Heart failure is a leading cause of morbidity and mortality with a prevalence that is rising throughout the world. Currently the pharmaceutical therapy of heart failure is mainly based on inhibition of the neurohumoral pathways that are activated secondary to the deterioration of cardiac function, and diuretics to alleviate the salt and water overload. With our increasing understanding of the pathophysiology of heart failure, it is now clear that the macroscopic and functional changes in the failing heart result from remodeling at the cellular, interstitial, and molecular levels. Therefore, emerging therapies propose to intervene directly in the remodeling process at the cellular and the molecular levels. Here, several experimental strategies that aim to correct the abnormalities in receptor and post-receptor-function, calcium handling, excitation and contraction coupling, signaling, and changes in the extra-cellular matrix in the failing heart will be discussed. These novel approaches, aiming to reverse the remodeling process at multiple levels, may appear on the clinical arena in the coming years.
The oldest-old are the fastest growing segment of the Western population. Over half of the oldest-old will have dementia, but the etiology is yet unknown. Age is the only risk factor consistently associated with dementia in the oldest-old. Many of the risk and protective factors for dementia in the young elderly, such as ApoE genotype, physical activity, and healthy lifestyle, are not relevant for the oldest-old. Neuropathology is abundant in the oldest-old brains, but specific pathologies of Alzheimer’s disease (AD) or vascular dementia are not necessarily correlated with cognition, as in younger persons. It has been suggested that accumulation of both AD-like and vascular pathologies, loss of synaptic proteins, and neuronal loss contribute to the cognitive decline observed in the oldest-old. Several characteristics of the oldest-old may confound the diagnosis of dementia in this age group. A gradual age-related cognitive decline, particularly in executive function and mental speed, is evident even in non-demented oldest-old. Hearing and vision losses, which are also prevalent in the oldest-old and found in some cases to precede/predict cognitive decline, may mechanically interfere in neuropsychological evaluations. Difficulties in carrying out every-day activities, observed in the majority of the oldest-old, may be the result of motor or physical dysfunction and of neurodegenerative processes. The oldest-old appear to be a select population, who escapes major illnesses or delays their onset and duration toward the end of life. Dementia in the oldest-old may be manifested when a substantial amount of pathology isaccumulated, or with a composition of a variety of pathologies. Investigating the clinical and pathological features of dementia in the oldest-old is of great importance in order to develop therapeutic strategies and to provide the most elderly of our population with good quality of life.
Age as a risk for diseases: We offer a different approach to delaying or preventing age-related diseases. To understand the necessity for a new approach we have plotted the mortality rates in Israelis in relation to specific age groups and diseases...(Click below to read the entire editorial.)
Successful deceased organ donation requires a reproducible—consistent (scientific) system that eva-luates the potential for organ donation and determines objectively whether the national system is achieving its goals. The science of organ donation also pertains to the determination of death. We are a common humanity that dies similarly— a humanity whose ultimate criterion of life resides in the function of the human brain. The recent brain death law of Israel encouragingly enables a determination of death by the loss of neurologic function but it has become complicated by a practice that may perpetuate societal misperceptions. As a result opportunities for deceased organ donation --to provide for Israelis in need of organ transplants are being lost. A statured task force of society could be assembled to convey its support for deceased donation to influence society and resolve these misperceptions.
The World Health Organization is now calling for each member state to achieve a self-sufficiency in organ donation and transplantation "equitably meeting the transplantation needs of a given population using resources from within that population". Patients should not be compelled to go to foreign countries for their organs. Israel has been a leader in the development of a model program intended to address transplant tourism. Insurance companies are no longer permitted to provide resources for Israelis to undergo illegal transplants in foreign destinations. The social necessity of a scientifically and medically applied system of deceased organ donation is now evident so that a sufficient number of organs can be available for patients from within the country they reside.
This paper examines the morality of schemes of payment to live donors/sellers of organs for transplantation. Following empirical and historical evidence it is argued that consent to sell organs is substantially different from consent to ordinary business transactions and that legalization of exchanges of organs with financial benefits deviates significantly from the scope of liberal toleration and human rights. Although altruistic giving is commendable, it is immoral for society to benefit from them without conferring to the donors benefits such as health and nursing insurance for life. Non-alienable and non-fungible benefits of this kind are moral as incentives to organ donation/giving
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.
Hereditary, environmental, and stochastic factors determine a child’s growth in his unique environ-ment, but their relative contribution to the phenotypic outcome and the extent of stochastic pro-gramming that is required to alter human phenotypes is not known because few data are available. This is an attempt to use evolutionary life-history theory in understanding child growth in a broad evolutionary perspective, using the data and theory of evolutionary predictive adaptive growth-related strategies. Transitions from one life-history phase to the next have inherent adaptive plasticity in their timing. Humans evolved to withstand energy crises by decreasing their body size, and evolutionary short-term adaptations to energy crises utilize a plasticity that modifies the timing of transition from infancy into childhood, culminating in short stature in times of energy crisis. Transition to juvenility is part of a strategy of conversion from a period of total dependence on the family and tribe for provision and security to self-supply, and a degree of adaptive plasticity is provided and determines body composition. Transition to adolescence entails plasticity in adapting to energy resources, other environmental cues, and the social needs of the maturing adolescent to determine life-span and the period of fecundity and fertility. Fundamental questions are raised by a life-history approach to the unique growth pattern of each child in his given genetic background and current environment.
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.
The past few decades have seen many advances in the treatment of a variety of cancers. Unfortunately, for ovarian cancer, which is the most lethal type of gynecologic malignancy, no new therapeutic approach has been successfully introduced since the 1990s. Ovarian cancer is usually detected in later stages, when remission rates are high and tumors are resistant to chemotherapy. Little is known about the primary lesion in ovarian cancer. Recently, it has been shown that the origin of ovarian cancer can be cells from adjacent tissue or cells from other primary tumors, which make their way to the ovaries due to the unique nature of their microenvironment during ovulation. The tumor in ovarian cancer is heterogeneous and hierarchically organized. In this review, we discuss the role of ovarian cancer stem cells in the process of tumor formation and recurrence. We propose the need to shift the paradigm away from the classification of ovarian cancer as a single disease with a single cellular origin. Understanding the complexity of the disease will facilitate devising new methods for fighting this cancer and improving the life of many women inflicted with the disease.
