Epidemiologic studies now strongly support the hypothesis, proposed over 2 decades ago , that developmental programming of the kidney impacts an individual’s risk for hypertension and renal disease in later life. Low birth weight is the strongest current clinical surrogate marker for an adverse intrauterine environment, and based on animal and human studies, is associated with a low nephron number. Other clinical correlates of low nephron number include female gender, short adult stature, small kidney size and prematurity. Low nephron number in Caucasian and Australian Aboriginal subjects has been shown to be associated with higher blood pressures, and conversely, hypertension is less prevalent in individuals with higher nephron numbers. In addition to nephron number, other programmed factors associated with the increased risk of hypertension include salt-sensitivity, altered expression of renal sodium transporters, altered vascular reactivity and sympathetic nervous system overactivity. Glomerular volume is universally found to vary inversely with nephron number, suggesting a degree of compensatory hypertrophy and hyperfunction in the setting of a low nephron number. This adaptation may become overwhelmed in the setting of superimposed renal insults e.g. diabetes mellitus, or rapid catch-up growth, leading to the vicious cycle of ongoing hyperfiltration, proteinuria, nephron loss and progressive renal functional decline. Many millions of babies are born with low birth weight every year, hypertension and renal disease prevalences are increasing around the globe. At present, little can be done clinically to augment nephron number; therefore adequate pre-natal care and careful post-natal nutrition are crucial to optimize an individual’s nephron number during development, and potentially to stem the tide of the growing cardiovascular and renal disease epidemics world-wide.
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.
Pharmacogenomics is the study of an individual’s interaction with a specific drug based upon the genetic make-up of the individual. Pharmacogenomic testing can be a powerful tool in testing a drug’s potential efficacy and toxicity on an individual patient. For this tool to be used correctly, certain criteria have to be met. First and foremost is the strength of association between the genetic variation and the drug’s interaction. The predictiveness of pharmacogenomics for the individual patient must be factored in as well. If these criteria are not met, requiring pharmacogenomic testing is at best a waste of money and in some cases can endanger the patient’s life. Stent thrombosis is a serious and many times fatal outcome in a small minority of patients who have received drug-eluting stents. Here, we discuss a case in which the FDA issued a “boxed warning” about the use of the anti-clotting medication, clopidogrel, used to prevent stent thrombosis, the pharmacogenomic data available at the time the warning was issued, and the medical community’s response to the FDA’s warning. This article also discusses developments in the field of anti-clotting therapy since the FDA’s warning.
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.
Crohn's disease (CD) is a heterogeneous disorder that can involve any segment of the gastrointestinal tract.The pathogenesis of CD is unknown but is thought to involve an uncontrolled immune response triggered by an environmental factor in a genetically susceptible host.The heterogeneity of disease pathogenesis and clinical course, combined with the variable response to treatment and its associated side effects creates an environment of complex therapeutic decisions.
Despite this complexity, significant progress has been made which allows physicians to start and predict disease behavior and natural course, response to therapy and factors associated with significant side effects.
In this manuscript the data pertaining to these variables including clinical, endoscopic and the various biological and genetic markers are reviewed and the possibility of tailoring personal treatment is discussed.
Studying complex biological systems in a holistic rather than a “one gene or one protein” at a time approach requires the concerted effort of scientists from a wide variety of disciplines. The Institute for Systems Biology (ISB) has seamlessly integrated these disparate fields to create a cross-disciplinary platform and culture in which “biology drives technology drives computation.” To achieve this platform/culture, it has been necessary for cross-disciplinary ISB scientists to learn one another’s languages and work together effectively in teams. The focus of this “systems” approach on disease has led to a discipline denoted systems medicine. The advent of technological breakthroughs in the fields of genomics, proteomics, and, indeed, the other “omics” is catalyzing striking advances in systems medicine that have and are transforming diagnostic and therapeutic strategies. Systems medicine has united genomics and genetics through family genomics to more readily identify disease genes. It has made blood a window into health and disease. It is leading to the stratification of diseases (division into discrete subtypes) for proper impedance match against drugs and the stratification of patients into subgroups that respond to environmental challenges in a similar manner (e.g. response to drugs, response to toxins, etc.). The convergence of patient-activated social networks, big data and their analytics, and systems medicine has led to a P4 medicine that is predictive, preventive, personalized, and participatory. Medicine will focus on each individual. It will become proactive in nature. It will increasingly focus on wellness rather than disease. For example, in 10 years each patient will be surrounded by a virtual cloud of billions of data points, and we will have the tools to reduce this enormous data dimensionality into simple hypotheses about how to optimize wellness and avoid disease for each individual. P4 medicine will be able to detect and treat perturbations in healthy individuals long before disease symptoms appear, thus optimizing the wellness of individuals and avoiding disease. P4 medicine will 1) improve health care, 2) reduce the cost of health care, and 3) stimulate innovation and new company creation. Health care is not the only subject that can benefit from such integrative, cross-disciplinary, and systems-driven platforms and cultures. Many other challenges plaguing our planet, such as energy, environment, nutrition, and agriculture can be transformed by using such an integrated and systems-driven approach.
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.
Coronary artery disease remains the leading cause of death in developed countries. Major recent studies such as SYNTAX and FREEDOM have confirmed that coronary artery bypass grafting (CABG) remains the gold standard treatment in terms of survival and freedom from myocardial infarction and the need for repeat revascularization. The current review explores the use of new technologies and future directions in coronary artery surgery, through 1) stressing the importance of multiple arterial conduits and especially the use of bilateral mammary artery; 2) discussing the advantages and disadvantages of off-pump coronary artery bypass; 3) presenting additional techniques, e.g. minimally invasive direct coronary artery bypass grafting, hybrid, and robotic-assisted CABG; and, finally, 4) debating a novel external stenting technique for saphenous vein grafts
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.
The coagulation system constitutes an important facet of the unique vascular microenvironment in which primary and metastatic brain tumors evolve and progress. While brain tumor cells express tissue factor (TF) and other effectors of the coagulation system (coagulome), their propensity to induce local and peripheral thrombosis is highly diverse, most dramatic in the case of glioblastoma multiforme (GBM), and less obvious in pediatric tumors. While the immediate medical needs often frame the discussion on current clinical challenges, the coagulation pathway may contribute to brain tumor progression through subtle, context-dependent, and non-coagulant effects such as induction of inflammation, angiogenesis, or by responding to iatrogenic insults (e.g. surgery). In this regard, the emerging molecular diversity of brain tumor suptypes (e.g. in glioma and medulloblastoma) highlights the link between oncogenic pathways and the tumor repertoire of coagulation system regulators (coagulome). This relationship may influence the mechanisms of spontaneous and therapeutically provoked tumor cell interactions with the coagulation system as a whole. Indeed, oncogenes (EGFR, MET) and tumor suppressors (PTEN, TP53) may alter the expression, activity, and vesicular release of tissue factor (TF), and cause other changes. Conversely, the coagulant microenvironment may also influence the molecular evolution of brain tumor cells through selective and instructive cues. We suggest that effective targeting of the coagulation system in brain tumors should be explored through molecular stratification, stage-specific analysis, and more personalized approaches including thromboprophylaxis and adjuvant treatment aimed at improvement of patient survival.
