Performance of retention soil filters for the reduction of hygienically-relevant microorganisms in combined sewage overflow and treated wastewater.

Environmental quality standards for surface waters have been significantly expanded through recent amendments to German regulations. Limit values are only established for applicable regulations if the water is indicated for certain uses, e.g. abstraction of irrigation water. Nevertheless, surface water bodies are often used for hygiene-sensitive purposes. In the course of climate change, stronger precipitation events will occur, which may lead to more frequent loading and discharge of combined sewer overflow (CSO) into surface water bodies. Retention soil filters (RSFs) are attracting attention as an extensive treatment technology for CSO and additional wastewater treatment. This study examined large-scale RSFs for CSO treatment, as well as the effectiveness of RSFs as a fourth purification stage. An RSF test facility was established at a municipal wastewater treatment plant (WWTP), consisting three semi-technical RSFs that were fed exclusively with treated water from the WWTP. The reduction of microorganisms mostly occurred within the first centimeters of the RSFs. For most hygienic-microbiological parameters, a 1-2 log unit reduction could be detected in addition to the reduction within the WWTP. Antibiotic-resistant bacteria were reduced to the same extent. Investigation of the large-scale RSFs showed that a flow rate reduced by half corresponded to better reduction performances.

The Notch Pathway in Breast Cancer Progression.

OBJECTIVE: Notch signaling pathway is a vital parameter of the mammalian vascular system. In this review, the authors summarize the current knowledge about the impact of the Notch signaling pathway in breast cancer progression and the therapeutic role of Notch's inhibition. METHODS: The available literature in MEDLINE, PubMed, and Scopus, regarding the role of the Notch pathway in breast cancer progression was searched for related articles from about 1973 to 2017 including terms such as "Notch," "Breast Cancer," and "Angiogenesis." Results. Notch signaling controls the differentiation of breast epithelial cells during normal development. Studies confirm that the Notch pathway has a major participation in breast cancer progression through overexpression and/or abnormal genetic type expression of the notch receptors and ligands that determine angiogenesis. The cross-talk of Notch and estrogens, the effect of Notch in breast cancer stem cells formation, and the dependable Notch overexpression during breast tumorigenesis have been studied enough and undoubtedly linked to breast cancer development. The already applied therapeutic inhibition of Notch for breast cancer can drastically change the course of the disease. CONCLUSION: Current data prove that Notch pathway has a major participation and multiple roles during breast tumor progression. Inhibition of Notch receptors and ligands provides innovative therapeutic results and could become the therapy of choice in the next few years, even though further research is needed to reach safe conclusions.

[Identification of Systemic Contaminations with Legionella Spec. in Drinking Water Plumbing Systems: Sampling Strategies and Corresponding Parameters]. / Identifikation systemweiter Kontaminationen mit Legionella spec. in Trinkwasser-Installationen: Untersuchungsstrategien und korrespondierende Parameter.

After the amendment of the Drinking Water Ordinance in 2011, the requirements for the hygienic-microbiological monitoring of drinking water installations have increased significantly. In the BMBF-funded project "Biofilm Management" (2010-2014), we examined the extent to which established sampling strategies in practice can uncover drinking water plumbing systems systemically colonized with Legionella. Moreover, we investigated additional parameters that might be suitable for detecting systemic contaminations. We subjected the drinking water plumbing systems of 8 buildings with known microbial contamination (Legionella) to an intensive hygienic-microbiological sampling with high spatial and temporal resolution. A total of 626 drinking hot water samples were analyzed with classical culture-based methods. In addition, comprehensive hygienic observations were conducted in each building and qualitative interviews with operators and users were applied. Collected tap-specific parameters were quantitatively analyzed by means of sensitivity and accuracy calculations. The systemic presence of Legionella in drinking water plumbing systems has a high spatial and temporal variability. Established sampling strategies were only partially suitable to detect long-term Legionella contaminations in practice. In particular, the sampling of hot water at the calorifier and circulation re-entrance showed little significance in terms of contamination events. To detect the systemic presence of Legionella,the parameters stagnation (qualitatively assessed) and temperature (compliance with the 5K-rule) showed better results.

Combination gene therapy targeting on interleukin-1ß and RANKL for wear debris-induced aseptic loosening.

This study investigated the efficacy of a combination gene therapy to repress interleukin-1 (IL-1) and receptor activator of nuclear factor NF-kappa B ligand (RANKL) for the treatment of particulate debris-induced aseptic loosening, and tried to explore the molecular mechanism of the exogenous gene modifications on osteoclastogenesis. RAW cells activated by titanium particles were transduced with DFG-IL-1Ra (retroviral vector encoding IL-1 receptor antagonist) and AAV-OPG (adeno-associated viral vectors-osteoprotegerin) individually or in combination for 4 weeks. Pro-inflammatory cytokines in culture media were determined by enzyme-linked immunosorbent assay, and gene expressions of RANK, IL-1ß, c-Fos, TRAF6, JNK1 and CPK were examined using real-time PCR. An established knee-implant-failure mouse model was employed to evaluate the efficacy of the in vivo double-gene therapy. The surgical implantation of a titanium alloy pin into the proximal tibia was followed by monthly challenge with titanium debris. Peri-implant gene transfers of IL-1Ra and OPG (respectively or in combination) were given 3 weeks after surgery. The combination of OPG and IL-1Ra gene transfer exhibited strong synergetic effects in blockage of inflammation and osteoclastogenesis at 8 weeks after gene modification. The combination therapy reversed peri-implant bone resorption and restored implant stability when compared with either single gene transduction. Real-time PCR data indicated that the action of IL-1Ra gene therapy may be mediated via the JNK1 pathway, while the reduction of osteoclastogenesis by OPG gene modification may be regulated by c-Fos expression. In addition, both gene modifications resulted in significant diminishment of TRAF6 expression.

Constructed wetlands for combined sewer overflow treatment: A state-of-the-art review.

Combined sewer overflows (CSOs) are a major source of surface water pollution and degradation. This is particularly visible where sewage collection with combined sewer and centralized treatment are well established, such as in Europe and North America: an overwhelming number of surface water bodies are in insufficient status of ecology, hydrology and physico-chemical parameters. Therefore, several countries have started implementing constructed wetlands (CWs) as mainstream on-spot treatment. This paper summarizes the main design approaches that can be adopted. We identified eight different schemes for the implementation of CSO-CWs, based on our international experience and documented by a literature analysis. The performance review includes conventional water quality parameters, as well as pathogen and emergent contaminant removal. Furthermore, modelling tools for advanced design and for understanding a wide applicability of these green infrastructures are presented. This paper also provides a review on other side benefits offered by the adoption of Nature-Based Solutions for CSO treatment, such as ecosystem services, and the most common issues related to their operation and maintenance. Our analysis has produced a list of key factors for design and operation, all derived from full-scale installations in operation up to more than ten years.

Association between antibiotic residues, antibiotic resistant bacteria and antibiotic resistance genes in anthropogenic wastewater - An evaluation of clinical influences.

The high use of antibiotics in human and veterinary medicine has led to a wide spread of antibiotics and antimicrobial resistance into the environment. In recent years, various studies have shown that antibiotic residues, resistant bacteria and resistance genes, occur in aquatic environments and that clinical wastewater seems to be a hot spot for the environmental spread of antibiotic resistance. Here a representative statistical analysis of various sampling points is presented, containing different proportions of clinically influenced wastewater. The statistical analysis contains the calculation of the odds ratios for any combination of antibiotics with resistant bacteria or resistance genes, respectively. The results were screened for an increased probability of detecting resistant bacteria, or resistance genes, with the simultaneous presence of antibiotic residues. Positive associated sets were then compared, with regards to the detected median concentration, at the investigated sampling points. All results show that the sampling points with the highest proportion of clinical wastewater always form a distinct cluster concerning resistance. The results shown in this study lead to the assumption that ciprofloxacin is a good indicator of the presence of multidrug resistant P. aeruginosa and extended spectrum ß-lactamase (ESBL)-producing Klebsiella spec., Enterobacter spec. and Citrobacter spec., as it positively relates with both parameters. Furthermore, a precise relationship between carbapenemase genes and meropenem, regarding the respective sampling sites, could be obtained. These results highlight the role of clinical wastewater for the dissemination and development of multidrug resistance.

Primary Malignant Melanoma of the Cervix: A Case Report and a Review of the Literature.

BACKGROUND: Gynecologic melanomas are extremely rare malignancies, and primary malignant melanoma of the cervix (PMMC) is the rarest among them all, with less than 100 cases reported so far. Although some conditions have been correlated with the pathogenesis of this entity, no specific risk factor has been yet identified, with vaginal bleeding being the most common symptoms. The diagnosis is based on physical examination with speculum assessment and cytologic and histopathologic findings accompanied with immunohistochemical staining of lesion's biopsies. Case Presentation. We report a case of PMMC in a 34-year-old para-2 patient, among the youngest cases of PMMC reported, that presented to our clinic for routine examination. Gynecologic examination demonstrated a dark, heavily fully pigmented cervical growth completely covering the entire external cervical os. Biopsy obtained and showed malignant melanoma. She underwent radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The pathological diagnosis was FIGO stage IB1 PMMC. Despite 2 courses of anti-PD-1 antibody (Nivolumab) treatment, the patient passed away 13 months after diagnosis (12 months after surgery). CONCLUSIONS: Early diagnosis and subsequently early treatment are of high importance regarding patients' prognosis and survival. No standardized protocols or treatment guidelines specific for this rare cancer have been issued; thus, clinicians are called to assess each case individually. Current treatment options are based on surgical excision mostly with radical hysterectomy, but in advanced or recurrent state of the disease, other treatment modalities, such as chemotherapy, radiotherapy, and immunotherapy, can be employed. Prognosis for these patients is very poor, and survival rate remains extremely low, with the median OS reported being less than 2 years. Reporting and publishing of such cases are both of paramount importance for the better understanding of this uncommon cervical malignancy, and further biological and clinical investigations are required for more suitable and effective therapies to be determined. A new staging system, specific to PMMC, could be of great use for the better correlation of the disease's stage and prognosis of these patients.

Combined elemental analysis of ancient glass beads by means of ion beam, portable XRF, and EPMA techniques.

Ion beam analysis (IBA)- and X-ray fluorescence (XRF)-based techniques have been well adopted in cultural-heritage-related analytical studies covering a wide range of diagnostic role, i.e., from screening purposes up to full quantitative characterization. In this work, a systematic research was carried out towards the identification and evaluation of the advantages and the limitations of laboratory-based (IBA, electron probe microanalyzer) and portable (milli-XRF and micro-XRF) techniques. The study focused on the analysis of an Archaic glass bead collection recently excavated from the city of Thebes (mainland, Greece), in order to suggest an optimized and synergistic analytical methodology for similar studies and to assess the reliability of the quantification procedure of analyses conducted in particular by portable XRF spectrometers. All the employed analytical techniques and methodologies proved efficient to provide in a consistent way characterization of the glass bead composition, with analytical range and sensitivity depending on the particular technique. The obtained compositional data suggest a solid basis for the understanding of the main technological features related to the raw major and minor materials utilized for the manufacture of the Thebian ancient glass bead collection.

Size matters: Grey matter brain reserve predicts executive functioning in the elderly.

Preserved executive functioning (EF) is crucial for daily functioning in the elderly and it appears to predict dementia development. We sought to clarify the role of atrophy-corrected cortical grey matter (GM) volume as a potential brain reserve (BR) marker for EF in the elderly. In total, 206 pre-surgical subjects (72.50 ±â€¯4.95 years; mean MMSE score 28.50) were investigated. EF was primarily assessed using the Trail Making Test B (TMT B). Global/ lobar GM volumes were acquired with T1 MP-RAGE. Adjusting for key covariates including a brain atrophy index (i.e. brain parenchymal fraction), multiple linear regression analysis was used to study associations of GM volumes and TMT B. All GM volumes - most notably of global GM - were significantly associated with TMT B independently of GM atrophy (ß = -0.201 to -0.275, p = 0.001-0.012). Using atrophy-corrected GM volume as an estimate of maximal GM size in youth may serve as a BR predictor for cognitive decline in future studies investigating BR in the elderly.

Personalized risk prediction of postoperative cognitive impairment - rationale for the EU-funded BioCog project.

Postoperative cognitive impairment is among the most common medical complications associated with surgical interventions - particularly in elderly patients. In our aging society, it is an urgent medical need to determine preoperative individual risk prediction to allow more accurate cost-benefit decisions prior to elective surgeries. So far, risk prediction is mainly based on clinical parameters. However, these parameters only give a rough estimate of the individual risk. At present, there are no molecular or neuroimaging biomarkers available to improve risk prediction and little is known about the etiology and pathophysiology of this clinical condition. In this short review, we summarize the current state of knowledge and briefly present the recently started BioCog project (Biomarker Development for Postoperative Cognitive Impairment in the Elderly), which is funded by the European Union. It is the goal of this research and development (R&D) project, which involves academic and industry partners throughout Europe, to deliver a multivariate algorithm based on clinical assessments as well as molecular and neuroimaging biomarkers to overcome the currently unsatisfying situation.

Effect of varying levels of fatty acids from palm oil on feed intake and milk production in Holstein cows.

To determine the optimum feeding level of fatty acids of palm oil (PALM; Energizer RP10; 86.6% palmitic acid) on milk production, lactating cows (n = 18) were randomly assigned to a treatment sequence in replicated 4 x 4 Latin squares. Animals were assigned to squares by parity (3 multiparous and 1 primiparous squares with primiparous in the incomplete square). The 4 diets were designed to provide 0, 500, 1,000, and 1,500 g of PALM per day. Cows were fed individually with feed intake measured daily. Each period lasted 16 d with milk production and composition determined the final 2 d. Milk production, milk composition and feed intake data were analyzed using the MIXED procedure of SAS. Milk yields were 30.9, 34.0, 34.2, and 34.2 kg/ d (SEM = 1.9) for the 0, 500, 1,000, and 1,500 g levels, respectively. Milk yield was increased by the addition of PALM; however, there were no differences among the levels of PALM. Milk fat percentage was also increased from 3.44% for 0 g to 3.95% (SEM = 0.17) across all levels of PALM but there were no differences among the PALM treatments. Dry matter intakes were 23.3, 26.4, 24.7, and 23.8 kg/d (SEM = 1.4) for the 0, 500, 1,000 and 1,500 g levels, respectively. The addition of PALM increased milk yield and milk fat percentage, and no adverse effects on dry matter intake were observed.

Equivalent dose (palaeodose) estimation in thermoluminescence dating using a single aliquot of polymineral fine grains.

A single aliquot protocol for the estimation of the natural dose in thermoluminescence dating (SATL) is presented that makes use of polymineral fine grains extracted from ceramic materials. The protocol is demonstrated using aliquots made from two Neolithic sherds and is compared with results from an additive dose polymineral technique. The results of both techniques are in close agreement and highlight the potential advantages of the new procedure, especially when sample availability is restricted, e.g. dating of small pottery fragments, or in cases of authenticity testing.

The tethered agonist approach to mapping ion channel proteins--toward a structural model for the agonist binding site of the nicotinic acetylcholine receptor.

BACKGROUND: The integral membrane proteins of neurons and other excitable cells are generally resistant to high resolution structural tools. Structure-function studies, especially those enhanced by the nonsense suppression methodology for unnatural amino acid incorporation, constitute one of the most powerful probes of ion channels and related structures. The nonsense suppression methodology can also be used to incorporate functional side chains designed to deliver novel structural probes to membrane proteins. In this vein, we sought to generalize a potentially powerful tool - the tethered agonist approach - for mapping the agonist binding site of ligand-gated ion channels. RESULTS: Using the in vivo nonsense suppression method for unnatural amino acid incorporation, a series of tethered quaternary ammonium derivatives of tyrosine have been incorporated into the nicotinic acetylcholine receptor. At three sites a constitutively active receptor results, but the pattern of activation as a function of chain length is different. At position alpha149, there is a clear preference for a three-carbon tether, while at position alpha93 tethers of 2-5 carbons are comparably effective. At position gamma55/delta57 all tethers except the shortest one can activate the receptor. Based on these and other data, a model for the receptor binding site can be developed by analogy to the acetylcholine esterase crystal structure. CONCLUSION: Through the use of nonsense suppression techniques, the tethered agonist approach has been made into a general tool for probing receptor structures. When applied to the nicotinic receptor, the method places new restrictions on developing models for the agonist binding site.

Luminescence quartz dating of lime mortars. A first research approach.

Lime mortars mixed with sand are well suited for connecting structural materials, like stones and bricks, due to the mechanical properties this material exhibits. Their extensive use in architectural and decorative works during the last 4000 years motivated the introduction of the 'Luminescence clock' for age determination of mortars. The same principles as for quartz optically stimulated luminescence (OSL) dating of sediments were applied for age estimation of a mortar fragment removed from a Byzantine church monument dated by archaeological means to 1050-1100 years ago (the first half of the 10th century). The OSL from the quartz was monitored under blue light stimulation and UV detection, using a single-aliquot-regenerative-dose protocol. The quartz-OSL dating of the mortar resulted in 870 +/- 230 a. TL polymineral fine grain dating was also performed on a brick fragment which was connected to the mortar, resulting in a TL age of 1095 +/- 190 a.

The hypolipidemic effect of onion (Allium cepa Linn) in sucrose fed rabbits.

Long term administration of sucrose significantly increased triglyceride levels in normal rabbits. Effects of an aqueous extract of onion on the sucrose fed rabbits have been investigated. Administration of onion extract significantly reduced serum, liver and aorta triglycerides and serum and liver proteins. On the other hand liver free amino acids have been significantly increased in the onion treated group as compared to the sucrose fed control. The effects of onion have been ascribed to its sulfur containing principles which oxidize thiol compounds either present free or combined in a protein and NADPH which are necessary for lipid synthesis.

Graft-versus-Host Disease after Living-Unrelated Kidney Transplantation.

Graft-versus-host disease (GVHD) is a rare complication after solid organ transplantation and consists of a reaction of donor derived immune cells directed against host tissues. The vast majority of cases reported in the literature involve liver, small intestine and pancreas transplantation. We report a case of GVHD in a 48-year-old man after living-unrelated kidney transplantation at another center. Six months postoperatively he developed a skin rash, anorexia, and diarrhea that resulted in malnutrition and a 90 pound weight loss. At this point he was transferred to our center with a BMI of 16 and severe cachexia. Intravenous hyperalimentation was initiated and an extensive work-up for an infectious etiology was performed and was negative. An esophagogastroduodenoscopy was performed and revealed nodularity of the gastric mucosa, atrophy, and edema in the first and second portion of his duodenum. Biopsy findings were consistent with GVHD. Aggressive immunosuppressive therapy was instituted with a good response. The anorexia and diarrhea resolved, and he was discharged on hospital day 20. Three months later, there had been no recurrence of the diarrhea, the patient had gained an additional 40 pounds, BMI of 25, and a repeat upper endoscopy revealed complete resolution of the initial endoscopic abnormalities.

Chemical reaction-induced multi-molecular polarization (CRIMP).

Here we present a novel hyperpolarization method, Chemical Reaction-Induced Multi-molecular Polarization (CRIMP), which could be applied to the study of several in vivo processes simultaneously including glycolysis, TCA cycle, fatty acid synthesis and pH mapping. Through the use of non-enzymatic decarboxylation, we generate four hyperpolarized imaging agents from hyperpolarized 1,2-(13)C pyruvic acid.

Skin cancer treatment by albumin/5-Fu loaded magnetic nanocomposite spheres in a mouse model.

Albumin/drug loaded magnetic nanocomposite spheres were fabricated using an oil-in-oil emulsion/solvent evaporation method, and tested on a mouse model (experimental squamous cell carcinoma) to determine the efficacy of the drug delivery system (DDS) on skin cancer. This novel DDS consists of human serum albumin, poly(lactic-co-glycolic acid) (PLGA), 5-fluorouracil (5-Fu), magnetic nanoparticles (10 nm) and fluorescent labeling molecule (diphenylhexatriene). One of the major purposes of using albumin is that it likely provides internal binding to and retention by the inflammatory tissues to reduce the amount of magnetic nanoparticles needed in the drug loaded microspheres (750­1100 nm). This study is aimed at reducing many negative side effects of conventionally used chemotherapy drugs by localizing the chemotherapy drug, controlling the release of the therapeutic agent and encouraging uptake of the DDS into cancerous cells. A group of mice treated with (1) the magnetic targeted DDS were compared to the other three groups, including, (2) DDS without a magnet, (3) 5-Fu local injection, and (4) untreated groups. The fluorescent tracer was ubiquitously identified inside the tumor tissue, and the DDS/tumor tissue boundary presented a leaky interface. The test results clearly showed that the magnetic targeted DDS exhibited significantly superior therapeutic effects in treating the skin cancer, with the increased efficacy to halt the tumor growth.

Estimation of the spatiotemporal structure of event-related desynchronization and synchronization in magnetoencephalography.

We present a comprehensive methodology for identifying cerebral areas involved in event-related changes of electromagnetic activity of the human brain, and also for tracing the temporal evolution of this activity. Information from pre- and peristimulus time intervals--in terms of event-related synchronization (ERS) and desynchronization (ERD) of the magnetoencephalographic (MEG) signal--was directly incorporated in the relevant test statistics. For the individual steps of the analysis, we used particular estimations of the time-frequency distribution of the energy along with particular error control methods, that is, short-time Fourier transform and false-discovery rate at the sensor level and multitapers and familywise error rate at the source level. This procedure was applied to two types of group-level tests, a within-condition test and a between-conditions test. The performance of the proposed methodology is assessed by (1) analyzing the event-related brain activity from two experimental conditions of an auditory MEG experiment--passive listening to a sequence of frequency-modulated sweeps and their active categorization with respect to the direction of frequency modulation, and (2) comparing the findings with those obtained with a widely used cluster-based analysis.