The term sociotype has been introduced to describe the dynamic relationship of an individual with his/her social environment throughout life. The sociotype is a conceptual framework to highlight, in addition to bio-medical pathways, the psycho-social and environmental factors necessary to understand responses to life stresses and patient self-management for chronic illness. The sociotype interacts with genotype expression through mate selection and metabolic programming, and with the phenotype to determine adaptation throughout life from birth to old age. Following on the work of Antonovsky, Engel, and McEwen, and others in the life and social sciences, the sociotype details and expands the many factors generally included in the environmental influences on a person’s life identified here as the domains of health, relationships, and environment. Physiological mediators for sociotypic influences include: adrenal steroids and the sympathetic nervous system (allostatic load), and oxytocin (social neuroscience). The biological pathways are multiple through nutrition (essential dietary-derived amino- and fatty acids for neurotransmitter synthesis, caloric restriction, and diet–gene interactions), epigenesis, and metabolic programming. Nutrition influences growth and development, fertility and longevity, and also determines susceptibility to non-communicable diseases such as cardiovascular disease and cancer, and particularly diabetes and obesity, through in-utero effects, the development of intestinal flora (microbiome), and chronic stress. Thus the sociotype and nutrition are reciprocally related in both health and disease.
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.
A very troubling issue for health care systems today is that of life-sustaining treatment for patients who have permanently lost their cognitive capacities. These include patients in persistent vegetative state (PVS), or minimally conscious state (MCS), as well as a growing population of patients at the very end stage of dementia. These patients are totally dependent on life-sustaining treatments and are, actually, kept alive “artificially.” This phenomenon raises doubts as to the ethics of sustaining the life of patients who have lost their consciousness and cognitive capacities, and whether there is a moral obligation to do so. The problem is that the main facts concerning the experiences and well-being of such patients and their wishes are unknown. Hence the framework of the four principles—beneficence, non-maleficence, autonomy, and justice—is not applicable in these cases; therefore we examined solidarity as another moral value to which we may resort in dealing with this dilemma.
This article shows that the source of the dilemma is the social attitudes towards loss of cognitive capacities, and the perception of this state as loss of personhood. Consequently, it is suggested that the principle of solidarity—which both sets an obligation to care for the worst-off, and can be used to identify obligations that appeal to an ethos of behavior—can serve as a guiding principle for resolving the dilemma. The value of solidarity can lead society to care for these patients and not deny them basic care and life-sustaining treatment when appropriate.
Evaluation of patients after penetrating neck injury has evolved over time. Previously, location of injury and symptoms were used to determine management. The contemporary management of penetrating neck injuries relies on physical examination. Patients with hard signs of vascular or aerodigestive tract injury require immediate operation, regardless of location of injury. Those with no signs can be observed. For the remainder with soft signs multidetector, computed tomographic angiography (MDCTA) is a highly sensitive and specific screening modality for evaluating the vasculature and aerodigestive structures in the neck. Utilizing MDCTA, the patient can be safely directed towards operative intervention, observation, or further investigation.
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.
Life expectancy has been increasing in the last few decades in the Western world and is accompanied by higher occurrence of age-related diseases like metabolic, cardiovascular, and renal diseases and also with a decline in immune functions. In HIV-infected people, due to the use of combination antiretroviral therapy cART, life expectancy has increased. As a result, non-AIDS conditions which are age-associated have become more prevalent and appear earlier, resulting in accelerated aging in HIV patients. These non-AIDS conditions in HIV patients are associated with CD4+ T cell counts: lower counts are associated with higher rates of liver, cardiovascular, renal, and neurocognitive disorders. The effect of viral load and cART on the earlier occurrence of age-associated diseases is less significant than the CD4 count effect. Thus, the loss of immune functions in HIV-infected patients may enhance aging.
Among the wide-spectrum contribution of the Rambam – the Maimonides – in philosophy to the word and to Judaism are his ideas on the body and on the soul and on the relations between them. His major approaches in these subjects are the following: 1) The body is the home of the soul, and the soul guides the body. That means the body and the soul are one unit. 2) The soul has five virtual parts. Each part is responsible for another activity in the human being. 3) Except for the treatment of diseases of the body and the soul with drugs, foods, physical exercise, etc., the Rambam believes that maintaining the health – of the body and of the soul – lies first of all, and probably exclusively, in observing the commandments and improving one’s ways, morals and conduct up to their highest levels, toward all of the world’s creatures. 4) The Rambam is of the opinion that one needs to persist in learning the Torah. One should worship God with awe and love and observe good values and virtues. All of these build the frameworks that maintain mental health and strengthen man’s abilities to develop skills for maintaining bodily health. This is so because body and soul are one – which is the basis of the Rambam’s philosophy of health and medicine.
This manuscript is a survey of the halachic attitudes toward organ transplant procedures from a living donor which can be defined as life-saving procedures for the recipient or at least life-prolonging proce-dures. Three fundamental problems concerning the halachic aspects of such transplantation are dis-cussed in detail: the danger to the donor, donation under coercion, and the sale of organs and tissues. The terms “halacha” and “Jewish law” are defined in the introduction.
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.
