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Objective To identify the appropriate treatment in the tonsillar region's infections, a distinction between tonsillitis with or without abscess formation is essential. Ultrasound proved to be a valuable method in identifying abscess formation in the head and neck region. However, no report described the assessment of the tonsil region. This study aims to determine the feasibility of transcervical ultrasound for abscess visualization in the palatal tonsillar region. Methods Retrospective analysis of 354 patients presenting with clinical suspicion of tonsillar abscess to a tertiary referral center and university hospital. All patients received a transcervical ultrasound to establish a primary diagnosis. The existence of an abscess was confirmed by puncture and incision, or final tonsillectomy. If no abscess could be delineated, non-abscessing tonsillitis was supposed, and conservative primary therapy and closed follow-up examinations were performed. Results After the first diagnostic ultrasound examination, in 257 cases (72.59%), the diagnosis of an abscess could be established, but in 97 cases (27.40%), due to missing abscess formation criteria, non-abscessing tonsillitis was documented. Overall, ultrasonography demonstrated an overall accuracy of 78.8% in this selected cohort. The sensitivity, specificity, PPV, and NPV after the first ultrasound examination were calculated with 75.1%, 88.6%, 94.6%, and 57.3%, respectively. Conclusion The presented data confirm that an abscess formation due to tonsillitis can be detected by transcervical ultrasound, enabling prompt, adequate management. As transcervical ultrasound can be conducted fast and is not associated with radiation, it can be regarded as a first-line diagnostic tool in this condition.

Background For Hepatocellular carcinoma (HCC) surgery either through resection or transplantation often provides the only chance for cure. Since hepatocarcinogenesis and postsurgical prognosis is not only dependent on cirrhosis but also on immune activation and exhaustion, many studies have investigated tumor infiltrating leukocyte (TIL) subsets. This systematic review and meta-analysis aims at describing the cell groups and their predictive power regarding overall (OS), disease free (DFS) and recurrence free survival (RFS). Material and methods A systematic search of the PubMed database was conducted (PROSPERO 172324). Data on CD3+, CD8+, Treg, B cells, macrophages, neutrophil and NK-cells were collected from Pubmed and related references up to December 2018. Overall (OS), disease-free (DFS) and recurrence free survival (RFS) in dependence of high vs. low infiltration rates were compared using a random effects meta-analysis. Results Altogether data from 3541 patients enrolled in 20 publications were included. Except for Tregs and Neutrophils, heterogeneity analysis was found to be moderate to high across the studies. High CD3+, CD8+, NK-cell infiltration predicted better survival (OS, DFS and RFS; p Discussion As with other solid tumors immune infiltration has a great influence on survival after resection. However, a considerable publication bias cannot be ruled out in mostly retrospective analyses. Nevertheless, in light of novel immune modulatory treatments this opens a new avenue towards effective and well-tolerated adjuvant treatment.

BACKGROUND Pancreatic panniculitis is an extremely rare condition associated with different underlying pancreatic disorders and characterized by subcutaneous fat necrosis induced by elevated serum lipase levels. These lesions usually affect the lower extremities and may precede abdominal symptoms of pancreatic disease. Acinar cell carcinoma (ACC) of the pancreas is a rare pancreatic neoplasm, accounting for only 1%-2% of pancreatic tumors in adults. CASE SUMMARY We present the case of a 72-year-old man with ACC of the pancreatic head and synchronous liver metastases. Both the primary tumor and liver metastases were resected. Serum lipase was elevated before surgery and decreased to normal postoperatively. Rising serum lipase levels at follow-up led to the diagnosis of hepatic recurrence. This disease progression was then accompanied by pancreatic panniculitis, with subcutaneous fat necrosis and acute arthritis. To the best of our knowledge, only 4 cases have been reported in the literature and each showed a similar association of serum lipase levels with pancreatic panniculitis and progression of ACC. CONCLUSION Clinical symptoms and progression of ACC may correlate with serum lipase levels, suggesting potential usefulness as a follow-up biomarker.

Surgical resection improves survival in pancreatic ductal adenocarcinoma (PDAC) and adjuvant chemotherapy adds an additional survival-benefit. While surgical technique has improved in recent years, it remains unclear whether these improvements translate into a survival benefit independent of adjuvant chemotherapy. Thus, we aimed to clarify whether survival of patients who were treated with either Gemcitabine (GEM) or who were observed only in randomized controlled trials on adjuvant chemotherapy of PDAC improved over time.A systematic search of MEDLINE/PubMed was performed to identify randomized controlled trials on adjuvant chemotherapy of PDAC. The search was limited to studies with arms on GEM monotherapy or postoperative observation and studies were grouped by the median year of enrolment and the use of GEM. Subsequently, a meta-regression on the effect of the median year of enrolment on patient survival was performed.A total of 13 studies with 2469 patients was included, with median years of enrollment ranging from 1996 to 2015. While disease-free survival decreased in patients with postoperative observation (18.0 vs. 5.0 months, p = 0.001), median survival improved over time in patients with postoperative observation (15.8 vs. 18.4 months, p = 0.01) and in patients treated with adjuvant GEM (22.8 vs. 35.0 months, p 0.001). One- (p ≤ 0.01) and two-year survival (p = 0.056) improved in both patients treated with adjuvant GEM and those observed only.Survival after surgical resection of PDAC has improved since 1996, even in patients who did not receive adjuvant chemotherapy. Improved surgical technique and postoperative management are likely to be causative factors.

Purpose 68Ga-PSMA-11-PET/CT is increasingly used in early-stage biochemical recurrence of prostate cancer to detect potential lesions for an individualized radiotherapy concept. However, subtle findings especially concerning small local recurrences can still be challenging to interpret and are prone to variability between different readers. Thus, we analyzed interobserver variability, detection rate, and lesion patterns systematically in a homogeneous patient population with low-level biochemical recurrence. Methods We analyzed 68Ga-PSMA-11-PET/CTs in 116 patients with status post-prostatectomy and PSA levels up to 0.6 ng/ml. None of them received ADT or radiotherapy beforehand. Images were interpreted and blinded by two nuclear medicine physicians (R1 and R2). Findings were rated using a 5-point scale concerning local recurrence, lymph nodes, bone lesions, and other findings (1: definitely benign, 2: probably benign, 3: equivocal, 4: probably malignant, 5: definitely malignant). In findings with substantial discrepancies of 2 or more categories and/or potentially leading to differences in further patient management, a consensus reading was done with a third reader (R3). Interobserver agreement was measured by Cohens Kappa analysis after sub-categorizing our classification system to benign (1 + 2), equivocal (3), and malignant (4 + 5). Time course of PSA levels after salvage treatment of patients rated as positive (4 + 5) was analyzed. Results The overall detection rate (categories 4 and 5) was 50% (R1/R2, 49%/51%) and in the PSA subgroups 0–0.2 ng/ml, 0.21–0.3 ng/ml, and 0.31–0.6 ng/ml 24%/27%, 57%/57%, and 65%/68%, respectively. Local recurrence was the most common lesion manifestation followed by lymphatic and bone metastases. The overall agreement in the Cohens Kappa analysis was 0.74 between R1 and R2. For local, lymphatic, and bone sites, the agreement was 0.76, 0.73, and 0.58, respectively. PSA levels of PSMA PET/CT-positive patients after salvage treatment decreased in 75% (27/36) and increased in 25% (9/36). A decrease of PSA, although more frequent in patients with imaging suggesting only local tumor recurrence (86%, 18/21), was also observed in 67% (10/15) of patients with findings of metastatic disease. Conclusions In a highly homogeneous group of prostate cancer patients with early-stage biochemical recurrence after radical prostatectomy, we could show that 68Ga-PSMA-11-PET/CT has a good detection rate of 50% which is in accordance with literature, with clinically relevant findings even in patients with PSA

Chronic pancreatitis (CP) is associated with alcohol abuse in 80% of cases. The primary treatment goals in CP are pain reduction and avoidance of pancreatitis-associated complications. CP should be treated in an interdisciplinary approach. A recent randomized clinical trial showed that early surgery compared with an endoscopy-first approach resulted in reduced pain levels. Surgical resections are, therefore, the most efficient treatment of pancreatitis-associated pain as well as other complications and should be performed early in the course of the disease. Since most of the patients pre­sent with chronic inflammation of the pancreatic head, pancreatic head resection is the most common treatment option. Duodenum-preserving pancreatic head resections are the surgical procedure of choice, but pancreaticoduodenectomies (Kausch-Whipple procedures) demonstrate similar outcome with regard to pain control, quality of life, and metabolic parameters. Other surgical procedures, including drainage procedures, pancreatic segmental resections, or left resections, are rarely indicated.

Primary care physicians (general practitioners (GPs)) are burdened for various reasons and are particularly affected by stress-related complaints and an increasing prevalence of burnout. Thus, the prevention of physician burnout has become a major interest for health care services. Although many studies have addressed this issue in recent years, little seems to be known about the work strain and burnout rates in GP trainees. Therefore the objective of this article is to review the psychosocial burden and relevant prevention strategies for GPs with a special emphasis on GP trainees. Regardless of the specialty, burnout is more prevalent among medical trainees and so-called 'early career' physicians than among the age-matched population. Accordingly, burnout seems to be frequent among GP trainees, although there is some evidence that there are fewer doctors working in general medicine who were already heavily burdened at the time of choosing their career. The sudden assumption of responsibility in patient care as well as the fear of showing imperfection in front of their supervisors, or lack of recognition from senior doctors, the medical team, or patients might be stressors typical to this career stage. GP trainees might also feel burdened by the new level of personal involvement and thus have to develop or increase their individual level of professionality to deal with the patients' medical and personal problems. In conclusion, interventions to promote physical and mental health of GP trainees are a necessity to ensure passionate GPs in the future and should therefore be integrated into any postgraduate training curriculum in general practice.

Objective To systematically examine clinical workflows before and after a major electronic health record (EHR) implementation, we performed this study. EHR implementation and/or conversion are associated with many challenges, which are barriers to optimal care. Clinical workflows may be significantly affected by EHR implementations and conversions, resulting in provider frustration and reduced efficiency. Patients and Methods Our institution completed a large EHR conversion and workflow standardization converting from 3 EHRs (GE Centricity and 2 versions of Cerner) to a system-wide Epic platform. To study this quantitatively and qualitatively, we collected and curated clinical workflows through rapid ethnography, workflow observation, video ethnography, and log-file analyses of hundreds of providers, patients, and more than 100,000 log files. The study included 5 geographic sites in 4 states (Arizona, Minnesota, Florida, and Wisconsin). This project began in April 2016, and will be completed by December 2019. Our study began on May 1, 2016, and is ongoing. Results Salient themes include the importance of prioritizing clinical areas with the most intensive EHR use, the value of tools to identify bottlenecks in workflow that cause delays, and desire for additional training to optimize navigation. Video microanalyses identified marked differences in patterns of workflow and EHR navigation patterns across sites. Log-file analyses and social network analyses identified differences in personnel roles, which led to differences in patient–clinician interaction, time spent using the EHR, and paper-based artifacts. Conclusion Assessing and curating workflow data before and after EHR conversion may provide opportunities for unexpected efficiencies in workflow optimization and information-system redesign. This project may be a model for capturing significant new knowledge in using EHRs to improve patient care, workflow efficiency, and outcomes.

Background: Previously we developed a structured case management for patients with multiple chronic conditions in primary care (called ‘PraCMan’), delivered by Health Care Assistants in General Practice (VERAHs). The ‘TelePraCMan’ project aims to develop a supplementary web-based application to ‘PraCMan’, including a digital symptom diary in which patients can enter individual data via smartphone/tablet. This application is targeted at patients suffering from diabetes mellitus type 2, COPD, hypertension and/or chronic heart failure. Objective: The objective of this study is to evaluate this mHealth-intervention for patients with chronic diseases, focused on patients’ quality of life and self-management capabilities.Methods: A two-armed patient-randomized pilot trial is planned, involving 200 multimorbid patients in 20 GP-practices that use ‘PraCMan’ regularly. Participants are randomly assigned (1:1) to receive either standard ‘PracMan’ treatment or standard ‘PracMan’ treatment complemented with the mHealth-intervention (TelePraCMan). As primary outcome, the health-related quality of life is measured by the German version of the Short Form Health Questionnaire (SF-12). Secondary outcomes include self-management capabilities, technical affinity, and user experience of patient and practice staff. Outcomes are measured at baseline (T0) and at follow-up after 6 months (T1). For the evaluation of the implementation process, GPs, VERAHs and patients will be invited to participate in semi structured interviews afterwards.The outcomes will be compared between study arms using multilevel regression analysis. Qualitative interviews will be transcribed and analysed using qualitative content analysis based on the Tailored Implementation for Chronic Diseases Framework. Discussion: ‘TelePraCMan’ is one of the first mHealth-Interventions addressing multimorbid patients in primary care.Trial registration: DRKS, DRKS00017320, Registered 18 June 2019, http://www.drks.de/DRKS00017320

Background Reporting of adverse events is an important aspect of patient safety management in hospitals, which may help to prevent future adverse events. Yet, only a small proportion of such events is actually reported in German hospitals. Therefore, it is crucial to evaluate attitudes of clinical staff towards reporting of adverse events. The aim of this study was to translate the Reporting of Clinical Adverse Events Scale (RoCAES) developed by Wilson, Bekker and Fylan (2008) and validate it in a sample of German-speaking health professionals. Methods The questionnaire covers five factors (perceived blame, perceived criteria for identifying events that should be reported, perceptions of colleagues’ expectations, perceived benefits of reporting, and perceived clarity of reporting procedures) and was translated into German language according to translation guidelines. Within a cross-sectional study in a sample of 120 health professionals in German hospitals, internal consistency (omega) and construct validity (confirmatory factor analysis) of the German scale RoCAES-D was assessed. Results The reliability was high (omega = 0.87) and the factor analysis showed a poor model fit (RMSEA: 0.074, χ2/df: 1.663, TLI: 0.690). Resulting from lower model fit of the original model (RMSEA: 0.082, χ2/df: 1.804, TLI: 0.606), one item was deleted due to low factor loadings and a low R2 (0.001), and two items were reallocated from the factor ‘perceived benefits’ to ‘perceived blame’. Conclusion The successful translation and initial validation of the RoCAES-D might be a good starting point for further research. A cultural adaptation of the scale needs to be done to initiate a large-scale usage of the questionnaire.

Simple Summary Biomarkers for cancer diagnosis, prognosis and prediction are important tools and an urgent need in precision medicine for pancreatic cancer. In recent years, many experimental and clinical studies aimed at identifying new biomarkers for pancreatic ductal adenocarcinoma. In the review, we summarized current investigations on using novel protein markers, cell-free DNA, metabolome compounds, immune and stroma signatures and microbiome compositions as biomarkers for pancreatic cancer. Our comprehensive overview shows that although there are new promising biomarkers, CA 19-9 remains currently the only regularly used and validated biomarker for pancreatic cancer in clinical routine. Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with a dismal prognosis that is frequently diagnosed at an advanced stage. Although less common than other malignant diseases, it currently ranks as the fourth most common cause of cancer-related death in the European Union with a five-year survival rate of below 9%. Surgical resection, followed by adjuvant chemotherapy, remains the only potentially curative treatment but only a minority of patients is diagnosed with locally resectable, non-metastatic disease. Patients with advanced disease are treated with chemotherapy but high rates of treatment resistance and unfavorable side-effect profiles of some of the used regimens remain major challenges. Biomarkers reflect pathophysiological or physiological processes linked to a disease and can be used as diagnostic, prognostic and predictive tools. Thus, accurate biomarkers can allow for better patient stratification and guide therapy choices. Currently, the only broadly used biomarker for PDAC, CA 19-9, has multiple limitations and the need for novel biomarkers is urgent. In this review, we highlight the current situation, recent discoveries and developments in the field of biomarkers of PDAC and their potential clinical applications.

The aim of this study was to evaluate the removal of sulfamethoxazole (SMX) and diclofenac (DCF) in a mesocosm two-stage constructed wetland system consisting of a subsurface-flow bed (first stage; CW-1) and a surface-flow system (second stage; CW-2) with an emphasis on the effect of artificial aeration as a potential performance intensification option. Furthermore, the additional aim was to identify the transformation products of DCF and SMX along the flow path of the treatment system. This two-stage system was fed for 442 days with an artificial municipal wastewater containing DCF and SMX at a concentration of 2 mg/L each. The removal of SMX in the CW-1 was found to be significantly higher under non-aerated conditions (>77%) as compared to aerated conditions (26%), but the aeration of the CW-2 was insignificant for the SMX removal. In contrast, the removal of DCF was not affected by aeration in the CW-1 (removal efficiency of approximately 50%), but was significantly positively influenced by the combined effect of plants and aeration in the CW-2. The overall removal of SMX and DCF in the two-stage system was 95.8% and 77.6%, respectively. The transformation products of SMX and DCF detected in the studied system indicated the potential contribution of both oxic and anoxic transformation pathways, potentially including also abiotic reaction between SMX and Fe(II) leading to the cleavage of the isoxazole ring in this compound. Some of the transformation products found in the CW-1 were not further detected in the CW-2. Based on the literature data the antimicrobial activity and potential activity of the identified transformation products cannot be ruled out. Giant miscanthus growing in the CW-1 was unaffected by the high concentrations of DCF and SMX in contrast to the emergent macrophytes (on the floating island) or the free-floating plants present in the CW-2, which failed to adapt to the presence of the pharmaceuticals. As a result, the CW-2 was colonized by an unidentified species of a water moss and algae.

Medication reconciliation (MedRec) is a mission-critical process which can serve to reduce adverse drug events (ADEs) in surgical settings. However, providing quality care is limited by current health information technology (IT), which is often inefficient and unintuitive due to poor usability, resulting in high cognitive burden. We have been characterizing EHR mediated workflow in the Mayo Clinic enterprise prior to a system-wide electronic health records (EHR) conversion in order to harmonize workflows. We compared and evaluated MedRec processes in pre-operative nursing assessments across two different EHRs in place in different locales at baseline. The interfaces differed both in their modes of interaction and cognitive support. Analyses surfaced interface elements that were unintuitive and inefficient, creating unnecessary complexities in clinicians’ interactive behavior. Keystroke level models (KLM), a modeling tool for predicting task completion time, showed that to access medication lists required a different series of operations across the two systems. Different designs can differentially mediate task performance, which can aid in the mitigation of errors for complex cognitive tasks. Identification of barriers in EHR-mediated workflow and barriers to interface usability could lead to system redesigns that minimize cognitive load while improving patient safety and efficiency.

Implant failures are primarily related to bacterial infections and inflammation. Nanocoating of implant devices with organic molecules is a method used for improving their integration into host tissues and limiting inflammation. Bioengineered plant-derived rhamnogalacturonan-Is (RG-Is) from pectins improve tissue regeneration and exhibit anti-inflammatory properties. Therefore, the aim of this study is to evaluate the in vitro effect of RG-I nanocoating on human gingival primary fibroblast (HGF) activity and proinflammatory response following Porphyromonas gingivalis (P. gingivalis) infection. Infected HGFs were incubated on tissue culture polystyrene (TCPS) plates coated with unmodified RG-I isolated from potato pectin (PU) and dearabinanated RG-I (PA). HGF morphology, proliferation, metabolic activity, and expression of genes responsible for extracellular matrix (ECM) turnover and proinflammatory response were examined. Following the P. gingivalis infection, PU and PA significantly promoted HGF proliferation and metabolic activity. Moreover, gene expression levels of IL1B, IL8, TNFA, and MMP2 decreased in the infected cells cultured on PU and PA, whereas the expression of COL1A1, FN1, and FGFR1 was upregulated. The results indicate that RG-Is are promising candidates for nanocoating of an implant surface, can reduce inflammation, and enhance implant integration, particularly in medically compromised patients with chronic inflammatory diseases such as periodontitis and rheumatoid arthritis. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 3475-3481, 2017.

Constructed wetlands (CW) are one of the biological wastewater treatment systems that reflect the natural processes occurring in swamps. Constructed wetlands use microbiological and physico-chemical processes as well as plant metabolism in order to purify wastewater. In such treatment systems, the role of microorganisms is crucial. In this experiment, synthetic communal wastewater containing sulfamethoxazole (SMX; chemotherapeutic) at a concentration of 5 mg/l was applied in the CW systems, both unplanted and planted with Phalaris arundinacea , also known as reed canary grass. Fourteen Gram-positive SMX-resistant bacteria strains were isolated from the CW column fillings and the plant rhizosphere. All of these were identified as representatives of Bacillus sp . based on 16S rRNA sequencing. Despite this molecular identification, the isolates differed significantly in their biochemical features. All 14 isolates presented resistance toward sulfamethoxazole and all 14 strains possessed a sul1 gene, while only 4 gave positive results in sul2 and 3 in sul3 PCR tests. None of the isolated strains possessed all three sul genes. A PCR-DGGE based analysis of the presence of SMX-resistant bacteria in the CW community was undertaken. It was found that none of the isolates represented the dominant genotype in the bacterial community.

Summary Background: The 2013 American College of Cardiology / American Heart Association Guidelines for the Treatment of Blood Cholesterol emphasize treatment based on cardiovascular risk. But finding time in a primary care visit to manually calculate cardiovascular risk and prescribe treatment based on risk is challenging. We developed an informatics-based clinical decision support tool, MayoExpertAdvisor, to deliver automated cardiovascular risk scores and guideline-based treatment recommendations based on patient-specific data in the electronic heath record. Objective: To assess the impact of our clinical decision support tool on the efficiency and accuracy of clinician calculation of cardiovascular risk and its effect on the delivery of guideline-consistent treatment recommendations. Methods: Clinicians were asked to review the EHR records of selected patients. We evaluated the amount of time and the number of clicks and keystrokes needed to calculate cardiovascular risk and provide a treatment recommendation with and without our clinical decision support tool. We also compared the treatment recommendation arrived at by clinicians with and without the use of our tool to those recommended by the guidelines. Results: Clinicians saved 3 minutes and 38 seconds in completing both tasks with MayoExpertAd-visor, used 94 fewer clicks and 23 fewer key strokes, and improved accuracy from the baseline of 60.61% to 100% for both the risk score calculation and guideline-consistent treatment recommendation. Conclusion: Informatics solution can greatly improve the efficiency and accuracy of individualized treatment recommendations and have the potential to increase guideline compliance.

Background Bioengineered plant-derived Rhamnogalacturonan-Is (RG-Is) from pectins are potential candidates for surface nanocoating of medical devices. It has recently been reported that RG-I nanocoatings may prevent bacterial infection and improve the biocompatibility of implants. The aim of the study was to evaluate in vitro impact of bioengineered RG-I nanocoatings on osteogenic capacity and proinflammatory cytokine response of murine osteoblasts following Porphyromonas gingivalis infection. Methods Murine MC3T3-E1 osteoblasts and isolated primary calvarial osteoblasts from C57BL/6J (B6J osteoblasts) mice were infected with P. gingivalis and incubated on tissue culture polystyrene plates with or without nanocoatings of unmodified RG-Is isolated from potato pulps (PU) or dearabinanated RG-Is (PA). To investigate a behavior of infected osteoblasts cultured on RG-Is cell morphology, proliferation, metabolic activity, mineralization and osteogenic and pro-inflammatory gene expression were examined. Results Following P. gingivalis infection, PA, but not PU, significantly promoted MC3T3-E1 and BJ6 osteoblasts proliferation, metabolic activity, and calcium deposition. Moreover, Il-1b, Il-6, TNF-α, and Rankl gene expressions were downregulated in cells cultured on PU and to a higher extent on PA as compared to the corresponding control, whereas Runx, Alpl, Col1a1, and Bglap gene expressions were upregulated vice versa. Conclusion Our data clearly showed that pectin RG-Is nanocoating with high content of galactan (PA) reduces the osteoblastic response to P. gingivalis infection in vitro and may, therefore, reduce a risk of inflammation especially in immunocompromised patients with rheumatoid or periodontal disorders.

Introduction Rapid diagnosis accompanied by appropriate treatment is essential in the therapy of sepsis. However, there is no blood marker available, which reliably predicts sepsis and associated mortality. Therefore, the aim of the present study was to evaluate presepsin and endotoxin in comparison with established blood markers in patients undergoing emergency visceral surgery for abdominal infection. Patients and methods This prospective study included 31 patients with abdominal infection undergoing emergency surgery between March and August 2014. The Sepsis-2 and Sepsis-3 definitions of sepsis were used. Blood markers (presepsin, endotoxin, C-reactive protein, procalcitonin (PCT), interleukin 6 (IL-6), white blood count) were analyzed preoperatively and correlated with the clinical course and mortality. Additionally, a combination of the three markers, which performed best, was tested. Results Twenty patients (64.5%) in the analyzed cohort developed sepsis from an abdominal focus according to the latest sepsis definition. Out of the analyzed blood markers, presepsin exhibited the highest area under the curve, sensitivity, and specificity for the prediction of the development of sepsis. Moreover, presepsin had the highest predictive value for mortality as opposed to both endotoxin and previously established blood markers (i.e., PCT, IL-6). The multimarker approach, which included PCT, IL-6, and presepsin, showed no additional predictive value over presepsin alone. Conclusion The present study suggests that presepsin is a novel predictor of sepsis and mortality from sepsis in patients undergoing surgery for intra-abdominal infections. The findings of the present study should be validated in a larger cohort.

Hintergrund: Menschen über 65 Jahre stellen die größte Patientengruppe im Gesundheitswesen dar. Dies unterstützt den Ansatz, Medizinstudierenden mit Hilfe von Selbsterfahrung die Bedeutung funktioneller Krankheitsfolgen und physiologischer Veränderungen des Alters zu vermitteln.[zum vollständigen Text gelangen Sie über die oben angegebene URL], 14. Internationales SkillsLab Symposium 2019

In patients with pancreatic ductal adenocarcinoma (PDAC), the tumor microenvironment consists of cellular and stromal components that influence prognosis. Hence, tumor-infiltrating lymphocytes (TILs) may predict prognosis more precisely than conventional staging systems. Studies on the impact of TILs are heterogeneous and further research is needed. Therefore, this study aims to point out the importance of peritumoral TILs, tumor-infiltrating neutrophils (TINs), and immune subtype classification in PDAC. Material from 57 patients was analyzed with immunohistochemistry performed for CD3, CD8, CD20, CD66b, &alpha, sma, and collagen. Hot spots with peritumoral TILs and TINs were quantified according to the QTiS algorithm and the distance of TILs hot spots to the tumor front was measured. Results were correlated with overall (OS) and progression-free survival (PFS). High densities of peritumoral hot spots with CD3+, CD8+, and CD20+ TILs correlated significantly with improved OS and PFS. Combined immune cell subtypes predicted improved OS and PFS. High infiltration of CD3+ TILs predicted progression after 12 months. The location of TILs&rsquo, hot spots and their distance to the tumor front did not correlate with patient survival. Peritumoral TILs and the composition of the stroma predict OS and PFS in PDAC.

For the evaluation of infectious-diseases interventions, the transmissible nature of such diseases plays a central role. Agent-based models (ABM) allow for dynamic transmission modeling but publications are limited. We aim to provide an overview of important characteristics of ABM for decision-analytic modeling of infectious diseases. A case study of dengue epidemics illustrates model characteristics, conceptualization, calibration and model analysis. First, major characteristics of ABM are outlined and discussed based on ISPOR and ISPOR-SMDM Good Practice guidelines. Second, in our case study, we modeled a dengue outbreak in Cebu City (Philippines) to assess the impact interventions to control the relative growth of the mosquito population. Model outcomes include prevalence and incidence of infected persons. The modular ABM simulates persons and mosquitoes over an annual time horizon considering daily time steps. The model was calibrated and validated. ABM is a dynamic, individual-level modeling approach that is capable to reproduce direct and indirect effects of interventions for infectious diseases. The ability to replicate emerging behavior and to include human behavior or the behavior of other agents is a distinguishing modeling characteristic (e.g., compared to Markov models). Modeling behavior may, however, require extensive calibration and validation. The analyzed hypothetical effectiveness of dengue interventions showed that a reduced human-mosquito ratio of 1:2.5 during rainy seasons leads already to a substantial decrease of infected persons. ABM can support decision-analyses for infectious diseases including disease dynamics, emerging behavior, and providing a high level of reusability due to modularity.

Background Patients with inflammatory rheumatic diseases are at higher risk for influenza and current guidelines recommend vaccination for this group of patients. The aim of this study was to evaluate the vaccination coverage and predictors for influenza vaccination among patients with inflammatory rheumatic diseases. Methods This survey was conducted at the outpatient rheumatology clinic at the Medical University of Vienna between July and October 2017. All patients diagnosed with an inflammatory rheumatic disease and receiving immunosuppressive therapy were asked to complete a questionnaire about their influenza vaccination status for 2016/17. Results 490 patients with rheumatic diseases completed a questionnaire (33% male, mean age 55.3 years). The influenza vaccination rate for the previous season was 25.3% (n = 124/490). Predictors for a positive influenza vaccination status were higher age (Adjusted Odds Ratio 5.0, 95% Confidence Interval 2.4–10.4) and treatment with biological disease-modifying antirheumatic drugs (AOR 2.0, 95% CI 1.3–3.1). Patients who received a recommendation for influenza vaccination by their general practitioner were significantly more likely to be vaccinated than those who did not (57% vs. 15%, AOR 6.6, 95% CI 4.1–10.8); even more so if they received a recommendation by their rheumatologist (62% vs. 19%, AOR 9.0, 95% CI 4.9–16.5). The main reasons for patients to decline influenza vaccination were fear of side effects (36%), concerns that vaccination might not be effective due to their immunosuppressed condition (38%) or that it might worsen the rheumatic disease (20%). Conclusions A moderate influenza vaccination rate of 25.3% was detected among patients with inflammatory rheumatic diseases. Recommendation of the influenza vaccine by a physician exerts the most effective impact on a positive vaccination status.

Proteases are involved in almost every important cellular activity, from embryonic morphogenesis to apoptosis. To study protease activity in situ, hydrogels provide a synthetic mimic of the extracellular matrix (ECM) and have utility as a platform to study activity, such as those related to cell migration, in three-dimensions. While 3-dimensional visualization of protease activity could prove quite useful to elucidate the proteolytic interaction at the interface between cells and their surrounding environment, there has been no versatile tool to visualize local proteolytic activity in real time. Here, micron-sized gels were synthesized by inverse suspension polymerization using thiolene photo-click chemistry. The size distribution was selected to avoid cellular uptake and to lower cytotoxicity, while simultaneously allowing the integration of peptide-based FRET sensors of local cell activity. Proteolytic activity of collagenase was detected within an hour via changes in fluorescence of embedded microgels; incubation of microgel sensors with A375 melanoma cells showed upregulated MMP activity in the presence of soluble fibronectins in media. The microgel sensors were readily incorporated into both gelatin and poly(ethylene glycol) (PEG) hydrogels and used to successfully detect spatiotemporal proteolytic activity of A375 melanoma cells. Finally, a tumor model was constructed from a hydrogel microwell array that was used to aggregate A375 melanoma cells, and local variations in proteolytic activity were monitored as a function of distance from the cell aggregate center.

The objectives of this study were to investigate the start-up removal of pharmaceutical compounds diclofenac and sulfamethoxazole in microcosm downflow constructed wetlands and their effect on the performance of the studied constructed wetlands, and also to assess the effect of plants on the removal of these compounds. The experimental system that was used in this 86-day experiment consisted of 24 columns filled up to 70 cm with predominantly sandy material. Four types of columns were used (six replicates) depending on the presence of plants (Phalaris arundinacea L. var. picta L.) and the presence of pharmaceutical compounds in the influent. The influent was synthetic municipal waste water to which a mixture of 5 mg/L of diclofenac and 5 mg/L of sulfamethoxazole was added. The observed removal of diclofenac was moderate (approx. 50%) and the removal of sulfamethoxazole was relatively low (24–30%). It was found that the removal of diclofenac and sulfamethoxazole was not affected by the vegetation. The presence of diclofenac and sulfamethoxazole in the influent had significant effect on the effluent concentration of N-NO3 and the water loss in the columns, which in both cases were lower than in the control columns. The scope for further research was discussed.

Background Disease Management Programmes (DMPs) aim to improve effectiveness and equity of care but may suffer from selective enrolment. We analysed social disparities in DMP enrolment among elderly patients with coronary heart disease (CHD) in Germany, taking into account contextual effects at municipality and primary care practice levels. Methods Cross-sectional analysis of effects of educational attainment and regional deprivation on physician-reported DMP enrolment in a subsample of a large population-based cohort study in Germany, adjusting for individual-level, practice-level and area-level variables. We calculated OR and their 95% CIs (95% CI) in cross-classified, multilevel logistic regression models. Results Among N=1280 individuals with CHD (37.3% women), DMP enrolment rates were 22.2% (women) and 35% (men). The odds of DMP enrolment were significantly higher for male patients (OR=1.98 (1.50 to 2.62)), even after adjustment for potential confounding by individual-level, practice-level and area-level variables (range: OR=1.60 (1.08 to 2.36) to 2.16 (1.57 to 2.98)). Educational attainment was not significantly associated with DMP enrolment. Compared to patients living in least-deprived municipalities, the adjusted propensity of DMP enrolment was statistically significantly lower for patients living in medium-deprived municipalities (OR=0.41 (0.24 to 0.71)), and it also tended to be lower for patients living in the most-deprived municipalities (OR=0.70 (0.40 to 1.21)). Models controlling for the social situation (instead of health-related behaviour) yielded comparable effect estimates (medium-deprived/most-deprived vs least-deprived areas: OR=0.45 (0.26 to 0.78)/OR=0.68 (0.33 to 1.19)). Controlling for differences in comorbidity attenuated the deprivation effect estimates. Conclusions We found evidence for marked gender, but not educational disparities in DMP enrolment among patients with CHD. Small-area deprivation was associated with DMP enrolment, but the effects were partly explained by differences in comorbidity. Future studies on DMPs should consider contextual effects when analysing programme effectiveness or impacts on equity and efficiency. &nbsp

In der kommunalen Gesundheitsforderung haben Hausarzte eine zunehmend wichtige Bedeutung. Bislang ist wenig bekannt, wieweit Konzepte der Gesundheitsforderung in der Praxis umgesetzt werden bzw. der Hausarzt als Akteur in die Prozesse der kommunalen Gesundheitsforderung integriert ist. Ziel der vorliegenden Studie ist es darum, zu erfahren, welche Rolle Hausarzte innerhalb der kommunalen Gesundheitsforderung aus ihrer Sicht bereits einnehmen und welches Verbesserungspotential dabei besteht. Innerhalb eines qualitativen Studienansatzes wurden 19 semistrukturierte Telefoninterviews durchgefuhrt, transkribiert und qualitativ-inhaltsanalytisch nach Mayring ausgewertet. Die Befragten sehen v. a. in der Vernetzung mit kommunalen Einrichtungen in verschiedenen Settings eine gute Moglichkeit, Hausarzte in die kommunale Gesundheitsforderung zu integrieren. Dabei werden v. a. die Settings Kindergarten und Schule sowie die betriebliche Gesundheitsforderung genannt. Hinderlich fur eine starkere Anbindung des Hausarztes in der Gesundheitsforderung sind dabei Zeitmangel und eine unzureichende Vergutung. Hausarzte spielen eine wichtige Rolle fur das nachhaltige Gelingen einer kommunalen Gesundheitsforderung, aufgrund von wahrgenommenen Barrieren wird diese aber haufig nur unzureichend ausgefullt. Politische Rahmenbedingungen sollten Pravention und Gesundheitsforderung auch im hausarztlichen Kontext starken. Die Rollen der einzelnen Akteure sollten dabei genauer definiert werden, sowie ausreichende Ressourcen zur Verfugung gestellt werden. Zukunftige Forschungen sollten Kooperationsmoglichkeiten von Hausarzten und der Gemeinde genauer untersuchen, um Bedingungen fur eine nachhaltig erfolgreiche Kooperation zu identifizieren.

Zum 1. Juli 2008 trat in Baden-Wurttemberg der Vertrag zur Hausarztzentrierten Versorgung (HzV) nach § 73b SGB V in Kraft. Die HzV zielt u. a. auf eine verbesserte Versorgung von Versicherten, insbesondere mit chronischen Erkrankungen und komplexem Versorgungsbedarf (z. B. bei Pflegebedurftigkeit), ab. Der vorliegende Beitrag fokussiert in vier verschiedenen Arbeitspaketen (AP I bis AP IV) auf die Beantwortung der Fragen, wie sich die Versorgung in der HzV auf darin eingeschriebene Versicherte der AOK Baden-Wurttemberg und deren Versorger auswirkt. Arbeitspaket I (AP I) untersucht auf Basis von AOK-Routinedaten explorativ Zusammenhange zwischen einer Einschreibung in die HzV und patientenseitiger Inanspruchnahme von Versorgungsleistungen. AP II beschaftigt sich mit der Frage, welche Veranderungen durch die Teilnahme an der HzV aus Sicht der Hausarzte und Versicherten eingetreten sind. AP III untersucht den Einsatz von VERAH (Versorgungsassistenten in der Hausarztpraxis), die im Rahmen der HzV eine besondere Rolle spielen. AP IV analysiert auf der Basis von Routinedaten Fragestellungen zur Versorgungsqualitat alterer Versicherter uber 65 Jahren. Die methodische Vorgehensweise der Evaluation folgt einem Mixed-Methods-Design, bei dem neben quantitativen auch qualitative Verfahren verwendet wurden. Dies ermoglicht, die Implementierung der HzV in die Regelversorgung aus verschiedenen Perspektiven eingehender zu betrachten. In allen vier Arbeitspaketen waren in grosen Teilen positive Assoziationen zwischen einer Einschreibung in die HzV und den jeweils untersuchten Zielgrosen zu beobachten, die im Folgenden detailliert dargestellt werden. Die bisherigen Ergebnisse sprechen klar dafur, die HzV sowie die dazu korrespondierende Begleitevaluation weiterzufuhren.

Travel sickness, which is a special kind of motion sickness or kinetosis, is unpleasant for many people while traveling. It is often caused by a mismatch between the perceived movement of the eyes and the movement sensed by the vestibular system. In a car, this condition is often caused by reading or staring at a mobile phone for a longer period of time. Looking outside the window at the trajectory of the vehicle helps most of those affected by kinetosis. But what if you want to read a book while traveling? In this paper, we present the Motion Sickness Prevention System (MSPS) --an approach that allows reading while driving easing the symptoms of kinetosis. It simply uses the live video stream of the road ahead as a background for reading. A preliminary study (N=12) shows that the MSPS, while not able to eliminate the symptoms of kinetosis, can still significantly decrease it.

OBJECTIVE: Disease management programmes (DMP) are supposed to improve the care of patients with type 2 diabetes or other chronic conditions. One stated aim is the improvement of the health-related quality of life. Within the ELSID study (controlled study for the evaluation of the DMP for patients with type 2 diabetes) there has been a survey of insurants of the general regional health funds (AOK) by means of the SF-36. The aim of this survey is a comparison of patients participating in the Diabetes DMP with those who are not participating in the program with regard to their quality of life. METHODS: A random sample of 3,546 patients with type 2 diabetes out of the total sample of the ELSID study (20,625) was asked to complete the SF-36. RESULTS: 1,532 questionnaires were returned (response rate 43.2%). 1,399 were analysed. Within all scales of the SF-36, men achieved higher scores than women. Differentiated in participants and non-participants in the DMP, in men there were lower scores for the participants than for the non-participants. In women this proportion was reversed. CONCLUSIONS: This cross-sectional-study provides first indications for gender-specific differences within the quality of life of patients with diabetes participating in the DMP compared to patients who are not participating. These differences should be considered more intensely within further research of DMP evaluation and the configuration of the programmes in the future.

Three major outbreaks of salmonellosis linked to consumption of peanut butter during the last 6 years have underscored the need to investigate the potential sources of Salmonella contamination in the production process flow. We conducted a study to determine the prevalence and levels of Salmonella in raw peanuts. Composite samples (1,500 g, n = 8) of raw, shelled runner peanuts representing the crop years 2009, 2010, and 2011 were drawn from 10,162 retained 22-kg lot samples of raw peanuts that were negative for aflatoxin. Subsamples (350 g) were analyzed for the presence of Salmonella and enterohemorrhagic Escherichia coli. Salmonella was found in 68 (0.67%) of 10,162 samples. The highest prevalence rate (P0.05) was for 2009 (1.35%) compared with 2010 (0.36%) and 2011 (0.14%). Among four runner peanut market grades (Jumbo, Medium, No. 1, and Splits), Splits had the highest prevalence (1.46%; P0.05). There was no difference (P0.05) in the prevalence by region (Eastern versus Western). Salmonella counts in positive samples (most-probable-number [MPN] method) averaged 1.05 (range, 0.74 to 5.25) MPN per 350 g. Enterohemorrhagic E. coli was found in only three samples (0.030%). Typing of Salmonella isolates showed that the same strains found in Jumbo and Splits peanuts in 2009 were also isolated from Splits in 2011. Similarly, strains isolated in 2009 were also isolated in 2010 from different peanut grades. These results indicated the persistence of environmental sources throughout the years. For five samples, multiple isolates were obtained from the same sample that had different pulsed-field gel electrophoresis types. This multistrain contamination was primarily observed in Splits peanuts, in which the integrity of the kernel is usually compromised. The information from the study can be used to develop quantitative microbial risk assessments models.

Hintergrund: Grunde fur die Wahl eines bestimmten Fachgebiets sind aufgrund des allgemeinen Arztemangels zunehmend von Relevanz. Ziel dieser Analyse war es, die Erfahrungen von Medizinstudierenden mit dem Gebiet Allgemeinmedizin und dem Hausarztberuf zu erfassen, um Strategien fur eine verstarkte Nachwuchsgewinnung abzuleiten. Methoden: Studierende aller funf Medizinischen Fakultaten in Baden-Wurttemberg wurden per E-Mail-Verteiler durch die Studiendekanate beziehungsweise Fachschaften uber die Online-Umfrage informiert. Im Rahmen der Umfrage wurde ein im Vorfeld entwickelter Fragebogen eingesetzt. Neben einer deskriptiven Analyse wurden im Rahmen einer partiellen Korrelationsanalyse (kontrolliert fur die Faktoren Alter, Geschlecht und Semesterzahl) Assoziationen zwischen der Variable „Ich halte den Hausarztberuf fur attraktiv" und 31 Aussagen zur Allgemeinmedizin berechnet. Mit linearer Regression wurde gepruft, welche Faktoren unabhangig voneinander mit der angegebenen Attraktivitat des Hausarztberufs assoziiert sind. Ergebnisse: 1299 Studierende nahmen an der Befragung teil. Annahernd die Halfte der Teilnehmer (49,7 %) hielt den Hausarztberuf fur attraktiv bzw. teilweise attraktiv. Positive Erfahrungen mit der Allgemeinmedizin hatten 49,6 % der Medizinstudierenden als Patient, 33,1 % als Angehoriger, 24,3 % als Blockpraktikant und 18,1 % als Famulant gemacht. Dass die Allgemeinmedizin in den Medien positiv dargestellt wird, glaubten 23,3 % und dass das Fach in der medizinischen Aus-, Fort- und Weiterbildung einen hohen Stellenwert einnimmt 13,7 %. Erfahrungen als Famulant (rpart= + 0,450) und Patient (rpart= + 0,218) in der Allgemeinmedizin waren positiv mit der Beurteilung der Attraktivitat des Hausarztberufs assoziiert, ebenso die Einschatzung, dass man in der Allgemeinmedizin einen abwechslungsreichen Arbeitstag (rpart= + 0,259) und gute Verdienstmoglichkeiten (rpart= + 0,242) hat. Schlussfolgerung: Den Studierenden bereits wahrend der Ausbildung einen praktischen Einblick in das Gebiet der Allgemeinmedizin zu ermoglichen, scheint ein wichtiger Baustein fur die Attraktivitat des Hausarztberufs zu sein.

Einleitung Der Vertrag zur Hausarztzentrierten Versorgung (HzV) in Baden-Württemberg von 2008 ist der erste (und in der Fläche bisher einzige) Vollversorgungsvertrag nach § 73b SGB V in Deutschland. Inzwischen liegen Evaluationsergebnisse aus der Etablierungsphase 2008-2011 vor. Evaluiert wurden die Inanspruchnahme und mögliche Steigerungen der Versorgungsqualität bei Patienten mit Herzinsuffizienz – beides im Kontrollgruppenvergleich – sowie die Hausarzt-, Mitarbeiterinnen- und Patientenzufriedenheit und der in diesem Vertrag erstmals vergütete Einsatz von Versorgungsassistentinnen in der Hausarztpraxis (VERAH).

Considering the demographic development models for primary care have to be focused on chronic illness care especially. The so called "Hausarztzentrierte Versorgung" (HzV) in Baden-Wuerttemberg constitutes such a model of an implementation of family doctor-centred health care. For evaluation purposes the perspective of patients is of particular interest. Therefore the aim of this study was to analyse how chronically ill patients assess their medical care. Altogether 53 primary care practices in Baden-Wuerttemberg took part in a patient survey. The quality of chronic illness care from the patients' perspective was assessed by means of the PACIC short form. Furthermore the general satisfaction with care as well as sociodemographic characteristics were determined. For analysis two different groups were regarded: HzV-doctor and HzV-patient with a chronic condition (group 1) and non-HzV-doctor and non-HzV-patient with a chronic condition (group 2). Altogether 2,535 patients were recruited for the survey (response rate 47.8%). Out of these, 836 patients could be assigned to group 1 and 319 patients could be assigned to group 2. Patients in both groups were very satisfied with their care. The patients in group 1 stated more frequently that they received a written treatment plan from their general practitioner and that they were asked about their state of health when leaving the practice. Overall satisfaction was positively associated with organisation of care (β= 0.484), support in difficult situations (β= 0.171) and information on the usefulness of consulting other doctors (β= 0.163) with an explained variation of R(2)=0.459. Irrespective of their group affiliation patients rate the medical care of their chronic condition very positively. Especially the assessment of the quality of care from the perspective of different patient groups (HzV participants and non-HzV participants) could contribute essentially as a feedback for physicians concerning the implementation of the main contents of the HzV for participating physicians.

Although resource orientation, as a part of health promotion, should play a major role in general practice, the anchoring and realization of resource-oriented approaches remain small in Germany. The aim of this study was to analyze what resource orientation means to general practitioners (GPs) and develop strategies as to how this can be facilitated in GP practice. Within a qualitative research approach, 19 semi-structured telephone interviews were recorded, transcribed, and analyzed using qualitative content analysis. Within the interviews, the inclusion of the patients’ individual resources is described as core competence of GPs. Supporting the patients’ disease coping strategies and self-help were seen as important by GPs. However, perceptions as to which resources are considered to be fundamental ranged widely across the participant group. The results confirm the important role of resource-oriented approaches in general practice. However, a general definition of resource orientation is needed. In addition, working conditions for GPs need to be taken into account to ensure that these contribute to a healthy work-life balance. The need for GP training was identified to improve communication skills. Further integration of GPs in health promotion and communal structures would be beneficial.

J Folkert,1 A Meresta,1 T Gaber,2 K Miksch,1 F Buttgereit,2 J Detert,2 N Pischon,3,* K Gurzawska3,4,* 1Environmental Biotechnology Department, Faculty of Power and Environmental, Silesian University of Technology, Gliwice, Poland; 2Department of Rheumatology and Clinical Immunology, 3Department of Periodontology, Charité-Universitätsmedizin, Berlin, Germany; 4Department of Oral Surgery, The School of Dentistry, University of Birmingham, Birmingham, UK *These authors contributed equally tothis work Abstract: A new strategy to improve osseointegration of implants is to stimulate adhesion of bone cells, bone matrix formation, and mineralization at the implant surface by modifying surface coating on the nanoscale level. Plant-derived pectins have been proposed as potential candidates for surface nanocoating of orthopedic and dental titanium implants due to 1)their osteogenic stimulation of osteoblasts to mineralize and 2) their ability to control pectin structural changes. The aim of this study was to evaluate in vitro the impact of the nanoscale plant-derived pectin Rhamnogalacturonan-I (RG-I) from potato on the osteogenic response of murine osteoblasts. RG-I from potato pulps was isolated, structurally modified, or left unmodified. Tissue culture plates were either coated with modified RG-I or unmodified RG-I or – as a control – left uncoated. The effect of nanocoating on mice osteoblast-like cells MC3T3-E1 and primary murine osteoblast with regard to proliferation, osteogenic response in terms of mineralization, and gene expression of Runt-related transcription factor 2 (Runx2), alkaline phosphate (Alpl), osteocalcin (Bglap), α-1 type I collagen (Col1a1), and receptor activator of NF-κB ligand (Rankl) were analyzed after 3, 7, 14, and 21 days, respectively. Nanocoating with pectin RG-Is increased proliferation and mineralization of MC3T3-E1 and primary osteoblast as compared to osteoblasts cultured without nanocoating. Moreover, osteogenic transcriptional response of osteoblasts was induced by nanocoating in terms of gene induction of Runx2, Alpl, Bglap, and Col1a1 in a time-dependent manner – of note – to the highest extent under the PA-coating condition. In contrast, Rankl expression was initially reduced by nanocoating in MC3T3-E1 or remained unaltered in primary osteoblast as compared to the uncoated controls. Our results showed that nanocoating of implants with modified RG-I beneficially 1) supports osteogenesis, 2) has the capacity to improve osseointegration of implants, and is therefore 3) a potential candidate for nanocoating of bone implants. Keywords: nanocoatings, osseointegration, osteoblasts, mineralization, Rhamnogalacturonan-I

The aim of this study was to analyze the occurrence of sulfonamide resistance genes (sul1–3) and other genetic elements as antiseptic resistance gene (qacEΔ1) and class 1 and class 2 integrons (int1–2) in the upper layer of substrate and in the effluent of microcosm constructed wetlands (CWs) treating artificial wastewater containing diclofenac and sulfamethoxazole (SMX), which is a sulfonamide antibiotic. The bacteria in the substrate and in the effluents were equipped with the sul1–2, int1, and qacEΔ1 resistance determinants, which were introduced into the CW system during inoculation with activated sludge and with the soil attached to the rhizosphere of potted seedlings of Phalaris arundinacea ‘Picta’ roots (int1). By comparing the occurrence of the resistance determinants in the upper substrate layer and the effluent, it can be stated that they neither were lost nor emerged along the flow path. The implications of the presence of antibiotic resistance genes in the effluent may entail a risk of antibiotic resistance being spread in the receiving environment. Additionally, transformation products of SMX were determined. According to the obtained results, four (potential) SMX transformation products were identified. Two major metabolites of SMX, 2,3,5-trihydroxy-SMX and 3,5-dihydroxy-SMX, indicated that SMX may be partly oxidized during the treatment. The remaining two SMX transformation products (hydroxy-glutathionyl-SMX and glutathionyl-SMX) are conjugates with glutathione, which suggests the ability of CW bacterial community to degrade SMX and resist antimicrobial stress. Electronic supplementary material The online version of this article (doi:10.1007/s11356-017-9079-1) contains supplementary material, which is available to authorized users.

This study investigated the quantity and distribution of extracellular polymeric substances (EPS) in aerobic granules. Results showed that EPS play an important role in the formation and stabilisation of granules. The content of EPS significantly increases during the first weeks of biogranulation. An analysis of EPS in the granules revealed that the protein level was 5 times higher than in polysaccharides. The increase of protein content correlated with the growth of cell hydrophobicity (r2 = 0.95). EPS and hydrophobicity are important factors in cell adhesion and formation of granules. The aim of this work was also to determine the distribution of EPS in the granule structure. In situ EPS staining showed that EPS are located mostly in the center of granules and in the subsurface layer. The major components of the EPE matrix are proteins, nucleic acids and β-polysaccharides. These observations confirm the chemical extraction data and indicate that granule formation and stability are dependent on protein content.