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Concussion is a frequent injury in many sports and is also common in para athletes. However, there is a paucity of concussion research related to para sport, and prior International Concussion in Sport (CIS) consensus papers have not substantively addressed this population. To remedy this and to improve concussion care provided to para athletes, the concussion in para sport (CIPS) multidisciplinary expert group was created. This group analysed and discussed in-depth para athlete-specific issues within the established key clinical domains of the current (2017) consensus statement on CIS. Due to the onset of the COVID-19 pandemic, the group held all meetings by video conferencing. The existing Sport Concussion Assessment Tool 5 (SCAT5) for the immediate on-field and office-based off-field assessment of concussion was evaluated as part of this process, to identify any para athlete-specific concerns. Regular preparticipation and periodic health examinations are essential to determine a baseline reference point for concussion symptoms but pose additional challenges for the interpreting clinician. Further considerations for concussion management for the para athlete are required within the remove, rest, reconsider and refer consensus statement framework. Considering return to sport (RTS), the 2017 CIS consensus statement has limitations when considering the RTS of the para athlete. Case-by-case decision making related to RTS following concussion is imperative for para athletes. Additional challenges exist for the evaluation and management of concussion in para athletes. There is a need for greater understanding of existing knowledge gaps and attitudes towards concussion among athlete medical staff, coaches and para athletes. Future research should investigate the use and performance of common assessment tools in the para athlete population to better guide their clinical application and inform potential modifications. Concussion prevention strategies and sport-specific rule changes, such as in Para Alpine Skiing and Cerebral Palsy Football, also should be carefully considered to reduce the occurrence of concussion in para athletes.

BackgroundA concussion is a common injury in many sports, including para sport. Aside from a more comprehensive need for concussion education, clinicians face difficulties applying concussion assessment and management guidelines to para athletes.1 At present, there is a lack of para-sport concussion research, and prior International Concussion in Sport (CIS) consensus papers have not addressed this specific population. To rectify this issue and improve concussion management provided to para athletes, the Concussion in Para Sport (CIPS) multidisciplinary expert group was created.2MethodsThe CIPS group undertook an in-depth analysis of issues specific to the para athlete within the established key clinical domains of the current (2017) Consensus Statement on Concussion in Sport.3 The existing Sports Concussion Assessment Tool 5 (SCAT5) was evaluated as part of this process and helped identify para athlete-specific concerns. Four CIPS working groups were tasked with exploring the following key clinical areas of concussion in para sport described in the most recent consensus statement of concussion in sport2: (Less)

Limited neural input results in muscle weakness in neuromuscular disease because of a reduction in the density of muscle innervation, the rate of neuromuscular junction activation or the efficiency of synaptic transmission. We developed a small-molecule fast-skeletal-troponin activator, CK-2017357, as a means to increase muscle strength by amplifying the response of muscle when neural input is otherwise diminished secondary to neuromuscular disease. Binding selectively to the fast-skeletal-troponin complex, CK-2017357 slows the rate of calcium release from troponin C and sensitizes muscle to calcium. As a consequence, the force-calcium relationship of muscle fibers shifts leftwards, as does the force-frequency relationship of a nerve-muscle pair, so that CK-2017357 increases the production of muscle force in situ at sub-maximal nerve stimulation rates. Notably, we show that sensitization of the fast-skeletal-troponin complex to calcium improves muscle force and grip strength immediately after administration of single doses of CK-2017357 in a model of the neuromuscular disease myasthenia gravis. Troponin activation may provide a new therapeutic approach to improve physical activity in diseases where neuromuscular function is compromised.

It has been hypothesized that in patients with benign prostatic hyperplasia, selective antagonism of the alpha1A-adrenoceptor-mediated contraction of lower urinary tract tissues may, via a selective relief of outlet obstruction, lead to an improvement in symptoms. The present study describes the alpha1-adrenoceptor (alpha1-AR) subtype selectivities of two novel alpha1-AR antagonists, Ro 70-0004 (aka RS-100975) and a structurally-related compound RS-100329, and compares them with those of prazosin and tamsulosin. Radioligand binding and second-messenger studies in intact CHO-K1 cells expressing human cloned alpha1A-, alpha1B- and alpha1D-AR showed nanomolar affinity and significant alpha1A-AR subtype selectivity for both Ro 70-0004 (pKi 8.9: 60 and 50 fold selectivity) and RS-100329 (pKi 9.6: 126 and 50 fold selectivity) over the alpha1B- and alpha1D-AR subtypes respectively. In contrast, prazosin and tamsulosin showed little subtype selectivity. Noradrenaline-induced contractions of human lower urinary tract (LUT) tissues or rabbit bladder neck were competitively antagonized by Ro 70-0004 (pA2 8.8 and 8.9), RS-100329 (pA2 9.2 and 9.2), tamsulosin (pA2 10.4 and 9.8) and prazosin (pA2 8.7 and 8.3 respectively). Affinity estimates for tamsulosin and prazosin in antagonizing alpha1-AR-mediated contractions of human renal artery (HRA) and rat aorta (RA) were similar to those observed in LUT tissues, whereas Ro 70-0004 and RS-100329 were approximately 100 fold less potent (pA2 values of 6.8/6.8 and 7.3/7.9 in HRA/RA respectively). The alpha1A-AR subtype selectivity of Ro 70-0004 and RS-100329, demonstrated in both cloned and native systems, should allow for an evaluation of the clinical utility of a 'uroselective' agent for the treatment of symptoms associated with benign prostatic hyperplasia.