Physiological and geometrical effects in the upper airways with and without mandibular advance device for sleep apnea treatment.

Sleep apnea is a sleep disorder that occurs when the breathing of a person is interrupted during the sleep. This interruption occurs because of the patient has narrowed airways and the upper airways muscles relax, closes in and blocks the airway. Therefore, any forces or reaction originated by the air flow dynamics over the relaxed upper airways muscles could make to close the upper airways, and consequently the air could not flow into your lungs, provoking sleep apnea. Fully describing the dynamic behavior of the airflow in this area is a severe challenge for the physicians. In this paper we explore the dynamic behavior of airflow in the upper airways of 6 patients suffering obstructive sleep apnea with/without a mandibular advancement device using computational fluid dynamics. The development of flow unsteadiness from a laminar state at entry to the pharynx through to the turbulent character in the soft palate area is resolved using an accurate numerical model. Combining the airflow solution with a geometrical analysis of the upper airways reveals the positive effects of mandibular advance device in the air flow behavior (pressure drop). Improved modeling of airflow and positioning of mandibular advance device could be applied to improve diagnosis and treatment of obstructive sleep apnea.

Immunotherapy for Alzheimer's disease: rational basis in ongoing clinical trials.

Amyloid-ß (Aß) immunotherapy has recently begun to gain considerable attention as a potentially promising therapeutic approach to reducing the levels of Aß in the Central Nervous System (CNS) of patients with Alzheimer's Disease (AD). Despite extensive preclinical evidence showing that immunization with Aß(1-42) peptide can prevent or reverse the development of the neuropathological hallmarks of AD, in 2002, the clinical trial of AN-1792, the first trial involving an AD vaccine, was discontinued at Phase II when a subset of patients immunized with Aß(1-42) developed meningoencephalitis, thereby making it necessary to take a more refined and strategic approach towards developing novel Aß immunotherapy strategies by first constructing a safe and effective vaccine. This review describes the rational basis in modern clinical trials that have been designed to overcome the many challenges and known hurdles inherent to the search for effective AD immunotherapies. The precise delimitation of the most appropriate targets for AD vaccination remains a major point of discussion and emphasizes the need to target antigens in proteins involved in the early steps of the amyloid cascade. Other obstacles that have been clearly defined include the need to avoid unwanted anti-Aß/APP Th1 immune responses, the need to achieve adequate responses to vaccination in the elderly and the need for precise monitoring. Novel strategies have been implemented to overcome these problems including the use of N-terminal peptides as antigens, the development of DNA based epitope vaccines and vaccines based on passive immunotherapy, recruitment of patients at earlier stages with support of novel biomarkers, the use of new adjuvants, the use of foreign T cell epitopes and viral-like particles and adopting new efficacy endpoints. These strategies are currently being tested in over 10,000 patients enrolled in one of the more than 40 ongoing clinical trials, most of which are expected to report final results within two years.