A new class of potent and selective PDE5 inhibitors is disclosed. Guided by X-ray crystallographic data, optimization of an HTS lead led to the discovery of a series of 2-aryl, (N8)-alkyl substituted-6-aminosubstituted pyrido[3,2b]pyrazinones which show potent inhibition of the PDE5 enzyme. Synthetic details and some structure-activity relationships are also presented.

This clinical study clearly shows the effects of balancing the foot and leg on the pedal and the usefulness of the technique for treatment of overuse cycling knee problems. Most of the cyclists perceived, reported, and were measured to have improved efficiency of their pedaling strokes.

The aim of this work was to assess the feasibility of a treatment based on volitional cycling augmented by Functional Electrical Stimulation (FES) on hemiparetic adolescents. Six chronic hemiparetic adolescents were included in a case series study. Patients underwent FES-cycling training combined with voluntary pedaling. The intervention consisted of 21 sessions lasting 30 minutes each. Patient...

Objective: To elucidate the value of early computed tomographic (CT) signs of stroke in predicting the occlusion site in the cerebral arteries. Patients: 105 consecutive patients with acute embolic stroke affecting the anterior circulation. Methods: Four early signs were evaluated on cranial CT within six hours of stroke onset: loss of the insular ribbon (LIR); attenuation of the lentiform nucl...

Transcranial magnetic stimulation-electroencephalogram (TMS-EEG) co-registration offers the opportunity to test reactivity of brain areas across distinct conditions through TMS-evoked potentials (TEPs). Several TEPs have been described, their functional meaning being largely unknown. In particular, short-latency potentials peaking at 5 (P5) and 8 (N8) ms after the TMS pulse have been recently d...