Loss of Nicastrin from Oligodendrocytes Results in Hypomyelination and Schizophrenia with Compulsive Behavior.

The biological underpinnings and the pathological lesions of psychiatric disorders are centuries-old questions that have yet to be understood. Recent studies suggest that schizophrenia and related disorders likely have their origins in perturbed neurodevelopment and can result from a large number of common genetic variants or multiple, individually rare genetic alterations. It is thus conceivable that key neurodevelopmental pathways underline the various genetic changes and the still unknown pathological lesions in schizophrenia. Here, we report that mice defective of the nicastrin subunit of γ-secretase in oligodendrocytes have hypomyelination in the central nervous system. These mice have altered dopamine signaling and display profound abnormal phenotypes reminiscent of schizophrenia. In addition, we identify an association of the nicastrin gene with a human schizophrenia cohort. These observations implicate γ-secretase and its mediated neurodevelopmental pathways in schizophrenia and provide support for the "myelination hypothesis" of the disease. Moreover, by showing that schizophrenia and obsessive-compulsive symptoms could be modeled in animals wherein a single genetic factor is altered, our work provides a biological basis that schizophrenia with obsessive-compulsive disorder is a distinct subtype of schizophrenia.

Ethical issues in the care of Jehovah's Witnesses.

PURPOSE OF REVIEW: To review the belief's of Jehovah's Witnesses regarding the use of blood and blood products, and how to ensure that those patients professing to be Jehovah's Witnesses are treated ethically. RECENT FINDINGS: There are a number of blog sites that have reported that Jehovah's Witnesses have changed their position on transfusion, but communications with them have revealed these reports to be untrue. Most articles about the treatment of Jehovah's Witnesses focus on respect for personal autonomy and the right to refuse treatment. Although this is imperative, especially in the USA, it is important not only to respect this right, but also to ensure that the patient understands all of his or her options, is making these decisions free of coercion, is optimally prepared for surgery and that the anesthesia provider is fully prepared. The anesthesiologist's rights should be respected as well. SUMMARY: When treating a patient that may be one of Jehovah's Witnesses, the principle of respect for autonomy is not the only principle that must be heeded. Adherence to the principles of beneficence, nonmaleficence and sometimes justice is paramount as well.

Ethical Issues in the Care of Patients Whose Personal, Religious, or Cultural Beliefs Impact Clinical Management Strategies.

Ethical principles regarding respect for patient autonomy in medical decision-making and the impact of religion, culture, and other issues on clinical care have been extensively reviewed in the medical literature. At the same time, despite physicians having an understanding of the underlying ethical principles in clinical decision-making, challenges arise when managing complicated clinical problems for which medical treatment is available, but not acceptable to the patient. For example, many anesthesiologists are challenged when caring for one of Jehohah's Witnesses who refuses to receive blood or blood products despite the potential consequences of doing so.

Ethics of Liver Transplantation: The Role of the Anesthesiologist.

Anesthesiologists have clearly established their place in the history of medical ethics. Our involvement goes back to 1966 when Henri Beecher published his landmark paper on research and informed consent. Participation in the ethics of transplantation is no less important than our previous work. Organ transplant has been life saving for many but also has given rise to many misunderstandings not just from the public but also among our own colleagues. These include methods of allocation and donation, the role that affluence may play in receiving an organ, the definition of death and donation after circulatory death. As perioperative physicians and important members of the transplant team, anesthesiologists are expected to participate in all aspects of care including ethical judgments. This article discusses some of the issues that seem to cause the most confusion and angst for those of us involved in both liver transplantation and in the procurement of organs. It will discuss the definition of death, donation after circulatory death, the anesthesiologists' role on the selection committee, living donor liver transplantation, and transplantation of patients with alcohol-related liver disease.