Accuracy of botulinum toxin type A injection into the forearm muscles of chronic stroke patients with spastic flexed wrist and clenched fist: manual needle placement evaluated using ultrasonography.

Objective: To investigate the accuracy of manual needle placement for injection of botulinum toxin type A into the forearm muscles of adults with spastic flexed wrist and clenched fist as a consequence of stroke. Design: Prospective clinical study. Patients: A total of 41 adults with chronic stroke who were scheduled to receive botulinum toxin type A injection into the following forearm muscles: flexor carpi radialis, flexor carpi ulnaris, flexor digitorum superficialis and flexor digitorum profundus. Methods: According to Huber & Heck's atlas suggestions on treatment of spasticity with botulinum toxin, surface identification of muscles to inject was performed by means of palpation and anatomical landmarks. Accuracy of needle placement and muscle thickness at the site of needle insertion were assessed using ultrasonography. Results: Overall accuracy of manual needle placement evaluated using ultrasonography was 51.2%. Accuracy was significantly higher for the finger flexors than for the wrist flexors (63.4% vs 39.0%). The finger flexors were significantly thicker than the wrist flexors (mean 1.58 vs 0.49 cm). Conclusion: Instrumental guidance should be used in order to achieve an acceptable accuracy of needle placement when performing botulinum toxin type A injections into the forearm muscles of chronic stroke patients with spastic flexed wrist and clenched fist

Psychological Treatments and Psychotherapies in the Neurorehabilitation of Pain: Evidences and Recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly recognized that treating pain is crucial for effective care within neurological rehabilitation in the setting of the neurological rehabilitation. The Italian Consensus Conference on Pain in Neurorehabilitation was constituted with the purpose identifying best practices for us in this context. Along with drug therapies and physical interventions, psychological treatments have been proven to be some of the most valuable tools that can be used within a multidisciplinary approach for fostering a reduction in pain intensity. However, there is a need to elucidate what forms of psychotherapy could be effectively matched with the specific pathologies that are typically addressed by neurorehabilitation teams.Objectives: To extensively assess the available evidence which supports the use of psychological therapies for pain reduction in neurological diseases.Methods: A systematic review of the studies evaluating the effect of psychotherapies on pain intensity in neurological disorders was performed through an electronic search using PUBMED, EMBASE, and the Cochrane Database of Systematic Reviews. Based on the level of evidence of the included studies, recommendations were outlined separately for the different conditions.Results: The literature search yielded 2352 results and the final database included 400 articles. The overall strength of the recommendations was medium/low. The different forms of psychological interventions, including Cognitive\u2014Behavioral Therapy, cognitive or behavioral techniques, Mindfulness, hypnosis, Acceptance and Commitment Therapy (ACT), Brief Interpersonal Therapy, virtual reality interventions, various forms of biofeedback and mirror therapy were found to be effective for pain reduction in pathologies such as musculoskeletal pain, fibromyalgia, Complex Regional Pain Syndrome, Central Post\u2014Stroke pain, Phantom Limb Pain, pain secondary to Spinal Cord Injury, multiple sclerosis and other debilitating syndromes, diabetic neuropathy, Medically Unexplained Symptoms, migraine and headache.Conclusions: Psychological interventions and psychotherapies are safe and effective treatments that can be used within an integrated approach for patients undergoing neurological rehabilitation for pain. The different interventions can be specifically selected depending on the disease being treated. A table of evidence and recommendations from the Italian Consensus Conference on Pain in Neurorehabilitation is also provided in the final part of the paper

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Botulinum toxin injection into the forearm muscles for wrist and fingers spastic overactivity in adults with chronic stroke: a randomized controlled trial comparing three injection techniques.

Objective: To compare the outcome of manual needle placement, electrical stimulation and ultrasonography-guided techniques for botulinum toxin injection into the forearm muscles of adults with arm spasticity. Design: Randomized controlled trial. Setting: University hospital. Subjects: Sixty chronic stroke patients with wrist and fingers spasticity. Intervention: After randomization into three groups, each patient received botulinum toxin type A in at least two of these muscles: flexor carpi radialis and ulnaris, flexor digitorum superficialis and profundus (no fascicles selection). The manual needle placement group underwent injections using palpation; the electrical stimulation group received injections with electrical stimulation guidance; the ultrasonography group was injected under sonographic guidance. A sole injector was used. Main measures: All patients were evaluated at baseline and four weeks after injection. Outcomes: Modified Ashworth Scale; Tardieu Scale; wrist and fingers passive range of motion. Results: One month after injection, Modified Ashworth Scale scores improved more in the electrical stimulation group than the manual needle placement group (wrist: P = 0.014; fingers: P = 0.011), as well as the Tardieu angle (wrist: P = 0.008; fingers: P = 0.015) and passive range of motion (wrist: P = 0.004). Furthermore, Modified Ashworth Scale scores improved more in the ultrasonography group than in the manual needle placement group (wrist: P = 0.001; fingers: P = 0.003), as well as the Tardieu angle (wrist: P = 0.010; fingers: P = 0.001) and passive range of motion (wrist: P < 0.001; proximal interphalangeal joints: P = 0.009). No difference was found between the ultrasonography and electrical stimulation groups. Conclusions: Instrumental guidance may improve the outcome of botulinum toxin injections into the spastic forearm muscles of stroke patients

Tyrosinase-Mediated Oxidative Coupling of Tyrosine Tags on Peptides and Proteins

We report a strategy for chemical protein modification by using tyrosinase enzymes to oxidize exposed tyrosine residues on protein N or C-termini. We explore the chemical space for coupling partners in this reaction and find combinations that can proceed in near quantitative conversion. This strategy is used to conjugate a dye onto a Trastuzumab antibody fragment and a Protein L fragment and demonstrate that these constructs can be used as immunostaining reagents

Profilo di sicurezza e tollerabilit\ue0.

L\u2019emicrania cronica (EC) \ue8 una condizione neurologica disabilitante che si manifesta secondo i criteri classificativi dell\u2019International Headache Society ICHD-II con cefalea di tipo emicranico presente per almeno 15 giorni al mese da pi\uf9 di 3 mesi, in assenza di un uso eccessivo di farmaci. Tra le opzioni terapeutiche profilattiche di secondo livello a disposizione per pazienti resistenti o intolleranti alla terapia di profilassi primaria, vi \ue8 la Tossina Botulinica di tipo A (onabotulinum toxin A)

Denying the Armenian Genocide in International and European Law

Several international and European legal instruments, both binding and non-binding, call on or allow for the criminalization of speech that denies, condones or minimizes international crimes. The aim of this essay is to verify the extent of those instruments, particularly the definitions of punishable behaviours and the identification of the object/target of such behaviours, with a view to ascertain whether the instruments apply to the Armenian massacres of 1915\u2013191

Synthesis of Multi-Protein Complexes through Charge-Directed Sequential Activation of Tyrosine Residues

Site-selective protein-protein coupling has long been a goal of chemical biology research. In recent years, that goal has been realized to varying degrees through a number of techniques, including the use of tyrosinase-based coupling strategies. Early publications utilizing tyrosinase from Agaricus bisporus showed the potential to convert tyrosine residues into ortho-quinone functional groups, but this enzyme is challenging to produce recombinantly and suffers from some limitations in substrate scope. Initial screens of several tyrosinase candidates revealed that the tyrosinase from Bacillus megaterium (megaTYR) as an enzyme that possesses a broad substrate tolerance. We use the expanded substrate preference as a starting point for protein design experiments and show that single point mutants of megaTYR are capable of activating tyrosine residues in various sequence contexts. We leverage this new tool to enable the construction of protein trimers via a charge-directed sequential activation of tyrosine residues (CDSAT)