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OBJECTIVEPrevious studies have demonstrated that human CSF contains membrane particles carrying the stem cell antigenic marker CD133 (prominin-1). Here, the authors analyzed the variation of the amount of these CD133-positive particles in the CSF of patients with subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH).METHODSConsecutive CSF samples from 47 patients with SAH or ICH were compared to 14 healthy control patients. After differential ultracentrifugation of CSF, the membrane particle fraction was separated on gel electrophoresis and its CD133 content was probed by immunoblotting using the mouse monoclonal antibody 80B258 directed against human CD133. The antigen-antibody complexes were detected by chemiluminescence reagents and quantified using human Caco-2 cell extract as positive control with a standardized curve.RESULTSAs compared to healthy controls (6.3 ± 0.5 ng of bound CD133 antibody; n = 14), the amount of membrane particle–associated CD133 immunoreactivities was significantly elevated in patients with SAH and ICH (38.2 ± 6.6 ng and 61.3 ± 11.0 ng [p < 0.001] for SAH [n = 18] and ICH [n = 29], respectively). In both groups the CD133 level dropped during the first 7 days (i.e., day 5–7: SAH group, 24.6 ± 10.1 ng [p = 0.06]; ICH group, 25.0 ± 4.8 ng [p = 0.002]). Whereas changes in the amount of CD133-positive membrane particles between admission and day 5–7 were not associated with clinical outcomes in patients with ICH (modified Rankin Scale [mRS] scores 0–3, −30.9 ± 12.8 ng vs mRS scores 4–6, −21.8 ± 10.7 ng; p = 0.239), persistent elevation of CD133 in patients with SAH was related to impaired functional outcome 3 months after ictus (mRS scores 0–2, −29.9 ± 8.1 ng vs mRS scores 3–6, 7.6 ± 20.3 ng; p = 0.027). These data are expressed as the mean ± standard error of the mean (SEM).CONCLUSIONSLevels of membrane particle–associated CD133 in the CSF of patients with SAH and ICH are significantly increased in comparison to healthy patients, and they decline during the hospital stay. Specifically, the persistent elevation of CD133-positive membrane particles within the first week may represent a possible surrogate measure for impaired functional outcome in patients with SAH.

Background and Purpose— Perihemorrhagic edema (PHE) is associated with poor outcome after intracerebral hemorrhage (ICH). Infiltration of immune cells is considered a major contributor of PHE. Recent studies suggest that immunomodulation via S1PR (sphingosine-1-phosphate receptor) modulators improve outcome in ICH. Siponimod, a selective modulator of sphingosine 1-phosphate receptors type 1 and type 5, demonstrated an excellent safety profile in a large study of patients with multiple sclerosis. Here, we investigated the impact of siponimod treatment on perihemorrhagic edema, neurological deficits, and survival in a mouse model of ICH. Methods— ICH was induced by intracranial injection of 0.075 U of bacterial collagenase in 123 mice. Mice were randomly assigned to different treatment groups: vehicle, siponimod given as a single dosage 30 minutes after the operation or given 3× for 3 consecutive days starting 30 minutes after operation. The primary outcome of our study was evolution of PHE measured by magnetic resonance-imaging on T2-maps 72 hours after ICH, secondary outcomes included evolution of PHE 24 hours after ICH, survival and neurological deficits, as well as effects on circulating blood cells and body weight. Results— Siponimod significantly reduced PHE measured by magnetic resonance imaging ( P =0.021) as well as wet-dry method ( P =0.04) 72 hours after ICH. Evaluation of PHE 24 hours after ICH showed a tendency toward attenuated brain edema in the low-dosage group ( P =0.08). Multiple treatments with siponimod significantly improved neurological deficits measured by Garcia Score ( P =0.03). Survival at day 10 was improved in mice treated with multiple dosages of siponimod ( P =0.037). Mice treated with siponimod showed a reduced weight loss after ICH ( P =0.036). Conclusions— Siponimod (BAF-312) attenuated PHE after ICH, increased survival, and reduced ICH-induced sensorimotor deficits in our experimental ICH-model. Findings encourage further investigation of inflammatory modulators as well as the translation of BAF-312 to a human study of ICH patients.

ObjectiveTo determine the occurrence of intracranial haemorrhagic complications (IHC) on heparin prophylaxis (low-dose subcutaneous heparin, LDSH) in primary spontaneous intracerebral haemorrhage (ICH) (not oral anticoagulation-associated ICH, non-OAC-ICH), vitamin K antagonist (VKA)-associated ICH and non-vitamin K antagonist oral anticoagulant (NOAC)-associated ICH.MethodsRetrospective cohort study (RETRACE) of 22 participating centres and prospective single-centre study with 1702 patients with VKA-associated or NOAC-associated ICH and 1022 patients with non-OAC-ICH with heparin prophylaxis between 2006 and 2015. Outcomes were defined as rates of IHC during hospital stay among patients with non-OAC-ICH, VKA-ICH and NOAC-ICH, mortality and functional outcome at 3 months between patients with ICH with and without IHC.ResultsIHC occurred in 1.7% (42/2416) of patients with ICH. There were no differences in crude incidence rates among patients with VKA-ICH, NOAC-ICH and non-OAC-ICH (log-rank p=0.645; VKA-ICH: 27/1406 (1.9%), NOAC-ICH 1/130 (0.8%), non-OAC-ICH 14/880 (1.6%); p=0.577). Detailed analysis according to treatment exposure (days with and without LDSH) revealed no differences in incidence rates of IHC per 1000 patient-days (LDSH: 1.43 (1.04–1.93) vs non-LDSH: 1.32 (0.33–3.58), conditional maximum likelihood incidence rate ratio: 1.09 (0.38–4.43); p=0.953). Secondary outcomes showed differences in functional outcome (modified Rankin Scale=4–6: IHC: 29/37 (78.4%) vs non-IHC: 1213/2048 (59.2%); p=0.019) and mortality (IHC: 14/37 (37.8%) vs non-IHC: 485/2048 (23.7%); p=0.045) in disfavour of patients with IHC. Small ICH volume (OR: volume ConclusionsHeparin administration for venous thromboembolism (VTE) prophylaxis in patients with ICH appears to be safe regarding IHC among non-OAC-ICH, VKA-ICH and NOAC-ICH in this observational cohort analysis. Randomised controlled trials are needed to verify the safety and efficacy of heparin compared with other methods for VTE prevention.

Background and Objectives:In patients with lobar intracerebral hemorrhage(ICH) etiological characterization represents a trade-off between feasibility, resource allocation, and diagnostic certainty. This study investigated the accuracy and clinical utility of the simplified Edinburgh CT criteria to identify underlying cerebral amyloid angiopathy(CAA).Methods:This external validation analyzed 210 consecutive patients with lobar ICH and available CT&MRI studies from a prospective single-center observational cohort study(2006-2015,UKER-ICH,NCT03183167). We investigated the simplified Edinburgh CT-based criteria’s inter-rater variability and diagnostic accuracy for identification of ICH associated with probable CAA according to MRI-based modified Boston criteria as a reference standard. We evaluated the simplified Edinburgh criteria’s utility by decision curve analysis, comparing the theoretical clinical net-benefit(weighted benefit–harm at varying threshold probabilities) of the high-risk category(finger-like-projections and subarachnoid hemorrhage) for ruling-in and the low-risk category(neither finger-like-projections nor subarachnoid hemorrhage) for ruling-out with the assumptions of no or all patients having CAA(default-strategies).Results:Of 210 patients, 70(33.3%) had high-risk, 67(31.9%) had medium-risk, and 73(34.8%) had low-risk for CAA associated ICH according to simplified Edinburgh CT criteria, showing moderate inter-rater variability. Discrimination was good(AUROC:0.74,95%CI 0.67–0.81) without evidence of poor calibration(Hosmer–Lemeshow,p=0.54) for validation of MRI-based diagnosis of probable CAA(n=94/210,44.8%). The rule-in criteria, i.e. high-risk, had 87.1%(79.3-92.3) specificity, and the rule-out criteria, i.e. low-risk, had 80.9%(71.1-88.0) sensitivity. Decision curve analysis suggested a theoretical clinical net-benefit for ruling-in but not for ruling-out probable CAA compared to default-strategies.Discussion:Applying the simplified Edinburgh CT criteria during diagnostic work-up seems clinically useful and may accurately identify CAA in patients with lobar ICH.Classification of Evidence:This study provides Class II evidence that in patients with lobar hemorrhages, simplified Edinburgh Criteria accurately identifies those at high risk of CAA.

The evolution of dense plasmas prior to the arrival of the peak of the laser irradiation is critical to understanding relativistic laser plasma interactions. The spectral properties of a reflected laser pulse after the interaction with a plasma can be used to gain insights about the interaction itself, whereas the effect of holeboring has a predominant role. Here we developed an analytical model, describing the non-relativistic temporal evolution of the holeboring velocity in the presence of an arbitrary overdense plasma density and laser intensity profile. We verify this using two-dimensional particle-in-cell simulations, showing a major influence on the holeboring dynamic depending on the density profile. The influence on the reflected laser pulse has been verified during an experiment at the PHELIX laser. We show that this enables the possibility to determine the sub-micrometer scale length of the preplasma by measuring the maximum holeboring velocity and acceleration during the laser-plasma interaction., Experimental measurements involving multiple laser and plasma parameters are useful in understanding the relativistic laser-plasma interactions. Here the authors extend the model of holeboring for arbitrary profiles of laser pulse and plasma scale lengths.

Failures to replicate evidence of new discoveries have forced scientists to ask whether this unreliability is due to suboptimal implementation of methods or whether presumptively optimal methods are not, in fact, optimal. This paper reports an investigation by four coordinated laboratories of the prospective replicability of 16 novel experimental findings using rigor-enhancing practices: confirmatory tests, large sample sizes, preregistration, and methodological transparency. In contrast to past systematic replication efforts that reported replication rates averaging 50%, replication attempts here produced the expected effects with significance testing (p

Introduction The number of patients with left ventricular assist devices (LVAD) is rapidly growing in industrialized countries. While cerebrovascular events comprise a significant complication, data on stroke etiology, clinical management and functional outcome are scarce. Methods Consecutive LVAD patients with ischemic or hemorrhagic stroke receiving treatment at an university stroke center between 2010 and 2018 were included into an institutional registry. Clinical characteristics, causes, management and functional outcome of stroke occurring within this cohort are reported. Acceptable functional outcome was defined as mRS 0-3. Results N = 30 acute strokes occurred in 20 patients (77% ischemic, 23% hemorrhagic, mean age 57 ± 13 years, 10% female, 8 patients (40%) had more than one event). 87% of all events happened with non-pulsatile devices, on average 9 (IQR 3-22) months after the implantation. All patients used oral anticoagulation with a Vitamin-K antagonist in combination with anti-platelets. The international normalized ratio (INR)-values were outside the therapeutic range in 39% of ischemic strokes and in 57% of hemorrhagic strokes. Ischemic strokes were predominantly of cardioembolic origin (92%) and of mild to moderate clinical severity (median NIHSS 6 (IQR 4-10). None qualified to receive intravenous thrombolysis or intra-arterial endovascular therapy. 61% of IS-patients showed an acceptable functional outcome after three months. 4/7 patients with hemorrhagic stroke received immediate reversal of anticoagulation without any thrombotic complications. Conclusion The majority of LVAD patients with ischemic stroke had an acceptable functional outcome after three months. Future clinical research is warranted to improve therapeutic strategies for acute care and stroke prevention.

Objective The microscopic review of hematoxylin-eosin-stained images of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex remains challenging. Both entities are distinct subtypes of human malformations of cortical development that share histopathological features consisting of neuronal dyslamination with dysmorphic neurons and balloon cells. We trained a convolutional neural network (CNN) to classify both entities and visualize the results. Additionally, we propose a new Web-based deep learning application as proof of concept of how deep learning could enter the pathologic routine. Methods A digital processing pipeline was developed for a series of 56 cases of focal cortical dysplasia type IIb and cortical tuber of tuberous sclerosis complex to obtain 4000 regions of interest and 200 000 subsamples with different zoom and rotation angles to train a neural network. Guided gradient-weighted class activation maps (Guided Grad-CAMs) were generated to visualize morphological features used by the CNN to distinguish both entities. Results Our best-performing network achieved 91% accuracy and 0.88 area under the receiver operating characteristic curve at the tile level for an unseen test set. Novel histopathologic patterns were found through the visualized Guided Grad-CAMs. These patterns were assembled into a classification score to augment decision-making in routine histopathology workup. This score was successfully validated by 11 expert neuropathologists and 12 nonexperts, boosting nonexperts to expert level performance. Significance Our newly developed Web application combines the visualization of whole slide images with the possibility of deep learning-aided classification between focal cortical dysplasia IIb and tuberous sclerosis complex. This approach will help to introduce deep learning applications and visualization for the histopathologic diagnosis of rare and difficult-to-classify brain lesions.

We trained a convolutional neural network (CNN) to classify H.E. stained microscopic images of focal cortical dysplasia type IIb (FCD IIb) and cortical tuber of tuberous sclerosis complex (TSC). Both entities are distinct subtypes of human malformations of cortical development that share histopathological features consisting of neuronal dyslamination with dysmorphic neurons and balloon cells. The microscopic review of routine stainings of such surgical specimens remains challenging. A digital processing pipeline was developed for a series of 56 FCD IIb and TSC cases to obtain 4000 regions of interest and 200.000 sub-samples with different zoom and rotation angles to train a CNN. Our best performing network achieved 91% accuracy and 0.88 AUCROC (area under the receiver operating characteristic curve) on a hold-out test-set. Guided gradient-weighted class activation maps visualized morphological features used by the CNN to distinguish both entities. We then developed a web application, which combined the visualization of whole slide images (WSI) with the possibility for classification between FCD IIb and TSC on demand by our pretrained and build-in CNN classifier. This approach might help to introduce deep learning applications for the histopathologic diagnosis of rare and difficult-to-classify brain lesions.

Background and Objective: Intraventricular hemorrhage (IVH) is a verified independent prognostic parameter in patients with intracerebral hemorrhage (ICH). However, the impact of the extent of IVH on clinical outcomes is unestablished. Methods: We analyzed 1,112 consecutive primary ICH patients of the UKER-ICH cohort (NCT03183167) and hypothesized that there is no difference in outcome between patients without IVH and patients with minor IVH not leading to obstructive hydrocephalus. Propensity score matching and multivariable analyses were performed to account for imbalances in baseline characteristics. Primary outcome was defined as functional outcome 3 months after ICH ­assessed using the modified Rankin Scale (mRS) dichotomized into favorable (mRS = 0–3) and unfavorable outcome (mRS = 4–6). Secondary outcomes included mortality at 3 months and a Graeb score-based threshold analysis for association of the extent of IVH with unfavorable clinical outcome. Results: Among the 461 out of 1,112 (41.5%) ICH patients with IVH, 191 out of 461 (41.4%) showed IVH without obstructive hydrocephalus and no requirement of external ventricular drain (EVD) placement. After adjusting for baseline imbalances we found no difference in functional outcome at 3 months between patients without IVH (No-IVH) and patients with IVH not requiring EVD (IVH-w/o-EVD): mRS 0–3: No-IVH 64/161 (39.8%) vs. IVH-w/o-EVD 53/170 (31.2%); p = 0.103. However, there was a trend toward a higher mortality in IVH-w/o-EVD patients (mRS 6: No IVH 40/161 [24.8%] vs. IVH-w/o-EVD 57/170 [33.5%]; p = 0.083). Multivariable analysis revealed that a Graeb score >2 was independently associated with unfavorable outcome (mRS 4–6: OR 3.16 [1.54–6.48]; p = 0.002), and higher mortality (mRS 6: OR 2.57 [1.40–4.74]; p = 0.002) in IVH patients. Conclusions: Small amounts of intraventricular blood (Graeb score ≤2) not leading to obstructive hydrocephalus are not associated with unfavorable outcome or death after ICH. Thus, IVH per se should not be considered a binary variable in outcome prediction for ICH patients.

O presente artigo descreve a validacao de um metodo espectrofotometrico UV simples, preciso, rapido e de baixo custo para a quantificacao de paracetamol em solucao oral. O metodo foi linear na faixa de 6,4 - 9,6 ?g mL -1 , apresentando um bom coeficiente de correlacao linear (r = 0,9988) e limites de quantificacao (2,22 ?g mL -1 ) e deteccao (0,67 ?g mL -1 ) satisfatorios. O estudo de precisao apresentou baixo coeficiente de variacao (

Introduction: This study determined the influence of concomitant antiplatelet therapy (APT) on hematoma characteristics and outcome in primary spontaneous intracerebral hemorrhage (non-OAC-ICH), vitamin K antagonist (VKA-) and non-vitamin K antagonist oral anticoagulant (NOAC-) associated ICH. Methods: Data of retrospective cohort studies and a prospective single-center study were pooled. Functional outcome, mortality and radiological characteristics were defined as primary and secondary outcomes. Propensity-score(PS)-matching and logistic regression analyses were performed to determine the association between single or dual antiplatelet therapy and hematoma volume. Results: A total of 3,580 ICH patients were screened, of whom 3,545 with information on antiplatelet therapy were analyzed. 346(32.4%) patients in non-OAC-ICH, 260(11.4%) in VKA-ICH and 30(16.0%) in NOAC-ICH were on APT and these patients had more severe comorbidities. After PS matching VKA-ICH patients on APT presented with less favorable functional outcome (mRS=0-3: APT:48/202[23.8%] vs no-APT:187/587[31.9%]; p=0.030) and higher mortality (APT:103/202[51.0%] vs no-APT:237/587[40.4%]; p=0.009), while no significant differences were present in non-OAC-ICH and NOAC-ICH. In VKA-ICH hematoma volume was significantly larger in patients with APT (21.9[7.4-61.4]ml vs 15.7[5.7-44.5]ml; p=0.005). Multivariable regression analysis revealed an association of APT and larger ICH volumes (OR: 1.80[1.20-2.70]; p=0.005), which was more pronounced in dual APT and supratherapeutically anticoagulated patients. Conclusions: APT does not affect ICH characteristics and outcome in non-OAC-ICH patients, however is associated with larger ICH volume and worse functional outcome in VKA-ICH, presumably by additive anti-hemostatic effects. Combination of anticoagulation and antiplatelet therapy should therefore be diligently evaluated and restricted to the shortest possible time frame.

IMPORTANCE: The association of surgical hematoma evacuation with clinical outcomes in patients with cerebellar intracerebral hemorrhage (ICH) has not been established. OBJECTIVE: To determine the association of surgical hematoma evacuation with clinical outcomes in cerebellar ICH. DESIGN, SETTING, AND PARTICIPANTS: Individual participant data (IPD) meta-analysis of 4 observational ICH studies incorporating 6580 patients treated at 64 hospitals across the United States and Germany (2006-2015). EXPOSURE: Surgical hematoma evacuation vs conservative treatment. MAIN OUTCOMES AND MEASURES: The primary outcome was functional disability evaluated by the modified Rankin Scale ([mRS] score range: 0, no functional deficit to 6, death) at 3 months; favorable (mRS, 0-3) vs unfavorable (mRS, 4-6). Secondary outcomes included survival at 3 months and at 12 months. Analyses included propensity score matching and covariate adjustment, and predicted probabilities were used to identify treatment-related cutoff values for cerebellar ICH. RESULTS: Among 578 patients with cerebellar ICH, propensity score–matched groups included 152 patients with surgical hematoma evacuation vs 152 patients with conservative treatment (age, 68.9 vs 69.2 years; men, 55.9% vs 51.3%; prior anticoagulation, 60.5% vs 63.8%; and median ICH volume, 20.5 cm(3) vs 18.8 cm(3)). After adjustment, surgical hematoma evacuation vs conservative treatment was not significantly associated with likelihood of better functional disability at 3 months (30.9% vs 35.5%; adjusted odds ratio [AOR], 0.94 [95% CI, 0.81 to 1.09], P = .43; adjusted risk difference [ARD], −3.7% [95% CI, −8.7% to 1.2%]) but was significantly associated with greater probability of survival at 3 months (78.3% vs 61.2%; AOR, 1.25 [95% CI, 1.07 to 1.45], P = .005; ARD, 18.5% [95% CI, 13.8% to 23.2%]) and at 12 months (71.7% vs 57.2%; AOR, 1.21 [95% CI, 1.03 to 1.42], P = .02; ARD, 17.0% [95% CI, 11.5% to 22.6%]). A volume range of 12 to 15 cm(3) was identified; below this level, surgical hematoma evacuation was associated with lower likelihood of favorable functional outcome (volume ≤12 cm(3), 30.6% vs 62.3% [P = .003]; ARD, −34.7% [−38.8% to −30.6%]; P value for interaction, .01), and above, it was associated with greater likelihood of survival (volume ≥15 cm(3), 74.5% vs 45.1% [P

In the present article it is described the validation of a simple, precise, accurate, rapid and low-cost UV spectrophotometric method for quantification of paracetamol in tablets. The method was linear in the range between 6.4 - 9.6 μg mL-1, presenting a good correlation coefficient (r = 0.9984) and adequate limits of quantification (2.64 μg mL-1) and detection (0.87 μg mL-1). Precision and analysis showed low coefficient of variation (< 4.0 %) and a good average recovery percentual (99.22% - reference and 101.78% - generic) was obtained. The method was applied for paracetamol determination in two tablet formulations and these results are in good accordance with the declared values of manufacturer, at a 95% confidence level. The experimental activity is simple, showing it to be used in experimental activities on teaching laboratories improve student learning. DOI: http://dx.doi.org/10.17807/orbital.v10i7.1330

Background and Purpose— This study determined the influence of concomitant antiplatelet therapy (APT) on hematoma characteristics and outcome in primary spontaneous intracerebral hemorrhage (ICH), vitamin K antagonist (VKA)- and non–VKA oral anticoagulant-associated ICH. Methods— Data of retrospective cohort studies and a prospective single-center study were pooled. Functional outcome, mortality, and radiological characteristics were defined as primary and secondary outcomes. Propensity score matching and logistic regression analyses were performed to determine the association between single or dual APT and hematoma volume. Results— A total of 3580 patients with ICH were screened, of whom 3545 with information on APT were analyzed. Three hundred forty-six (32.4%) patients in primary spontaneous ICH, 260 (11.4%) in VKA-ICH, and 30 (16.0%) in non–VKA oral anticoagulant-associated ICH were on APT, and these patients had more severe comorbidities. After propensity score matching VKA-ICH patients on APT presented with less favorable functional outcome (modified Rankin Scale score, 0–3; APT, 48/202 [23.8%] versus no APT, 187/587 [31.9%]; P =0.030) and higher mortality (APT, 103/202 [51.0%] versus no APT, 237/587 [40.4%]; P =0.009), whereas no significant differences were present in primary spontaneous ICH and non–VKA oral anticoagulant-associated ICH. In VKA-ICH, hematoma volume was significantly larger in patients with APT (21.9 [7.4–61.4] versus 15.7 [5.7–44.5] mL; P =0.005). Multivariable regression analysis revealed an association of APT and larger ICH volumes (odds ratio, 1.80 [1.20–2.70]; P =0.005), which was more pronounced in dual APT and supratherapeutically anticoagulated patients. Conclusions— APT does not affect ICH characteristics and outcome in primary spontaneous ICH patients; however, it is associated with larger ICH volume and worse functional outcome in VKA-ICH, presumably by additive antihemostatic effects. Combination of anticoagulation and APT should, therefore, be diligently evaluated and restricted to the shortest possible time frame.

It is not known how long it takes from the initial neoplastic transformation of a cell to the detection of a tumor, which would be valuable for understanding tumor growth dynamics. Meningiomas show a broad histological, genetic and clinical spectrum, are usually benign and considered slowly growing. There is an intense debate regarding their age and growth pattern and when meningiomas should be resected. We have assessed the age and growth dynamics of 14 patients with meningiomas (WHO grade I: n = 6 with meningothelial and n = 6 with fibrous subtype, as well as n = 2 atypical WHO grade II meningiomas) by combining retrospective birth-dating of cells by analyzing incorporation of nuclear-bomb-test-derived 14C, analysis of cell proliferation, cell density, MRI imaging and mathematical modeling. We provide an integrated model of the growth dynamics of benign meningiomas. The mean age of WHO grade I meningiomas was 22.1 ± 6.5 years, whereas atypical WHO grade II meningiomas originated 1.5 ± 0.1 years prior to surgery (p, Highlights • The age of meningiomas has been difficult to study and is not understood, however age and growth dynamics may affect clinical decision making regarding surgery • We determined the age and dynamics of meningioma tumor cells using 14C retrospective birth dating strategy together with MR imaging and histological parameters • We demonstrate that the average time between initial tumorous cell transformation and detection with resection is 26.3 years in fibrous and years in 17.8 meningothelial meningiomas Meningiomas are usually benign, slowly growing and frequently occurring brain tumors that are detected incidentally upon imaging or because of causing symptoms. Many tumors remain stable, while others keep growing, why there is a debate whether or not meningiomas need surgical resection upon diagnosis. Specifically, if tumors grow in difficultly accessible brain areas, it would be clinically valuable to predict their age and growth dynamics. The 14C (radiocarbon) retrospective birth dating technique, an approach taking advantage of the above-ground atomic bomb tests during the Cold War, harbors the unique feature of dating the tumor age, thus providing insights into tumor origination and growth. Using this technique we here establish the age of meningiomas and provide an integrated model – using also MRI and histological parameters – to predict future growth of detected meningiomas, which may help in clinical decision making whether to resect the tumor.

Aims Evidence is lacking regarding acute anticoagulation management in patients after intracerebral haemorrhage (ICH) with implanted mechanical heart valves (MHVs). Our objective was to investigate anticoagulation reversal and resumption strategies by evaluating incidences of haemorrhagic and thromboembolic complications, thereby defining an optimal time-window when to restart therapeutic anticoagulation (TA) in patients with MHV and ICH. Methods and results We pooled individual patient-data (n = 2504) from a nationwide multicentre cohort-study (RETRACE, conducted at 22 German centres) and eventually identified MHV-patients (n = 137) with anticoagulation-associated ICH for outcome analyses. The primary outcome consisted of major haemorrhagic complications analysed during hospital stay according to treatment exposure (restarted TA vs. no-TA). Secondary outcomes comprised thromboembolic complications, the composite outcome (haemorrhagic and thromboembolic complications), timing of TA, and mortality. Adjusted analyses involved propensity-score matching and multivariable cox-regressions to identify optimal timing of TA. In 66/137 (48%) of patients TA was restarted, being associated with increased haemorrhagic (TA = 17/66 (26%) vs. no-TA = 4/71 (6%); P

In the present article it is described, a simple, precise, rapid and low-cost conductometric titration of tetracycline hydrochloride in pharmaceutical formulations using silver nitrate as titrant. The method is based on the precipitation of chloride ions derived from tetracycline hydrochloride with silver ions, yielding silver chloride precipitate and the conductance of the solution is measured as a function of the volume of titrant. The coefficient of variation for six successive measurements was 0.64% and no interferences were observed in the presence of common components of the pharmaceutical formulations. Recovery values from two samples, ranging from 99.0 to 105%, were obtained. The method was applied for tetracycline hydrochloride determination in two pharmaceuticals formulations and these results are in good accordance with the declared values of manufacturer and an official method of the Brazilian Pharmacopoeia, based on spectrophotometric analysis, at a 95% confidence level.

Small nucleolar RNAs (snoRNAs) have been used for normalization in glomerular microRNA (miRNA) quantification without confirmation of validity. Our aim was to identify glomerular reference miRNAs in IgA nephropathy. We compared miRNAs in human paraffin-embedded renal biopsies from patients with cellular-crescentic IgA-GN (n = 5; crescentic IgA-GN) and non-crescentic IgA-GN (n = 5; IgA-GN) to mild interstitial nephritis without glomerular abnormalities (controls, n = 5). Laser-microdissected glomeruli were used for expression profiling of 762 miRNAs by low-density TaqMan arrays (cards A and B). The comparison of different normalization methods (GeNormPlus, NormFinder, global mean and snoRNAs) in crescentic IgA-GN, IgA-GN and controls yielded similar results. However, levels of significance and the range of relative expression differed. In median, two normalization methods demonstrated similar results. GeNormPlus and NormFinder gave different top ranked reference miRNAs. Stability ranking for snoRNAs varied between cards A and B. In conclusion, we suggest the geometric mean of the most stable reference miRNAs found in GeNormPlus (miR-26b-5p), NormFinder (miR-28-5p) and snoRNAs (RNU44) as reference. It should be considered that significant differences could be missed using one particular normalization method. As a starting point for glomerular miRNA studies in IgA nephropathy we provide a library of miRNAs.

The glycoprotein CD44 is barely detected in normal mouse and human glomeruli, but is increased in glomerular parietal epithelial cells following podocyte injury in focal segmental glomerulosclerosis (FSGS). To determine the biological role and regulation of CD44 in these cells, we employed an in vivo and in vitro approach. Experimental FSGS was induced in CD44 knockout and wild-type mice with a cytotoxic podocyte antibody. Albuminuria, focal and global glomerulosclerosis (periodic acid–Schiff stain), and collagen IV staining were lower in CD44 knockout compared with wild-type mice with FSGS. Parietal epithelial cells had lower migration from Bowman's capsule to the glomerular tuft in CD44 knockout mice with disease compared with wild type mice. In cultured murine parietal epithelial cells, overexpressing CD44 with a retroviral vector encoding CD44 was accompanied by significantly increased collagen IV expression and parietal epithelial cell migration. Because our results showed de novo co-staining for activated ERK1/2 (pERK) in parietal epithelial cells in experimental FSGS, and also in biopsies from patients with FSGS, two in vitro strategies were employed to prove that pERK regulated CD44 levels. First, mouse parietal epithelial cells were infected with a retroviral vector for the upstream kinase MEK-DD to increase pERK, which was accompanied by increased CD44 levels. Second, in CD44-overexpressing parietal epithelial cells, decreasing pERK with U0126 was accompanied by reduced CD44. Finally, parietal epithelial cell migration was higher in cells with increased and reduced in cells with decreased pERK. Thus, pERK is a regulator of CD44 expression, and increased CD44 expression leads to a pro-sclerotic and migratory parietal epithelial cell phenotype.

Research into the authenticity of facial emotion expressions often focuses on the physical properties of the face while paying little attention to the role of beliefs in emotion perception. Further, the literature most often investigates how people express a pre-determined emotion rather than what facial emotion expressions people strategically choose to express. To fill these gaps, this paper proposes a non-verbal zero-sum game – the Face X Game – to assess the role of contextual beliefs and strategic displays of facial emotion expression in interpersonal interactions. This new research paradigm was used in a series of three studies, where two participants are asked to play the role of the sender (individual expressing emotional information on his/her face) or the observer (individual interpreting the meaning of that expression). Study 1 examines the outcome of the game with reference to the sex of the pair, where senders won more frequently when the pair was comprised of at least one female. Study 2 examines the strategic display of facial emotion expressions. The outcome of the game was again contingent upon the sex of the pair. Among female pairs, senders won the game more frequently, replicating the pattern of results from study 1. We also demonstrate that senders who strategically express an emotion incongruent with the valence of the event (e.g., smile after seeing a negative event) are able to mislead observers, who tend to hold a congruent belief about the meaning of the emotion expression. If sending an incongruent signal helps to explain why female senders win more frequently, it logically follows that female observers were more prone to hold a congruent, and therefore inaccurate, belief. This prospect implies that while female senders are willing and/or capable of displaying fake smiles, paired-female observers are not taking this into account. Study 3 investigates the role of contextual factors by manipulating female observers’ beliefs. When prompted to think in an incongruent manner, these observers significantly improve their performance in the game. These findings emphasize the role that contextual factors play in emotion perception—observers’ beliefs do indeed affect their judgments of facial emotion expressions.

Prior work suggests that awareness of stereotypes about a person’s in-group can affect a person’s behavior and performance when they complete a stereotype-relevant task, a phenomenon called stereotype susceptibility ( Shih, Pittinsky, & Ambady, 1999 ). In a preregistered confirmatory design, we found that priming Asian women with social identities associated with math stereotypes did not influence their performance on a subsequent mathematics exam, and hypothesized moderators did not account for the effect. The conditions necessary to obtain the original results are not yet fully understood.

Numerous investigations have demonstrated efficiencies of different disinfection methods, but until now only little is known about long-term effects on community compositions of drinking water biofilms. Changes in the community structure, especially regrowth of hygienically relevant microorganisms could be critical for the drinking water quality. In this study the long-term effect of disinfection methods on biofilm communities in drinking water systems was analysed. Old drinking water biofilms grown in silicone tubes were exposed to different preparations of disinfectants (free chlorine, chlorine dioxide, hydrogen peroxide combined with fruit acid, silver and silver with peracetic acid, respectively) and subsequently further exposed in the original drinking water. The comparison of the treated and regrown biofilm populations with untreated ones by the DNA-fingerprinting method denaturing gradient gel electrophoresis (DGGE) revealed a considerable population shift caused by the disinfectants. The disinfection methods induced a selection pressure on the biofilm populations depending on the composition and concentrations. The similarities between the treated and untreated biofilms were generally low. Compared to preparations with peracetic acid the disinfection with hydrogen peroxide and silver resulted in higher similarities of the treated and untreated biofilms, but the microbial diversity increased. It can be concluded that the disinfectants have a major impact on the drinking water biofilm communities and that possibly the intervention selects persisters and microorganisms, which can live on the residuals of the dead biofilm cells. For the evaluation of the efficiency of disinfection methods in drinking water installations it is necessary not only to consider reduction of certain bacteria but also to pay attention to the biofilm community.

Kidney aging is accompanied by characteristic changes in the glomerulus, but little is known about the effect of aging on glomerular parietal epithelial cells (PECs), nor if the characteristic glomerular changes in humans and rats also occur in very old mice. Accordingly, a descriptive analysis was undertaken in 27-mo-old C57B6 mice, considered advanced age. PEC density was significantly lower in older mice compared with young mice (aged 3 mo), and the decrease was more pronounced in juxtamedullary glomeruli compared with outer cortical glomeruli. In addition to segmental and global glomerulosclerosis in older mice, staining for matrix proteins collagen type IV and heparan sulfate proteoglycan were markedly increased in Bowman's capsules of older mouse glomeruli, consistent with increased extracellular matrix production by PECs. De novo staining for CD44, a marker of activated and profibrotic PECs, was significantly increased in aged glomeruli. CD44 staining was more pronounced in the juxtamedullary region and colocalized with phosphorylated ERK. Additionally, a subset of aged PECs de novo expressed the epithelial-to-mesenchymal transition markers α-smooth muscle and vimentin, with no changes in epithelial-to-mesenchymal transition markers E-cadherin and β-catenin. The mural cell markers neural/glial antigen 2, PDGF receptor-β, and CD146 as well as Notch 3 were also substantially increased in aged PECs. These data show that mice can be used to better understand the aging kidney and that PECs undergo substantial changes, especially in juxtamedullary glomeruli, that may participate in the overall decline in glomerular structure and function with advancing age.

Based on the cross (Triticum aestivum L. × Secale cereale L.) × T. aestivum L., wheat-rye substitution lines (2n = 42) were produced with karyotypes containing, instead of a pair of homologous wheat chromosomes, a homeologous pair of rye chromosomes. The chromosome composition of these lines was described by GISH and C-banding methods, and SSR analysis. The results of genomic in situ hybridization demonstrated that karyotype of these lines included one pair of rye chromosomes each and lacked wheat-rye translocations. C-banding and SSR markers were used to identify rye chromosomes and determine the wheat chromosomes at which the substitution occurred. The lines were designated 1R(1D), 2R(2D)2, 2R(2D)3, 3R(3B), 6R(6A)2. The chromosome composition of lines 1R(1A), 2R(W)1, 5R(W), 5R(5A), and 6R(W)1, which were earlier obtained according to the same scheme for crossing, was characterized using methods of telocentric analysis, GISH, C-banding, and SSR analysis. These lines were identified as 1R(1A), 2R(2D)1, 5R(5D), 5R(5A), and 6R(6A)1, C-banding of chromosomes belonging to line 1R(1A) revealed the presence of two translocated chromosomes (3DS.3DL-del. and 4AL.W) during simultaneous amplification of SSR markers located on 3DL and 4AS arms. The “combined” long arm of the newly derived chromosome 4A is assumed to be formed from the long arm of chromosome 4AS itself and a deleted segment 3DL. All examined lines are cytologically stable, except for 3R(3B), which does not affect the stability of rye 3R chromosome transfer. Chromosome identification and classification of the lines will permit them to be models for genetic studies that can be used thereafter as promising “secondary gene pools” for the purpose of plant breeding.

Research has demonstrated that people systematically overrate their knowledge, intelligence, and skills in various domains. Confronting people with evidence of their miscalibration, however, causes them to reassess these claims. For example, simply asking people to explain how a sewing machine works leads them to subsequently report understanding it less — a bias called the illusion of explanatory depth (Rozenblit & Keil, 2002). While previous work argues that this process is domain-bound, we demonstrate in several experiments that the bias to inflate subjective knowledge is attenuated not only by explanations of the focal item itself but also by explanations of other, entirely different things, implying the existence of a more parsimonious, domain-agnostic process for this bias.

As adult podocytes cannot adequately proliferate following depletion in disease states, there has been interest in the potential role of progenitors in podocyte repair and regeneration. To determine whether parietal epithelial cells (PECs) can serve as adult podocyte progenitors following disease-induced podocyte depletion, PECs were permanently labeled in adult PEC-rtTA/LC1/R26 reporter mice. In normal mice, labeled PECs were confined to Bowman's capsule, whereas in disease (cytotoxic sheep anti-podocyte antibody) labeled PECs were found in the glomerular tuft in progressively higher numbers by days 7, 14, and 28. Early in disease, the majority of PECs in the tuft coexpressed CD44. By day 28, when podocyte numbers were significantly higher and disease severity was significantly lower, the majority of labeled PECs coexpressed podocyte proteins but not CD44. Neither labeled PECs on the tuft nor podocytes stained for the proliferation marker BrdU. The de novo expression of phospho-ERK colocalized to CD44 expressing PECs, but not to PECs expressing podocyte markers. Thus, in a mouse model of focal segmental glomerulosclerosis typified by abrupt podocyte depletion followed by regeneration, PECs undergo two phenotypic changes once they migrate to the glomerular tuft. Initially these cells are predominantly activated CD44 expressing cells coinciding with glomerulosclerosis, and later they predominantly exhibit a podocyte phenotype, which is likely reparative.

The budding yeast MSH4 gene encodes a MutS homolog produced specifically in meiotic cells. Msh4 is not required for meiotic mismatch repair or gene conversion, but it is required for wild-type levels of crossing over. Here, we show that a msh4 null mutation substantially decreases crossover interference. With respect to the defect in interference and the level of crossing over, msh4 is similar to the zip1 mutant, which lacks a structural component of the synaptonemal complex (SC). Furthermore, epistasis tests indicate that msh4 and zip1 affect the same subset of meiotic crossovers. In the msh4 mutant, SC formation is delayed compared to wild type, and full synapsis is achieved in only about half of all nuclei. The simultaneous defects in synapsis and interference observed in msh4 (and also zip1 and ndj1/tam1) suggest a role for the SC in mediating interference. The Msh4 protein localizes to discrete foci on meiotic chromosomes and colocalizes with Zip2, a protein involved in the initiation of chromosome synapsis. Both Zip2 and Zip1 are required for the normal localization of Msh4 to chromosomes, raising the possibility that the zip1 and zip2 defects in crossing over are indirect, resulting from the failure to localize Msh4 properly.

The pachytene checkpoint prevents meiotic nuclear division in cells that fail to complete meiotic recombination and chromosome synapsis. This control mechanism prevents chromosome missegregation that would lead to the production of aneuploid gametes. The pachytene checkpoint requires a subset of proteins that function in the mitotic DNA damage checkpoint. In budding yeast, the pachytene checkpoint also requires meiosis-specific chromosomal proteins and, unexpectedly, proteins concentrated in the nucleolus. Progress has been made in identifying components of the cell-cycle machinery that are impacted by the checkpoint.

Economical methods by which gene function may be analysed on a genomic scale are relatively scarce. To fill this need, we have developed a transposon-tagging strategy for the genome-wide analysis of disruption phenotypes, gene expression and protein localization, and have applied this method to the large-scale analysis of gene function in the budding yeast Saccharomyces cerevisiae. Here we present the largest collection of defined yeast mutants ever generated within a single genetic background--a collection of over 11,000 strains, each carrying a transposon inserted within a region of the genome expressed during vegetative growth and/or sporulation. These insertions affect nearly 2,000 annotated genes, representing about one-third of the 6,200 predicted genes in the yeast genome. We have used this collection to determine disruption phenotypes for nearly 8,000 strains using 20 different growth conditions; the resulting data sets were clustered to identify groups of functionally related genes. We have also identified over 300 previously non-annotated open reading frames and analysed by indirect immunofluorescence over 1,300 transposon-tagged proteins. In total, our study encompasses over 260,000 data points, constituting the largest functional analysis of the yeast genome ever undertaken.

Mutants in the meiosis-specific RED1 gene of S. cerevisiae fail to make any synaptonemal complex (SC) or any obvious precursors to the SC. Using antibodies that specifically recognize the Red1 protein, Red1 has been localized along meiotic pachytene chromosomes. Red1 also localizes to the unsynapsed axial elements present in a zip1 mutant, suggesting that Red1 is a component of the lateral elements of mature SCs. Anti-Red1 staining is confined to the cores of meiotic chromosomes and is not associated with the loops of chromatin that lie outside the SC. Analysis of the spo11 mutant demonstrates that Red1 localization does not depend upon meiotic recombination. The localization of Red1 has been compared with two other meiosisspecific components of chromosomes, Hop1 and Zip1; Zip1 serves as a marker for synapsed chromosomes. Double labeling of wild-type meiotic chromosomes with anti-Zip1 and anti-Red1 antibodies demonstrates that Red1 localizes to chromosomes both before and during pachytene. Double labeling with anti-Hop1and anti-Red1 antibodies reveals that Hop1 protein localizes only in areas that also contain Red1, and studies of Hop1 localization in a red1 null mutant demonstrate that Hop1 localization depends on Red1 function. These observations are consistent with previous genetic studies suggesting that Red1 and Hop1 directly interact. There is little or no Hop1 protein on pachytene chromosomes or in synapsed chromosomal regions.

Previous studies have shown that the RAD51 and DMC1 genes of Saccharomyces cerevisiae encode homologs of the Escherichia coli RecA strand exchange enzyme. Results presented here demonstrate that the dmc1 and rad51 mutants undergo nearly complete chromosome synapsis, but synaptonemal complex formation is delayed substantially compared with wild type. In the zip1 mutant, chromosomes are paired homologously, but not synapsed, and the protein backbones (axial elements) of each pair of chromosomes are connected intimately to each other at a few sites referred to herein as axial associations. dmc1 zip1 and rad51 zip1 double mutants assemble axial elements that are not obviously associated, demonstrating that the Dmc1 and Rad51 proteins are required to establish or stabilize axial associations. We propose that axial associations serve to promote meiotic chromosome synapsis and that the absence of these associations accounts for the delayed and inefficient synapsis observed in dmc1 and rad51 strains. During meiosis in haploid yeast, chromosome synapsis takes place between nonhomologous chromosome segments. In a zip1 haploid, axial associations are not apparent, suggesting that these associations depend on interactions between homologous sequences.

Previous studies of Saccharomyces cerevisiae have identified several meiosis-specific genes whose products are required for wild-type levels of meiotic recombination and for normal synaptonemal complex (SC) formation. Several of these mutants were examined in a physical assay designed to detect heteroduplex DNA (hDNA) intermediates in meiotic recombination. hDNA was not detected in the rec102, mei4 and hop1 mutants; it was observed at reduced levels in red1, mek1 and mer1 strains and at greater than the wild-type level in zip1. These results indicate that the REC102, MEI4, HOP1, RED1, MEK1 and MER1 gene products act before hDNA formation in the meiotic recombination pathway, whereas ZIP1 acts later. The same mutants assayed for hDNA formation were monitored for meiotic chromosome pairing by in situ hybridization of chromosome-specific DNA probes to spread meiotic nuclei. Homolog pairing occurs at wild-type levels in the zip1 and mek1 mutants, but is substantially reduced in mei4, rec102, hop1, red1 and mer1 strains. Even mutants that fail to recombine or to make any SC or SC precursors undergo a significant amount of meiotic chromosome pairing. The in situ hybridization procedure revealed defects in meiotic chromatin condensation in mer1, red1 and hop1 strains.

The transcript of the Saccharomyces cerevisiae MER2 gene is spliced efficiently during meiosis but not during vegetative growth. Efficient splicing of the wild-type MER2 transcript requires the Mer1 protein, which is produced only in meiotic cells. Analysis of deletion and substitution mutations in the MER2 5' exon demonstrates that the unusually large size of this exon plays an important role in splicing regulation. The cis-acting sequences essential for Mer1-dependent splicing of MER2 RNA were determined by the analysis of MER2 deletion mutants and hybrid genes. The 80-base MER2 intron is sufficient for Mer1-dependent splicing in vivo, but sequences in the 5' exon enhance splicing efficiency. The Mer1 protein contains the KH motif found in some RNA-binding proteins, and RNA gel mobility shift assays demonstrate that Mer1 binds specifically to MER2 RNA. Both the transcript derived from the intronless MER2 gene and the transcript consisting only of the intron are able to bind to Mer1 in vitro, but neither has as high affinity for the protein as the intact substrate. RNase T1 footprinting indicates that the Mer1 protein contacts MER2 RNA at several points in the 5' exon and in the intron. Thus, Mer1 interacts directly with a regulatory element in MER2 RNA and promotes splicing.

We have developed a large-scale screen to identify genes expressed at different times during the life cycle of Saccharomyces cerevisiae and to determine the subcellular locations of many of the encoded gene products. Diploid yeast strains containing random lacZ insertions throughout the genome have been constructed by transformation with a mutagenized genomic library. Twenty-eight hundred transformants containing fusion genes expressed during vegetative growth and 55 transformants containing meiotically induced fusion genes have been identified. Based on the frequency of transformed strains producing beta-galactosidase, we estimate that 80-86% of the yeast genome (excluding the rDNA) contains open reading frames expressed in vegetative cells and that there are 93-135 meiotically induced genes. Indirect immunofluorescence analysis of 2373 strains carrying fusion genes expressed in vegetative cells has identified 245 fusion proteins that localize to discrete locations in the cell, including the nucleus, mitochondria, endoplasmic reticulum, cytoplasmic dots, spindle pole body, and microtubules. The DNA sequence adjacent to the lacZ gene has been determined for 91 vegetative fusion genes whose products have been localized and for 43 meiotically induced fusions. Although most fusions represent genes unidentified previously, many correspond to known genes, including some whose expression has not been studied previously and whose products have not been localized. For example, Sec21-beta-gal fusion proteins yield a Golgi-like staining pattern, Ty1-beta-gal fusion proteins localize to cytoplasmic dots, and the meiosis-specific Mek1/Mre4-beta-gal and Spo11-beta-gal fusion proteins reside in the nucleus. The phenotypes in haploid cells have been analyzed for 59 strains containing chromosomal fusion genes expressed during vegetative growth; 9 strains fail to form colonies indicating that the disrupted genes are essential. Fifteen additional strains display slow growth or are impaired for growth on specific media or in the presence of inhibitors. Of 39 meiotically induced fusion genes examined, 14 disruptions confer defects in spore formation or spore viability in homozygous diploids. Our results will allow researchers who identify a yeast gene to determine immediately whether that gene is expressed at a specific time during the life cycle and whether its gene product localizes to a specific subcellular location.

A mutant at the yeast MED1 locus was isolated in a screen for sporulation-proficient, meiotic-lethal mutants. Synaptonemal complex formation in the med1 mutant is apparently normal and med1 strains undergo meiotic crossing over at approximately 50% of the wild-type level. The med1 mutant undergoes homolog nondisjunction at meiosis I, presumably as a consequence of the decrease in crossing over. In addition, the mutant undergoes precocious separation of sister chromatids, resulting in chromosome missegregation at both meiotic divisions. We suggest that the med1 mutation perturbs chromosome structure, leading to a reduction in recombination and a defect in sister chromatid cohesion.

Amoklaufe haben in den vergangenen Jahren ein derartig groses mediales Interesse gefunden wie kaum ein anderes Verbrechen. Es erscheint unfassbar, dass ein Schuler Lehrer und andere Schuler kaltblutig und gezielt ermordet und das Leiden von unzahligen Menschen beabsichtigt. Die betroffenen Lehrer und Schuler, die mit ansehen mussten, wie Klassenkameraden verbluteten, erschossen wurden oder die Schreie Sterbender anhorten, die Eltern, die ihre Kinder, Eheleute, die ihren Partner verloren haben, leiden teilweise ein ganzes Leben lang unter den Folgen.

The composition of biofilm populations in drinking water will mainly depend on the nutrient availability and the temperature. The nutrients may originate either from the raw water or from the installation materials. To determine the effect of drinking water pipe materials on the composition of biofilm populations, biofilms grown on different materials (EPDM materials, PEXb, PEXc and copper) were analyzed by cloning (16S rDNA) and the community fingerprinting method denaturing gradient gel electrophoresis (DGGE). Additionally the long-term effect of mechanical cleaning and disinfection with chlorine dioxide (0.2 mg/l, 24h) on the biofilm populations was tested. The biofilm populations had high diversities on growth supporting materials like EPDM and comparatively low diversity on PEX. The biofilms were dominated by Proteobacteria and the composition of the subdivisions was influenced by the applied material. Flavobacteria and members of the family Sphingomonadaceae, which are known to degrade several organic compounds, were found on EPDM materials and might be suitable as indicators for hygienical relevant materials. Comparison of biofilms previously treated with disinfectants with untreated ones by DGGE revealed a considerable population shift depending on the pipe material.