The response of muscle to volitional or electrically induced stimuli is affected by its contractile history. Fatigue is the most obvious effect of contractile history reflected by the inability of a muscle to generate an expected level of force. However, fatigue can coexist with post-activation potentiation (PAP), which serves to improve muscular performance, especially in endurance exercise and activities involving speed and power. The measured response of muscular performance following some form of contractile activity is the net balance between processes that cause fatigue and the simultaneous processes that result in potentiation. Optimal performance occurs when fatigue has subsided but the potentiated effect still exists. PAP has been demonstrated using electrically induced twitch contractions and attributed to phosphorylation of myosin regulatory light chains, which makes actin and myosin more sensitive to Ca(2+). The potentiated state has also been attributed to an increase in alpha-motoneuron excitability as reflected by changes in the H-reflex. However, the significance of PAP to functional performance has not been well established. A number of recent studies have applied the principles of PAP to short-term motor performance as well as using it as a rationale for producing long-term neuromuscular changes through complex training. Complex training is a training strategy that involves the execution of a heavy resistance exercise (HRE) prior to performing an explosive movement with similar biomechanical characteristics, referred to as a complex pair. The complex pair is then repeated for a number of sets and postulated that over time will produce long-term changes in the ability of a muscle to generate power. The results of these studies are equivocal at this time and, in fact, no training studies have actually been undertaken. The discrepancies among the results of the various studies is due in part to differences in methodology and design, with particular reference to the mode and intensity of the HRE, the length of the rest interval within and between the complex pairs, the type of explosive activity, the training history of the participants, and the nature of the dependent variables. In addition, few of the applied studies have actually included measures of twitch response or H-reflex to determine if the muscles of interest are potentiated. There is clearly more research required in order to clarify the functional significance of PAP and, in particular, the efficacy of complex training in producing long-term neuromuscular adaptations.

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Recently there has been considerable interest and research into the functional significance of postactivation potentiation (PAP) on sport performance. The interest has evolved around the potential for enhancing acute performance or the long-term training effect, typically in the form of complex training. Complex training usually involves performing a weight-training exercise with high loads before executing a plyometric exercise with similar biomechanical demands. Despite a considerable amount of research in the past 10 years it would seem there is still much research to be done to fully determine whether PAP has a functional role and, if so, how to best exploit it. It is clear from the research that there are many factors that need to be considered when attempting to apply PAP to an athlete. It is possible that a well-conceived sport-specific warm-up might be as or more effective in enhancing acute performance and easier to apply in a practical setting. In addition, despite its current popularity, there has not been 1 study that has effectively examined the efficacy of complex training and whether it has any advantage over other forms of training that combine weight training and plyometrics but not in the same training session.

The contractile history of muscle can potentiate electrically evoked force production. A link to voluntary force production, related in part to an increase in reflex excitability, has been suggested.Purpose:Our purpose was to quantify the effect of postactivation potentiation on voluntary force production and spinal H-reflex excitability during explosive plantar fexion actions.Methods:Plantar flexor twitch torque, soleus H-reflex amplitudes, and the rate of force development of explosive plantar fexion were measured before and after 4 separate conditioning trials (3 × 5 s maximal contractions).Results:Twitch torque and rate of force production during voluntary explosive plantar flexion were significantly increased (P < .05) while H-reflex amplitudes remained unchanged. Although twitch torque was significantly higher after conditioning, leading to a small increase in the rate of voluntary force production, this was unrelated to changes in reflex excitability.Conclusion:We conclude that postactivation potentiation may result in a minor increase in the rate of voluntary isometric force production that is unrelated to neural excitability.

Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a standard treatment option for patients with advanced non-small-cell lung cancer. However, a substantial proportion of patients will not benefit from these treatments, and robust biomarkers are required to help clinicians select patients who are most likely to benefit. Here, we discuss the available evidence on the utility of clinical characteristics in the selection of patients with advanced non-small-cell lung cancer as potential candidates for single-agent anti-PD-1/PD-L1 therapy, and provide practical guidance to clinicians on identifying those patients who are most likely to benefit. Recommendations on the use of immune checkpoint inhibitor in clinically challenging populations are also provided.

Aim: To conduct a systematic review and meta-analysis feasibility of clinical, quality of life and economic evidence for neurotrophic tropomyosin-related receptor tyrosine kinases ( NTRK) inhibitors in patients with NTRK gene fusion-positive tumors. Materials & methods: Databases were searched for studies on NTRK inhibitors in adult and pediatric patients. Results: 27 publications reported clinical data for seven interventions. Efficacy/safety data were available for two interventions only. Four trials each reported data for larotrectinib and entrectinib with pooled analyses reporting objective response rates of 75% (95% CI: 61–85) and 57.4% (43.2–70.8), respectively. No publications reported economic or quality of life evidence. Conclusion: Preliminary data demonstrate that NTRK inhibitors are well tolerated and show impressive clinical benefit; corroboration of existing studies and real-world data are required.

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