Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

The abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and prion-like propagation. However, the identities of the assembled tau species and EVs, as well as how they associate, are not known.

Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known.

MICOS assembly controls mitochondrial inner membrane remodeling and crista junction redistribution to mediate cristae formation.

Mitochondrial function is critically dependent on the folding of the mitochondrial inner membrane into cristae; indeed, numerous human diseases are associated with aberrant crista morphologies. With the MICOS complex, OPA1 and the F F -ATP synthase, key players of cristae biogenesis have been identified, yet their interplay is poorly understood. Harnessing super-resolution light and 3D electron microscopy, we dissect the roles of these proteins in the formation of cristae in human mitochondria.

Proteogenomic Refinement of the Neomegalonema perideroedes Genome Annotation.

Neomegalonema perideroedes (formerly Meganema perideroedes) str. G1 is the type strain and only described isolate of the genus Neomegalonema (formerly Meganema) which belongs to the Alphaproteobacteria. N.

A 4-Week Intervention Involving Mobile-Based Daily 6-Minute Micro-Sessions of Functional High-Intensity Circuit Training Improves Strength and Quality of Life, but Not Cardio-Respiratory Fitness of Young Untrained Adults.

The present study was designed to assess the psycho-physiological responses of physically untrained individuals to mobile-based multi-stimulating, circuit-like, multiple-joint conditioning (Circuit) performed either once (1xCircuit) or twice (2xCircuit) daily for 4 weeks. In this single-center, two-arm randomized, controlled study, 24 men and women (age: 25 ± 5 years) first received no training instructions for 4 weeks and then performed 4 weeks of either 1xCircuit or 2xCircuit (5 men and 7 women in each group) daily. The 1xCircuit and 2xCircuit participants carried out 90.

Spectral and temporal multiplexing for multispectral fluorescence and reflectance imaging using two color sensors.

Fluorescence imaging can reveal functional, anatomical or pathological features of high interest in medical interventions. We present a novel method to record and display in video rate multispectral color and fluorescence images over the visible and near infrared range. The fast acquisition in multiple channels is achieved through a combination of spectral and temporal multiplexing in a system with two standard color sensors.

Simultaneous real-time multicomponent fluorescence and reflectance imaging method for fluorescence-guided surgery.

Fluorescence-guided surgical procedures are employed in an increasing number of applications such as tumor delineation, blood perfusion, and sentinel lymph node detection. A new generation of fluorescent probes is expected to increase the number of applications and improve efficiency. Yet, there are no available imaging methods to take full advantage of the forthcoming targeting technologies.

Sulfur-34S stable isotope labeling of amino acids for quantification (SULAQ34) of proteomic changes in Pseudomonas fluorescens during naphthalene degradation.

The relative quantification of proteins is one of the major techniques used to elucidate physiological reactions. Because it allows one to avoid artifacts due to chemical labeling, the metabolic introduction of heavy isotopes into proteins and peptides is the preferred method for relative quantification. For eukaryotic cells, stable isotope labeling by amino acids in cell culture (SILAC) has become the gold standard and can be readily applied in a vast number of scenarios.

Optimizing of thienopyridine therapy by multiple electrode platelet aggregometry in clopidogrel low responders undergoing PCI.

Aims: One possible cause of stent thrombosis is an insufficient effect of clopidogrel. In a prospective study, we aimed to optimize the platelet inhibition of clopidogrel low responders (CLR) by multiple electrode platelet aggregometry (MEA)-guided therapy modifications and to evaluate specific major adverse cardiac and cerebrovascular events (MACCE).

Methods And Results: ADP-induced platelet aggregation was measured by MEA in 1,005 consecutive patients after stent implantation and 600 mg clopidogrel loading dose.

Scintigraphic assessment of salivary gland function in a rat model.

Background: Salivary gland dysfunction with xerostomia is a major clinical problem without a causal therapy in most cases. The development of an animal model for scintigraphic assessment of salivary gland function has great clinical relevance for the investigation of promising new diagnostic and therapeutic strategies for chronic salivary gland diseases. This study reports the first experiences with scintigraphic analyses of salivary gland function in a rat model.

Incidental non-secreting adrenal masses in cancer patients: intra-individual comparison of 18F-fluorodeoxyglucose positron emission tomography/computed tomography with computed tomography and shift magnetic resonance imaging.

The ability of integrated (18)F-fluorodeoxyglucose positron emission tomography and computed tomography (FDG PET/CT) to distinguish between benign and malignant incidental non-secreting adrenal masses was evaluated in cancer patients. Results were compared with those of CT and shift magnetic resonance imaging (MRI). A total of 1832 cancer patients who had undergone FDG PET/CT scans were retrospectively evaluated.

[Diagnosis of fever of unknown origin (FUO). Positron emission tomography/computed tomography (PET-CT)].

Nuclear medicine imaging is now well accepted for the localization of septic foci. But in patients the results of infection scintigraphy, radiology and ultrasound remain unsatisfactory in the diagnosis of fever of unknown origin (FUO). In contrast to septic infections, patients with FUO - mostly in elderly patients - tend to have such conditions as occult tumours, atypical pneumonia, hematoblastosis, malignant lymphomas.

Nonviral siRNA delivery to the lung: investigation of PEG-PEI polyplexes and their in vivo performance.

This study describes the physicobiological characterization of PEI- and PEG-PEI polyplexes containing partially 2'-OMe modified 25/27mer dicer substrate siRNAs (DsiRNAs) and their in vivo behavior regarding biodistribution and systemic bioavailability after pulmonary application as well as their ability to knock down gene expression in the lung. Biophysical characterization included circular dichroism of siRNA in polyplexes, condensation efficiency of polymers and in vitro stability. After in vivo application, biodistribution and kinetics of radiolabeled polyplexes were quantified and recorded over time in three-dimensional SPECT images and by end point scintillation counting.

Effective treatment of pancreatic neuroendocrine tumours transfected with the sodium iodide symporter gene by 186Re-perrhenate in mice.

Purpose: ReO(4)(-) has similar kinetics regarding the sodium iodide symporter (NIS) to I(-) and TcO(4)(-) in NIS-expressing tissue. We investigated the therapeutic potential of (186)ReO(4)(-) in NIS-transfected neuroendocrine tumour tissue.

Methods: For experiments, the stably NIS-transfected pancreatic neuroendocrine cancer cell line Bon1C was used.

(99m)Tc-Fab' fragments (sulesomab) for imaging septically loosened total knee arthroplasty.

The diagnostic accuracy of infection scintigraphy with (99m)Tc-labelled monoclonal antibody Fab' fragments (sulesomab) was studied in patients with suspected total knee arthroplasty (TKA) infection. Images from 26 patients were evaluated by two independent readers and compared with a quantitative interpretation of time-activity courses. Microbiological examinations and joint aspiration results were used as reference standards.

Unexpected 99mTc-tetrofosmin findings during myocardial perfusion scintigraphy: intraindividual comparison with PET/computed tomography.

Objective: 99mTc-tetrofosmin single photon emission computed tomography (SPECT) is routinely used in the evaluation of coronary artery disease. A variety of different tumors, however, also demonstrate 99mTc-tetrofosmin uptake. We report six patients found with unexpected mediastinal and thoracic tumor uptake during Tc-tetrofosmin myocardial perfusion scintigraphy (MPS).

Peripheral and central biodistribution of (111)In-labeled anti-beta-amyloid autoantibodies in a transgenic mouse model of Alzheimer's disease.

Active as well as passive immunization against beta-amlyoid (Abeta) has been proposed as a treatment to lower cerebral amyloid burden and stabilize cognitive decline in Alzheimer's disease (AD). To clarify the mechanism of action underlying passive immunization, the in vivo distribution (and sites of degradation) of peripherally administered radiolabeled human and mouse anti-Abeta antibodies were analyzed in a transgenic mouse model of AD. In APP23 mice, a model in which mutated human amyloid precursor protein is overexpressed, the biodistribution of intravenously applicated (111)indium-conjugated affinity-purified human polyclonal autoantibodies (NAbs-Abeta) was compared to that of monoclonal anti-Abeta(1-17) (6E10), anti-Abeta(17-24) antibodies (4G8) and anti-CD-20 (Rituximab), a non-Abeta targeting control.

[Nuclear medical imaging in case of painful knee arthroplasty].

Rationale: The aim of the present study was to calculate the overall diagnostic accuracy of nuclear medical imaging in patients with painful knee arthroplasty.

Material And Methods: This retrospective study of all patients (n=87) where a (99m)Tc-triple phase bone scintigraphy (TPBS; n=120) and (99m)Tc-anti-granulocyte scintigraphy (BW 250/183; n=20) for a painful knee arthroplasty was performed between 2003 and 2007.

Results: A total of 87 patients with 94 knee arthroplasties were examined to detect septic and aseptic loosening and to differentiate between them.

Does fine-needle aspiration cytology optimize the surgical management of thyroid disorders in endemic goiter region?

Aim: The aim of this study was to determine the diagnostic value of fine-needle aspiration cytology (FNAC) before thyroidectomy in an endemic goiter region.

Methods: One hundred patients with preoperative FNAC of thyroid nodules who underwent thyroidectomy were recruited. FNAC were classified into five groups.

Imaging of gastrinomas by nuclear medicine methods.

Somatostatin receptor scintigraphy (SRS) is a valuable method for the detection of somatostatin receptor-positive lesions. Most gastrinomas (over-)express the somatostatin receptor subtype 2 which can be targeted by In-111 labeled Octreotide. Different studies show a high sensitivity of SRS for the localization and staging of gastrinomas.

Quantitative [(123)I]FP-CIT pinhole SPECT imaging predicts striatal dopamine levels, but not number of nigral neurons in different mouse models of Parkinson's disease.

Single photon emission computed tomography (SPECT) using [(123)I]FP-CIT as radioligand for the dopamine transporter has become a widely used tool to monitor the integrity of the nigrostriatal dopaminergic projection in Parkinson's disease (PD). Previous studies with pinhole SPECT in small animals have demonstrated that the striatal [(123)I]FP-CIT binding indeed correlates with the striatal dopamine transporter protein level. It is unclear, however, if there is a stable relationship between the striatal [(123)I]FP-CIT binding and other functionally important parameters of the nigrostriatal system, such as the striatal dopamine levels and the number of dopaminergic neurons in the substantia nigra.

Scintigraphy with 99mTc-labeled heat-altered erythrocytes in diagnosing hyposplenia: prospective comparison to 99mTc-labeled colloids and colour-coded duplex ultrasonography.

Aim: Ultrasound may be a cheap alternative to scintigraphic determination of splenic function. We directly compared nanocolloid scintigraphy (NS), scintigraphy with heat-altered erythrocytes (ES), and colour-coded Doppler sonography (DS) in patients with chronic inflammatory bowel disease (CIBD).

Patients, Methods: 35 patients were included into the study.

Role of p38 mitogen-activated protein kinase in cardiac remodelling.

Background And Purpose: Mitogen-activated protein kinases (MAPK) are centrally involved in several mechanisms important for heart failure such as apoptosis, activation of inflammatory responses and cell proliferation. We therefore evaluated the effect of the selective p38 MAPK inhibitor SB 239063 on progression of left ventricular remodelling after myocardial infarction (MI) in rats.

Experimental Approach: Rats were treated for 9 weeks with placebo or SB 239063 by gavage (15 mg kg(-1)) twice daily starting 7 days after ligation of the left anterior descending artery.

Efficacy of 99mTc pertechnetate and 131I radioisotope therapy in sodium/iodide symporter (NIS)-expressing neuroendocrine tumors in vivo.

Purpose: There is growing interest in the human sodium/iodide symporter (NIS) gene both as a molecular imaging reporter gene and as a therapeutic gene. Here, we show the feasibility of radioisotope therapy of neuroendocrine tumors. As a separate application of NIS gene transfer, we image NIS-expressing tumors with pinhole SPECT in living subjects.

Added value of gastrin receptor scintigraphy in comparison to somatostatin receptor scintigraphy in patients with carcinoids and other neuroendocrine tumours.

Gastrin receptor scintigraphy (GRS) is a new imaging method primarily developed for the detection of metastases of medullary thyroid carcinoma (MTC). As gastrin-binding CCK(2) receptors are also expressed on a variety of other neuroendocrine tumours (NET), we compared GRS to somatostatin receptor scintigraphy (SRS) in patients with NET. SRS and GRS were performed within 21 days in a series of 60 consecutive patients with NET.