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.
The immune system is critical for protection and health maintenance and is likely required for a long lifespan. Yet, despite its importance for health, the ability to assess its quality of function has been poor, nor is much known on its variation between individuals. Hence direct assessment of immune health has largely been missing from medicine, and metrics of immune health are not well defined, especially in non-extreme states. This is chiefly due to the high complexity of the immune system. Recently emerging technologies now enable broad surveying of many immune system components at high resolution, setting forth a transformation of immunology and, through it, medicine. Such technologies enable, for the first time, high resolution monitoring of an individual’s immune system. The resulting information can be used for diagnostic and prognostic purposes, as well as to provide a quantitative, global view of the immune system, i.e. ‘systems immunology.’ This is especially relevant in the context of aging, in which the immune system exhibits profound alterations in state and function.
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.
As more reports emerge of improved mortality and morbidity rates in infants born at the edge of viability, there may be need to reassess protocols and recommendations that encourage only comfort care for infants who are born at less than 24 weeks’ gestation. Analysis of those studies that report extremely poor survival of these infants reveals that, all too often, the results are measures of a self-fulfilling prophesy that reflects a predetermined non-aggressive global policy of no resuscitation and minimal investment in intensive care. Furthermore, little distinction is made between high- and low-risk infants of the same gestational age despite repeated studies that indicate that one can identify - subpopulations that have as much as a 20-50% increased chance of surviving with little if any long-term neurodevelopmental impairment. Thus, the need to reassess current policies is discussed.
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 ketogenic diet has been in use for the last 90 years, and its role in the treatment of epilepsy in the pediatric population has been gaining recognition. It can be helpful in many types of epilepsies, even the more severe ones, and has a beneficial effect on the child’s alertness and cognition, which can be impaired by both the condition and the medications needed for controlling it. Parental compliance is good in spite of the inconveniences inherent in following the diet. The significant advancements in understanding the nature of the diet are in better defining when its use is contraindicated and in validating its application in severe epilepsies in infancy, such as infantile spasms. Although most neurologists do not consider it as being the preferred first-line therapy, it is often a reasonable option when two medications have already failed.
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.
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.
Pomegranate is a source of some very potent antioxidants (tannins, anthocyanins) which are considered to be also potent anti-atherogenic agents. The combination of the above unique various types of pomegranate polyphenols provides a much wider spectrum of action against several types of free radicals. Indeed, pomegranate is superior in comparison to other antioxidants in protecting low-density lipoprotein (LDL, “the bad cholesterol”) and high-density lipoprotein (HDL, “the good cholesterol”) from oxidation, and as a result, it attenuates atherosclerosis development and its consequent cardiovascular events. Pomegranate antioxidants are not free, but are attached to the pomegranate sugars, and hence were shown to be beneficial even in diabetic patients. Furthermore, pomegranate antioxidants are unique in their ability to increase the activity of the HDL-associated paraoxonase 1 (PON1), which breaks down harmful oxidized lipids in lipoproteins, in macrophages, and in atherosclerotic plaques. Finally, unique pomegranate antioxidants beneficially decrease blood pressure. All the above beneficial characteristics make the pomegranate a uniquely healthy fruit.
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.
