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Principal neurons in the adult cerebral cortex undergo synaptic, dendritic, and spine remodeling in response to different stimuli, and several reports have demonstrated that the polysialylated form of the neural cell adhesion molecule (PSA-NCAM) participates in these plastic processes. However, there is only limited information on the expression of this molecule on interneurons and on its role in the structural plasticity of these cells. We have found that PSA-NCAM is expressed in mature interneurons widely distributed in all the extension of the cerebral cortex and have excluded the expression of this molecule in most principal cells. Although PSA-NCAM expression is generally considered a marker of immature neurons, birth-dating analyses reveal that these interneurons do not have an adult or perinatal origin and that they are generated during embryonic development. PSA-NCAM expressing interneurons show reduced density of perisomatic and peridendritic puncta expressing different synaptic markers and receive less perisomatic synapses, when compared with interneurons lacking this molecule. Moreover, they have reduced dendritic arborization and spine density. These data indicate that PSA-NCAM expression is important for the connectivity of interneurons in the adult cerebral cortex and that its regulation may play an important role in the structural plasticity of inhibitory networks.

Down's syndrome (DS), with an incidence of one in 800 live births, is the most common genetic disorder associated with mental retardation. This trisomy on chromosome 21 induces a variable phenotype in which the only common feature is the presence of mental retardation. The neural mechanisms underlying mental retardation might include defects in the formation of neuronal networks and neural plasticity. DS patients have alterations in the morphology, the density and the distribution of dendritic spines in the pyramidal neurons of the cortex. Our hypothesis is that the deficits in dendritic arborization observed in the principal neurons of DS patients and Ts65Dn mice (a model for DS that mimics most of the structural alterations observed in humans) may be mediated to some extent by changes in their inhibitory inputs. Different types of interneurons control different types of inhibition. Therefore, to understand well the changes in inhibition in DS, it is necessary to study the different types of interneurons separately. We have studied the expression of synaptophysin, Glutamic acid decarboxylase-67 (GAD-67) and calcium-binding protein-expressing cells in the primary somatosensory cortex of 4-5 month old Ts65Dn mice. We have observed an increment of GAD67 immunoreactivity that is related mainly to an increment of calretinin-immunoreactive cells and among them the ones with bipolar morphology. Since there is a propensity for epilepsy in DS patients, this increase in interneurons might reflect an attempt by the system to block overexcitation rather than an increment in total inhibition and could explain the deficit in interneurons and principal cells observed in elderly DS patients.

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The aims of the study were to assess efficacy and safety of TNF-alpha antagonists (anti-TNF) in a cohort of patients with juvenile idiopathic arthritis (JIA) who began treatment under 4 years old and to assess relapse rate after methotrexate and/or anti-TNF withdrawal. We made a retrospective charts review of our non-systemic JIA patients treated with anti-TNF under 4 years of age between January 2006 and April 2013. Demographics, epidemiologic, clinical, laboratory data and rate of relapse after treatment withdrawal due to clinical remission were collected. Efficacy and safety end points included side effects (SE) and time to achieve clinical remission. We included 27 patients, 23 received etanercept and 4 adalimumab with a median age of 3.01 (range 0.88-3.97) years at anti-TNF beginning and 1.94 (range 0.18-5.44) and 2.39 (range 0.18-7.24) years of treatment and follow-up, respectively. All patients had previously received disease-modifying antirheumatic drugs at optimal dose. Nineteen patients reached clinical remission on treatment in a median time of 9.1 (range 6.23-21.17) months. Four of those relapsed during treatment. Six developed mild SE, mostly mild infections. No serious SE were described. Eleven patients who reached clinical remission relapsed after treatment withdrawal. None achieved clinical remission off treatment. Most patients reached clinical remission on anti-TNF. In our cohort of patients, etanercept and adalimumab were safe, with mostly mild infections and no serious SE. We observed a high relapse rate during treatment withdrawal.

INTRODUCTION Chronic kidney disease has reached epidemic levels in several Central American countries since the early years of this century. In El Salvador, it is the second cause of death in men, the fi fth in persons over 18 years old and the third cause of hospital deaths in the adult population. Its features, especially those of a subtype unassociated with traditional risk factors such as diabetes and high blood pressure, are only partially understood.OBJECTIVE Estimate the magnitude of chronic kidney disease in the adult population of El Salvador, considering both prevalence of the disease in its diverse forms as well as presence of potential risk factors nationally and in major subpopulations.METHODS A descriptive, cross-sectional analysis was conducted on data obtained from the Survey of Chronic Non-communicable Diseases in Adults in El Salvador, completed in 2015. The original data (interviews and measurements) were collected between October 2014 and March 2015 from 4817 adults employing a two-stage probabilistic cluster sample, with stratifi cation of primary sampling units. Our analysis, using 20 of the 118 primary variables included in the original survey, focused on point estimation of prevalence rates and means, related to both traditional biological risk factors and nontraditional ones, such as insuffi cient hydration, strenuous working conditions and exposure to toxic agents. A separate analysis was performed to estimate prevalence of chronic kidney disease from nontraditional causes. Corresponding confi dence intervals were calculated with proper weighting. RESULTSThe general prevalence of chronic kidney disease in El Salvador was 12.8% (men 18.0%; women 8.7%). Of the chronically ill kidney patients, 13.1% were between 20 and 40 years of age. Among biological risk factors, the most frequent was high blood pressure (37.0%). Among nontraditional risk factors, high levels of sugary drink consumption (81.0%), insuffi cient hydration (65.9%) and high levels of exposure to agrochemicals in the work environment (12.6%) were also observed. Prevalence of chronic kidney disease from nontraditional causes was 3.9% (men 6.1%; women 2.2%).CONCLUSIONS Chronic kidney disease has reached epidemic proportions in El Salvador. The data confi rm a health tragedy that, although especially striking older men, also takes a severe toll on young men and women. The results confi rm fi ndings of previous research in several Salvadoran agricultural communities. The relatively high level of population exposure to agrochemicals is important and alarming, especially in rural areas, meriting health-impact studies that include and go beyond possible impact on chronic kidney disease.

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