract and suffer from a disease of the upper or lower respiratory tract according to the ICD-10 code (e.g. J31.0 chronic rhinitis).

Synthesis, Coordination Chemistry, and Mechanistic Studies of P,N-Type Phosphaalkene-Based Rh(I) Complexes.

The synthesis of P,N-phosphaalkene ligands, py-CH═PMes* (1, py = 2-pyridyl, Mes* = 2,4,6-tBu-C6H2) and the novel quin-CH═PMes* (2, quin = 2-quinolinyl) is described. The reaction with [Rh(µ-Cl)cod]2 produces Rh(I) bis(phosphaalkene) chlorido complexes 3 and 4 with distorted trigonal bipyramidal coordination environments. Complexes 3 and 4 show a pronounced metal-to-ligand charge transfer (MLCT) from Rh into the ligand P═C π* orbitals. Upon heating, quinoline-based complex 4 undergoes twofold C-H bond activation at the o-tBu groups of the Mes* substituents to yield the cationic bis(phosphaindane) Rh(I) complex 5, which could not be observed for the pyridine-based analogue 3. Using sub- or superstoichiometric amounts of AgOTf the C-H bond activation at an o-tBu group of one or at both Mes* was detected, respectively. Density functional theory (DFT) studies suggest an oxidative proton shift pathway as an alternative to a previously reported high-barrier oxidative addition at Rh(I). The Rh(I) mono- and bis(phosphaindane) triflate complexes 6 and 7, respectively, undergo deprotonation at the benzylic CH2 group of the phosphaindane unit in the presence of KOtBu to furnish neutral, distorted square-planar Rh(I) complexes 8 and 9, respectively, with one of the P,N ligands being dearomatized. All complexes were fully characterized, including multinuclear NMR, vibrational, and ultraviolet-visible (UV-vis) spectroscopy, as well as single-crystal X-ray and elemental analysis.

[Occupational Safety and Health and Company Integration Management in Germany - A Systematic Review on Implementation of Legal Requirements]. / Arbeits- und Gesundheitsschutz und Betriebliches Eingliederungsmanagement in Deutschland ­ Ein systematisches Review zum Umsetzungsstand gesetzlicher Vorgaben.

AIM: Several studies have pointed out considerable deficits in the implementation of legal requirements regarding occupational safety and health (OSH) as well as company integration management in Germany. The aim of this review was a quantitative analysis of company size and fulfilment of legal requirements in OSH and company integration management in German companies over a period of time. METHODS: In October 2019, we performed a systematic literature search of German and English language publications with representative data which include the rates of OSH implementation along with company integration management in Germany. This was done using the databases Pubmed, PsycInfo and WISO. The study was updated in October 2020, while cross-referencing, with grey literature also included in the search. The analysis was carried out by 2 independent reviewers. RESULTS: A total of 16 relevant studies were examined with respect to OSH and company integration management. A slight decline in implementation rates of OSH care was apparent over time. In the care model, an increase in the number of employees resulted in increased need for both regular and demand-oriented care. Regardless of size, all companies were characterized by a steady rise in the implementation rates of risk assessment (including psychosocial risk assessment). In addition, the implementation rates of company inspections and company integration management exhibited an increase over time. CONCLUSION: Despite moderately increasing implementation rates in almost all sub-areas of OSH and company integration management over the last 20 years, it is evident that an area-wide implementation of legal requirements has not yet been achieved. The results indicate a standardization of methodological aspects for further studies. The implementation of legal requirements is an important factor for maintaining the employability of employees.

Syncarcinogenesis of natural UV radiation and polycyclic aromatic hydrocarbons in the development of squamous cell carcinomas of the skin?

Squamous cell carcinomas (SCC) of the skin can be induced by occupational exposures to polycyclic aromatic hydrocarbons (PAHs), as in tar and soot, or to UV radiation and can be recognized and compensated as occupational diseases. A possible syncarcinogenic effect of these exposures in the development of SCC in humans is under discussion. For the scientific validation of this question, a systematic literature search was conducted using the databases PubMed, Web of Science, and Scopus. Studies on individuals with SCC of the skin and their precursors as well as occupational, non-occupational, or therapeutic exposure to UV radiation and PAHs were selected. In addition, animal studies with exposure to UV radiation and PAHs were evaluated. After screening the abstracts of 510 identified studies, the full texts of 131 studies were reviewed. None of the epidemiological studies provided robust evidence for a syncarcinogenesis of PAHs and UV radiation in the development of SCC of the skin in humans. Nevertheless, as there are indications for a (super-)additive effect of UV radiation and PAH exposure from animal studies and mechanistic investigations, syncarcinogenesis seems possible. However, quantitative dose-response relationships are lacking which would allow comparison of the onset of an adverse effect between the different exposure levels.

Molecular Genetics of Pre-B Acute Lymphoblastic Leukemia Sister Cell Lines during Disease Progression.

For many years, immortalized tumor cell lines have been used as reliable tools to understand the function of oncogenes and tumor suppressor genes. Today, we know that tumors can comprise subclones with common and with subclone-specific genetic alterations. We sequenced DNA and RNA of sequential sister cell lines obtained from patients with pre-B acute lymphoblastic leukemia at different phases of the disease. All five pairs of cell lines carry alterations that are typical for this disease: loss of tumor suppressors (CDKN2A, CDKN2B), expression of fusion genes (ETV6-RUNX1, BCR-ABL1, MEF2D-BCL9) or of genes targeted by point mutations (KRAS A146T, NRAS G12C, PAX5 R38H). MEF2D-BCL9 and PAX R38H mutations in cell lines have hitherto been undescribed, suggesting that YCUB-4 (MEF2D-BCL9), PC-53 (PAX R38H) and their sister cell lines will be useful models to elucidate the function of these genes. All aberrations mentioned above occur in both sister cell lines, demonstrating that the sisters derive from a common ancestor. However, we also found mutations that are specific for one sister cell line only, pointing to individual subclones of the primary tumor as originating cells. Our data show that sequential sister cell lines can be used to study the clonal development of tumors and to elucidate the function of common and clone-specific mutations.

Catalyst Deactivation During Rhodium Complex-Catalyzed Propargylic C-H Activation.

Detailed mechanistic investigations on our previously reported synthesis of branched allylic esters by the rhodium complex-catalyzed propargylic C-H activation have been carried out. Based on initial mechanistic studies, we present herein more detailed investigations of the reaction mechanism. For this, various analytical (NMR, X-ray crystal structure analysis, Raman) and kinetic methods were used to characterize the formation of intermediates under the reaction conditions. The knowledge obtained by this was used to further optimize the previous conditions and generate a more active catalytic system.

NKL Homeobox Gene VENTX Is Part of a Regulatory Network in Human Conventional Dendritic Cells.

Recently, we documented a hematopoietic NKL-code mapping physiological expression patterns of NKL homeobox genes in human myelopoiesis including monocytes and their derived dendritic cells (DCs). Here, we enlarge this map to include normal NKL homeobox gene expressions in progenitor-derived DCs. Analysis of public gene expression profiling and RNA-seq datasets containing plasmacytoid and conventional dendritic cells (pDC and cDC) demonstrated HHEX activity in both entities while cDCs additionally expressed VENTX. The consequent aim of our study was to examine regulation and function of VENTX in DCs. We compared profiling data of VENTX-positive cDC and monocytes with VENTX-negative pDC and common myeloid progenitor entities and revealed several differentially expressed genes encoding transcription factors and pathway components, representing potential VENTX regulators. Screening of RNA-seq data for 100 leukemia/lymphoma cell lines identified prominent VENTX expression in an acute myelomonocytic leukemia cell line, MUTZ-3 containing inv(3)(q21q26) and t(12;22)(p13;q11) and representing a model for DC differentiation studies. Furthermore, extended gene analyses indicated that MUTZ-3 is associated with the subtype cDC2. In addition to analysis of public chromatin immune-precipitation data, subsequent knockdown experiments and modulations of signaling pathways in MUTZ-3 and control cell lines confirmed identified candidate transcription factors CEBPB, ETV6, EVI1, GATA2, IRF2, MN1, SPIB, and SPI1 and the CSF-, NOTCH-, and TNFa-pathways as VENTX regulators. Live-cell imaging analyses of MUTZ-3 cells treated for VENTX knockdown excluded impacts on apoptosis or induced alteration of differentiation-associated cell morphology. In contrast, target gene analysis performed by expression profiling of knockdown-treated MUTZ-3 cells revealed VENTX-mediated activation of several cDC-specific genes including CSFR1, EGR2, and MIR10A and inhibition of pDC-specific genes like RUNX2. Taken together, we added NKL homeobox gene activities for progenitor-derived DCs to the NKL-code, showing that VENTX is expressed in cDCs but not in pDCs and forms part of a cDC-specific gene regulatory network operating in DC differentiation and function.

Small molecular modulators of JMJD1C preferentially inhibit growth of leukemia cells.

Histone demethylases are promising therapeutic targets as they play fundamental roles for survival of Mixed lineage leukemia rearranged acute leukemia (MLLr AL). Here we focused on the catalytic Jumonji domain of histone H3 lysine 9 (H3K9) demethylase JMJD1C to screen for potential small molecular modulators from 149,519 natural products and 33,765 Chinese medicine components via virtual screening. JMJD1C Jumonji domain inhibitor 4 (JDI-4) and JDI-12 that share a common structural backbone were detected within the top 15 compounds. Surface plasmon resonance analysis showed that JDI-4 and JDI-12 bind to JMJD1C and its family homolog KDM3B with modest affinity. In vitro demethylation assays showed that JDI-4 can reverse the H3K9 demethylation conferred by KDM3B. In vivo demethylation assays indicated that JDI-4 and JDI-12 could induce the global increase of H3K9 methylation. Cell proliferation and colony formation assays documented that JDI-4 and JDI-12 kill MLLr AL and other malignant hematopoietic cells, but not leukemia cells resistant to JMJD1C depletion or cord blood cells. Furthermore, JDI-16, among multiple compounds structurally akin to JDI-4/JDI-12, exhibits superior killing activities against malignant hematopoietic cells compared to JDI-4/JDI-12. Mechanistically, JDI-16 not only induces apoptosis but also differentiation of MLLr AL cells. RNA sequencing and quantitative PCR showed that JDI-16 induced gene expression associated with cell metabolism; targeted metabolomics revealed that JDI-16 downregulates lactic acids, NADP+ and other metabolites. Moreover, JDI-16 collaborates with all-trans retinoic acid to repress MLLr AML cells. In summary, we identified bona fide JMJD1C inhibitors that induce preferential death of MLLr AL cells.

IG-MYC + neoplasms with precursor B-cell phenotype are molecularly distinct from Burkitt lymphomas.

The WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue notes instances of Burkitt lymphoma/leukemia (BL) with IG-MYC rearrangement displaying a B-cell precursor immunophenotype (termed herein "preBLL"). To characterize the molecular pathogenesis of preBLL, we investigated 13 preBLL cases (including 1 cell line), of which 12 were analyzable using genome, exome, and targeted sequencing, imbalance mapping, and DNA methylation profiling. In 5 patients with reads across the IG-MYC breakpoint junctions, we found evidence that the translocation derived from an aberrant VDJ recombination, as is typical for IG translocations arising in B-cell precursors. Genomic changes like biallelic IGH translocations or VDJ rearrangements combined with translocation into the VDJ region on the second allele, potentially preventing expression of a productive immunoglobulin, were detected in 6 of 13 cases. We did not detect mutations in genes frequently altered in BL, but instead found activating NRAS and/or KRAS mutations in 7 of 12 preBLLs. Gains on 1q, recurrent in BL and preB lymphoblastic leukemia/lymphoma (pB-ALL/LBL), were detected in 7 of 12 preBLLs. DNA methylation profiling showed preBLL to cluster with precursor B cells and pB-ALL/LBL, but apart from BL. We conclude that preBLL genetically and epigenetically resembles pB-ALL/LBL rather than BL. Therefore, we propose that preBLL be considered as a pB-ALL/LBL with recurrent genetic abnormalities.

Impact of Daily Antiperspirant Use on the Systemic Aluminum Exposure: An Experimental Intervention Study.

BACKGROUND AND OBJECTIVES: Adverse health effects such as neurotoxic and carcinogenic effects through aluminum from cosmetic products have been repeatedly discussed. The dermal uptake and impact on the systemic aluminum load is still poorly understood. Therefore, we investigated the effect of daily antiperspirant use on the systemic aluminum load under real-life conditions. METHODS: 21 healthy subjects meeting certain selection criteria to ensure a low systemic aluminum background load were asked to use a commercial aluminum-containing antiperspirant for 14 days. A questionnaire enquired about shaving habits and other sources of aluminum. Aluminum levels were measured before and after the exposure in 24-h urine and plasma using atomic absorption spectroscopy. Urine samples (n = 6) with <700 mg/day creatinine excretion or more than 30% difference in 24-h creatinine excretion were excluded from further analysis. RESULTS: No significant increase in plasma aluminum concentration or total excreted aluminum per day before and after exposure was measurable. No sample exceeded the reference values of the general population (maximum: 9.42 µg/g creatinine and 2.1 µg/L plasma). Shaving habits did not have a significant influence on the systemic aluminum load. Also, no correlation between the total amount of antiperspirant applied and the systemic aluminum level could be demonstrated. CONCLUSIONS: No measurable contribution to the overall systemically available aluminum load due to daily use of an antiperspirant for 14 days could be shown, but real-life data concerning long-term use or higher concentrations are still lacking. Considering toxicological occupational exposure data, adverse neurotoxic changes are unlikely in the case of urinary excretion of <50 µg aluminum/g creatinine (= no observed adverse effect level), even following long-term exposure.

The LL-100 Cell Lines Panel: Tool for Molecular Leukemia-Lymphoma Research.

Certified cell line models provide ideal experimental platforms to answer countless scientific questions. The LL-100 panel is a cohort of cell lines that are broadly representative of all leukemia-lymphoma entities (including multiple myeloma and related diseases), rigorously authenticated and validated, and comprehensively annotated. The process of the assembly of the LL-100 panel was based on evidence and experience. To expand the genetic characterization across all LL-100 cell lines, we performed whole-exome sequencing and RNA sequencing. Here, we describe the conception of the panel and showcase some exemplary applications with a focus on cancer genomics. Due diligence was paid to exclude cross-contaminated and non-representative cell lines. As the LL-100 cell lines are so well characterized and readily available, the panel will be a valuable resource for identifying cell lines with mutations in cancer genes, providing superior model systems. The data also add to the current knowledge of the molecular pathogenesis of leukemia-lymphoma. Additional efforts to expand the breadth of available high-quality cell lines are clearly warranted.

Low-temperature aqueous-phase methanol dehydrogenation to hydrogen and carbon dioxide.

Hydrogen produced from renewable resources is a promising potential source of clean energy. With the help of low-temperature proton-exchange membrane fuel cells, molecular hydrogen can be converted efficiently to produce electricity. The implementation of sustainable hydrogen production and subsequent hydrogen conversion to energy is called "hydrogen economy". Unfortunately, its physical properties make the transport and handling of hydrogen gas difficult. To overcome this, methanol can be used as a material for the storage of hydrogen, because it is a liquid at room temperature and contains 12.6 per cent hydrogen. However, the state-of-the-art method for the production of hydrogen from methanol (methanol reforming) is conducted at high temperatures (over 200 degrees Celsius) and high pressures (25-50 bar), which limits its potential applications. Here we describe an efficient low-temperature aqueous-phase methanol dehydrogenation process, which is facilitated by ruthenium complexes. Hydrogen generation by this method proceeds at 65-95 degrees Celsius and ambient pressure with excellent catalyst turnover frequencies (4,700 per hour) and turnover numbers (exceeding 350,000). This would make the delivery of hydrogen on mobile devices--and hence the use of methanol as a practical hydrogen carrier--feasible.

Toxicokinetics of urinary 2-ethylhexyl salicylate and its metabolite 2-ethyl-hydroxyhexyl salicylate in humans after simulating real-life dermal sunscreen exposure.

Chemical UV filters are common components in sunscreens and cosmetic products. The question of adverse health risks is not completely resolved, partly owing to lacking human data from dermal exposure, which are essential for sound risk assessment. Therefore, we investigated the urinary toxicokinetics of 2-ethylhexyl salicylate (EHS) after a 1-day dermal real-life sunscreen application scenario. Twenty human volunteers were dermally exposed to a commercial sunscreen for 9 h under real-life conditions (2 mg/cm2 body surface area; double re-application; corresponding to 3.8 g EHS). Urine samples were analyzed for EHS and one of its specific metabolites 2-ethyl-5-hydroxyhexyl salicylate (5OH-EHS) using a two-dimensional liquid chromatographic electrospray-ionization tandem mass spectrometric procedure. EHS and 5OH-EHS were excreted after sunscreen application and reached up to 525 µg/g and 213 µg/g creatinine, respectively. The toxicokinetic models showed concentration peaks between 7 and 8 h after first application. First-phase terminal half-lives were 8-9 h. For 5OH-EHS, a second-phase terminal half-life could be determined (87 h). EHS and 5OH-EHS showed a faster elimination with 70-80% of the overall excretion occurring within 24 h after application compared to more lipophilic UV filters. Cumulative excreted amounts over 24 h reached up to 334 µg EHS and 124 µg of 5OH-EHS. Simulated real-life sunscreen use for 1 day leads to the bioavailability of the UV filter EHS in humans. The kinetic profiles with a prolonged systemic availability indicate a skin depot and make accumulation during consecutive multi-day exposure likely.

Validity of different biomonitoring parameters in human urine for the assessment of occupational exposure to naphthalene.

Up to date, information on the validity of human biomonitoring (HBM) parameters of naphthalene exposure is poor. This study was performed to reveal the relation between occupational exposure to naphthalene and biological exposure markers. Therefore, ten lowly and highly exposed workers from the abrasives industry were selected to characterise a broad exposure range. Naphthalene in air was determined by personal air monitoring during one shift. For biological monitoring, pre- and post-shift urine samples collected on 2 days of a working week were analysed for 1,2-dihydroxynaphthalene (1,2-DHN), 1- and 2-naphthol, 1- and 2-naphthylmercapturic acid (NMA). The naphthalene concentration in air was in the range of 0.5 to 11.6 mg/m3. The biomarkers in urine showed post-shift concentration in the range of 114-51,809 µg/L for 1,2-DHN, 0.8-666 µg/L for 1-NMA, 2-2698 µg/L for 1-naphthol and 4-1135 µg/L for 2-naphthol, respectively. 2-NMA was not detected. The urinary levels increased significantly from pre- to post-shift for all analysed parameters and an accumulation over the working week was observed. Significant positive correlations were observed between 1,2-DHN, 1-NMA, 1- and 2-naphthol in post-shift urine samples and personal exposure to naphthalene in the air. 1-NMA and 1,2-DHN, 1- and 2-naphthol have been demonstrated as suitable biomarkers for naphthalene exposure monitoring. Of the determined biomarkers, 1,2-DHN is by far the metabolite with the highest concentration in the urine samples.