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.
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.
Results of clinical studies are often contradictory in real time, and in other instances therapies may be adopted due to information from clinical studies where the data may be premature or resulting from small studies. Much of the data may have inherent selection biases, and their interpretation may be confusing and difficult. The hematological literature is full of such examples, and this review will describe some such instances in the hope of introducing both a cautionary note and encouraging more precise description of study conditions as well as an appreciation of the importance of allowing data from clinical studies to mature. Several examples will be drawn from clinical studies in lymphomas, leukemia, and bone marrow transplantation.
Cardiovascular disease (CVD), associated with vascular atherosclerosis, is the major cause of death in Western societies. Current risk estimation tools, such as Framingham Risk Score (FRS), based on evaluation of multiple standard risk factors, are limited in assessment of individual risk. The majority (about 70%) of the general population is classified as low FRS where the individual risk for CVD is often underestimated but, on the other hand, cholesterol lowering with statin is often excessively administered. Adverse effects of statin therapy, such as muscle pain, affect a large proportion of the treated patients and have a significant influence on their quality of life.
Coronary artery calcification (CAC), as assessed by computed tomography, carotid artery intima-media thickness (CIMT), and especially presence of plaques as assessed by B-mode ultrasound are directly correlated with increased risk for cardiovascular events and provide accurate and relevant information for individual risk assessment. Absence of vascular pathology as assessed by these imaging methods has a very high negative predictive value and therefore could be used as a method to reduce significantly the number of subjects who, in our opinion, would not benefit from statins and only suffer from their side-effects.
In summary, we suggest that in very-low-risk subjects, with the exception of subjects with low FRS with a family history of coronary artery disease (CAD) at young age, if vascular imaging shows no CAC or normal CIMT without plaques, statin treatment need not be administered.
Four decades of innovations in the field of interventional cardiology are presented as an example for the great growth of high technology in medicine, sidebyside with the development of general technology and science. The field of percutaneous coronary intervention (PCI) was enabled by the development of X-ray systems,allowing us to view the pathology,and was critically dependent on courageous and imaginative physicians and scientists who developed percutaneous transluminal coronary angioplasty (PTCA), stents, and transarterial aortic valve replacement (TAVR). Today, outstanding research continues to progress, with stem cell research and IPC technologiespresenting new challenges and yet taller mountains to climb. The rapid development we have witnessed was due to tight collaborations between clinical and academic institutions and industry. The combination of all these elements, with a proper mechanism to handle conflict of interest,is an essential linkage for any progress in this field. We will continue to see exponential growth of innovations and must be prepared with appropriate bodies to encourage such developments and to provide early-stage funding and support for novel ideas.
Therapy of Hodgkin lymphoma (HL) is a rapidly changing field due to plenty of currently emerging data. Treatment approaches are currently based on tailoring of therapy in order to achieve a maximal response with minimal toxicity. Since the median age of HL patients is 33 years and their prospective life expectancy another half a century, a major emphasis needs to be put on dramatic reduction of later toxicity. The assessment of the treatment effect should be based not only on progression-free survival, but should include evaluation of cardiac toxicity, secondary neoplasms, and fertility in the long-term follow-up. The ancient principle “first do no harm” should be central in HL therapy. Completion of ongoing and currently initiated trials could elucidate multiple issues related to the management of HL patients.
Non-Hodgkin lymphoma (NHL) is one of the most common hematologic malignancies worldwide. The incidence of NHL has been rising for several decades; however, in the last 20 years, it reached a plateau. NHL incidence among males is significantly higher than in females. In addition to gender itself, gravidity has a protective role against NHL occurrence. Gender also matters in terms of NHL clinical characteristics. For example, female predominance was found in three extra-nodal sites (the breast, thyroid, and the respiratory system) occasionally involved in NHL. The diagnosis of NHL during pregnancy is associated with a unique clinical behavior. It is usually diagnosed in the second or third trimester and in advanced stage. Furthermore, the histological subtype is highly aggressive, and reproductive organ involvement is common. The reduced rate of NHL among females may be explained by direct effects of estrogens on lymphoma cell proliferation or by its effect on anti-tumor immune response. Gender has an important role in responsiveness to standard B cell NHL treatment. Among older adults, women benefited more from the addition of the anti-CD20 antibody rituximab to standard chemotherapy regimens. This phenomenon can be explained by the difference in clearance rate of rituximab that was found to be significantly lower among older females than older males. In mantle cell lymphoma, women receiving lenalidomide have higher rates of response. An understanding of the mechanisms responsible for gender-associated NHL differences will ultimately improve the clinical approach, allowing for a more accurate assessment of prognosis and patient-tailored treatment.
Objectives: This study was aimed at establishing an ideal method for performing three-dimensional measurements of the fetus in order to improve the estimation of fetal weight.
Methods: The study consisted of two phases. Phase I was a prospective cross-sectional study performed between 28 and 40 weeks’ gestation. The study population (n=110) comprised low-risk singleton pregnancies who underwent a routine third-trimester sonographic estimation of fetal weight. The purpose of this phase was to establish normal values for the fetal abdominal and head volumes throughout the third trimester. Phase II was a prospective study that included patients admitted for an elective cesarean section or for induction of labor between 38 and 41 weeks’ gestation (n=91). This phase of the study compared the actual birth weight to two- (2D) and three-dimensional (3D) measurements of the fetus. Conventional 2D ultrasound fetal biometry was performed measuring the biparietal diameter (BPD), head circumference (HC), abdominal circumference (AC), and femur diaphysis length (FL). Volume estimates were computed utilizing Virtual Organ Computer-aided AnaLysis (VOCAL), and the correlation between measured volumes and actual neonatal weight was calculated.
Results: Overall, this longitudinal study consisted of 110 patients between 28 and 41 weeks’ gestation. Normal values were computed for the fetal abdomen and head volume throughout the third trimester. Ultrasound examination was performed within three days prior to delivery on 91 patients. A good correlation was found between birth weight and abdominal volume (r=0.77) and between birth weight and head volume (r=0.5). Correlation between bidimensional measurements and actual fetal weights was found to be comparable with previously published correlations.
Conclusion: Volume measurements of the fetus may improve the accuracy of estimating fetal size. Additional studies using different volume measurement of the fetus are necessary.
Mueller is to be congratulated for a comprehensive and detailed exposition on medical professionalism. There is no question but that professionalism is important—however, Mueller is correct to point out the complexities of the subject and the fact that there is no single or simple way to teach or assess professionalism. ...
This brief introduction is followed by a published version of my Nobel Laureate lecture, re-published herein with the kind permission of the Nobel Foundation. Much has happened since my original research, for which that prize was awarded. Hence, I am pleased to offer a few thoughts about the future of my research and its possible impact on humankind.
Although the original work on nuclear transfer and reprogramming was done over half a century ago, advances continue to be made. In particular the Takahashi and Yamanaka induced pluripotent stem cells (iPS) procedure has opened up the field of cell replacement to a great extent. Now, more recently, further advances make this whole field come closer to actual usefulness for humans. Recently, in the UK, the government approved the use of mitochondrial replacement therapy to avoid the problems associated with genetically defective mitochondria in certain women. Although the House of Commons (members of Parliament) and the House of Lords had to debate and discuss whether to allow this kind of human therapy, I was very pleased to find that both bodies approved this procedure. This means that a patient can choose to make use of the procedure; it does not in any way force an individual to have a procedure that they are not comfortable with. In my view, this is a great advance in respect to giving patients a choice about the treatment they receive. I am told that the UK is the first country in the world to approve mitochondrial replacement therapy.
Now that the Clustered Regularly Interspaced Short Palindromic Repeat (CRISPr) technology is being widely used and works well, one can foresee that there will be those who wish to use this technology to make genetic changes to humans. For example, if a human has a gene that makes it susceptible to infection or any other disorder, the removal of that gene might give such a person immunity from that disease. If this gene deletion is done within the germ line, the genetic change will be inherited. However, one can imagine that various people will strongly object and say that this technology should not be allowed. I would very much hope that various regulatory bodies, governments, etc. will allow the choice to remain with the individual. I can see no argument for such bodies to make a law that removes any choice whatsoever by an individual.
