Treatment of micropollutants in wastewater: Balancing effectiveness, costs and implications.

In this contribution, we analyse scenarios of advanced wastewater treatment for the removal of micropollutants. By this we refer to current mainstream, broad spectrum processes including ozonation and sorption onto activated carbon. We argue that advanced treatment requires properly implemented tertiary (nutrient removal) treatment in order to be effective. We review the critical aspects of the main advanced treatment options, their advantages and disadvantages. We propose a quantification of the costs of implementing advanced treatment, as well as upgrading plants from secondary to tertiary treatment when needed, and we illustrate what drives the costs of advanced treatment for a set of standard configurations. We propose a cost function to represent the total costs (investment, operation and maintenance) of advanced treatment. We quantify the implications of advanced treatment in terms of greenhouse gas emissions. Based on the indicators of total toxic discharge, toxicity at the discharge points and toxicity across the stream network discussed in Pistocchi et al. (2022), we compare costs and effectiveness of different scenarios of advanced treatment. In principle the total toxic load and toxicity at the points of discharge could be reduced by about 75 % if advanced treatment processes were implemented virtually at all wastewater treatment plants, but this would entail costs of about 4 billion euro/year for the European Union as a whole. We consider a "compromise" scenario where advanced treatment is required at plants of 100 thousand population equivalents (PE) or larger, or at plants between 10 and 100 thousand PE if the dilution ratio at the discharge point is 10 or less. Under this scenario, the length of the stream network exposed to high toxicity would not increase significantly compared to the previous scenario, and the other indicators would not deteriorate significantly, while the costs would remain at about 1.5 billion Euro/year. Arguably, costs could be further reduced, without a worsening of water quality, if we replace a local risk assessment to generic criteria of plant capacity and dilution in order to determine if a WWTP requires advanced treatment.

Large-scale determination of micropollutant elimination from municipal wastewater by passive sampling gives new insights in governing parameters and degradation patterns.

A simple balancing method using passive samplers over a week's period has been developed and tested successfully to determine elimination rates of 22 common micropollutants of household and industrial sources in 18 full-scale wastewater treatment plants of different design and performance. Independent reactor tests to delineate elimination rates with native sludge of the treatment plants correlated very well with the full-scale elimination rate determinations. As opposed to common assumptions, this large dataset indicated that shorter sludge retention times - read: higher active biomass - showed higher micropollutant elimination rates in many cases. Multivariate statistical analysis of the elimination rates over the 18 treatment plants was able to group compounds according to common degradation pathways and showed that sensitivity to SRT drove the grouping. The dataset also allowed to determine population equivalent normalized loads of the investigated micropollutants. The application of WWTP balancing with passive sampling makes it relatively easy to gather elimination rates and inlet loads on a much broader basis than before and gives orientation for more in-depth analysis of degradation pathways.

New developed urological protocols for the Uro Dyna-CT reduce radiation exposure of endourological patients below the levels of the low dose standard CT scans.

PURPOSE: Cross-sectional imaging by computed tomography (CT) is associated with higher radiation dose compared to plain X-ray. The Uro Dyna-CT provides CT-like images in the endourological operating room. Our aim was to reduce the radiation exposure of endourological patients with the Uro Dyna-CT and optimize the cross-sectional image quality. MATERIALS AND METHODS: For the hard contrast protocol, two artificial stones were placed in a Rando-Alderson phantom's left kidney region. Relevant parameters of the standard abdomen protocol were changed. After each modification, two urologists subjectively evaluated the image quality. We developed two customized protocols (standard, low-dose) for hard contrast imaging. To optimize the examination protocol for soft tissue imaging a standardized cone beam phantom was used. Parameters of the preset high-resolution protocol were changed to develop a protocol with similar objective image quality but lower radiation dose. To evaluate the effective radiation dose we embedded 129 thermoluminescence dosimeters in the kidney and ureter region of the Rando-Alderson phantom and performed each protocol five times (stone, soft tissue) and ten times (low-dose protocol). Mean effective dose values per 3D-examination were calculated. RESULTS: We detected a dose area product (DAP) 776.2 (standard) and 163.5 µGym(2) (low-dose) for the stone protocols with an effective dose of 1.96 and 0.33 mSv, respectively. The soft tissue protocol produced a DAP of 5,070 µGym(2) and an effective dose of 7.76 mSv. CONCLUSION: Our newly developed examination protocols for the Uro Dyna-CT provide CT-like image quality during urological interventions with low radiation dose.

Effects of salinomycin on human bone marrow-derived mesenchymal stem cells in vitro.

Various hypotheses on the origin of cancer stem cells (CSCs) exist, including that CSCs develop from transformed human bone marrow mesenchymal stem cells (hBMSC). Since the polyether antibiotic salinomycin selectively kills CSCs, the present study aims to elucidate the effects of salinomycin on normal hBMSC. The immunophenotype of hBMSC after salinomycin exposure was observed by flow cytometry. The multi-differentiation capacity of hBMSC was evaluated by Oil Red O and van Kossa staining. Cytotoxic effects of salinomycin were monitored by the [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) assay. Furthermore, spheroid formation and migration capacity were assessed. There were no differences in the immunophenotype and multi-differentiation capacity of hBMSC induced by salinomycin treatment. Cytotoxic effects were observed at concentrations of 30 µM and above. Neither the migration capability nor the ability to form spheroids was affected. Essential functional properties of hBMSC were unaffected by salinomycin. However, dose-dependent cytotoxicity effects could be observed. Overall, low dose salinomycin showed no negative effects on hBMSC. Since mesenchymal stem cells from various sources respond differently, further in vitro studies are needed to clarify the effect of salinomycin on tissue-specific stem cells.

Short-term severe thyroid hormone deficiency does not influence sleep parameters.

PURPOSE: The influence of short-term severe thyroid hormone deficiency on sleep is currently still unknown. Several studies have demonstrated an effect of long-term hypothyroidism on sleep disorders due to anatomical changes of the pharynx or body mass. The aim of this preliminary study, however, is to evaluate the changes in sleep patterns of patients with short-term hypothyroidism to elucidate the isolated effect of thyroid hormone withdrawal before anatomical changes can potentially occur. METHODS: Ten patients with differentiated thyroid carcinoma were enrolled in this study. Two patients discontinued the study and one patient was finally excluded due to obesity, so that the datasets of seven patients were available for study analysis. During the course of carcinoma treatment, each patient had previously undergone total thyroidectomy and I-131 remnant ablation. Polysomnographic measurements were performed twice: (1) over the course of two consecutive nights during severe thyroid hormone deficiency after levothyroxine withdrawal and prior to further diagnostics and therapy and (2) during euthyroidism after substitution with levothyroxine. RESULTS: Comparison of the Epworth Sleepiness Scale during hypo- and euthyroidism for each patient revealed no statistically significant difference. Furthermore, the comparison of polysomnographic parameters like (1) apnea-hypopnea index, (2) the duration of various sleep stages, (3) duration of rapid eye movement sleep, (4) latency until rapid eye movement sleep, (5) total sleep time, (6) periodic leg movements, and (7) arousal index showed no statistically significant differences between the hypothyroid or euthyroid state. CONCLUSIONS: We conclude that, in this preliminary experimental setting, short-term severe thyroid hormone deficiency per se does not cause sleep disturbances and a feeling of fatigue as described in other studies may be due to changes in perception or brain metabolism during hypothyroidism.

From laparoscopic assisted radical vaginal hysterectomy to vaginal assisted laparoscopic radical hysterectomy.

Radical hysterectomy with pelvic lymphadenectomy is the standard surgical treatment for patients with early stage cervical cancer. The majority of radical hysterectomies are performed with the open technique. However, laparoscopic, combined laparoscopic and vaginal, and robotic-assisted approaches may also be used. Compared with the abdominal radical hysterectomy (ARH), laparoscopic techniques are associated with less blood loss, shorter hospital stay, better cosmesis, and faster recovery. A further breakthrough in laparoscopic technique can only be made if safety and oncological clearance are comparable with ARH. We describe the technique and results of laparoscopic assisted radical vaginal hysterectomy and the transition to vaginal assisted laparoscopic radical hysterectomy.

Ex vivo toxicity of nitrogen dioxide in human nasal epithelium at the WHO defined 1-h limit value.

Current pollution limits indicating potential harm to human health caused by nitrogen dioxide have prompted a variety of studies on the cytotoxicity and genotoxicity of nitrogen dioxide (NO2) in vitro. The present study focuses on toxic effects of NO2 at the WHO defined 1-h limit value of 200 µg NO2/m(3) air, equivalent to 0.1 ppm NO2. Nasal epithelial mucosa cells of 10 patients were cultured as an air-liquid interface and exposed to 0.1 ppm NO2 for 0.5 h, 1 h, 2 h and 3 h and synthetic air as negative control. After exposure, analysis of genotoxicity was performed by the alkaline single cell microgel electrophoresis (comet) assay and by the micronucleus test. Depression of proliferation and cytotoxic effects were checked by the micronucleus assay and the trypan blue exclusion assay. The experiments demonstrated significant DNA fragmentation even at the shortest exposure duration of half an hour in the comet assay. The amount of DNA fragmentation significantly increased with extended NO2 exposure durations. The amount of DNA fragmentation increased with extended exposure durations to synthetic air at a significantly lower level as compared to NO2 exposure. Micronucleus inductions were seen only at the longest exposure duration of 3h. There were no changes in proliferation seen in the micronucleus assay under any experimental setup. Moreover, no signs of necrosis, apoptosis or changes in viability were detected. Data demonstrate genotoxicity of NO2 at concentrations found in the urban atmosphere during short exposure durations. DNA alterations in the micronucleus assay at an exposure time of 3h indicate a significant DNA alteration possibly being hazardous to humans.

Relationship between HbA1c on target, risk of silent hypoglycemia and glycemic variability in patients with type 2 diabetes mellitus.

OBJECTIVE: We aimed to compare time spent at low glucose level (silent hypoglycemia, glucose <3.0 mmol/l) and glycemic variability in patients who reached HbA1c <7.0% with those who did not. RESEARCH DESIGN AND METHODS: In 108 type 2 diabetic patients the interstitial glucose concentration was measured with CGMS (Continuous Glucose Monitoring System) over 72 h. Patients were divided in group 1 with an HbA1c <7.0% (n=63) and group 2 with an HbA1c≥7.0% (n=45). RESULTS: 24% in group 1 experienced silent hypoglycemia vs. 11% in group 2 (n. s.), duration of silent hypoglycemia over 48 h was 27±71 min vs. 7±36 min (n. s.). This was also valid for the subgroups treated with insulin. Patients in group 2 had a significantly higher standard deviation of average glucose (2.3±0.8 vs. 1.3±0.6; p<0.001) and MAGE (mean amplitude of glycemic excursions) (4.8±2.1 vs. 2.6±1.1; p<0.001). CONCLUSION: Silent hypoglycemia tended to occur more often and to last longer in patients with HbA1c <7%. However, patients with HbA1c >7% had a higher glycemic variability. HbA1c >7% wasn't a reliable indicator of lower risk of hypoglycemia.

Alcohol consumption and other psycho-social conditions as important factors in the development of diabetic foot ulcers.

AIMS: To characterize bio-psycho-social factors, particularly mental disorders and self-harm behaviour, associated with the development of diabetic foot ulcers. METHODS: Two groups of diabetic patients with and without foot ulcers (n=47 in each group) with similar sex, age and diabetes duration were assessed for mental disorders using the Composite International Diagnostic Interview. Self-harm behaviour, quality of life, depressive symptoms and self-compassion were rated using different standard questionnaires. RESULTS: Patients from the ulcer group visited their practitioners and/or psychotherapists less frequently in the last 12 months than patients in the control group 0 vs. 13%; P=0.026). The ulcer group patients had a history of increased alcohol consumption (43 vs. 19%; P=0.025), lower levels of education (8 vs. 10 grades; P=0.014) and income (1190 vs. 1535 €/month; P=0.039). Additionally, they were less likely to be diagnosed with anxiety disorders (11 vs. 32%; P=0.022). No significant differences in glycated haemoglobin, body mass index, smoking and direct self-harm behaviour were identified. CONCLUSIONS: Patients with foot ulcers tend to exhibit lower health-conscious behaviour, particularly higher lifetime alcohol consumption, lower utilization of medical services and less general anxiety. Practitioners should be aware of these behaviours, since early detection of diabetes patients at psycho-social risk and consecutive psychological intervention may be an effective preventive strategy in avoiding the development of foot ulcers.

Effect of targeting normal fasting glucose levels with basal insulin glargine on glycaemic variability and risk of hypoglycaemia: a randomized, controlled study in patients with early Type 2 diabetes.

AIMS: The purpose of this sub-study of the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial was to determine efficacy and safety of targeting normal fasting plasma glucose (FPG) levels in patients with early Type 2 diabetes treated with insulin glargine in comparison with standard care. METHODS: Participants were randomly allocated to insulin or standard care. Insulin was titrated to reach FPG

Aspects of nitrogen dioxide toxicity in environmental urban concentrations in human nasal epithelium.

Cytotoxicity and genotoxicity of nitrogen dioxide (NO(2)) as part of urban exhaust pollution are widely discussed as potential hazards to human health. This study focuses on toxic effects of NO(2) in realistic environmental concentrations with respect to the current limit values in a human target tissue of volatile xenobiotics, the epithelium of the upper aerodigestive tract. Nasal epithelial cells of 10 patients were cultured as an air-liquid interface and exposed to 0.01 ppm NO(2), 0.1 ppm NO(2), 1 ppm NO(2), 10 ppm NO(2) and synthetic air for half an hour. After exposure, genotoxicity was evaluated by the alkaline single-cell microgel electrophoresis (Comet) assay and by induction of micronuclei in the micronucleus test. Depression of proliferation and cytotoxic effects were determined using the micronucleus assay and trypan blue exclusion assay, respectively. The experiments revealed genotoxic effects by DNA fragmentation starting at 0.01 ppm NO(2) in the Comet assay, but no micronucleus inductions, no changes in proliferation, no signs of necrosis or apoptosis in the micronucleus assay, nor did the trypan blue exclusion assay show any changes in viability. The present data reveal a possible genotoxicity of NO(2) in urban concentrations in a screening test. However, permanent DNA damage as indicated by the induction of micronuclei was not observed. Further research should elucidate the effects of prolonged exposure.

Effect of acarbose on postmeal mononuclear blood cell response in patients with early type 2 diabetes: the AI(I)DA study.

So far little is known about how the antidiabetic drugs acting at the level of gastrointestinal mucosa may affect immune and cellular response to food intake. The following study investigated the association between acarbose treatment and postprandial metabolism, immune- and inflammatory activity in patients with early type 2 diabetes: The Acarbose action on low grade Inflammation and Immune response in type 2 Diabetes on Atherosclerosis risk (AIIDA) study. Middle-aged patients (n=87) with early type 2 diabetes (2 h-plasma-glucose >or=11.1 mmol/l and/or HbA1c >or=6.5%) and sub-clinical inflammation (leucocytes >or=6.2 GPt/l and/or hsCRP >or=1.0 mg/l) underwent a mixed meal load (527 kcal). Metabolic parameters and markers of subclinical inflammation were measured at fasting (0'), 2 h-postprandial (2-hpp) and 4-hpp before and after 20 weeks of treatment with acarbose or placebo. Leukocytes and lymphocytes excursion after 20 weeks of treatment was significantly reduced with acarbose 4 h after testmeal [GPt/l] (7.5 vs. 7; p<0.05; and 2.29 vs. 2.14; p<0.05, respectively). Acarbose had only marginal effects on pp glucose, FFA, triglycerides, and insulin excursion. Biomarkers of inflammation (hsCRP, MBL, and PAI1) were not affected by acarbose. Multivariate analysis reveals only baseline leukocytes and of acarbose as independent determinant of 4-h leucocytes excursion. Postprandial metabolic and inflammatory parameters were strongly interrelated. These results suggest pleiotropic effects of acarbose, which may contribute to its vasoprotective potentials.

Effects of the alpha glucosidase inhibitor acarbose on endothelial function after a mixed meal in newly diagnosed type 2 diabetes.

Endothelial dysfunction (ED) has been suggested as a possible causal link between postprandial hyperglycemia and cardiovascular events in patients with type 2 diabetes. Recent trials demonstrated a reduction of cardiovascular events by treatment with alpha-glucosidase inhibitor acarbose - a drug which mainly reduces postprandial glucose excursions. We were interested to know whether patients with newly diagnosed type 2 diabetes showed postprandial ED and if so whether acarbose was able to improve this condition. Forearm blood flow (FBF) measurements for assessment of ED were performed in the fasting and postprandial state in 20 newly diagnosed type 2 diabetic patients and 10 healthy control subjects. After baseline examination, patients were randomly assigned to a 20-week treatment of acarbose 100 mg t.i.d or matching placebo, thereafter FBF measurements were repeated. FBF of patients in the fasting state was significantly impaired compared to healthy control subjects (max. FBF 5.3+/-0.7 vs. 8.0+/-0.9 ml/100 ml, p<0.02) and did not change in the postprandial state (max. FBF 5.6+/-0.7 ml/100 ml). In contrast, healthy controls showed a significant improvement of FBF in the postprandial state (11.5+/-1.2 ml/100 ml), which is compatible with postprandial ED in the group of patients. Twenty weeks of acarbose treatment did not affect either fasting or postprandial FBF in patients. Early type 2 diabetes is a state of both fasting and postprandial ED, which is not sensitive to acarbose treatment. Protective cardiovascular effects of acarbose might involve other mechanisms.

Comparison of the prevalence of the metabolic syndrome by WHO, AHA/NHLBI, and IDF definitions in a German population with type 2 diabetes: the Diabetes in Germany (DIG) Study.

UNLABELLED: This study investigated the prevalence of the metabolic syndrome (MetS) in a German population with type 2 diabetes (T2DM) using the three definitions for MetS according to WHO 1999, AHA/NHLBI 2005, and IDF 2005 criteria. Four-thousand and twenty participants as a cross section of daily practice of diabetes care in Germany (238 unselected sites) were included in the Diabetes in Germany (DIG) study. INCLUSION CRITERIA: T2DM and age between 35-80 years. EXCLUSION CRITERIA: major cardiovascular event < 3 months before entry, NYHA-IV, macroproteinuria, and cancer < 5 years before entry. The components of MetS were measured following a standard protocol for anthropometric and laboratory control. The average diabetes duration was 8.4 years and HbA (1C) 7.0%. The prevalence of MetS by WHO criteria was 26.1%, by AHA/NHLBI 79.3%, and by IDF 82.6%. The degree of agreement (kappa statistic) was kappa = 0.69 between AHA/NHLBI and IDF definitions, but only 0.12 for WHO VS. IDF, and 0.17 for WHO vs. AHA/NHLBI. The frequency of central obesity by WHO was 50.9%, by AHA/NHLBI 72.9%, and by IDF 92.0% and for hypertension 29.3%, 92.6%, and 92.6%, respectively. However, the frequencies of lipid components by the three definitions were in the same range (57.8%, 59.5%, 59.5%). In this representative German sample of patients with type 2 diabetes, the prevalence of MetS was very highly independent of using the IDF or AHA/NHLBI definition. Females were significantly more affected than males. The distinctly lower prevalence delineated from WHO criteria is due to low frequency of central obesity and hypertension as consequence of higher cutoff limits for these components used in the WHO definition.

[Limb salvage for the diabetic foot - disease management program]. / Extremitätenerhalt für den diabetischen Fuss - Disease-Management-Programm.

OBJECTIVE: Lower-extremity amputation (LEA) is a common complication among patients with diabetes. This study tests the effects of a structured disease management program for the diabetic foot (DF) aiming to reduce the number of LEA. DESIGN, METHODS: In a prospective study design we investigate patients with DF in a system of outpatient treatment, acute in-patient care and rehabilitative treatment. Subjects were recruited since January 1(st), 2000, with the latest admission being December 31, 2004. All study participants undergo a five-year follow-up observation period. The University of Texas Wound Classification System (UT) of foot ulcers serves as basis of the documentation and analysis. We evaluated numbers of LEA, rates of ulcer healing and underlying forms of peripheral vascular disease. RESULTS: We report the results of the first patient group completing the two-year follow-up examination. In 2000, 102 subjects with new foot ulcers were consecutively included into the study. 68.6% were men, the mean age of the study population was 68.1 +/- 11.4 years and the mean diabetes duration was 19.4 +/- 10.3 years. After two years, 68 patients can still be examined. Altogether, 22 patients (21.6%) died, and 12 (11.8%) dropped out for various reasons. At the point of discharge from the clinics 35.3% of the ulcers had healed and another 44.1% were in UT grade 1. After two years, a complete healing could still be determined with 51 patients (50.0% of the cohort of the original 102 patients, or 75.0% of the subjects reaching the two-year follow-up). 10 subjects (9.8% or 14.5%) were in the UT grade 1. Eight diabetics underwent major amputation (MA) during the two-year examination period (amputation rate 7.8%). CONCLUSIONS: The primary objective of the study, a significant reduction of MA with DF patients, has been achieved. The ulcer healing rates are comparable to the reports of leading centers.

Should human chondrocytes fly? The impact of electromagnetic irradiation on chondrocyte viability and implications for their use in tissue engineering.

A significant logistic factor as to the successful clinical application of the autologous tissue engineering concept is efficient transportation: the donor cells need to be delivered to tissue processing facilities which in most cases requires air transportation. This study was designed to evaluate how human chondrocytes react to X-ray exposure. Primary cell cultures were established, cultured, incubated and exposed to different doses and time periods of radiation. Subsequently, quantitative cell proliferation assays were done and qualitative evaluation of cellular protein production were performed. Our results show that after irradiation of chondrocytes with different doses, no significant differences in terms of cellular viability occurred compared with the control group. These results were obtained when chondrocytes were exposed to luggage transillumination doses as well as exposure to clinically used radiation doses. Any damage affecting cell growth or quality was not observed in our study. However, information about damage of cellular DNA remains incomplete.

Relationship between diurnal glucose levels and HbA1c in type 2 diabetes.

AIMS AND METHODS: Study results still conflict on the contribution of diurnal blood glucose (BG) values to Hb (A1c) in type 2 diabetes. We investigated the relationship between Hb (A1c) and diurnal BG obtained under standardized conditions - before breakfast, two hours after breakfast, before lunch, two hours after lunch, before dinner, two hours after dinner, and at 10 PM, 12 midnight and 3 AM in 68 type 2 diabetic patients before and after optimizing glycemic control. The areas under the curve above fasting BG (AUC1) and above 5.6 mmol/l (AUC2) were calculated for further evaluation. Hb (A1c) was measured at baseline and after a mean of 89 (74 to 108) days. RESULTS: Each BG value at baseline and after treatment optimization significantly correlated with baseline and follow-up Hb (A1c), respectively. The pre-breakfast BG showed the closest correlation with Hb (A1c). The relative contribution of postprandial BG concentrations (AUC1) to overall hyperglycemia (AUC2) decreased with poorer glycemic control. However, treatment optimization mainly resulted in improved blood glucose values in patients with the poorest glycemic control at baseline. Multiple regression analysis demonstrated that fasting (AUC2-AUC1) and postprandial (AUC1) hyperglycemia independently determined Hb (A1c) or the change in Hb (A1c) after treatment optimization. CONCLUSIONS: Our findings indicate that intensive blood glucose monitoring during fasting and postprandial states is important for glycemic control, and is therefore an essential part of good clinical practice.