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The Liquid Organic Hydrogen Carrier (LOHC) technology offers a technically attractive way for hydrogen storage. If LOHC systems were to fully replace liquid fossil fuels, they would need to be handled at the multi-million tonne scale. To date, LOHC systems on the market based on toluene or benzyltoluene still offer potential for improvements. Thus, it is of great interest to investigate potential LOHCs that promise better performance and environmental/human hazard profiles. In this context, we investigated the acute aquatic toxicity of oxygen-containing LOHC (oxo-LOHC) systems. Toxic Ratio (TR) values of oxo-LOHC compounds classify them baseline toxicants (0.1 < TR < 10). Additionally, the mixture toxicity test conducted with D. magna suggests that the overall toxicity of a benzophenone-based system can be accurately predicted using a concentration addition model. The estimation of bioconcentration factors (BCF) through the use of the membrane-water partition coefficient indicates that oxo-LOHCs are unlikely to be bioaccumulative (BCF < 2000). None of the oxo-LOHC compounds exhibited hormonal disrupting activities at the tested concentration of 2 mg/L in yeast-based reporter gene assays. Therefore, the oxo-LOHC systems seem to pose a low level of hazard and deserve more attention in ongoing studies searching for the best hydrogen storage technologies., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Peter Wasserscheid reports a relationship with Hydrogenious LOHC Technologies GmbH that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

To carry out risk assessments of benzophenone-type UV filters (BPs), fast and accurate analytical methods are crucial to determine and monitor levels in the environment. This study presents an LC-MS/MS method that requires minimal sample preparation and yet can identify 10 different BPs in environmental samples such as surface or wastewater resulting in a LOQ range from 2 to 1060 ng/L. The method suitability was tested through environmental monitoring, which showed that, BP-4 is the most abundant derivative found in the surface waters of Germany, India, South Africa and Vietnam. BP-4 levels correlate with the WWTP effluent fraction of the respective river for selected samples in Germany. Peak values of 171 ng/L for 4-hydroxybenzophenone (4-OH-BP), as measured in Vietnamese surface water, already exceed the PNEC value of 80 ng/L, elevating 4-OH-BP to the status of a new pollutant that needs more frequent monitoring. Moreover, this study reveals that during biodegradation of benzophenone in river water, the transformation product 4-OH-BP is formed which contain structural alerts for estrogenic activity. By using yeast-based reporter gene assays, this study provides bio-equivalents of 9 BPs, 4-OH-BP, 2,3,4-tri-OH-BP, 4-cresol and benzoate and complements the existing structure-activities relationships of BPs and their degradation products., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures Angela Velleca None Michael A Shullo Consulting- Natera Kumud Dhital None Estela Azeka MD None Monica Colvin MD Grants- Natera-Grant funding; Advisory board- Natera; Consulting- Mescape Eugene DePasquale Grants- CareDX; Advisory Board- Yale Marta Farrero Speakers bureaus- Novatris, AstraZeneca, Boehringer, Chiesi; Meeting support- Novartis, Chiesi; Material support/ Other Services- AstraZeneca Luis García-Guereta None Gina Jamero None Kiran Khush Grants- National Institutes of Health, Enduring Hearts; Royalties- Stanford; Consulting, speakers bureaus- CareDx Jacob Lavee None Stephanie Pouch None Jignesh Patel Grants- Alexion; Consulting- CareDx, Natera; Advisory Board- CareDx, Natera; CJ Michaud None Stephan Schubert Consulting- Medtronic, Edwards; Speakers Bureaus- Abbott, Lifetech, Medtronic; Meeting support- Medtronic, Edwards Annalisa Angelini None Lilibeth Carlos None Sonia Mirabet None Michael Pham Grants- CareDx, Royalties-Up to Date Simon Urschel Grants- Canadian Institute for Health Research, Enduring Hearts, Heart and Stroke foundation; Speaker/Educational- University of Alabama; Meeting support- Lange Symposium; Advisory Board- SMB of the Canadian Donation and Transplantation Research Program Kyung-Hee Kim None Shelly Miyamoto None Sharon Chih Grants- Heart and Stroke Foundation Ontario, Canadian Institutes of Health Research Kevin Daly Grants- US Department of Defense, Novartis, AHA/Enduring Hearts, Consulting- AstraZeneca; Advisory Board- CareDx Paolo Grossi Consulting- Merck, Sharp & Dohme Allovir, Takeda; Speakers Bureaus- Atara, Gilead, Shionogi; Advisory Board- Reithera Doug Jennings None In-cheol Kim None Hoong Sern Lim Speakers bureaus- Abiomed Tara Miller None Luciano Potena Consulting- Biotest, Novartis; Speakers bureaus- Biotest, Takada, Paragonix, Boeringher Ingheleim, AstraZeneca Howard Eisen None Lavanya Bellumkonda Grants- Natera, CareDx; Meeting support- Conformal Medical; Advisory Board- CareDx Lara Danziger-Isakov Grants- NIH, Ansun BioPharma, Astellas, Merck, Pfizer, Takada, AiCuris; Consulting- Takeda; Speakers Bureaus- RMEI; Meeting support- ID SAFE: Swiss Infectious Disease; Advisory Board/DSMB- Merck Fabienne Dobbels None Michelle Harkess None Daniel Kim None Haifa Lyster None Yael Peled None Zdenka Reinhardt None

Wastewater-based epidemiology provides a conceptual framework for the evaluation of the prevalence of public health related biomarkers. In the context of the Coronavirus disease-2019, wastewater monitoring emerged as a complementary tool for epidemic management. In this study, we evaluated data from six wastewater treatment plants in the region of Saxony, Germany. The study period lasted from February to December 2021 and covered the third and fourth regional epidemic waves. We collected 1065 daily composite samples and analyzed SARS-CoV-2 RNA concentrations using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Regression models quantify the relation between RNA concentrations and disease prevalence. We demonstrated that the relation is site and time specific. Median loads per diagnosed case differed by a factor of 3-4 among sites during both waves and were on average 45 % higher during the third wave. In most cases, log-log-transformed data achieved better regression performance than non-transformed data and local calibration outperformed global models for all sites. The inclusion of lag/lead time, discharge and detection probability improved model performance in all cases significantly, but the importance of these components was also site and time specific. In all cases, models with lag/lead time and log-log-transformed data obtained satisfactory goodness-of-fit with adjusted coefficients of determination higher than 0.5. Back-estimation of testing efficiency from wastewater data confirmed state-wide prevalence estimation from individual testing statistics, but revealed pronounced differences throughout the epidemic waves and among the different sites., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests that could influence this study. Ethics application (BO-EK-383072021) has been confirmed by the Ethic Committee of Technische Universität Dresden, which is registered as institutional review board (IRB00001473) at the Office of Human Research Protection., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The Gram-positive bacterium Staphylococcus epidermidis (SE) is an abundant skin commensal. It plays an important role in cutaneous defense by activation of IL-1 signaling. In keratinocytes (KCs), SE induces the release of mature IL-1β. IL-1β serves as an important cytokine of host defense. It contains an N-terminal prodomain that has to be cleaved off to generate active mature IL-1β. Typically, the processing and release of IL-1β are associated with inflammasome assembly and activation of the protease caspase-1. In this study, we report that the bacterial challenge of KCs with SE induced the release of mature IL-1β in a caspase-1‒independent manner. Instead, the SE-derived serine protease Esp was identified as a pro‒IL-1β‒processing factor leading to a proteolytic maturation of active IL-1β. Esp production and secretion by various SE strains correlated with their capacity to induce the release of mature IL-1β in human primary KCs. Reconstitution of Esp-lacking SE strains with Esp enhanced their capacity to induce IL-1β release in KCs and skin. Intracellular abundance of pro‒IL-1β and cytotoxic effects of SE suggest a release of pro‒IL-1β during injury, followed by extracellular Esp-mediated processing to mature IL-1β. These findings provide further insights into how a skin commensal interacts with KCs to activate cutaneous host innate defense., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

People routinely give humans moral priority over other animals. Is such moral anthropocentrism based in perceived differences in mental capacity between humans and non-humans or merely because humans favor other members of their own species? We investigated this question in six studies (N = 2217). We found that most participants prioritized humans over animals even when the animals were described as having equal or more advanced mental capacities than the humans. This applied to both mental capacity at the level of specific individuals (Studies 1a-b) and at the level typical for the respective species (Study 2). The key driver behind moral anthropocentrism was thus mere species-membership (speciesism). However, all else equal, participants still gave more moral weight to individuals with higher mental capacities (individual mental capacity principle), suggesting that the belief that humans have higher mental capacities than animals is part of the reason that they give humans moral priority. Notably, participants found mental capacity more important for animals than for humans-a tendency which can itself be regarded as speciesist. We also explored possible sub-factors driving speciesism. We found that many participants judged that all individuals (not only humans) should prioritize members of their own species over members of other species (species-relativism; Studies 3a-b). However, some participants also exhibited a tendency to see humans as having superior value in an absolute sense (pro-human species-absolutism, Studies 3-4). Overall, our work demonstrates that speciesism plays a central role in explaining moral anthropocentrism and may be itself divided into multiple sub-factors., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Heart failure (HF) due to myocarditis might not respond in the same way to standard therapy as HF due to other aetiologies. The aim of this study was to investigate the value of endomyocardial biopsies (EMB) for clinical decision-making and its relation to the outcome of paediatric patients with myocarditis., Methods: Clinical and EMB data of children with myocarditis collected for the MYKKE-registry between 2013 and 2020 from 23 centres were analysed. EMB studies included histology, immunohistology, and molecular pathology. The occurrence of major adverse cardiac events (MACE) including mechanical circulatory support (MCS), heart transplantation, and/or death was defined as a combined endpoint., Results: Myocarditis was diagnosed in 209/260 patients: 64% healing/chronic lymphocytic myocarditis, 23% acute lymphocytic myocarditis (AM), 14% healed myocarditis, no giant cell myocarditis. The median age was 12.8 (1.4-15.9) years. Time from symptom-onset to EMB was 11.0 (4.0-29.0) days. Children with AM and high amounts of mononuclear cell infiltrates were significantly younger with signs of HF compared to those with healing/chronic or healed myocarditis. Myocardial viral DNA/RNA detection had no significant effect on outcome. The worst event-free survival was seen in patients with healing/chronic myocarditis (24%), followed by acute (31%) and healed myocarditis (58%, p = 0.294). A weaning rate of 64% from MCS was found in AM., Conclusions: EMB provides important information on the type and stage of myocardial inflammation and supports further decision-making. Children with fulminant clinical presentation, high amounts of mononuclear cell infiltrates or healing/chronic inflammation and young age have the highest risk for MACE., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Aims: The LPA gene encodes apolipoprotein (a), a key component of Lp(a), a potent risk factor for cardiovascular disease with no specific pharmacotherapy. Here we describe the pharmacological data for SLN360, a GalNAc-conjugated siRNA targeting LPA, designed to address this unmet medical need., Methods: SLN360 was tested in vitro for LPA knockdown in primary hepatocytes. Healthy cynomolgus monkeys received single or multiple subcutaneous doses of the SLN360 sequence ranging from 0.1 to 9.0 mg/kg to determine the pharmacokinetic and pharmacodynamic effects. Liver mRNA and serum biomarker analyses were performed., Results: In vitro, the SLN360 sequence potently reduces LPA mRNA in primary cynomolgus and human hepatocytes, while no effect was observed on the expression of APOB or PLG. In vivo, SLN360 exposure peaks 2 h after subcutaneous injection with near full elimination by 24 h. Specific LPA mRNA reduction (up to 91% 2 weeks after dosing) was observed with only the 3 mg/kg group showing appreciable return to baseline (40%). No consistent dose- or time-dependent effect on the expression of APOB, PLG or a panel of sensitive markers of liver lipid accumulation was observed. Potent (up to 95%) and long lasting (≥9 weeks) serum Lp(a) reduction was observed, peaking in all active groups at day 21. The minimally effective dose was determined to be 0.3 mg/kg with an ED 50 of 0.6 mg/kg., Conclusions: SLN360 induces a sustained reduction in serum Lp(a) levels in cynomolgus monkeys following subcutaneous dosing. SLN360 has potential to address the unmet need of Lp(a) reduction in cardiovascular diseases., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Human precision-cut lung slices (PCLS) have proven to be an invaluable tool for numerous toxicologic, pharmacologic, and immunologic studies. Although a cultivation period of <1 week is sufficient for most studies, modeling of complex disease mechanisms and investigating effects of long-term exposure to certain substances require cultivation periods that are much longer. So far, data regarding tissue integrity of long-term cultivated PCLS are incomplete. More than 1500 human PCLS from 16 different donors were cultivated under standardized, serum-free conditions for up to 28 days and the viability, tissue integrity, and the transcriptome was assessed in great detail. Even though viability of PCLS was well preserved during long-term cultivation, a continuous loss of cells was observed. Although the bronchial epithelium was well preserved throughout cultivation, the alveolar integrity was preserved for about 2 weeks, and the vasculatory system experienced significant loss of integrity within the first week. Furthermore, ciliary beat in the small airways gradually decreased after 1 week. Interestingly, keratinizing squamous metaplasia of the alveolar epithelium with significantly increasing manifestation were found over time. Transcriptome analysis revealed a significantly increased immune response and significantly decreased metabolic activity within the first 24 hours after PCLS generation. Overall, this study provides a comprehensive overview of histomorphologic and pathologic changes during long-term cultivation of PCLS., (Copyright © 2022 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Across eight experiments (N = 2310), we studied whether people would prioritize rescuing individuals who may be thought to contribute more to society. We found that participants were generally dismissive of general rules that prioritize more socially beneficial individuals, such as doctors instead of unemployed people. By contrast, participants were more supportive of one-off decisions to save the life of a more socially beneficial individual, even when such cases were the same as those covered by the rule. This generality effect occurred robustly even when controlling for various factors. It occurred when the decision-maker was the same in both cases, when the pairs of people differing in the extent of their indirect social utility was varied, when the scenarios were varied, when the participant samples came from different countries, and when the general rule only covered cases that are exactly the same as the situation described in the one-off condition. The effect occurred even when the general rule was introduced via a concrete precedent case. Participants' tendency to be more supportive of the one-off proposal than the general rule was significantly reduced when they evaluated the two proposals jointly as opposed to separately. Finally, the effect also occurred in sacrificial moral dilemmas, a general phenomenon occurring in multiple moral contexts. We discuss possible explanations of the effect, including concerns about negative consequences of the rule and a deontological aversion against making difficult trade-off decisions unless they are absolutely necessary., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Antimicrobial peptides (AMPs) play an important role in the host defense against various microbes. One of the most efficient human AMPs is the human beta defensin-3 (hBD-3) which is produced by, e.g. keratinocytes and lung epithelial cells. However, the structure-function relationship for AMPs and in particular for defensins with their typical three disulfide bonds is still poorly understood. In this study the importance of the three disulfide bonds for the activity of the AMPs is investigated with biological assays and with biophysical experiments utilizing different membrane reconstitution systems. The activities of natural hBD-3, hBD-3-c (cyclic variant with one disulfide bond), and hBD-3-l (linear variant without disulfide bonds) and fragments thereof were tested against specific Gram-negative bacteria. Furthermore, hemolytic and cytotoxic activities were analyzed as well as the potency to neutralize immune cell stimulation of lipopolysaccharide (LPS). Experiments using reconstituted lipid matrices composed of phospholipids or LPS purified from the respective Gram-negative bacteria, showed that the membrane activity of all three hBD-3 peptides is decisive for their capability to kill bacteria and to neutralize LPS. In most of the test systems the linear hBD-3-l showed the highest activity. It was also the only peptide significantly active against polymyxin B-resistant Proteus mirabilis R45. However, the stability of hBD-3 against protease activity decreases with decreasing number of disulfide bonds. This study demonstrates that the refining of AMP structures can generate more active compounds against certain strains., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Endomyocardial biopsies (EMB) are the gold standard for the diagnosis of myocarditis in children and adults. The existing WHO/ISFC criteria for lymphocytic cell infiltrates by are based on the myocardium of adults. The aim of this study was to present a paediatric control cohort for the evaluation of inflammation in EMB of children., Methods: In this study endomyocardial tissue from 62 children under 4 years of age was investigated, being collected during a planned open heart surgery with routine resection from ventricular site. Patients had no history of infection or myocardial inflammation. The heart tissue was formalin fixed and embedded in paraffin. Four μm thick tissue sections were stained with haematoxylin and eosin, Masson's trichrome, and Giemsa. Immunohistochemical stainings included quantitative evaluation of CD3 + T cells, CD20 +  B cells, CD68 +  macrophages and MHCII expression., Results: The myocardium was obtained in 96.8% (n = 60) of the cases from the right and in 3.2% (n = 2) from the left ventricle. The median age (interquartile range) at biopsy was 0.5 years (0.3-0.9), 66.1% male. Within this cohort, a median of 2.5/mm 2 (1.0-4.0) CD3 + T cells, 0.5/mm 2 (0.0-0.6) CD20 +  B cells and 4.0/mm 2 (2.5-6.0) CD68 +  macrophages were detected. The MHC II grade was 0 in 71.0% (n = 44) and 1 in 29.0% (n = 18)., Conclusion: This is the first paediatric control cohort being relevant for the correct interpretation of inflammatory heart diseases in EMB. The lymphocytic cell numbers in children needing congenital heart surgery without myocardial inflammation are below the existing values in adults., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objectives: This study sought to describe the initial findings from the International Pediatric Optical Coherence Tomography (OCT) registry in pediatric heart transplant recipients., Background: Cardiac allograft vasculopathy (CAV) is a common cause of late graft failure and mortality in pediatric heart transplant recipients. Early diagnosis may improve outcomes. OCT is a high-resolution intravascular imaging technique that has the potential to identify CAV earlier than angiography., Methods: OCT and angiography of the coronary arteries were performed in pediatric heart transplant recipients at participating centers. Demographics, clinical data, medications, episodes of rejection, and angiographically confirmed CAV were collected for each case. OCT and angiography images were analyzed in a central core imaging laboratory. Intimal thickness and intima/media cross sectional area (I/M CSA) ratios were calculated for each case. Intimal thickness ≥0.25 mm was defined as abnormal and ≥0.4 mm as severe intima thickening. I/M CSA ratio of ≥1 was defined as abnormal. OCT findings were compared to angiographic findings for each case., Results: Across 3 centers, 110 cases were analyzed from 76 patients. Intimal thickening was present in 26 of 110 cases. Eleven of these cases had severe intima thickening (≥0.4 mm) and notably, angiography results were normal in 8 cases. All 5 cases with a median I/M CSA ratio of ≥2 had normal angiography. The maximal intima thickness was ≥0.25 mm in 24% and ≥0.4 mm in 10% of cases. Median I/M CSA ratio was ≥1 for 80% of cases. I/M CSA ratio was significantly higher in cases with concurrent CAV (p = 0.03). Maximal intima thickness was significantly greater in cases with current or previous rejection (p = 0.01). I/M CSA ratio was significantly lower in patients treated with statins (p = 0.01). OCT findings alone prompted a change to medical management in 17% of cases., Conclusions: OCT provides important insights into coronary vascular changes not detected by angiography in pediatric transplant recipients. The use of OCT for pediatric heart transplant recipients should be further investigated, given its potential to impact the management of CAV., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Food insecurity and declining availability of freshwater and new productive land in water-scarce areas and countries necessitate effective use of marginal-quality waters and underperforming soils. High‑magnesium waters and soils are emerging examples of water quality deterioration and land degradation leading to environmental and food security constraints in several irrigation schemes. A ratio of magnesium-to-calcium > 1 in irrigation waters and an exchangeable magnesium percentage > 25% in soils are considered high enough to result in soil degradation and impact crop yields negatively. These soil and water resources occur in the Aral Sea Basin in Central Asian countries, the Cauca River Valley in Colombia, the Central Plateau Basin in Iran, the Indus Basin in Pakistan, the Indo-Gangetic Plains in India, the Murray-Darling Basin in Australia, and the Coastal Mountain Range in California, among others. With limited and scattered information, their occurrence remains hidden or unnoticed in many cases due to the lack of criteria in water quality assessment and soil classification systems. Managing high‑magnesium waters and soils requires a source of calcium to mitigate magnesium effects, in addition to an effective drainage system for safe disposal of excess magnesium salts. There is a need to put high‑magnesium waters and soils on the public policy agenda. Pertinent policies can catalyze stakeholders' involvement in supporting water and land quality monitoring systems and introducing innovative financial mechanisms to facilitate provision of calcium-supplying amendments in affected areas. Equally important would be strengthening institutional and professionals' capacity, enhancing institutional collaboration, encouraging private sector involvement in at-risk areas, and engaging local communities and farmers. These efforts will support the 2030 Sustainable Development Agenda. Eradicating extreme poverty and meeting the Sustainable Development Goals in water-scarce areas without adequately addressing underperforming land and water resources is highly unlikely., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Sepsis is the number one cause of lung injury in adults. Ex vivo lung perfusion (EVLP) is gaining clinical acceptance for donor lung evaluation and rehabilitation and may expand the use of marginal organs for transplantation. We hypothesized that 4 hours of normothermic EVLP would improve compliance and oxygenation in a porcine model of sepsis-induced lung injury., Methods: We used intravenous lipopolysaccharide (LPS) to induce a systemic inflammatory response in a porcine model of lung injury. Two groups of 4 animals each received a 2-hour infusion of LPS through the external jugular vein. Serial measurements of blood gases were performed every 30 minutes until the partial pressure of oxygen/fraction of inspired oxygen ratio dropped below 150 on two consecutive readings. Lungs were then randomized to treatment with 4 hours of normothermic EVLP with STEEN Solution (XVIVO Perfusion Inc, Englewood, CO) or 4 additional hours of in vivo perfusion (control). Airway pressures and blood gases were recorded for calculation of dynamic lung compliance and partial pressure of oxygen/fraction of inspired oxygen ratios. EVLP was performed with hourly recruitment maneuvers and oxygen challenge., Results: All animals reached a partial pressure of oxygen/fraction of inspired oxygen ratio of less than 150 mm Hg within 3 hours after start of the LPS infusion. Oxygenation and compliance in the control animals continued to decline during the 4-hour in vivo perfusion period, and 3 of the 4 animals died of severe hypoxia within 4 hours. The EVLP group demonstrated significant improvements hour 1 to hour 4 in oxygenation (365.8 ± 53.0 vs 584.4 ± 21.0 mm Hg, p = 0.02) and dynamic compliance (9.0 ± 2.8 vs 15.0 ± 3.6, p = 0.02 mL/cm H 2 O)., Conclusions: EVLP successfully rehabilitated LPS-induced lung injury in this preclinical porcine model and may thus provide a means to rehabilitate many types of acute lung injury., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

We hypothesized that local infection plays a critical role in the pathogenesis of medication-related osteonecrosis of the jaw (MRONJ). Recent developments in molecular methods have revolutionized new approaches for the rapid detection of microorganisms including those difficult to culture. The aim of our study is to identify the bacterial profiles in MRONJ by microbiological culture and polymerase chain reactions (PCR). A retrospective analysis was performed on MRONJ patients from 2008 to 2014. The bacterial profile from MRONJ bone samples was determined using microbiological culture and PCR. Ninety five patients fulfilled the inclusion criteria with mean age of 69.85 ± 8.71 years. A female predilection was detected. The mandible was more commonly affected than maxilla. Tooth extraction was the frequent triggering factor. Breast cancer was the primary cause for administration and intravenous bisphosphonates were the most commonly administrated antiresorptive drugs. The majority of patients were classified as stage 2. Posterior teeth were most commonly affected. Based on bone culture results, the most common microorganism were both actinomyces and mixed flora. PCR confirmed the presence of actinomyces in 55 patients. Our data suggest that PCR might be an innovative method for detection of microorganisms difficult to culture using traditional microbiological techniques., (Copyright © 2017 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Objective: The aim of this study is to investigate the relationship between five domain-specific skills of health literacy: Find Health Information (FHI), Appraise Health Information (AHI), Understand Health Information to act (UHI), Actively Manage One's Health (AMH), and E-health literacy (e-Heals), and health information seeking behaviors and three categories of health outcomes., Methods: A survey was implemented and data was collected from 1062 college going adults and analyzed using bivariate tests and multiple regression analysis., Results: Among the five domain-specific Health Literacy skills, AHI and e-Heals were significantly associated with the use of traditional sources and the Internet for healthcare information respectively. Similarly and AMH and e-Heals were significantly associated with the use of traditional sources and the Internet for health lifestyle information respectively. Lastly AHI, AMH and e-Heals were significantly associated with the three categories of outcomes, and AFH was significantly associated with cognitive and instrumental outcomes, but not doctor-patient communication outcomes., Conclusion: Consumers' ability to use different health sources for both healthcare and health lifestyle information, and the three categories of health outcomes are associated with different domain-specific health literacy skills., Practice Implications: Health literacy initiatives may be improved by focusing on clients to develop domain-specific skills that increase the likelihood of using health information sources and accrue benefits., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Wastewater treatment plants (WWTPs) are not designed to purposefully eliminate antibiotics and therefore many previous investigations have been carried out to assess their fate in biological wastewater treatment processes. In order to consolidate previous findings regarding influencing factors like the solid and hydraulic retention time an intensive monitoring was carried out in a municipal WWTP in Germany. Over a period of 12months daily samples were taken from the in- and effluent as well as diverse sludge streams. The 14 selected antibiotics and one metabolite cover the following classes: cephalosporins, diaminopyrimidines, fluoroquinolones, lincosamide, macrolides, penicillins, sulfonamides and tetracyclines. Out of the 15 investigated substances, the removal of only clindamycin and ciprofloxacin show significant correlations to SRT, temperature, HRT and nitrogen removal. The dependency of clindamycin's removal could be related to the significant negative removal (i.e. production) of clindamycin in the treatment process and was corrected using the human metabolite clindamycin-sulfoxide. The average elimination was adjusted from -225% to 3% which suggests that clindamycin can be considered as an inert substance during the wastewater treatment process. Based on the presented data, the mass flow analysis revealed that macrolides, clindamycin/clindamycin-sulfoxide and trimethoprim were mainly released with the effluent, while penicillins, cephalosporins as well as sulfamethoxazole were partly degraded in the studied WWTP. Furthermore, levofloxacin and ciprofloxacin are the only antibiotics under investigation with a significant mass fraction bound to primary, excess and digested sludge. Nevertheless, the sludge concentrations are highly inconsistent which leads to questionable results. It remains unclear whether the inconsistencies are due to insufficiencies in sampling and/or analytical determination or if the fluctuations can be considered reasonable for digesters. Hence, future investigations have to address antibiotic's temporal dynamics during the sludge treatment to decide whether or not the widely reported standard deviations of sludge concentrations reflect realistic fluctuations., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The present study determines removal rates (RR) of 56 pharmaceuticals and metabolites, respectively, in an urban sewage treatment plant using mass flow analysis by comparing influent and effluent loads over a consecutive ten-day monitoring period. Besides well investigated compounds like carbamazepine and metoprolol, less researched targets, such as topiramate, pregabalin, telmisartan, and human metabolites of pharmaceuticals were included. Another aim was to determine the ratio of pharmaceuticals and corresponding metabolites in raw wastewater. Valsartan and gabapentin were detected at the highest average concentrations in influent (c(val) = 29.7 (± 8.1) μg/L, c(gab) = 13.2 (± 3.3) μg/L) and effluent (c(val) = 22.1 (± 5.1) μg/L, c(gab) = 12.1 (± 2.6) μg/L) samples. The comparison of mass loads in influent and effluent showed a significant removal (p<0.1) for 20 compounds but only enalapril, eprosartan, losartan, pregabalin, and quetiapine were removed from the aqueous phase by more than 50%. Another 20 compounds were determined without significant difference and for five compounds (clindamycin, lamotrigine, oxcarbazepine, O-desmethyl venlafaxine, triamterene), a significant higher mass load in the effluent than in the influent was observed. It has to be noticed that metabolites like 10,11-dihydro-10-hydroxy carbamazepine (MHD) are found in higher mass loads than the corresponding parent compound in the sewage samples. Furthermore, metabolites and parent compound behave differently in the sewage treatment process. While MHD (RR = 15.1%) was detected with lower mass load in the effluent than in the influent, oxcarbazepine (RR = -73.2%) showed the contrary pattern. When comparing expected and measured ratios of parent compound and metabolite in raw sewage, citalopram/N-desmethyl citalopram for example, showed good results. However, a major problem exists due to insufficient data regarding metabolism and excretion of many pharmaceuticals. This complicates the prediction of relevant metabolites and further efforts are needed to overcome this problem., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The European eel (Anguilla anguilla) is regarded as a critically endangered species. Scientists are in agreement that the "quality of spawners" is a vital factor for the survival of the species. This quality can be impaired by parasites, disease and pollution. Especially endocrine disrupting organic chemicals pose a potential threat to reproduction and development of offspring. To our knowledge, the findings in this publication for the first time describe maternal transfer of contaminants in eels. We analysed the concentrations of in total 53 polybrominated diphenyl ethers (PBDEs) and their halogenated substitutes in muscle, gonads and eggs of artificially matured European eels and in muscle and gonads of untreated European eels that were used for comparison. We found evidence that persistent organic pollutants such as PBDEs, as well as their brominated and chlorinated substitutes are redistributed from muscle tissue to gonads and eggs. Concentrations ranged from 0.001 ng g(-1)ww for sum Dechlorane metabolites (DPMA, aCL10DP, aCl11DP) to 2.1 ng g(-1)ww for TBA in eggs, 0.001 ng g(-1)ww for Dechlorane metabolites to 9.4 ng g(-1)ww for TBA in gonads and 0.002 ng g(-1)ww for Dechlorane metabolites to 54 ng g(-1)ww for TBA in muscle tissue. Average egg muscle ratios (EMRs) for compounds detectable in artificially matured eels from both Schlei Fjord and Ems River ranged from 0.01 for Dechlorane 602 (DDC-DBF) to 10.4 for PBEB. Strong correlations were found between flame retardant concentrations and lipid content in the analysed tissue types, as well as transfer rates and octanol-water partitioning coefficient, indicating that these parameters were the driving factors for the observed maternal transfer. Furthermore, indications were found, that TBP-DBPE, TBP-AE, BATE and TBA have a significant uptake from the surrounding water, rather than just food and might additionally be formed by metabolism or biotransformation processes. Dechloranes seem to be of increasing relevance as contaminants in eels and are transferred to eggs. A change of the isomer pattern in comparison to the technical product of Dechlorane Plus (DP) was observed indicating a redistribution of DP from muscle tissue to gonads during silvering with a preference of the syn-isomer. The highly bioaccumulative DDC-DBF was the most abundant Dechlorane in all fish of the comparison group even though it is not produced or imported in the EU. The aldrin related "experimental flame retardant" dibromoaldrin (DBALD) was detected for the first time in the environment in similar or higher concentrations than DP., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Based on regional prescription data several pharmaceuticals with variable amounts of prescription and corresponding metabolites were selected and analyzed in influent and effluent samples of the sewage treatment plant (STP) in Dresden, Germany. Pharmaceuticals of the following most prescribed therapeutic groups were chosen: antibiotics, antifungals, anticonvulsants, antipsychotics, antidepressants, and cardiovascular active compounds like beta blockers and angiotensin-converting enzyme inhibitors. To analyze the selected compounds, a multi-target method was developed and applied to 24-h composite wastewater samples for three single days in May and June 2014. The method was based on a cleanup of a sample with a volume of 1mL using solid phase extraction followed by a high performance liquid chromatography coupled to a tandem mass spectrometer. Analytes were separated in a 15min chromatographic separation and quantified using 23 Internal Standards and a calibration curve in 40-fold diluted blank urine. The limit of quantification varied between 50 and 200ng/L and for all analytes good accuracy and precision as well as linearity for the calibration curve with the correlation coefficient R(2) higher than 0.99 was reached. A total of 41 and 40 of the selected 55 analytes were detected and quantified in the influent and effluent samples of the studied STP, respectively. Valsartan was the compound with the highest maximum concentration in influent (27.1μg/L) and effluent (15.7μg/L). Furthermore, analytes like bezafibrate, candesartan, carbamazepine, gabapentin, metoprolol, levetiracetam, pregabalin and telmisartan as well as the metabolite O-desmethyl venlafaxine were detectable in influent and effluent samples, respectively, with a concentration higher than 1μg/L., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Social support and resilience were considered to be two significant influential factors for depression in late life. The study aims to present a mediation model for understanding the interrelations among social support, resilience, and geriatric depression. A cross-sectional survey study was conducted among 162 community-dwelling Chinese older adults in Singapore. Findings indicated a significant indirect effect of social support on geriatric depression through the mediation of resilience, by controlling demographic variables. Further, an identical influencing pattern between problem-solving resilience and emotion regulation resilience were found in the two individual models, suggesting a similar mediation role in linking social support and geriatric depression. These results extended and integrated earlier findings on the relationship of psychosocial factors and geriatric depression, and pointed out practical implications for future work on depression interventions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

A rapid analytical method was developed for the application of a long-term monitoring (>one year) of the most prescribed and often in hospitals used antibiotics in diverse wastewaters of an urban sewage treatment plant (STP). Additionally to the selected multi-class antibiotics amoxicillin, penicillin V and piperacillin (penicillins), cefotaxime and cefuroxime (cephalosporins), azithromycin, clarithromycin and roxithromycin (macrolids), ciprofloxacin and levofloxacin-ofloxacin (fluoroquinolones), clindamycin (lincosamide), doxycycline (tetracycline), sulfamethoxazole (sulfonamide) and trimethoprim (dihydrofolate reductase inhibitor), the bioactive metabolite clindamycin-sulfoxide, the reserve antibiotic vancomycin (glycopeptide) and as tracer of the STP the anticonvulsant carbamazepine and the antifungal fluconazole were involved. The analytical method combines a low-sample-volume solid phase extraction (SPE), followed by a chromatographic separation using a reversed phase (RP) and hydrophilic interaction liquid chromatography (HILIC) technique, respectively, coupled to a triple quadrupole mass spectrometer. Detection was performed with multiple reaction monitoring (MRM) measured with positive electrospray ionization (ESI+). The extraction efficiency of different SPE cartridges and optimized pH-values of the preparation procedure were tested. Finally, the extraction of antibiotics was realized with the Oasis HLB cartridge and a pH adjustment at 3.5. An external calibration curve in diluted blank urine was used for quality control of the sample set of daily composite samples of the STP for the duration of one year monitoring. The squared coefficient of determination (r(2)) in the concentration range (20-20,000ng/L or 100-100,000ng/L) of the calibration curves for the method was higher than 0.99 for all determined substances. The limit of quantification (LoQ) ranged between 0.8ng/L (azithromycin) and 245.1ng/L (vancomycin). Furthermore, a standard addition was used for quantification in wastewater samples. The process efficiencies ranged from 20% (doxycycline) to 134% (cefuroxime) in influent samples and from 31% (doxycycline) to 171% (cefuroxime) in effluent samples of the STP. All selected substances have been found in wastewater samples. Cefuroxime, doxycycline, levofloxacin, piperacillin, sulfamethoxazole and carbamazepine showed highest concentrations up to 6.2μg/L., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This study compared pressure fields by 4-dimensional (4D), velocity-encoded cine (VEC) cardiac magnetic resonance imaging (CMR) with pressures measured by the clinical gold standard catheterization. Thirteen patients (n = 7 male, n = 6 female) with coarctation were studied. The 4D-VEC-CMR pressure fields were computed by solving the Pressure-Poisson equation. The agreement between catheterization and CMR-based methods was determined at 5 different measurement sites along the aorta. For all sites, the correlation coefficients between measures varied between 0.86 and 0.97 (p < 0.001). The Bland-Altman test showed good agreement between peak systolic pressure gradients across the coarctation. The nonsignificant (p > 0.2) bias was +2.3 mm Hg (± 6.4 mm Hg, 2 SDs) for calibration with dynamic pressures and +1.5 mm Hg (± 4.6 mm Hg, 2 SDs) for calibration with static pressure. In a clinical setting of coarctation, pressure fields can be accurately computed from 4D-VEC-CMR-derived flows. In patients with coarctation, this noninvasive technique might evolve to an alternative to invasive catheterization., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The RNA code found within a platelet and alterations of that code continue to shed light onto the mechanistic underpinnings of platelet function and dysfunction. It is now known that features of messenger RNA (mRNA) in platelets mirror those of nucleated cells. This review serves as a tour guide for readers interested in developing a greater understanding of platelet mRNA. The tour provides an in-depth and interactive examination of platelet mRNA, especially in the context of next-generation RNA sequencing. At the end of the expedition, the reader will have a better grasp of the topography of platelet mRNA and how it impacts platelet function in health and disease., (© 2014 by The American Society of Hematology.)

In the first phase of salt stress the elongation growth of maize shoots is severely affected. The fixation of shape at the end of the elongation phase in Poaceae leaves has frequently been attributed to the formation of phenolic cross-links in the cell wall. In the present work it was investigated whether this process is accelerated under salt stress in different maize hybrids. Plants were grown in nutrient solution in a growth chamber. Reduction of shoot fresh mass was 50% for two hybrids which have recently been developed for improved salt resistance (SR 03, SR 12) and 60% for their parental genotype (Pioneer 3906). For SR 12 and Pioneer 3906, the upper three leaves were divided into elongated and elongating tissue and cell walls were isolated from which phenolic substances and neutral sugars were determined. Furthermore, for the newly developed hybrids the activity of phenolic peroxidase in the cell wall was analysed in apoplastic washing fluids and after sequential extraction of cell-wall material with CaCl2 and LiCl. The concentration of ferulic acid, the predominant phenolic cross-linker in the grass cell wall, was about 5mgg(-1) dry cell wall in elongating and in elongated tissue. The concentration of diferulic acids (DFA) was 2-3mgg(-1) dry cell wall in both tissues. Salt stress increased the concentration of ferulic acid (FA) and DFA in the parental genotype Pioneer 3906, but not in SR 12. Both genotypes showed an increase in arabinose, which is the molecule at which FA and DFA are coupled to interlocking arabinoxylan polymers. In SR 12, the activity of phenolic peroxidase was not influenced by salt stress. However, in SR 03 salt stress clearly increased the phenolic peroxidase activity. Results are consistent with the hypothesis that accelerated oxidative fixation of shape contributes to growth suppression in the first phase of salt stress in a genotype-specific manner., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Satellite cells (SCs) are the resident stem cells of skeletal muscle tissue which play a major role in muscle adaptation, e.g. as a response to physical training. The aim of this study was to examine the effects of an intermittent lactate (La) treatment on the proliferation and differentiation of C2C12 myoblasts, simulating a microcycle of high intensity endurance training. Furthermore, the involvement of reactive oxygen species (ROS) in this context was examined. C2C12 myoblasts were therefore repeatedly incubated for 2 h each day with 10 mM or 20 mM La differentiation medium (DM) and in some cases 20 mM La DM plus different antioxidative substances for up to 5 days. La free (0 mM) DM served as a control. Immunocytochemical staining, Western blot analysis and colorimetric assays were used to assess oxidative stress, proliferation, and differentiation. Results show that La induces oxidative stress, enhances cell-cycle withdrawal, and initiates early differentiation but delays late differentiation in a timely and dose-dependent manner. These effects can be reversed by the addition of antioxidants to the La DM. We therefore conclude that La has a regulatory role in C2C12 myogenesis via a ROS-sensitive mechanism which elicits implications for reassessing some aspects of training and the use of nutritional supplements., (Copyright © 2014. Published by Elsevier B.V.)

Tuberculosis (TB) is a major public health problem in India which accounts for nearly one-fifth of the global TB burden. Though India has been gaining success in eliminating TB, the disease still kills 1000 people daily. It is of prime importance to control the TB situation in India. Motivated by the need to explore factors influencing TB, a qualitative study was conducted with 14 doctors and key TB informants in India over a period of one month involving face-to-face interviews. The interviewees came from diverse backgrounds and vocations, thus providing a rich data on varied issues in controlling the spread of TB in India for enhanced patient care. The data was coded and analyzed. The findings suggest the need to address mental and social well-being of the TB patients through three main themes, namely, Alerts, Care and Education, in order to control the TB situation in India., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This paper describes a social media system to prevent dengue in Sri Lanka and potentially in the rest of the South and Southeast Asia regions. The system integrates three concepts of public health prevention that have thus far been implemented only in silos. First, the predictive surveillance component uses a computer simulation to forewarn health authorities and the general public about impending disease outbreaks. The civic engagement component allows the general public to use social media tools to interact and engage with health authorities by aiding them in surveillance efforts by reporting symptoms, mosquito bites and breeding sites using smartphone technologies. The health communication component utilizes citizen data gathered from the first two components to disseminate customized health awareness messages to enhance knowledge and increase preventive behaviors among citizens. The system, known as "Mo-Buzz," will be made available on a host of digital platforms like simple mobile phones, smart phones and a website. We present challenges and lessons learnt including content validation, stakeholder collaborations and applied trans-disciplinary research., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Melanoma is one of the deadliest human cancers, responsible for approximately 80% of skin cancer mortalities. The aggressiveness of melanoma is due to its capacity to proliferate and rapidly invade surrounding tissues, leading to metastases. A recent model suggests melanoma progresses by reversibly switching between proliferation and invasion transcriptional signatures. Recent studies show that cancer cells are more sensitive to microRNA (miRNA) perturbation than are non-cancer cells; however, the roles of miRNAs in melanoma plasticity remain unexplored. Here, we use the gene expression profiles of melanoma and normal melanocytes to characterize the transcription factor-miRNA relationship that modulates the proliferative and invasive programs of melanoma. We identified two sets of miRNAs that likely regulate these programs. Interestingly, one of the miRNAs involved in melanoma invasion is miR-211, a known target of the master regulator microphthalmia-associated transcription factor (MITF). We demonstrate that miR-211 contributes to melanoma adhesion by directly targeting a gene, NUAK1. Inhibition of miR-211 increases NUAK1 expression and decreases melanoma adhesion, whereas upregulation of miR-211 restores adhesion through NUAK1 repression. This study defines the MITF/miR-211 axis that inhibits the invasive program by blocking adhesion. Furthermore, we have identified NUAK1 as a potential target for the treatment of metastatic melanoma.

Only 16 XPG-defective patients with 20 different mutations have been described. The current hypothesis is that missense mutations impair repair (xeroderma pigmentosum (XP) symptoms), whereas truncating mutations impair both repair and transcription (XP and Cockayne syndrome (CS) symptoms). We identified three cell lines of XPG-defective patients (XP40GO, XP72MA, and XP165MA). Patients' fibroblasts showed a reduced post-UVC cell survival. The reduced repair capability, assessed by host cell reactivation, could be complemented by XPG cDNA. XPG mRNA expression of XP165MA, XP72MA, and XP40GO was 83%, 97%, and 82.5%, respectively, compared with normal fibroblasts. XP165MA was homozygous for a p.G805R mutation; XP72MA and XP40GO were both compound heterozygous (p.W814S and p.E727X, and p.L778P and p.Q150X, respectively). Allele-specific complementation analysis of these five mutations revealed that p.L778P and p.W814S retained considerable residual repair activity. In line with the severe XP/CS phenotypes of XP72MA and XP165MA, even the missense mutations failed to interact with the transcription factor IIH subunits XPD and to some extent cdk7 in coimmunoprecipitation assays. Immunofluorescence techniques revealed that the mutations destabilized early recruitment of XP proteins to localized photodamage and delayed their redistribution in vivo. Thus, we identified three XPG missense mutations in the I-region of XPG that impaired repair and transcription and resulted in severe XP/CS.

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is widely used for rapid and reliable identification of bacteria and yeast grown on agar plates. Moreover, MALDI-TOF MS also holds promise for bacterial identification from blood culture (BC) broths in hospital laboratories. The most important technical step for the identification of bacteria from positive BCs by MALDI-TOF MS is sample preparation to remove blood cells and host proteins. We present a method for novel, rapid sample preparation using differential lysis of blood cells. We demonstrate the efficacy and ease of use of this sample preparation and subsequent MALDI-TOF MS identification, applying it to a total of 500 aerobic and anaerobic BCs reported to be positive by a Bactec 9240 system. In 86.5% of all BCs, the microorganism species were correctly identified. Moreover, in 18/27 mixed cultures at least one isolate was correctly identified. A novel method that adjusts the score value for MALDI-TOF MS results is proposed, further improving the proportion of correctly identified samples. The results of the present study show that the MALDI-TOF MS-based method allows rapid (<20 minutes) bacterial identification directly from positive BCs and with high accuracy., (Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: To propose a comprehensive set of competencies and educational objectives for communication and social competencies in undergraduate medical education and to support the nationwide implementation of these issues in all medical schools., Methods: Thirty experts from different medical and psychosocial disciplines participated in a 2-day workshop using the Nominal Group Technique (NGT) to develop an initial set of educational objectives. These were refined, structured, and rated according to their importance by means of a two-step Delphi Survey involving additional experts in medical education., Results: The initial workshop resulted in 188 educational objectives assigned to 26 different topics. After the Delphi Survey, 131 objectives remained, assigned to 19 different topics. Some objectives that could be assigned to more than one topic were subsumed under a new more general category., Conclusion: The described consensus process proved successful as one method to develop a set of educational objectives., Practical Implications: The Basel consensus statement can be used to orientate curriculum reform and development in medical education., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Antimicrobial resistance in genital mycoplasmas is increasing and shows global variation. We determined the susceptibilities of 469 mycoplamas, comprising 290 Mycoplasma hominis and 179 ureaplasma isolates collected during 1983 and 1989-2004, to eleven antibacterials by agar dilution. Additionally, we analyzed the results of routine E-testing during 2005-2008. Doxycycline was the most active tetracycline with (MIC₉₀ of 1 and 8 mg/L for ureaplasmas and M. hominis, respectively. Significantly more M. hominis isolates (approximately 10-13%) than ureaplasmas (approximately 1-3%) were resistant to tetracyclines. Ofloxacin was effective against both species (>95% susceptibility). Ciprofloxacin was moderately active against M. hominis and less active against ureaplasmas (70.3% and 35.2% susceptibility, respectively). Clarithromycin and josamycin were the most potent macrolides (MIC₉₀ of 0.5 mg/L) against ureaplasmas. Erythromycin had the lowest activity (MIC₉₀ of 8 mg/L) against ureaplasmas like clindamycin which was the most potent agent against M. hominis. Cross-resistance was found between tetracyclines (53-93%), macrolides and erythromycin (70-100%), and between erythromycin and ciprofloxacin (43-55%). M. hominis became more resistant to tetracyclines and fluoroquinolones between 1989 and 2004, although there was little change during 2005-2008. Ureaplasmas became more resistant to cipfloxacin during 1997 – 2004 and showed high resistance rates to erythromycin during 1989-2008. Doxycycline is still the drug of first-choice for the treatment of ureaplasmal infections and may be used for co-infection with M. hominis.

Purpose: At present, neonatal seizures are usually treated with Phenobarbital (PB) despite the limited efficacy and the potential risk this treatment holds for the developing brain. We report here a prospective pilot feasibility study on the use of Levetiracetam as monotherapy in the treatment of neonatal seizures., Methods: Six newborns (body weight>2000 g, gestational age>30 weeks) presenting with neonatal seizures were enrolled. Patients whose seizures were caused by electrolyte disturbances or hypoglycemia, or whose seizures did respond to pyridoxine were excluded. Patients previously treated with other antiepileptic drugs (AEDs), with the exception of single PB doses before and during titration, were excluded. LEV was administered orally, increasing the dose by 10mg/(kg day) over 3 days. Endpoint was the need of any additional AEDs (or PB) after day 3, or 3 months of LEV treatment. A decision regarding further treatment was made on an individual basis and follow-up was documented up to 8 months of age., Results: No severe adverse effects were observed. Mild sedation was reported in one infant. All six patients treated with oral LEV became seizure free within 6 days. Five patients remained seizure free after 3 months with ongoing LEV monotherapy. One infant developed pharmacoresistant epilepsy. Seizures relapsed later in the clinical course of two more patients, one of whom was no longer under LEV therapy., Discussion: Results from our small patient group indicate that LEV may be an alternative therapeutic option in neonatal seizures., ((c) 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

The chromatographic behaviour of a recombinant human antibody (IgG(1)-subtype, kappa-light chain, MW: 149.5 kD, pI: 9.3) was investigated as a function of the buffer pH and buffer type (HEPES, phosphate, borate) on fluoroapatite and hydroxyapatite stationary phases. HEPES buffer was used at pH 7.0, phosphate buffer at pH 8.2 and borate buffer between pH 8.5 and 11. Elution was by a double gradient method of first a salt gradient from 0 to 1 M NaCl in the corresponding buffer, followed by a step gradient to 0.4 M sodium phosphate. Regardless of the pH and buffer type, the antibody eluted in the NaCl gradient; capacity factors decreased with increasing pH. At pH 11 the antibody eluted in the flow-through. Retention was thus dominated by electrostatic interaction throughout the investigated pH-range. Investigation of antibody fragments obtained by papain digestion (fc- and fab-fragments) and deglycosylated fc-fragments showed that the sugar structures had no influence on the chromatographic behaviour. Instead the chromatographic behaviour was dominated by that of the fab-fragment. zeta-Potential measurements verified that the apatite surface bore a negative surface charge in the investigated pH range, while the antibody net surface charge switched from positive to negative as the pH increased. The corresponding isoionic point was a function of both the buffer concentration and the buffer species. However, above a pH of 8.3 the zeta-potential of the antibody generally was negative. Simulations of the molecular electrostatic potential of the antibody and the two fragments revealed the presence of a positively charged patch within the fab-fragment, which only disappeared above a pH of 10. Most likely this patch was responsible for the observed behaviour.

The ultrafast internal conversion (IC) dynamics of adonixanthin in organic solvents were studied by pump-supercontinuum probe (PSCP) and transient lens (TL) spectroscopy after photoexcitation to the S(2) state. Transient PSCP spectra in the range 344-768 nm provided the spectral evolution of the S(0)-->S(2) ground state bleach and S(1)-->S(n) excited state absorption. Time constants were tau(2) =115 and 111 fs for the S(2)-->S(1) IC and tau(1)=6.4 and 5.8 ps for the S(1)-->S(0) IC in acetone and methanol, respectively. There was only an insignificant polarity dependence of tau(1), underlining the negligible importance of intramolecular charge transfer (ICT) in the lowest-lying excited state of C(40) carotenoids with carbonyl substitution on the beta-ionone ring. A blueshift and a spectral narrowing of the S(1)-->S(n) ESA band, likely due to solvation dynamics, and formation of the adonixanthin radial cation at high pump energies via resonant two-photon ionization were found.

Objectives: We examined the spectrum of oral pathogens found in odontogenic abscesses and their susceptibility to penicillin as well as to amoxicillin with clavulanic acid, doxycycline, clindamycin and moxifloxacin. The in vitro results were compared with clinical observations., Patients and Methods: One hundred and eighty eight swabs were obtained from 94 patients with odontogenic abscesses. Bacterial strains were isolated for susceptibility tests. The same patients were investigated for their clinical outcome after standard therapy., Results: A total of 517 bacterial strains were isolated from 94 patients. Ninety eight per cent of abscesses were polymicrobial. The most prevalent bacteria were Viridans streptococci representing 54% of the aerobic/facultative anaerobic bacteria. Prevotella spp. comprised 53% of the anaerobes. No multiresistant strains were detected. Susceptibility testing revealed a sensitivity of over 99% of aerobes/facultative aerobes and 96% of anaerobes sensitivity for moxifloxacin. The corresponding values for penicillin were lowest at 61% and 79%, respectively. In the clinical collective, patients with minor abscesses and no risk of further progression received surgical treatment without antibiotics (36%). Penicillin was administered additionally in 30%. Amoxicillin with clavulanic acid was given in 18% and clindamycin in 15%. Ninety two of the 94 patients showed significant recovery with the described treatment. Only in two cases was a change to the latest broader spectrum antibiotics necessary., Conclusion: In contrast to the moderate in vitro results, penicillin successfully treated the pathogens derived from odontogenic abscess sufficiently when adequate surgical treatment was provided. One third of the patients was treated successfully with incision and drainage only. We suggest that one good reason for its clinical efficacy is the susceptibility of the dominant aerobe/facultative aerobe and anaerobe strains to penicillin.