Determinantes de la desigualdad económica. Evidencia para países desarrollados y en vías de desarrollo

La presente investigación busca analizar empíricamente los determinantes de la desigualdad económica en 53 países, desarrollados y en vías de desarrollo, durante el periodo 2000-2021. Tomando como variables macroeconómicas explicativas a la inflación y desempleo; así también variables de política fiscal como el gasto público en salud, gasto público en educación y los impuestos de los países analizados, se estimó un modelo de regresión de datos de panel por Mínimos Cuadrados Generalizados Factibles (MCGF). Los resultados obtenidos son estadísticamente significativos y con el signo esperado para todas las variables independientes. En este sentido, se puede afirmar que escenarios macroeconómicos desfavorables aumentan la desigualdad económica y las herramientas de política fiscal correctamente aplicadas contribuyen a la igualdad económica para los países de la muestra.This study empirically analyzes the determinants of the economic inequality from 53 countries, which includes developed and developing, for the period 2000-2021. Employing as relevant variables the inflation, unemployment, public spending on health, public spending on education and taxes of the sampled countries, we estimate a regression model by Feasible Generalized Least Squares (FGLS). The results are statistically significant and have the expected sign for all the variables. In particular, we find that unfavorable macroeconomic scenarios increase the economic inequality and correctly applied fiscal policy tools contribute to economic equality for the countries in the sampl

Análisis de seguridad y productividad del suministro de energía eléctrica en el sistema eléctrico de Nicaragua en el periodo comprendido desde el año 2010 hasta el 2018

El propósito de este estudio fue el de estudiar la seguridad y productividad del suministro de energía eléctrica en el sistema eléctrico de Nicaragua en el periodo desde el año 2010 hasta el 2018 utilizando el Indicador Stirling, indicador margen de reserva, indicador pérdida del mayor generador, el indicador de concentración de mercado y herramienta metodológica de análisis envolvente de datos (DEA) y los índices de Malmquist. Se estudió el comportamiento del sector energético de Nicaragua, en el periodo 2005 – 2013. Como resultado del indicador Stirling se obtuvo, que Nicaragua en estos momentos cuenta con seguridad en el sistema eléctrico, Del indicador margen de reserva se obtuvo como resultado, que el nivel de seguridad desde el punto de evaluación de este indicador el sistema cuenta con la suficiente seguridad como para no incurrir en afectaciones a los consumidores finales, Como resultado del indicador pérdida del mayor generador (LU), concluye en que se posee un sistema seguro. Por otra parte, El índice de concentración de mercado mostro que Nicaragua no posee un mercado energético competitivo. En la evaluación de productividad del uso de recursos energéticos se encontró que solo el uso de biomasa presenta un ritmo promedio anual de crecimiento de productividad

Height and body-mass index trajectories of school-aged children and adolescents from 1985 to 2019 in 200 countries and territories: a pooled analysis of 2181 population-based studies with 65 million participants

Summary Background Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents. Methods For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence. Findings We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls. Interpretation The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks

Neuroprotective Surgical Strategies in Parkinson’s Disease: Role of Preclinical Data

Although there have been many pharmacological agents considered to be neuroprotective therapy in Parkinson’s disease (PD) patients, neurosurgical approaches aimed to neuroprotect or restore the degenerative nigrostriatal system have rarely been the focus of in depth reviews. Here, we explore the neuroprotective strategies involving invasive surgical approaches (NSI) using neurotoxic models 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which have led to clinical trials. We focus on several NSI approaches, namely deep brain stimulation of the subthalamic nucleus, glial neurotrophic derived factor (GDNF) administration and cell grafting methods. Although most of these interventions have produced positive results in preclinical animal models, either from behavioral or histological studies, they have generally failed to pass randomized clinical trials to validate each approach. We argue that NSI are promising approaches for neurorestoration in PD, but preclinical studies should be planned carefully in order not only to detect benefits but also to detect potential adverse effects. Further, clinical trials should be designed to be able to detect and disentangle neuroprotection from symptomatic effects. In summary, our review study evaluates the pertinence of preclinical models to study NSI for PD and how this affects their efficacy when translated into clinical trials

Stimulation cérébrale profonde hypothalamique pour l'obésité chez le primate non humain : Une approche préclinique.

Abstract Object: Deep brain stimulation (DBS) has become an effective therapy in a variety of brain disorders. Recently, Hypothalamic DBS in cases of chronic intractable cluster headache has revived the interest in this region, which is also well-known to be involved in food intake and energy balance regulation. In the other hand, risks and problems related with implantation in this area has raised several questions regarding the safety of this approach. In this study, the authors proposed an Intraventricular “floating” electrode inserted in the third ventricle adjacent to the ventromedial hypothalamus (VMH) in freely moving Macaca fascicularis to modulate food intake and weight and as a potential treatment of morbid obesity. Methods: Five adults Macaca fascicularis (4 subjects and 1 sham) monkeys were implanted stereotactically in the third ventricle contiguous to the VMH with chronic indwelling 3389 and 3388 Medtronic electrodes used for Deep Brain Stimulation (DBS). The study was divided in two phases: acute tests and chronic 8-weeks trials. In the acute tests, the meal size, eating time and locomotor activity were recorded after short periods of electrical stimulation (ES) in 24 hrs fasting animals at different frequencies and intensities of stimulation, in order to obtain the most effective sets of ES parameters able to reduced food intake (FI) and consequently weight and fat during chronic stimulation. In the chronic trials, three cycles of continuous ES of 8 weeks each were performed at the most effective frequency reducing FI in the acute test (or 80Hz), at 130Hz (considered High Frequency ES and used in Parkinson Disease DBS) , and 30Hz (considered Low frequency ES and used in Pain DBS). Body Mass Index, weight, fat content, subcutaneous skinfolds and hormones were measured during baseline and at the end of each 8 week stimulation trials. Results: Results: During Acute 24 hrs-fasting trials, there was a decrease in FI in all subjects at 80 Hz, (mean 15 ±4.4%). During Chronic 8 weeks stimulation trials, a decrease in weight and BMI was observed in three out four monkeys at 80 HZ (mean 8% ± 4.4%), and slight increase at 130HZ (mean 2% ± 2.5) and at 30HZ (mean 5%±2,93). Fat mass decreased at the end of 80 Hz trials to ratio 0.82±0.08. (18% reduction).Subcutaneous skinfolds were reduced in all four subjects at 80 Hz and slightly increased at 130 Hz. Sham monkey remained stable. FI increased during off stimulation period (washout) following effective weight loss. Glucose also increased during hyperphagic period. Hormones and Leptin did not show significative variations in relation to different frequencies stimulation. No major adverse effects were recorded. Conclusion: We conclude that stimulating the VMH region throughout an Intraventricular approach might modulate acutely food ingestion and induce a sustained decrease in weight and in fat content in normal non obese human primates.Résume Objet: La stimulation cérébrale profonde (SCP) est devenue une thérapie efficace dans une série de maladies cérébrales. Récemment, dans les cas des algies vasculaires de la face résistantes au traitement (intraitables), chroniques, la SCP hypothalamique a suscité un nouvel intérêt pour cette région, également bien connue pour son implication dans la régulation de la prise alimentaire et de la balance énergétique. Cependant, les risques et les problèmes connexes liés à l'implantation dans cette aire cérébrale ont soulevé plusieurs questions concernant la sûreté de cette technique chirurgicale. Dans cette étude, les auteurs ont proposé l'implantation d'une électrode intraventriculaire insérée dans le troisième ventricule au niveau de l'hypothalamus ventromedial (VMH) chez des singes macaca fascicularis non obèses dans le but de moduler la prise alimentaire et le masse corporelle des sujets. Cette méthode de SCP pourrait s'avérer être un traitement potentiel de l'obésité morbide. Méthodes: Cinq singes de macaca fascicularis adultes (4 sujets et 1 contrôle ou sham) ont été implantés de façon stéréotaxique dans le troisième ventricule. Une électrode chronique Medtronic®, habituellement utilisée dans le cadre de la SCP chez les patients atteints de la maladie de Parkinson, a été positionnées dans l'espace intraventriculaire adossée à la paroi de ce dernier au niveau du VMH. Dans la première phase de l'étude, le comportement alimentaire de chaque animal (durée du repas, quantité de nourriture avalée) et son activité motrice ont été enregistrés et analysés en fonction différents paramètres de stimulation (fréquence et intensité) après une période de jeun de 24 heures. Dans la seconde phase du protocole, trois cycles de stimulation intraventriculaire de 8 semaines chacun ont été réalisés à 130Hz, à 80Hz et à 30Hz, suivi des périodes de « washout » de 4 semaines entre les périodes« on - stimulation ». L'index de masse corporelle, le poids (masse corporelle), la « teneur « en graisse, l'épaisseur cutanée et les concentrations hormonales ont été mesurés au début de l'étude pour établir une ligne de base et après chaque session de stimulation. Résultats: Lors de la première phase du protocole réalisée sur des animaux a jeun depuis 24 heures, nous avons remarqué une diminution de la prise alimentaire comprise entre 11 et 19% chez tous les sujets stimulés à une fréquence 80 hertz. A partie de ces résultats, , une diminution de la masse corporelle et du BMI (body mass index indice de masse corporelle) ont été observés chez trois de quatre singes lors des phases de stimulation chronique à une fréquence de 80 hertz : la moyenne de perte pondérale était de 8± 4.4%. Une augmentation de 2-6 ± 2.5% et de 5 ±2,93 %de la masse corporelle a été observée respectivement chez les animaux stimulés à une fréquence de 130Hzet de 30Hz. Une diminution importante des épaisseurs sous-cutanées ( )a été observée pour chacun des quatre sujets à une fréquence de 80 hertz et dans une moindre mesure, une augmentation de cette variable ( ) a été remarquée une fréquence de 130 Hz. Tout au long de l'étude, les variables relevées sur le singe Sham sont restées stables. Sur la durée de l'étude, aucun effet potentielle ment délétère n'a été remarqués sur les animaux. Conclusion: La stimulation de la région de VMH par voie intraventriculaire pourrait s'avérer efficace pour moduler le comportement alimentaire et induire une diminution soutenue de la masse corporelle caractérisée par réduction de la masse graisseuse chez les primates non humains non obèses

Stimulation cérébrale profonde hypothalamique pour l'obésité chez le primate non humain (une approche préclinique)

Objet : La stimulation cérébrale profonde (SCP) est devenue une thérapie efficace dans une série de maladies cérébrales. Récemment, dam les cas des algies vasculaires de la face résistantes au traitement (intraitables), chroniques, la SCP hypothalamique a suscité un nouvel intérêt pour cette région, également bien connue pour son implication dans la régulation de la prise alimentaire et de la balance énergétique. Cependant, les risques et les problèmes connexes liés à l'implantation dans cette aire cérébrale ont soulevé plusieurs questions concernant la sûreté de cette technique chirurgicale. Dans cette étude, les auteurs ont proposé l'implantation d'une électrode intraventriculaire insérée dans le troisième ventricule au niveau de l'hypothalamus ventromedial (VMH) chez des singes macaca fasciculari, non obèses dans le but de moduler la prise alimentaire et le masse corporelle des sujets. Cette méthode de SCP pourrait s'avérer être un . traitement potentiel de l'obésité morbide. Méthodes : Cinq singes de macaca fascicularis adultes (4 sujets et 1 contrôle ou sham) ont été implantés de façon stéréotaxique dans le troisième ventricule. Une électrode chronique Medtronic@, habituellement utilisée dans le cadre de la SCP chez les patients atteints de la maladie de Parkinson, a été positionnées dans l'espace intraventriculaire adossée à la paroi de ce dernier au niveau du VMH. Dans la première phase de l'étude, le comportement alimentaire de chaque animal (durée du repas, quantité de nourriture avalée) et son activité motrice ont été enregistrés et analysés en fonction différents paramètres de stimulation (fréquence et intensité) après une période de jeu de 24 heures. Dans la seconde phase du protocole, trois cycles de stimulation intraventriculaire de 8 semaines chacun ont été réalisés à 130Hz, à 80Hz et à 30Hz, suivi des périodes de washout " de 4 semaines entre les périodes on - stimulation". L'index de masse corporelle, le poids (masse corporelle), la teneur en graisse, l'épaisseur cutanée et les concentrations hormonales ont été mesurés au début de l'étude pour établir une ligne de base et après chaque session de stimulation. Résultats : Lors de la première phase du protocole réalisée sur des animaux ajeun depuis 24 heures, nous avons remarqué une diminutio de la prise alimentaire comprise entre 11 et 19% chez tous les sujets stimulés à une fréquence 80 hertz. A partie de ces résultats, , une diminution de la masse corporelle et du BMI (body mass index indice de masse corporelle) ont été observés chez trois de quatre singes lors des phases de stimulation chronique à une fréquence de 80 hertz: la moyenne de perte pondérale était de 8:!: 4.4%. Une augmentation de 2-6 :!: 2.5% et de 5 :!:2,93 %de la masse corporelle a été observée respectivement chez les animaux stimulés à une fréquence de 130Hzet de 30Hz. Une diminution importante des épaisseurs sous-cutanées ( )a été observée pour chacun des quatre sujet à une fréquence de 80 hertz et dans une moindre mesure, une augmentation de cette variable ( ) a été remarquée une fréquence de 130 Hz. Tout au long de l'étude, les variables relevées sur le singe Sham sont restées stables. Sur la durée de l'étude, aucun effet potentielle ment délétère n'a été remarqués sur les animaux.Conclusion : La stimulation de la région de VMH par voie intraventriculaire pourrait s'avérer efficace pour moduler le comportement alimentaire et induire une diminution soutenue de la masse corporelle caractérisée par réduction de la masse graisseuse chez les primatE non humains non obèses.Intractable cluster headache has revived the interest in this region, which is also well-known to be involved in food intake and energy balance regulation. ln the other hand, risks and problems related with implantation in this area has raised several questions regarding the safety of this approach. ln this study, the authors proposed an Intraventricular "floating" electrode inserted in the third ventricle adjacent to the ventromedial hypothalamus (VMH) in freely moving Macaca fascicularis to modulate food intake and weight and as a potential treatment of morbid obesity. Methods: Five adults Macaca fascicularis (4 subjects and 1 sham) monkeys were implanted stereotactically in the third ventricle contiguou to the VMH with chronic indwelling 3389 and 3388 Medtronic electrodes used for Deep Brain Stimulation (DBS). The study was divided in two phases: acute tests and chronic 8-weeks trials. ln the acute tests, the meal size, eating time and locomotor activity were recorded aftel short periods of electrical stimulation (ES) in 24 hrs fasting animais at different frequencies and intensities of stimulation, in order to obtail the most effective sets of ES parameters able to reduced food intake (FI) and consequently weight and fat during chronic stimulation. ln the chronic trials, three cycles of continuous ES of 8 weeks each were performed at the most effective frequency reducing FI in the acute test (or 80Hz), at 130Hz (considered High Frequency ES and used in Parkinson Disease DBS) , and 30Hz (considered Low frequency ES and used in Pain DBS). Body Mass Index, weight, fat content, subcutaneous skinfolds and hormones were measured during baseline and at th, end of each 8 week stimulation trials. Results: Results: During Acute 24 hrs-fasting trials, there was a decrease in FI in ail subjects at 80 Hz, (mean 15 :!:4.4%). During Chronic 8 weeks stimulation trials, a decrease in weight and BMI was observed in three out four monkeys at 80 HZ (mean 8% :!: 4.4%), and slight increase at 130HZ (mean 2% :!: 2.5) and at 30HZ (mean 5%:!:2,93). Fat mass decreased at the end of 80 Hz trials to ratio 0.82:!:0.08. (18% reduction).Subcutaneous skinfolds were reduced in ail four subjects at 80 Hz and slightly increased at 130 Hz. Sham monkey remained stable. FI increased during off stimulation period (washout) following effective weight loss. Glucose also increased during hyperphagic period. Hormones and Leptin did not show significative variations in relation to different frequencies stimulation. No major adverse effects were recorded.Conclusion: We conclude that stimulating the VMH region throughout an Intraventricular approach might modulate acutely food ingestio and induce a sustained decrease in weight and in fat content in normal non obese human primates.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Neuroprotective Surgical Strategies in Parkinson’s Disease: Role of Preclinical Data

Although there have been many pharmacological agents considered to be neuroprotective therapy in Parkinson’s disease (PD) patients, neurosurgical approaches aimed to neuroprotect or restore the degenerative nigrostriatal system have rarely been the focus of in depth reviews. Here, we explore the neuroprotective strategies involving invasive surgical approaches (NSI) using neurotoxic models 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine (6-OHDA), which have led to clinical trials. We focus on several NSI approaches, namely deep brain stimulation of the subthalamic nucleus, glial neurotrophic derived factor (GDNF) administration and cell grafting methods. Although most of these interventions have produced positive results in preclinical animal models, either from behavioral or histological studies, they have generally failed to pass randomized clinical trials to validate each approach. We argue that NSI are promising approaches for neurorestoration in PD, but preclinical studies should be planned carefully in order not only to detect benefits but also to detect potential adverse effects. Further, clinical trials should be designed to be able to detect and disentangle neuroprotection from symptomatic effects. In summary, our review study evaluates the pertinence of preclinical models to study NSI for PD and how this affects their efficacy when translated into clinical trials

Survival of midbrain dopaminergic cells after lesion or deep brain stimulation of the subthalamic nucleus in MPTP-treated monkeys.

International audienceWe have examined dopaminergic cell survival after alteration of the subthalamic nucleus (STN) in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys. The STN was lesioned with kainic acid (B series) or underwent deep brain stimulation (DBS) at high frequency (C series). In another series, MPTP-treated and non-MPTP-treated monkeys had no STN alteration (intact animals; A series). Animals were treated with MPTP either after (B1, C1) or before (B2, C2) STN alteration. We also explored the long-term ( approximately 7 months) effect of DBS in non-MPTP-treated monkeys (D series). Brains were aldehyde-fixed and processed for routine Nissl staining and tyrosine hydroxylase immunocytochemistry. Our results showed that there were significantly more (20-24%) dopaminergic cells in the substantia nigra pars compacta (SNc) of the MPTP-treated monkeys that had STN alteration, either with kainic acid lesion or DBS, compared to the non-MPTP-treated monkeys (intact animals). We suggest that this saving or neuroprotection was due to a reduction in glutamate excitotoxicity, as a result of the loss or reduction of the STN input to the SNc. Our results also showed that SNc cell number in the B1 and C1 series were very similar to those in the B2 and C2 series. In the cases that had long-term DBS of the STN (D series), there was no adverse impact on SNc cell number. In summary, these results indicated that STN alteration offered neuroprotection to dopaminergic cells that would normally die as part of the disease process

A Long-Term BCI Study With ECoG Recordings in Freely Moving Rats

International audienceBackgroundBrain Computer Interface (BCI) studies are performed in an increasing number of applications. Questions are raised about electrodes, data processing and effectors. Experiments are needed to solve these issues. ObjectiveTo develop a simple BCI set-up to easier studies for improving the mathematical tools to process the ECoG to control an effector. MethodWe designed a simple BCI using transcranial electrodes (17 screws, three mechanically linked to create a common reference, 14 used as recording electrodes) to record Electro-Cortico-Graphic (ECoG) neuronal activities in rodents. The data processing is based on an online self-paced non-supervised (asynchronous) BCI paradigm. N-way partial least squares algorithm together with Continuous Wavelet Transformation of ECoG recordings detect signatures related to motor activities. Signature detection in freely moving rats may activate external effectors during a behavioral task, which involved pushing a lever to obtain a reward. ResultsAfter routine training, we showed that peak brain activity preceding a lever push (LP) to obtain food reward was located mostly in the cerebellar cortex with a higher correlation coefficient, suggesting a strong postural component and also in the occipital cerebral cortex. Analysis of brain activities provided a stable signature in the high gamma band (approximate to 180Hz) occurring within 1500 msec before the lever push approximately around -400 msec to -500 msec. Detection of the signature from a single cerebellar cortical electrode triggers the effector with high efficiency (68% Offline and 30% Online) and rare false positives per minute in sessions about 30 minutes and up to one hour (approximate to 2 online and offline). ConclusionsIn summary, our results are original as compared to the rest of the literature, which involves rarely rodents, a simple BCI set-up has been developed in rats, the data show for the first time long-term, up to one year, unsupervised online control of an effector

Monophasic but not biphasic pulses induce brain tissue damage during monopolar high-frequency deep brain stimulation.

International audienceOBJECTIVE: Electrical high-frequency stimulation (HFS) of deep brain structures has been successfully used as a treatment for patients with movement disorders. The mechanisms of HFS allowing therapeutic clinical effects remain unclear, which justifies experimental studies to address these questions. These experiments require an external stimulator, which may offer the possibility to deliver a current with monophasic or biphasic pulses. The aim of the present study was to quantify the evolution of a potentially deleterious effect of HFS according to the duration and/or intensity in monophasic and biphasic conditions. METHODS: In all rats, HFS was performed with monophasic pulses in deep brain structures of 1 hemisphere and with biphasic pulses symmetrically in the other hemisphere. The effect of HFS was tested, first for various durations of HFS at a constant intensity (100 microA) and, second, for measuring the effect of various current intensities of HFS at constant duration (10 minutes). At the end of each stimulation test, the volume of lesion was determined and analyzed. RESULTS: In all hemispheres in which stimulation using biphasic pulses was delivered, we never found any relevant lesions. Conversely, monophasic electrical stimulation always created a lesion: at 100 microA, a minimal duration of HFS of 5 minutes induced a tissue damage volume of 0.0055 +/- 0.0015 mm(3). For 10 minutes of HFS, a minimal intensity of 100 microA induced a tissue damage volume of 0.0062 +/- 0.0017 mm(3). Regression analysis showed that the extent of lesion increased linearly with the intensity and duration. CONCLUSION: In conclusion, this study proved that HFS using monophasic pulses systematically created tissue damage after 5 minutes of stimulation at 100 microA. HFS is safe when biphasic pulses are used for intensities as high as 2 mA and durations as long as 120 minutes. Monophasic pulses can be safely used only during short stimulation and at low intensities