Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic cardiac disorder characterized by life-threatening arrhythmias induced by physical or emotional stress, in the absence structural heart abnormalities. The arrhythmias may cause syncope or degenerate into cardiac arrest and sudden death which usually occurs during childhood. Recent studies have shown that CPVT is caused by mutations in the cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) genes. Both proteins are key contributors to the intracellular Ca2+ handling process, and play a pivotal role in Ca2+ release from the SR to the cytosol during systole. Although the molecular pathogenesis of CPVT is not entirely clear, it was suggested that the CPVT mutations promote excessive SR Ca2+ leak, which initiates delayed afterdepolarizations (DADs) and triggered arrhythmias in cardiac myocytes. The recent breakthrough discovery of induced pluripotent stem cells (iPSC) generated from somatic cells (e.g., fibroblasts, keratinocytes), now enables researches to investigate mutated cardiomyocytes generated from the patient's iPSC. To this end, in the present article we review recent studies on CPVT iPSC-derived cardiomyocytes, thus demonstrating in the mutated cells catecholamine-induced DADs and triggered arrhythmias.
Late onset is a key unifying feature of human neurodegenerative maladies such as Alzheimer’s and Parkinson’s diseases and prion disorders. While sporadic cases typically emerge during the patient’s seventh decade of life or later, mutation-linked, familial cases manifest during the fifth or sixth decade. This common temporal emergence pattern raises the prospect that slowing aging may prevent the accumulation of toxic protein aggregates that lead to the development of these disorders, postpone the onset of these maladies, and alleviate their symptoms once emerged. Invertebrate-based studies indicated that reducing the activity of insulin/IGF signaling (IIS), a prominent aging regulatory pathway, protects from neurodegeneration-linked toxic protein aggregation. The validity of this approach has been tested and confirmed in mammals as reducing the activity of the IGF-1 signaling pathway protected Alzheimer’s model mice from the behavioral and biochemical impairments associated with the disease. Here I review the recent advances in the field, describe the known mechanistic links between toxic protein aggregation and the aging process, and delineate the future therapeutic potential of IIS reduction as a treatment for various neurodegenerative disorders.
The sirtuins are highly conserved enzyme homologues of the yeast Sir2, with activities of NAD+ dependent deacetylase and/or mono ADP ribosyltransferase. A long line of evidence has implicated sirtuins in regulating the aging process of yeast, worms, flies, and rodents. Moreover, much work has been published on the important role of sirtuins in several age-related diseases such as diabetes type II, cancer, cardio¬vascular diseases, and dyslipidemia. However, despite the many publications supporting a pro-longevity role for sirtuins, there has been emerging debate about the direct role of Caenorhabditis elegans and Drosophila melanogaster sirtuins in aging and in lifespan extension in response to dietary restriction. In addition, until recently, the role of the seven mammalian sirtuins, SIRT1 to SIRT7, in regulating lifespan was unclear. Here, we review the history of the scientific debate on the role of sirtuins in regulating lifespan, especially in light of a recent publication showing a direct regulation of mammalian lifespan by a sirtuin family member, SIRT6.
Organ transplantation has progressed tremendously with improvements in surgical methods, organ preservation, and pharmaco-immunologic therapies and has become a critical pathway in the management of severe organ failure worldwide. The major sources of organs are deceased donors after brain death; however, a substantial number of organs come from live donations, and a significant number can also be obtained from non-heart-beating donors. Yet, despite progress in medical, pharmacologic, and surgical techniques, the shortage of organs is a worldwide problem that needs to be addressed internationally at the highest possible levels. This particular field involves medical ethics, religion, and society behavior and beliefs. Some of the critical ethical issues that require aggressive interference are organ trafficking, payments for organs, and the delicate balance in live donations between the benefit to the recipient and the possible harm to the donor and others. A major issue in organ transplantation is the definition of death and particularly brain death. Another major critical factor is the internal tendency of a specific society to donate organs. In the review below, we will discuss the various challenges that face organ donation worldwide, and particularly in Israel, and some proposed mechanisms to overcome this difficulty.
The effects of genomic medicine on child health promise to be profound. Medical applications will eventually include characterizing patients’ genomes to detect predictive mutations for pre-symptomatic counseling where treatment exists; to search for causes of diseases of unknown etiology, and to detect carriers for prenatal counseling; to define cancer and other disease-based genomes to design individualized therapy; and to understand our microbiomes to modify these in health and disease. Rapid advances in technology and bioinformatics has reduced the cost and the time and increased the accuracy necessary to sequence whole genomes or whole exomes. However, complete understanding of disease will also require correlation of genomic information with high-quality phenotypic data. In addition, several critical ethical, psycho-social, and public policy issues will require clarity in the coming years. Ultimately these advances will improve the effectiveness of health care for children and for society.
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.
We review three decades of unsuccessful efforts by public policy-makers in the United States to develop programs to lower the rate of preterm birth. We analyze why these efforts had been unsuccessful. Finally, we will speculate about whether something has changed in the last few years that might finally bend the curve and reverse the trend of a steadily rising preterm birth rate.
The first Jewish medical graduates at the University of Padua qualified in the fifteenth century. Indeed, Padua was the only medical school in for most of the medieval period in Europe where Jewish students could study freely. Though Jewish students came to Padua from many parts of Europe the main geographical sources of its Jewish students were from the Venetian lands. However, the virtual Padua monopoly on Jewish medical education came to an end during the seventeenth century as the reputation of the Dutch medical school in Leiden grew. For Jews seeking to enter the medical profession aspiring medieval Jewish physicians Padua was, for around three hundred years, the first, simplest and usually the only choice.
The Cox maze procedure developed originally in 1987 by Dr James Cox has evolved from a “cut and sew” surgical procedure, where the maze was applied using multiple surgical cuts, to an extensive use of surgical ablation technology where ablation lesions are placed with alternative energy sources (radiofrequency, cryothermy, microwave, and high-frequency ultrasound). Furthermore, the procedure has changed from a median sternotomy approach only to one that can be performed minimally invasively and robotically. The purpose of this paper is to review the current available technology for the ablation of atrial fibrillation as well as the different procedural approaches for the surgical ablation of atrial fibrillation.
The surgical repair of complex congenital heart defects frequently requires additional tissue in various forms, such as patches, conduits, and valves. These devices often require replacement over a patient’s lifetime because of degeneration, calcification, or lack of growth. The main new technologies in congenital cardiac surgery aim at, on the one hand, avoiding such reoperations and, on the other hand, improving long-term outcomes of devices used to repair or replace diseased structural malformations. These technologies are: 1) new patches: CorMatrix® patches made of decellularized porcine small intestinal submucosa extracellular matrix; 2) new devices: the Melody® valve (for percutaneous pulmonary valve implantation) and tissue-engineered valved conduits (either decellularized scaffolds or polymeric scaffolds); and 3) new emerging fields, such as antenatal corrective cardiac surgery or robotically assisted congenital cardiac surgical procedures. These new technologies for structural malformation surgery are still in their infancy but certainly present great promise for the future. But the translation of these emerging technologies to routine health care and public health policy will also largely depend on economic considerations, value judgments, and political factors.
