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BACKGROUND: The current gold standard for the diagnosis of Carpal tunnel syndrome (CTS) is a topic of debate. Nerve conduction studies (NCS) traditionally have been used as the confirmatory test; however, ultrasound (USG) has garnered interest as an alternative diagnostic test for CTS. Ultrasound measurement of the cross sectional area of the median nerve at the carpal tunnel has been proposed as an alternative for confirmation of CTS. AIM: The aim of the study was to compare the sensitivity and specificity between Ultrasound and Electro-diagnostic Studies in the diagnosis of Carpal Tunnel Syndrome with reference to a validated clinical diagnostic tool i.e. CTS- 6; that combines findings from the history and physical examination. MATERIALS AND METHODS: 40 (20 Cases and 20 controls) adult patients and adolescents of both sexes with complain of pain and paraesthesia in upper limb were included in this cross sectional study. All patients were evaluated using CTS-6 clinical diagnostic tool. Those patients with CTS score12 were considered as positive diagnosis for Carpal Tunnel Syndrome (cases) (Main group). Those patients with CTS Score12 were taken as Controls. Ultrasound and Electro-diagnostic Studies were performed by individuals blinded to the results of the CTS-6 and ultrasound examination. RESULTS: We found that USG have sensitivity of 90%, specificity of 85%, and positive predictive value of 85.71% and negative predictive value of 89.47%. Whereas NCS have sensitivity of 85%, specificity of 80%, positive predictive value of 80.95% and negative predictive value of 84.21%. CONCLUSION: Using CTS-6 clinical tool as a standard reference, the sensitivity and specificity of USG is more than that of NCS.

There is a great deal of excitement around the concept of targeting proteins for degradation as an alternative to conventional inhibitory small molecules and antibodies. Protein degradation can be undertaken by bifunctional molecules that bind the target for ubiquitin mediated degradation by complexing them with Cereblon (CRBN), von Hippel-Lindau or other E-3 ligases. Alternatively, E-3 ligase receptors such as CRBN or DCAF15 can also be used as a 'template' to bind IMiD or sulphonamide like compounds to degrade multiple context specific proteins by the selected E-3 ligases. The 'template approach' results in the degradation of neo-substrates, some of which would be difficult to drug using conventional approaches. The chemical properties necessary for drug discovery, the rules by which neo-substrates are selected by E-3 ligase receptors and defining the optimal components of the ubiquitin proteasome for protein degradation are still to be fully elucidate. Theis review will aim to critically evaluate the different approaches and principles emerging for targted protein degradation.

Additional file 1. Additional materials.

As multiple myeloma (MM) progresses, Natural Killer (NK) cell responses decline against malignant plasma cells. The immunomodulatory drug lenalidomide is widely used for the treatment of MM but its influence on NK cell biology is unclear. Here, we report that lenalidomide lowers the threshold for NK cell activation, causing a 66% decrease in the EC50 for activation through CD16, and a 38% decrease in the EC50 for NKG2D-mediated activation, allowing NK cells to respond to lower doses of ligand. In addition, lenalidomide augments NK cell responses, causing a 2-fold increase in the proportion of primary NK cells producing IFN-γ, and a 20-fold increase in the amount of IFN-γ produced per cell. Importantly, lenalidomide did not trigger IFN-γ production in unstimulated NK cells. Thus, lenalidomide enhances the NK cell arm of the immune response, without activating NK cells inappropriately. Of particular clinical importance, lenalidomide also allowed NK cells to be activated by lower doses of rituximab, an anti-CD20 mAb widely used to treat B cell malignancies. This supports the combined use of lenalidomide and rituximab in a clinical setting. Finally, super-resolution microscopy revealed that lenalidomide increased the periodicity of cortical actin at immune synapses, resulting in an increase in the area of the actin mesh predicted to be penetrable to vesicles containing IFN-γ. NK cells from MM patients also responded to lenalidomide in this way. This establishes that nanometre-scale rearrangements in cortical actin, a recently discovered step in immune synapse assembly, are a potential new target for therapeutic compounds.

【Abstract】Posterior dislocation of the shoulder may be missed or neglected at initial presentation especially in developing countries. We present a case of 40-year-old In- dian man who had 3-month missed posterior dislocation of the right shoulder along with malunited fracture of the ana- tomical neck of the humerus. Open reduction and stabiliza- tion with modified McLaughlin procedure was performed. Rotational osteotomy of proximal humerus had to be per- formed as supplementary procedure to keep the humeral head stable in glenoid cavity during functional range of movements. The patient had excellent result of the shoulder at 3 years follow-up. Key words: Shoulder dislocation; Humerus; Osteotomy

Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic and microenvironmental properties of neural tissues. In an attempt to encourage progress in our understanding and ability to successfully treat patients with brain tumours, Cancer Research UK convened an international panel of clinicians and laboratory-based scientists to identify challenges that must be overcome if we are to cure all patients with a brain tumour. The seven key challenges summarized in this Position Paper are intended to serve as foci for future research and investment.