The transition of new biotechnologies into clinical trials is a critical step in approving a new drug or therapy in health care. Ethically recruiting appropriate volunteers for these clinical trials can be a challenging task for both the pharmaceutical companies and the US Food and Drug Administration. In this paper we analyze the Jewish halachic perspectives of volunteering for clinical trials by focusing on an innovative technology in reproductive medicine, mitochondrial replacement therapy. The halachic perspective encourages individuals to volunteer for such clinical trials under the ethical principles of beneficence and social responsibility, when animal studies have shown that health risks are minimal.
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.
Medicine is developing through biomedical technology and innovations. The goal of any innovation in medicine is to improve patient care. Exponential growth in technology has led to the unprecedented growth of medical technology over the last 50 years. Clinician-scientists need to understand the complexity of the innovation process, from concept to product release, when working to bring new clinical solutions to the bedside. Hence, an overview of the innovation process is provided herein. The process involves an invention designed to solve an unmet need, followed by prototype design and optimization, animal studies, pilot and pivotal studies, and regulatory approval. The post-marketing strategy relative to funding, along with analysis of cost benefit, is a critical component for the adoption of new technologies. Examples of the road to innovation are provided, based on the experience with development of the transcatheter aortic valve. Finally, ideas are presented to contribute to the further development of this worldwide trend in innovation.
Objective: Urology practice has undergone several changes in recent years mainly related to novel technologies introduced. We aimed to get the residents’ perspective on the current residency program in Israel and propose changes in it.
Methods: A web-based survey was distributed among urology residents.
Results: 61 residents completed the survey out of 95 to whom it was sent (64% compliance). A total of 30% replied that the 9 months of mandatory general surgery rotation contributed to their training, 48% replied it should be shortened/canceled, and 43% replied that the Step A exam (a mandatory written certifying exam) in general surgery was relevant to their training. A total of 37% thought that surgical exposure during the residency was adequate, and 28% considered their training “hands-on.” Most non-junior residents (post-graduate year 3 and beyond) reported being able to perform simple procedures such as circumcision and transurethral resections but not complex procedures such as radical and laparoscopic procedures. A total of 41% of non-junior residents practice at a urology clinic. A total of 62% of residents from centers with no robotics replied its absence harmed their training, and 85% replied they would benefit from a robotics rotation. A total of 61% of residents from centers with robotics replied its presence harmed their training, and 72% replied they would benefit from an open surgery rotation. A total of 82% of the residents participated in post-graduate courses, and 81% replied they would engage in a clinical fellowship.
Conclusion: Given the survey results we propose some changes to be considered in the residency program. These include changes in the general surgery rotation and exam, better surgical training, possible exchange rotations to expose residents to robotic and open surgery (depending on the availability of robotics in their center), greater out-patient urology clinic exposure, and possible changes in the basic science period.
The strong relationship between cardiovascular diseases (CVD), atherosclerosis, and endogenous or exogenous lipids has been recognized for decades, underestimating the contribution of other dietary components, such as amino acids, to the initiation of the underlying inflammatory disease. Recently, specific amino acids have been associated with incident cardiovascular disorders, suggesting their significant role in the pathogenesis of CVD. Special attention has been paid to the group of branched-chain amino acids (BCAA), leucine, isoleucine, and valine, since their plasma values are frequently found in high concentrations in individuals with CVD risk. Nevertheless, dietary BCAA, leucine in particular, have been associated with improved indicators of atherosclerosis. Therefore, their potential role in the process of atherogenesis and concomitant CVD development remains unclear. Macrophages play pivotal roles in the development of atherosclerosis. They can accumulate high amounts of circulating lipids, through a process known as macrophage foam cell formation, and initiate the atherogenesis process. We have recently screened for anti- or pro-atherogenic amino acids in the macrophage model system. Our study showed that glycine, cysteine, alanine, leucine, glutamate, and glutamine significantly affected macrophage atherogenicity mainly through modulation of the cellular triglyceride metabolism. The anti-atherogenic properties of glycine and leucine, and the pro-atherogenic effects of glutamine, were also confirmed in vivo. Further investigation is warranted to define the role of these amino acids in atherosclerosis and CVD, which may serve as a basis for the development of anti-atherogenic nutritional and therapeutic approaches.
OBJECTIVE: Right-sided endocarditis (RSE) accounts for 5%–10% of all cases of infective endocarditis (IE) and frequently has different etiological, pathogenetic, and clinical presentations compared with left-sided endocarditis (LSE). The aims of this study were to evaluate the epidemiologic and clinical characteristics and prognosis of RSE patients and to compare them with those of LSE patients. This study’s importance relates to the local understanding of RSE and LSE, since Israeli demographics are different compared to the Unites States and Europe with regard to intravenous drug abuse and rheumatic valvular disease prevalence.
MATERIAL AND METHODS: A retrospective cohort study of 215 patients with infective endocarditis was performed. The primary outcome was in-hospital mortality. The secondary outcomes were duration of hospitalization, recurrent hospitalization, recurrent infective endocarditis, and one-year mortality.
RESULTS: Of the 215 patients in the study, 176 had LSE and 39 had RSE. The RSE patients were younger than the LSE patients (48.1±18.9 years versus 61.8±17.0 years, P<0.001). The most common pathogen in both groups was Staphylococcus aureus, which occurred more in the RSE group (51%) versus the LSE group (19%). In-hospital mortality was lower among patients with RSE (2.6% versus 17%, P<0.037).
CONCLUSIONS: Our study demonstrated an increasing percentage of RSE compared to LSE among patients with IE. Pacemaker lead infection has become the leading cause of RSE in intravenous drug users (IVDU), although less common in Southern Israel. The etiological and clinical differences between RSE and LSE are noteworthy. Patients with RSE have a better prognosis than those with LSE.
Background: The importance of emotional intelligence (EI) to the success of health professionals has been increasingly acknowledged. Concurrently, medical schools have begun integrating non-cognitive measures in candidate selection processes. The question remains whether these newly added processes correctly assess EI skills.
Objectives: Measuring EI levels among medical students; examining the correlations between participants’ EI levels and their scores on the non-cognitive MOR test; and exploring students’ attitudes regarding the importance of EI in medical practice.
Methods: The study included 111 first-year and sixth-year students at the Faculty of Medicine at the Technion, Haifa, Israel. Emotional intelligence was assessed by the Bar-On EQ-i 2.0, and MOR evaluation scores were provided by the faculty. An additional questionnaire was designed to rate students’ attitudes toward the importance of EI to the success of medical doctors (MDs).
Results: No significant correlations were found between MOR test scores and EI evaluation scores. Of the 15 EI competencies evaluated, mean scores for flexibility, problem-solving, and independence were lowest for both the first-year and the sixth-year study groups. No differences in EI levels between first-year and sixth-year students were found. Both groups of students considered EI to be highly important to their success as MDs.
Conclusions: While further studies of the links between MOR tests and EI are required, the current findings indicate that MOR test scores may not be predictive of medical students’ EI levels and vice versa. As previous evidence suggests that EI contributes to professional success and to better outcomes in the field of medicine, integrating it into selection processes for medical students and into the curricula in medical schools is recommended.
We are proud to introduce you to the Fifteenth Annual Rambam Research Day, now established as a key annual event at Rambam Health Care Campus, Haifa, Israel, reflecting the diverse research activities on our campus.
Public health is connected to cannabis with regard to food, animal feed (feed), and pharmaceuticals. There¬fore, the use of phytocannabinoids should be examined from a One Health perspective. Current knowledge on medical cannabis treatment (MCT) does not address sufficiently diseases which are of epidemiological and of zoonotic concern. The use of cannabinoids in veterinary medicine is illegal in most countries, mostly due to lack of evidence-based medicine. To answer the growing need of scientific evidence-based applicable medicine in both human and veterinary medicine, a new approach for the investigation of the therapeutic potential of cannabinoids must be adopted. A model that offers direct study of a specific disease in human and veterinary patients may facilitate development of novel therapies. Therefore, we urge the regulatory authorities—the ministries of health and agriculture (in Israel and worldwide)—to publish guidelines for veterinary use due to its importance to public health, as well as to promote One Health-related preclinical translational medicine studies for the general public health.
Anti-citrullinated protein antibodies (ACPAs) are highly specific serologic markers for rheumatoid arthritis (RA) and can pre-date clinical disease onset by up to 10 years, also predicting erosive disease. The process of citrullination, the post-translational conversion of arginine to citrulline residues, is mediated by peptidylarginine deiminase (PAD) enzymes present in polymorphonuclear cells (PMNs). Calcium ions (Ca2+) are required for PAD activation, but the intracellular Ca2+ concentration in normal cells is much lower than the optimal Ca2+ concentration needed for PAD activation. For this reason, it has been proposed that PAD activation, and thus citrullination, occurs only during PMN cell death when PAD enzymes leak out of the cells into the extracellular matrix, or extracellular Ca2+ enters the cells, with the high Ca2+ concentration activating PAD. Recently, using artificial in vitro systems to corroborate their hypothesis, Romero et al. demonstrated that “hypercitrullination,” citrullination of multiple intracellular proteins, occurs within synovial fluid (SF) cells of RA patients, and that only modes of death leading to membranolysis such as perforin-granzyme pathway or complement membrane attack complex activation cause hypercitrullination. In order for Romero’s hypothesis to hold, it is reasonable to surmise that PMN-directed lysis should occur in the rheumatoid joint or the circulation of RA patients. Research conducted thus far has shown that immunoglobulin G (IgG) targeting PMNs are present in RA SF and mediate PMN activation. However, the role of anti-PMN IgG in mediating complement activation and subsequent PMN lysis and hypercitrullination has not been fully evaluated.
