The attribution of a protein to an ultrastructural element by optical microscopy represents a major challenge in biology. Here, we report a method of near-native expansion microscopy (U-ExM), enabling the visualization of preserved ultrastructures of macromolecules by optical microscopy. Combined with super-resolution, U-ExM unveiled the centriolar chirality, only visualizable by electron microscopy. We demonstrate the general applicability of U-ExM by imaging different cellular structures including microtubules and mitochondria in cellulo .

IMPORTANCE Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood. OBJECTIVE To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis.

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We report a controlled, prospective study to investigate the effect of treatment by low-energy extracorporeal shock waves on pain in tennis elbow. We assigned at random 100 patients who had had symptoms for more than 12 months to two groups to receive low-energy shock-wave therapy. Group I received a total of 3000 impulses of 0.08 mJ/mm 2 and group II, the control group, 30 impulses. The patients were reviewed after 3, 6 and 24 weeks. There was significant alleviation of pain and improvement of function after treatment in group I in which there was a good or excellent outcome in 48% and an acceptable result in 42% at the final review, compared with 6% and 24%, respectively, in group II.J Bone Joint Surg [Br] 1996;78-B:233-7. Received 30 November 1994; Accepted after revision 17 November 1995 Although tennis elbow was first described more than 100 years ago its aetiology and pathophysiology remain uncertain (Ernst 1992;Foley 1993). The best method of treatment has not been established (Labelle et al 1992) and both conservative (Mucha and Wannske 1989;Haker and Lundeberg 1991) and operative regimes (Wittenberg, Schaal and Muhr 1992;Verhaar et al 1993) have been advocated.Low-dose extracorporeal shock-wave therapy has been found to be effective in treating persistent elbow pain in isolated cases. In this form of hyperstimulation analgesia, pain is alleviated by a moderate-to-intense sensory input which is usually applied at the site of greatest discomfort for a period ranging from a few seconds to 20 or 30 minutes. This may relieve chronic pain for days, weeks and sometimes permanently (Melzack 1989).We have studied the use of this treatment in patients with tennis elbow. PATIENTS AND METHODSOver a three-year period we treated 115 patients with lateral elbow pain by low-dose extracorporeal shock-wave therapy. During the first six weeks 15 patients discontinued the treatment leaving 100 who completed the full course.Patients were included in the study if they had had pain in the lateral epicondyle for more than 12 months and had received unsuccessful conservative therapy in the previous six months. In addition, the pain had to be induced by two or more of the following tests: 1) Palpation of the lateral epicondyle. 2) Resisted wrist extension (Thomsen test). With the shoulder flexed to 60°, the elbow extended, the forearm pronated and the wrist extended about 30°, pressure is applied to the dorsum of the second and third metacarpal bones in the direction of flexion and ulnar deviation to stress the extensor carpi radialis brevis and longus. 3) Resisted finger extension. With the shoulder flexed to 60°, the elbow extended, the forearm pronated and the fingers extended the middle finger is actively extended against resistance. 4) Chair test. With the shoulder flexed to 60° and the elbow extended the patient attempts to lift a chair weighing 3.5 kg.Patients were excluded if they were under 18 years of age or had dysfunction of the shoulder, neck and/or thoracic region, local arthritis, generalised polyarthritis, ne...

The concepts called STED/RESOLFT superresolve features by a light-driven transfer of closely packed molecules between two different states, typically a nonfluorescent "off" state and a fluorescent "on" state at well-defined coordinates on subdiffraction scales. For this, the applied light intensity must be sufficient to guarantee the state difference for molecules spaced at the resolution sought. Relatively high intensities have therefore been applied throughout the imaging to obtain the highest resolutions. At regions where features are far enough apart that molecules could be separated with lower intensity, the excess intensity just adds to photobleaching. Here, we introduce DyMIN (standing for Dynamic Intensity Minimum) scanning, generalizing and expanding on earlier concepts of RESCue and MINFIELD to reduce sample exposure. The principle of DyMIN is that it only uses as much on/ off-switching light as needed to image at the desired resolution. Fluorescence can be recorded at those positions where fluorophores are found within a subresolution neighborhood. By tuning the intensity (and thus resolution) during the acquisition of each pixel/voxel, we match the size of this neighborhood to the structures being imaged. DyMIN is shown to lower the dose of STED light on the scanned region up to ∼20-fold under common biological imaging conditions, and >100-fold for sparser 2D and 3D samples. The bleaching reduction can be converted into accordingly brighter images at <30-nm resolution.fluorescence nanoscopy | superresolution | STED microscopy | photobleaching | adaptive illumination