There is universal agreement that the Nobel Prizes, given to individuals who have made an extraordinarily notable contribution to humankind in the fields of chemistry, physics, physiology or medicine, literature, and peace, are the most prestigious prizes offered for human achievement. This commentary gives an overview of the basis for Alfred Nobel writing his third will that established the five prizes and includes a discussion of why those five fields were chosen. The commentary includes factors that influenced his choices and contains examples of controversial selections or omissions, especially in the earlier years. A few were errors of omission (e.g. Tolstoy, Tesla, Edison, Best, Gandhi, Franklin), some errors of commission (e.g. Fibiger, Moniz); but, given the complexity of the task, the error rate is small. In some cases, the conclusion that an error had been made is debatable. Such decisions are difficult. Arne Tiselius, a Nobel laureate in chemistry and President of the Nobel Foundation said that one cannot in practice apply the principle that the Nobel Prize should be given to the person who is best; it is impossible to define who is best. Hence, there is only one alternative: to try to find a particularly worthy candidate. This paper includes a brief review of the integration of the Sveriges Riksbank Prize in Economic Sciences in Memory of Alfred Nobel, established in 1968, and added to the original five Nobel Prizes; the prize was first awarded in 1969. A short discussion on the absence of a Nobel Prize in mathematics is provided. Adaptations to the development of “big” science, especially in physics, may require the Nobel Foundation to extend its limit of no more than three awardees for the prize in physics and, perhaps, other scientific disciplines.
Alternating hemiplegia of childhood (AHC) is a complex neurodevelopmental disorder characterized by paroxysmal and transient events of unilateral or bilateral paresis, usually occurring before 18 months of age. Mutations in the ATP1A3 gene, mainly p.Asp801Asn, p.Glu815Lys, and p.Gly947Arg at the protein level, are found in around 80% of the individuals with AHC. Interestingly, these mutations reflect the degree of severity of the neurological symptoms (p.Glu815Lys > p.Asp801Asn > p.Gly947Arg). Some channels involved in this disorder are N-type voltage-gated calcium channels, ATP-sensitive potassium channels, and the sodium/calcium exchanger. In this context, the management of AHC should be divided into the treatment of attacks, prophylactic treatment, and management of comorbidities commonly found in this group of individuals, including epilepsy, attention-deficit/hyperactivity disorder, aggressive behavior, cognitive impairment, movement disorders, and migraine. The importance of an integrated approach with a multidisciplinary team, such as neuropsychologists and dietitians, is worth mentioning, as well as the follow-up with a neurologist. In the present study, we propose new diagnostic criteria for AHC, dividing it into clinical, laboratory, supporting, and atypical features. Also, we review the location of the mutations in the ATP1A3 protein of individuals with AHC, rapid-onset dystonia-parkinsonism (RDP) variants, and early infantile epileptic encephalopathy (variants with hemiplegic attack). We also include a section about the animal models for ATP1A3 disorders.
Objectives: This document provides an English translation of the Israeli Joint Commission’s national guidelines for triaging severely ill patients during the coronavirus disease 2019 (COVID-19) pandemic.
Methods: Four subcommittees of medical, legal, ethical-social, and religious experts developed the general principles and practical medical criteria for triaging scarce life-saving resources.
Results: The guidelines provide an overview of general principles as well as pragmatic medical criteria and a practical triage protocol to be followed should the healthcare system be overwhelmed due to COVID-19. Issues covered include triggers for activating the guidelines, guiding ethical, legal, and religious principles, equity in access, fair distribution, transparency, consistency, palliation, medical policy prioritization, problem-solving mechanisms, and public trust.
Conclusions: The Israeli consensus document and pragmatic medical triage protocol offer a societal and medical roadmap for allocating scarce resources during the COVID-19 pandemic or other disasters.
Introduction: Antisemitism and antisemitic incidents have been increasing in United States medical institutions since the Hamas attack of October 7, 2023. Such incidents include anecdotal reports of antisemitic displays at medical school commencements. This study examined unprofessional behavior observed at the commencement ceremonies of the 25 US medical schools top-ranked for research excellence. This issue is significant since these graduates are expected to become future leaders in the field of medicine.
Materials and Methods: Based on publicly available videotaped commencements, we assessed the number of students in the graduating classes wearing non-school-provided regalia, carrying signs, wearing protest buttons, or engaging in verbal protests related to the Israel–terror groups conflict that were either openly antisemitic or potentially offensive or insensitive.
Results: Symbols representing antisemitic themes (keffiyehs and three-part graduation stoles conveying antisemitic messages) were worn by students at just under half (12) of the medical schools. The mean number of students in each school wearing keffiyehs or non-official school stoles was 4.0 (95% confidence interval [CI] 2.2–5.8), ranging from 0%–13% of the classes, or 2.5% of the overall graduating cohort. The wearing of buttons, carrying of banners or signs, verbal protests interrupting the ceremony, or students deviating from script ranged from 0% to 22.5% of graduating students, with a mean of 2.7 per school (95% CI -0.8–6.2), or 1.7% of the medical schools graduating cohort.
Conclusions: We identified unprofessional behavior at commencements of top-ranked medical schools consisting of antisemitism and displaying offensive and insensitive symbols and messaging. There is an urgent need for medical schools in the US to educate medical trainees about the dangers of antisemitism and all forms of hate and insensitivity.
This review describes some of the recent developments in imaging aspects of pain in the periphery. It is now possible to image nerves in the cornea non-invasively, to image receptor level expression and inflammatory processes in injured tissue, to image nerves and alterations in nerve properties, to image astrocyte and glial roles in neuroinflammatory processes, and to image pain conduction functionally in the trigeminal ganglion. These advances will ultimately allow us to describe the pain pathway, from injury site to behavioral consequence, in a quantitative manner. Such a development could lead to diagnostics determining the source of pain (peripheral or central), objective monitoring of treatment progression, and, hopefully, objective biomarkers of pain.
More than 11,000 articles lauding alternative medicine appear in the PubMed database, but there are only a few articles describing the complications of such care. Two patients suffering from complications of alternative medicine were treated in our hospital: one patient developed necrotizing fasciitis after acupuncture, and the second developed an epidural hematoma after chiropractic manipulation. These complications serve as a clarion call to the Israeli Health Ministry, as well as to health ministries around the world, to include complementary medicine under its inspection and legislative authority.
Heparanase is an endo-beta-D-glucuronidase that cleaves heparan sulfate (HS) side chains at a limited number of sites, activity that is strongly implicated with cell invasion associated with cancer metastasis, a consequence of structural modification that loosens the extracellular matrix barrier. Heparanase activity is also implicated in neovascularization, inflammation, and autoimmunity, involving migration of vascular endothelial cells and activated cells of the immune system. The cloning of a single human heparanase cDNA 10 years ago enabled researchers to critically approve the notion that HS cleavage by heparanase is required for structural remodeling of the extracellular matrix (ECM), thereby facilitating cell invasion. Heparanase is preferentially expressed in human tumors and its over-expression in tumor cells confers an invasive phenotype in experimental animals. The enzyme also releases angiogenic factors residing in the tumor microenvironment and thereby induces an angiogenic response in vivo. Heparanase up-regulation correlates with increased tumor vascularity and poor postoperative survival of cancer patients. These observations, the anticancerous effect of heparanase gene silencing and of heparanase-inhibiting molecules, as well as the unexpected identification of a single functional heparanase suggest that the enzyme is a promising target for anticancer drug development. Progress in the field expanded the scope of heparanase function and its significance in tumor progression and other pathologies such as inflammatory bowel disease and diabetic nephropathy. Notably, while heparanase inhibitors attenuated tumor progression and metastasis in several experimental systems, other studies revealed that heparanase also functions in an enzymatic activity-independent manner. Thus, point-mutated inactive heparanase was noted to promote phosphorylation of signaling molecules such as Akt and Src, facilitating gene transcription (i.e. VEGF) and phosphorylation of selected Src substrates (i.e. EGF receptor). The concept of enzymatic activity-independent function of heparanase gained substantial support by elucidation of the heparanase C-terminus domain as the molecular determinant behind its signaling capacity and the identification of a human heparanase splice variant (T5) devoid of enzymatic activity, yet endowed with protumorigenic characteristics. Resolving the heparanase crystal structure will accelerate rational design of effective inhibitory molecules and neutralizing antibodies, paving the way for advanced clinical trials in patients with cancer and other diseases involving heparanase.
This article focuses on contemporary Islamic attitudes towards the question of compensation to a non-relative live organ donor. This article presents the history of the debate on organ transplantation in Islam since the 1950s the key ethical questions. It continues by presenting the opinions of the main-stream ulema such as Tantawi and Qaradawi. The article ends with a conclusion that there must be no compensation made to a non-related live organ donor even a symbolic gift of honor (ikramiyya).
Phase 1 first-in-human studies with anti-cancer products differ from other phase 1 studies in that they are evaluated in patients rather than healthy volunteers. The rationale design of targeted drugs triggers changes in the design of these studies. Patient populations are more precisely defined and pose a challenge to the efficient inclusion of study patients. Objectives shift from the definition of a maximum tolerated dose to the evaluation of a recommended phase 2 dose. Other challenges related to the efficacy and safety profile of novel targeted anti-cancer drugs call for changes in designing first-in-human studies, such as definitions of biological doses, collection of fresh tumor tissue for surrogate marker analyses, and the management of infusion-related reactions with monoclonal antibodies.
Consequently, the conduct of phase 1 clinical trials in oncology requires changes. Corresponding education with particular focus on phase 1 trials and on the complex drug development process needs to be an integrated part of the medical oncology curriculum for physicians and nursing staff. This is a crucial element for institutions to remain or become clinical research sites for phase 1 studies, and to participate in the drug development process of novel anti-cancer compounds in the future.
Objective. To understand high-performing front-line employees’ values as reflected in their narratives of day-to-day interactions in a large health care organization.
Methods. A total of 150 employees representing various roles within the organization were interviewed and asked to share work-life narratives (WLNs) about value-affirming situations (i.e. situations in which they believed their actions to be fully aligned with their values) and value-challenging situations (i.e. when their actions or the actions of others were not consistent with their values), using methods based on appreciative inquiry.
Results. The analysis revealed 10 broad values. Most of the value-affirming WLNs were about the story-teller and team providing care for the patient/family. Half of the value-challenging WLNs were about the story-teller or a patient and barriers created by the organization, supervisor, or physician. Almost half of these focused on “treating others with dis/respect”. Only 15% of the value-challenging WLNs contained a resolution reached by the participants, often leaving them describing unresolved and frequently negative feelings.
Conclusions. Appreciative inquiry and thematic analysis methods were found to be an effective tool for understanding the important and sometimes competing role personal and institutional values play in day-to-day work. There is remarkable potential in using WLNs as a way to surface and reinforce shared values and, perhaps more importantly, respectfully to identify and discuss conflicting personal and professional values.
