Environment and obesity.

The aim of this review was to identify and, particularly, to classify all the numerous environmental factors that play a significant role in the environment-dependent body weight dysregulation. The main environmental obesogenic factors are related to build environment such as city plan, transport and school, inactivity, TV and screen-related immobility, smart-phone, video games; they are followed by agroalimentary factors such as imbalanced ingredients, pollutants, speed eating, portion size, sweet drinks, nibbling and junk foods supported by publicity, sociocultural and ethnic factors beside the global environmental changes and seasonal light/dark photoperiod. Beside the analytical examination of the obesogenic factors it is mentioned the cumulative effect that tends to coexist in the same population and thus magnify their pathogenic consequences. In addition, more than one obesogenic factors are present in the same population because they are the expression of another underlying common cause - poverty; such a recognition leads towards socio-economic considerations and consequently towards 'political' solutions that are beyond our scientific approach. The mechanism of action of the environmental influence includes the serotonergic system and insulin resistance. More recently, it was shown an environment dependent powerful microbiotic implication. Since obesity is influenced by genetically transmitted changes modulated by environment and lifestyle risk factors it is important to understand the genomic mechanism that allows these interactions. It was shown that obesity-predisposing gene variants that interact with environmental exposures use the DNA methylation epigenetic mechanism.

Neurosurgery of the future: Deep brain stimulations and manipulations.

Important advances are afoot in the field of neurosurgery-particularly in the realms of deep brain stimulation (DBS), deep brain manipulation (DBM), and the newly introduced refinement "closed-loop" deep brain stimulation (CLDBS). Use of closed-loop technology will make both DBS and DBM more precise as procedures and will broaden their indications. CLDBS utilizes as feedback a variety of sources of electrophysiological and neurochemical afferent information about the function of the brain structures to be treated or studied. The efferent actions will be either electric, i.e. the classic excitatory or inhibitory ones, or micro-injection of such things as neural proteins and transmitters, neural grafts, implants of pluripotent stem cells or mesenchymal stem cells, and some variants of gene therapy. The pathologies to be treated, beside Parkinson's disease and movement disorders, include repair of neural tissues, neurodegenerative pathologies, psychiatric and behavioral dysfunctions, i.e. schizophrenia in its various guises, bipolar disorders, obesity, anorexia, drug addiction, and alcoholism. The possibility of using these new modalities to treat a number of cognitive dysfunctions is also under consideration. Because the DBS-CLDBS technology brings about a cross-fertilization between scientific investigation and surgical practice, it will also contribute to an enhanced understanding of brain function.

Biomarkers of glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common and lethal primary malignancy of the central nervous system. Modern treatments using surgery and/or chemotherapy and/or radiotherapy are improving survival of patients, but prognosis is still very poor, depending inter alia on the patients' individual genomic traits. Most GBMs are primary; however, secondary GBMs have a better prognosis. Aberrant gene expression and copy number alterations make it possible to identify four subtypes: classical, mesenchymal, proneural, and neural. More and more biomarkers continue to be identified in GBM patients. Such biomarkers are related with varying degrees of specificity to one or more of GBM's subtypes and, in many instances, may provide useful information about prognosis. Biomarkers fall into either the imaging or molecular category. Molecular biomarkers are identified by use of such platforms as genomics, proteomics, and metabolomics. In the future, biomarkers, either individually or in some combination, will more reliably identify the pathogenic type of GBM and determine choice of therapy.

Personalized medicine in neurosurgery.

Personalized medicine (PM) in neurosurgery is possible today thanks to newly accessible imaging technologies, and to genomic, proteomic and epigenetic biomarkers capable of providing clinically useful information about individual patients. PM is becoming increasingly indispensable in neurosurgery because this specialty offers a wide range of therapeutic options such as surgery and/or radiotherapy and/or chemotherapy. Moreover, the effectiveness of these procedures varies from one patient to another, depending inter alia on the patients' individual genomic traits. A prime example is glioblastoma multiforme, which exhibits at least five genomic biomarkers related to distinct therapeutic and prognostic outcomes. At least one of these biomarkers, the ω-6 methylguanine-DNA methyltransferase promoter of methylation status, has already been used in clinical trials. New functional imaging techniques allow the surgeon to circumvent crucial brain areas whose location may vary among patients, thus allowing the safe and complete excision of an adjacent tumor. Functional imaging, together with an increasing number of genomic and other 'omic' biomarkers, has also given rise to an improved classification based on molecular signatures of tumors like glioblastoma multiforme that will facilitate the correspondence between type of glioma and choice of biologically tailored-to-patient therapy.

Metabolic and humoral mechanisms of feeding and genesis of the ATP/ADP/AMP concept.

The organization of the regulatory system of feeding and of the parallel metabolic changes is schematized by a cyclical cartoon depicting the 8 phases of regulation. As I proposed in 1974, the cycle starts with the detection by hypothalamic sensors of decrease of the ATP/ADP/AMP turnover that reflects the post-prandial slow decline of general metabolic rate. That detection is translated into a signal of hunger. Experimental evidence is provided. Once initiated, this 'basic' signal follows the 7 remaining steps of the cycle, particularly the steps 2 and 4, where it receives multiple 'modulating' positive and negative signals (particularly peptides) that inform the central regulator, on the state of peripheral organs such as the adipocytes, stomach, intestine, and liver, on the outside world like day/light and on the available foods. Particular attention is given to the homeostatic and "homeoreutic" (see definition in the text) regulation of adipose reserves that are announced to brain specialized glio-neuronal "lipo-counters". The role of insulin alongside leptin is shown. The conception of a part of the above mechanisms postulates and shows that some specialized glio-neuronal populations in the antero-ventral hypothalamus share metabolic properties along with somatic cells. Finally, the signal resulting from the algebraic sum of the main (the metabolic) signal and of the modulating pluses and minuses (peptides) leaves the integrative units and reaches the efferent phases (steps 5 and 6) that finish by inducing both metabolic adjustments and consequently food intake. The last steps (4 to 8) are only shortly commented.

Neurosurgical treatments of intractable pain.

Intractable pain may require neurosurgical intervention. This review provides a critical update of neurosurgical techniques available to treat this condition. Neurosurgery can affect pain's pathways from the receptor up to the "centers" of its reception and perception, either by destroying or by stimulating them. Early in neurosurgery's development, and still today, ablative procedures are able to suppress or alleviate pain. However, in most cases, such ablations have only remained effective for a few months or, at best, a few years. This is why, from the 1960s on, a better understanding of the mechanism of pain inspired development of electrical and chemical neuromodulation procedures at every level of the nociceptive system (peripheral nerve, cord, thalamic, periventricular/aqueductal gray, and cortical centers). The encouraging outcomes that resulted are attracting increasing attention and interest among clinicians. The indications for undertaking an ablative vs a neurostimulative procedure, as well as selection of the anatomical target, depend largely on whether pain is nociceptive or neuropathic, given that most of these indications overlap to some extent. In addition, because the published outcomes are not based on universal criteria, it is difficult for the attending physician to select the type of procedure most suitable to the pain problem. This brief review surveys the various neurosurgical procedures together with their corresponding indications in the hope that the information provided will help practitioners choose (1) the type of neurosurgical therapy most appropriate to their patients' needs and (2) the neurosurgical group best equipped to implement that choice.

Prenatal imprinting of postnatal specific appetites and feeding behavior.

Epigenetic influences on the fetus's genotype have been shown to occur during intrauterine life. Experimentally imposed extracellular dehydration in pregnant rats (a model for human hyponatremia caused by gravidic vomiting) brings about a dramatic enhancement of salt appetite not only in the dam, but also in offspring when they reach adulthood. This phenomenon has been verified in human newborn infants and adults whose mothers experienced nausea and/or vomiting during pregnancy. Alcohol consumption during pregnancy enhances its palatability for the offspring. Ingestion of olfactory test substances like anise or carrot by the mother during pregnancy gives rise to a preference for the same testants in the offspring. Under- or overnutrition in the pregnant mother appears to play a role in reprogramming the postnatal regulation of both feeding and fat reserves in offspring. Both maternal under- and overnutrition during pregnancy predispose the offspring to later development of obesity and type 2 diabetes mellitus. A careful examination of the systems concerned with the regulation of food intake, and the neurosubstances involved in such regulation, reveals some of the mechanisms by which maternal nutritional status can affect the offspring and their food-related behaviors.

Metabolic mechanism of wakefulness (and hunger) and sleep (and satiety): Role of adenosine triphosphate and hypocretin and other peptides.

The concurrent background level of metabolic activity may control state of vigilance, promoting wakefulness (and hunger) when it is low, or sleep (and satiety) when it is high. In a series of experiments, we have shown that sleep is dependent on feeding, but only because of the metabolic consequences of food ingestion. These consequences are sensed by glioneuronal populations (at least in the rostromedial hypothalamus), which probably respond to channel-bound adenosine triphosphate/diphosphate turnover (ischymetric monitoring) rather than to the binding of such downstream molecules as adenosine and cytochrome c oxidase. This basic signal is communicated to the vigilance-controlling centers by a cascade of peptidic and nonpeptidic messengers-messengers that promote wakefulness and hunger, possibly via a hypometabolic action (as in the case of neuropeptide Y or hypocretins), or somnolence and satiety, possibly via a hypermetabolic action (as in the case of leptin or certain serotonergic agents).

Depression and neurosurgery: past, present, and future.

Neurosurgery has been used to treat depression since 1935, when open surgery was first used to isolate relatively large areas of the limbic system from the rest of the brain. Soon thereafter, more selective leucotomies were performed based on a growing knowledge of the role played by brain limbic circuitry in processing the emotions. Subsequent discovery of the effectiveness in depression of both electroconvulsive therapy and various pharmacotherapies raised serious doubts about "psychosurgical" treatments, but the introduction of stereotactic techniques revived interest in the selective-lesion, neurobiology-based approach. However, neurosurgery has only come to be regarded as an appropriate treatment of severe depression since Benabid introduced the frequency-dependent chronic electric stimulation technique. Because of its nondestructive nature, this procedure will undoubtedly be favored in the future. One can anticipate that, eventually, frequency-dependent chronic electric stimulation will be complemented by newer techniques such as microdialysis and reverse dialysis, with concomitant functional magnetic resonance imaging and/or positron emission tomography scanning, and the use of chemodes for microinfusion or for in situ insertion of reactivated-stem cells. To optimize success, these modern methods will require a new taxonomy of "depressions" based on up-to-date neurobiological criteria.

A hormone-based characterization and taxonomy of stress: possible usefulness in management.

"Stress" is being increasingly implicated in the pathogenesis of a variety of psychological and somatic disturbances. Because responses to stress can vary widely, the absence of a suitable, pathophysiologically based taxonomy of stress responses has hindered physicians in their efforts to devise treatments tailored to deal with specific stress-related problems. It is proposed herein that classical endocrinologic criteria be employed to characterize stress responses in terms of the associated hormonal secretion ratios and their temporal evolution. Ratios of the responses to stressors of the sympathoadrenal system (SA) and the hypothalamo-pituitary-adrenal (HPA) axis can be either unity (ratio = 1) or dissociated in varying degree, with SA or HPA dominance and for more or less prolonged periods. Published reports of studies in both laboratory animals and patients with stress-associated illnesses (eg, post-traumatic stress disorder [PTSD]) suggest that such hormone-secretion ratios together with their temporal patterns can be used to characterize the particular stress response under examination, thereby providing strong support for further study of the proposed taxonomy. Such a classification of responses to stress stimuli will make it possible to test the overall concept by establishing a correspondence between the suggested hormonal profile and the associated clinical/psychological picture, as well as enable assessment of the benefit of a therapeutic strategy designed to fit the particular category of stress response exhibited by the patient.

Behavioral, plasma, and calorimetric changes related to food texture modification in men.

We hypothesized that food texture modifications might alter anticipatory reflexes, feeding behavior, and the postabsorptive consequences of ingestion. Two sets of complete meals with different textures but the same macronutrient composition were prepared. The first set was either a soup containing chunks of food (mixture) or the same soup blended until smooth (purée). The second set was either a rusk (R), a sandwich loaf (SL), or a liquid rusk meal (LR). We measured hunger and fullness feelings after ingestion of each food in a calibrated lunch, the ingestion rate, the duration between lunch and a spontaneous dinner request, the energy value, and the macronutrient composition of the ad libitum dinner. We also studied plasma modifications and respiratory gas exchanges from lunch to dinner. Feelings of hunger and fullness were not affected by texture modifications. The purée soup was consumed faster than the mixture (P < 0.05), and insulin, triacylglycerol, and energy expenditure were greater with the purée (P < 0.05). LR was less palatable than the other rusk lunch versions (P < 0.001), and R was ingested more slowly (P < 0.05). The lowest increase in plasma glucose occurred with SL, and the highest energy expenditure was seen with LR (P < 0.05). In humans, food texture modification affects not only eating patterns and palatability of ingestants but also metabolic management.

Body weight, body composition, and energy metabolism in lean and obese Zucker rats fed soybean oil or butter.

BACKGROUND: Dietary fat composition is thought to affect body weight regulation independent of the amount of fat ingested. OBJECTIVE: We analyzed the feeding behavior, body weight gain, body composition, and energy metabolism in lean and obese rats fed a diet in which fat was in the form of either butter or soybean oil. DESIGN: Ten lean (Fa/?) and 10 obese (fa/fa) adult Zucker rats were divided into 4 groups according to a 2 x 2 experimental design. They were fed a normally balanced diet over 11 wk in which 30% of energy was either soybean oil or butter. Food intake, body weight gain, and body composition were measured. Indirect calorimetry was used to study energy metabolism at rest and in relation to feeding and activity. RESULTS: Food intake increased similarly in lean and obese rats after butter feeding. Body weight gain increased in obese rats and decreased in lean rats after butter feeding. Body weight gain in obese rats was due mainly to an increase in the weight of lean tissues besides muscle, whereas adiposity and distribution of fat between the various pads did not change. Resting metabolic rates and postprandial lipid oxidation increased in butter-fed obese rats. Lipid oxidation during exercise was not significantly different between obese and lean rats. Fat oxidation increased in butter-fed lean rats during treadmill running at moderate intensity. CONCLUSIONS: In obese rats, basal metabolism and postprandial lipid oxidation increased during butter feeding, which appeared to prevent fat accumulation in the long term. In lean rats, butter feeding favored lipid utilization by working muscles, an observation that deserves further investigation in terms of endurance and performance.