Recanalisation of middle cerebral artery occlusion after intra-arterial thrombolysis: different recanalisation grading systems and clinical functional outcome

Background: Different grading systems of arterial recanalisation have never been compared in large series of stroke patients treated with intra-arterial thrombolysis (IAT). Methods: Clinical and angiographic findings and outcome were analysed in 147 patients with M1 or M2 segment occlusion of the middle cerebral artery treated with IAT. Associations of the thrombolysis in myocardial infarction (TIMI) grading system and the Mori grading system with clinical outcome were compared. Results: The median NIHSS score on admission was 15 and the mean time from symptom onset to IAT was 242 minutes. After three months the outcome was favourable (defined as modified Rankin scale score (mRS) ⩽2) in 85 patients (58%) and poor (mRS 3 to 5) in 44 (30%); 18 patients (12%) were dead. Recanalisation was categorised as TIMI grade 0 in 17 patients (12%), TIMI 1 in 16 (11%), TIMI 2 in 83 (56%), and TIMI 3 in 31(21%). Seventeen patients (12%) showed Mori grade 0 reperfusion, 16 (11%) Mori 1, 37 (25%) Mori 2, 46 (31%) Mori 3, and 31 (21%) Mori 4. In both TIMI and Mori grading systems, reopening the artery was an independent predictor of a favourable clinical outcome (p<0.0001). When recanalisation was partial, outcome was better in patients with reperfusion >50% (Mori 3) than in those with reperfusion <50% (Mori 2) (p = 0.008). Conclusions: Both TIMI and Mori grading systems are useful for predicting outcome after stroke and IAT. When recanalisation is partial the Mori classification is more refined in giving prognostic information

Gender differences in spontaneous cervical artery dissection

We analyzed sex differences in 696 patients with spontaneous cervical artery dissection. There were more men (n = 399; p < 0.0001), and men showed a higher frequency of hypertension (31% vs 15%; p < 0.0001). Women were younger (42.5 +/- 9.9 vs 47.5 +/- 9.3 years; p < 0.0001), had more often multiple dissections (18 vs 10%; p = 0.001), migraine (47 vs 20%; p < 0.0001), and tinnitus (16 vs 8%; p = 0.001). Outcome and mortality were similar in both sexes

Comparison of rapid methods for detection of Giardia spp. and Cryptosporidium spp. (Oo)cysts using transportable instrumentation in a field deployment

Reliable, sensitive, quantitative, and mobile rapid screening methods for pathogenic organisms are not yet readily available, but would provide a great benefit to humanitarian intervention units in disaster situations. We compared three different methods (immunofluorescent microscopy, IFM; flow cytometry, FCM; polymerase chain reaction, PCR) for the rapid and quantitative detection of Giardia lamblia and Cryptosporidium parvum (oo)cysts in a field campaign. For this we deployed our mobile instrumentation and sampled canal water and vegetables during a 2 week field study in Thailand. For purification and concentrations of (oo)cysts, we used filtration and immunomagnetic separation. We were able to detect considerably high oo(cysts) concentrations (ranges: 15-855 and 0-240 oo(cysts)/liter for Giardia and Cryptosporidium, respectively) in 85 to 300 min, with FCM being fastest, followed by PCR, and IFM being slowest due to the long analysis time per sample. FCM and IFM performed consistently well, whereas PCR reactions often failed. The recovery, established by FCM, was around 30% for Giardia and 13% for Cryptosporidium (oo)cysts. It was possible to track (oo)cysts from the wastewater further downstream to irrigation waters and confirm contamination of salads and water vegetables. We believe that rapid detection, in particular FCM-based methods, can substantially help in disaster management and outbreak prevention

Engineered peptide barcodes for in-depth analyses of binding protein libraries

Binding protein generation typically relies on laborious screening cascades that process candidate molecules individually. We have developed NestLink, a binder selection and identification technology able to biophysically characterize thousands of library members at once without the need to handle individual clones at any stage of the process. NestLink uses genetically encoded barcoding peptides termed flycodes, which were designed for maximal detectability by mass spectrometry and support accurate deep sequencing. We demonstrate NestLink's capacity to overcome the current limitations of binder-generation methods in three applications. First, we show that hundreds of binder candidates can be simultaneously ranked according to kinetic parameters. Next, we demonstrate deep mining of a nanobody immune repertoire for membrane protein binders, carried out entirely in solution without target immobilization. Finally, we identify rare binders against an integral membrane protein directly in the cellular environment of a human pathogen. NestLink opens avenues for the selection of tailored binder characteristics directly in tissues or in living organisms

Immunotherapy of uveal melanoma: vaccination against cancer. Multicenter adjuvant phase 3 vaccination study using dendritic cells laden with tumor RNA for large newly diagnosed uveal melanoma

Uveal melanomas are the most common malignant tumors of the eye. With modern molecular biological diagnostic methods, such as chromosome 3 typing and gene expression analysis, these tumors can be categorized into highly aggressive (monosomy 3, class II) and less aggressive forms. This molecular biological stratification is primarily important for determining the risk of these tumors as no therapy is currently available that is able to prevent or delay metastases. A randomized study of patients with a poor prognosis (monosomy 3) is currently being carried out in order to determine whether a cancer vaccine prepared from autologous (patient's own) dendritic cells and uveal melanoma RNA can prevent or delay progression and further metastases of this extremely aggressive form of cancer. Inclusion in the uveal melanoma study, which hopes to provide a potential therapeutic option for patients, is only possible if patients are referred to an institution that is able to manufacture and provide this vaccination before the patient is operated on or treated with radiation. Untreated tumor material is necessary for producing the vaccine on an individualized patient basis