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The main objectives of this trial are to investigate safety, tolerability and pharmacokinetics (PK) of BI 1819479 in healthy female subjects of non-childbearing potential.
The main purpose of this study is to measure how much of Imlunestrant (LY3484356) gets into the bloodstream and how long it takes the body to eliminate it in female participants with impaired liver function compared to female participants with normal liver function. The side effects and tolerability of Imlunestrant will also be evaluated. The study may last up to 46 days for each participant.
The main purpose of this study is to evaluate the safety and tolerability of LY3462817 in healthy Japanese and non-Japanese participants. The study will also assess how fast LY3462817 gets into the blood stream and how long it takes the body to remove it. The study is open to healthy participants. The study will last up to approximately 12 weeks.
Recent research evidence suggests that cottonseed oil (CSO) may have both direct and indirect anti-inflammatory and anti-oxidative impacts linked to bioactive components of CSO and favorable alterations in lipid metabolism. These impacts are directly related to non-communicable diseases such as diabetes, cardiovascular diseases, and cancer. Our overarching hypothesis is that the effect of CSO consumption on oxidative stress markers (isoprostanes), inflammatory cytokines, metabolic biomarkers, and bile acid metabolism will be beneficial for reversing disease pathophysiology linked to oxidative stress, inflammation, and bile acids. Our long-term goal is to establish effective and practical therapeutic strategies utilizing dietary incorporation of CSO to prevent or reverse these diseases. The following hypotheses will be tested in the proposed investigation: H1: CSO consumption will lower exercise-induced oxidative stress, and the effect of CSO will be greater than that of OO for lowering of exercise-induced oxidative stress. H2: CSO consumption will lower inflammatory cytokines and metabolic markers linked to the inflammation process in human participants, and the effect of CSO will be greater than that of OO for lowering inflammation. H3: Features of serum bile acids, serum metabolomes, and lipidomes distinguishing CSO and OO treatment correspond to metabolic pathways illuminating the health benefits of CSO treatment. H4: Metabolic and inflammatory impacts of dietary oils will be greater for 60 g/d of CSO compared to 30 g/d.
Stroke survivors experience motor deficits, weak voluntary muscle activations, and low weight-bearing capacity that impair ambulation. Restoring motor function is a priority for people post-stroke, whose gait patterns are slow, and metabolically inefficient. The role of the ankle is crucial for locomotion because it stores mechanical energy throughout the stance phase, leading to a large activation of plantarflexor muscles during push-off for propulsion. After a stroke, paretic plantarflexors undergo changes in their mechanics and activation patterns that yield diminished ankle power, propulsion, and gait speed. Recovery of lost plantarflexor function can increase propulsion and mitigate unnatural gait compensations that occur during hemiparetic walking. In the stance phase, dorsiflexion is imposed at the ankle and the plantarflexors are loaded, which results in excitation of group Ia and II afferents, and group Ib afferents. Load sensing Ib afferents are active in mid-late stance, and through spinal excitatory pathways, reinforces the activation of plantarflexors and propulsive force generation at the ankle. Targeting the excitability of the load sensitive Ib excitatory pathway, propulsive soleus activity and resulting force generation (and thereby gait speed) can be improved after stroke. The long-term research goal is to develop a novel hybrid gait paradigm integrating operant conditioning and powered wearable devices to advance neuro-behavioral training and enhance locomotor ability after stroke. The overall objectives are to 1) modulate the soleus muscle loading response within the stance phase, and 2) develop a dynamic protocol to operantly condition the soleus response in stroke survivors. The central hypothesis is that enhancing the soleus loading response in mid-late stance phase through operant up-conditioning can increase plantarflexor power and forward propulsion after stroke. In working towards attaining the research objective and testing the central hypothesis, the objective of this pilot study is to modulate the soleus loading response in the stance phase during treadmill walking. The specific aims in this study are to 1) apply ankle perturbations in mid-late stance phase combining a control algorithm and a powered device to characterize the changes in soleus EMG between perturbed and unperturbed (i.e., when no perturbations are applied) step cycles in 15 able-bodied individuals; and 2) determine the feasibility of the wearable ankle device and its algorithm in 5 participants with hemiparesis and gait deficits due to a stroke. The testing of the device and its algorithm will provide foundational evidence to adjust the soleus stimuli continuously and reliably, and develop the new walking operant conditioning protocol for stroke survivors. An expected outcome in this pilot is to lay the groundwork to develop the soleus up-conditioning protocol as a potential strategy to improve paretic leg function. If successfully developed, this new protocol proposed in a subsequent study will be the first neurobehavioral training method that targets spinal load-sensitive pathways to improve ankle plantarflexor power and forward propulsion after stroke.
This project will study the feasibility of motor rehabilitation in people with cerebellar ataxia using real-time functional magnetic resonance imaging neurofeedback (rt-fMRI NF) in conjunction with motor imagery. To do so, data will be collected from healthy adults in this protocol, to be compared with data from cerebellar ataxia participants.
The purpose of this study is to evaluate the bioequivalence of macitentan on the primary pharmacokinetics (PK) parameters between the dispersible final market image (FMI) macitentan tablet and the opsumit tablet in healthy adult participants in fasted conditions.
This study is designed to evaluate the safety and tolerability, pharmacokinetics and pharmacodynamics of single and multiple doses of ALXN2080 in healthy adult participants.
The main objective of this trial is to investigate the relative bioavailability of BI 1015550 intended Commercial Formulation (iCF) compared with Trial Formulation 2 (TF2) and the effect of food on the pharmacokinetics of BI 1015550 iCF following oral administration.
This study will investigate the effect of caffeine and time of day on brain excitability using excitatory brain stimulation. We will recruit a healthy participant and conduct a concurrent iTBS/fNIRS protocol for 20 consecutive sessions over four weeks with or without caffeine consumption before the stimulation. Moreover, the experiment will be conducted at different times of the day (morning or afternoon)