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  • Representation and Learning in Neuronal Networks: A Conceptual Nervous System Approach

    The work presented in this review describes the use of large cortical networks developing ex-vivo, in a culture dish, to study principles underlying synchronization, adaptation, learning, and representation in neuronal assemblies. The motivation to study neuronal networks ex-vivo is outlined together with a short description of recent results in this field. Following a short description of the experimental system, a set of basic results will be presented that concern self-organization of activity, dynamical and functional properties of neurons, and networks in response to external stimulation. This short review ends with an outline of future questions and research directions.
  • An Update on the Ketogenic Diet, 2012

    The ketogenic diet has been in use for the last 90 years, and its role in the treatment of epilepsy in the pediatric population has been gaining recognition. It can be helpful in many types of epilepsies, even the more severe ones, and has a beneficial effect on the child’s alertness and cognition, which can be impaired by both the condition and the medications needed for controlling it. Parental compliance is good in spite of the inconveniences inherent in following the diet. The significant advancements in understanding the nature of the diet are in better defining when its use is contraindicated and in validating its application in severe epilepsies in infancy, such as infantile spasms. Although most neurologists do not consider it as being the preferred first-line therapy, it is often a reasonable option when two medications have already failed.
  • The Role of the Physician-Scientist in Our Evolving Society

    The physician-scientist represents the medical-scientific version of the “triple threat” athlete. Yet, in medicine as in sports, specialization and business are ever more in the forefront. As the field of medicine evolves, it is likely that the role of the physician, the scientist, and the physician-scientist will continue to change. Whether this is for the good or bad will only be known in hindsight.
  • Intracellular Protein Degradation: From a Vague Idea through the Lysosome and the Ubiquitin-Proteasome System and onto Human Diseases and Drug Targeting

    Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code was transcribed to RNA and translated to proteins, but how proteins were degraded had remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis was largely non-lysosomal, but the mechanisms involved have remained obscure. The discovery of the ubiquitin-proteasome system resolved the enigma. We now recognize that degradation of intracellular proteins is involved in regulation of a broad array of cellular processes, such as cell cycle and division, regulation of transcription factors, and assurance of the cellular quality control. Not surprisingly, aberrations in the system have been implicated in the pathogenesis of human disease, such as malignancies and neurodegenerative disorders, which led subsequently to an increasing effort to develop mechanism-based drugs.
  • At the Edge of Viability: Moral and Ethical Guideline Proposals

    The paper proposes moral and ethical guidelines for medical treatment at the edge of viability. The proposed principles are defended on the grounds of a general conceptual framework presented by elucidating the notions of viability, the edge of viability, person, sanctity of human life, dignity, and the slope of dignity protection, as well as the distinction between ethics and morality.
  • Heparanase – A Link Between Coagulation, Angiogenesis and Cancer

    Heparanase that was cloned from and is abundant in the placenta is implicated in cell invasion, tumor metastasis, and angiogenesis. Recently we have demonstrated that heparanase may also affect the hemostatic system in a non-enzymatic manner. Heparanase was shown to up-regulate tissue factor (TF) expression and interact with tissue factor pathway inhibitor (TFPI) on the cell surface, leading to dissociation of TFPI from the cell membrane of endothelial and tumor cells, resulting in increased cell surface coagulation activity. More recently, we have shown that heparanase directly enhances TF activity, resulting in increased factor Xa production and activation of the coagulation system. Data indicate increased levels and possible involvement of heparanase in vascular complications in pregnancy. Taking into account the prometastatic and proangiogenic functions of heparanase, overexpression in human malignancies, and abundance in platelets and placenta, its involvement in the coagulation machinery is an intriguing novel arena for further research.
  • Toward Becoming an Accomplished Physician: Maimonides versus Galen

    Although Maimonides stated that perfection in the medical art, both in theoretical and in practical expertise, is very difficult to achieve, he did not accept Galen's opinion, i.e. that perfection is beyond human capability. Any person seeking intellectual perfection should, according to Maimonides' view, be fully trained in logic, in the natural sciences, and in theology. A physician is moreover requested to study and memorize basic medical literature; he must consider each patient as a sick individual, without neglecting the patient's psychological disposition; and he should aim at inspiring confidence and trust, not only to his patient, but also to the latter's environment. Even when feeling competent and trustworthy, the physician should not be conceited; here Maimonides insists on offering his personal experience, in a quite impressive way. This approach of Maimonides to the practice of medicine should be considered, even today, as a valuable incentive for patient-oriented medical education, as already expressed in the late eleventh century.
  • New Insights in Celiac Disease

    Celiac disease (CD) is an autoimmune disorder occurring in genetically susceptible subjects. The incidence of CD is around 1%, and it is much more common in first-degree relatives of CD patients, 10%–18%. However, the pattern of the genetic inheritance is still obscure. Environmental factors are undoubtedly affecting the disease’s clinical presentation, time at presentation, and maybe effect on the characteristics of the disease. The clinical presentation of CD has shifted during the previous decades from the classical presentation in which the toddler suffers from diarrhea, constipation, vomiting, failure to thrive, abdominal distension, etc., to the child with a monosymptomatic presentation, such as anemia, as well as an enlarged list of extra-intestinal disorders. The diagnosis of CD is being established by symptoms consistent with CD and positive serology. The ultimate diagnosis should be made upon histological evaluation of the small bowel mucosa. The treatment of CD is a lifelong, strict gluten-free diet (GFD). Compliance with a GFD is quite difficult. Therefore, new strategies for prevention and treatment modalities other than GFD are greatly needed. Recently several promising therapeutic modalities have been developed; these include resuming traditional baking techniques. Another methodology is using probiotic-driven prolylendopeptidase. Another pathway to tackle the therapeutic option in CD is by down-regulation of the activity of zonulin—the active pump enabling gluten to enter the enterocytes. We are facing an era where other modalities beyond a GFD might allow CD patients to be able to tolerate occasionally a small amount of gluten in their diet.
  • Patient-Centered Bedside Education and Traditional Jewish Law and Ethics

    Background—Bedside rounds have long been a time-honored component of medical education. Recently, there have been various recommendations that residency training programs further incorporate bedside teaching into clinical curricula. Objectives—To compare these current attitudes regarding bedside education with the position of traditional Jewish law and ethics. Methods—Relevant medical journal articles and traditional Jewish sources were reviewed. Results—Halakha (the corpus of traditional Jewish law and ethics) gives greater focus to a patient-centered rather than student-centered bedside education experience. Conclusion—Residency training programs should give greater consideration to the importance of a patient-centered bedside education experience.
  • The Future in Craniofacial Surgery: Computer-Assisted Planning

    Advancements in computers, prototyping, and imaging, especially over the last 10 years, have permitted the adoption of three-dimensional imaging protocols in the health care field. In this article, the authors present an integrated simulation system for craniofacial surgical planning and treatment. Image fusion technology, which involves combining different imaging modalities, was utilized to create a realistic prototype and virtual image that can be manipulated in real time. The resultant data can then be shared over the Internet with distantly located practitioners.