Update of the classification of midpalatal suture behaviour after surgically assisted rapid maxillary expansion using computed tomography.

The aim of this study was to update the midpalatal suture classification after surgically assisted rapid maxillary expansion (SARME) using computed tomography (CT). Thirty-five patients with a transverse maxillary deficiency and unilateral or bilateral posterior crossbite underwent SARME with osteotomy of the pterygoid apophysis of the sphenoid. CT was performed before installation of the Hyrax expander appliance and after the final activation. Opening of the midpalatal suture was classified into three types: type I, total midpalatal suture opening from anterior nasal spine (ANS) to posterior nasal spine (PNS); type II, partial midpalatal suture opening from ANS to the transverse palatine suture, with partial or non-existent opening of the midpalatal suture posterior to the transverse palatine suture; type III, complete maxillary opening from ANS, but not of PNS, because a paramedian fracture completed the opening of the hard palate. Type I was observed in 42.8% of the patients, type II in 40%, and type III in 17.2%. Opening of the transverse palatine suture was found in all midpalatal suture opening patterns and was more frequent in type III, followed by type II and type I. CT was used to update the classification of midpalatal suture patterns, with the inclusion of type III: total opening of the hard palate due partly to opening of the midpalatal suture and partly to a paramedian fracture.

Prognostic factors in neoadjuvant treatment followed by surgery in stage IIIA-N2 non-small cell lung cancer: a multi-institutional study by the Oncologic Group for the Study of Lung Cancer (Spanish Radiation Oncology Society).

PURPOSE: To evaluate the prognostic factors associated with survival in patients treated with neoadjuvant treatment [chemoradiotherapy (CRT) or chemotherapy] followed by surgery (CRTS) in patients with stage IIIA-N2 non-small cell lung cancer (NSCLC). METHODS: A retrospective study was conducted of 118 patients diagnosed with stage T1-T3N2M0 NSCLC and treated with CRTS at 14 hospitals in Spain between January 2005 and December 2014. Overall survival (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was performed. RESULTS: Surgery consisted of lobectomy (74.5% of cases), pneumectomy (17.8%), or bilobectomy (7.6%). Neoadjuvant treatment was CRT in 62 patients (52.5%) and chemotherapy alone in 56 patients (47.5%). Median follow-up was 42.5 months (5-128 months). 5-year OS and PFS were 51.1% and 49.4%, respectively. The following variables were independently associated with worse OS and PFS: pneumonectomy (vs. lobectomy); advanced pathologic T stage (pT3 vs. pT0-pT2); and presence of persistent N2 disease (vs. ypN0-1) in the surgical specimen. CONCLUSIONS: In this sample of patients with stage IIIA-N2 NSCLC treated with CRTS, 5-year survival (both OS and PFS) was approximately 50%. After CRTS, the patients with the best prognosis were those whose primary tumour and/or mediastinal nodal metastases were downstaged after induction therapy and those who underwent lobectomy. These findings provide further support for neoadjuvant therapy followed by surgery in selected patients.

Neoadjuvant treatment followed by surgery versus definitive chemoradiation in stage IIIA-N2 non-small-cell lung cancer: A multi-institutional study by the oncologic group for the study of lung cancer (Spanish Radiation Oncology Society).

OBJECTIVES: The role of surgery in stage IIIA-N2 non-small cell lung cancer (NSCLC) is an actively debated in oncology. To evaluate the value of surgery in this patient population, we conducted a multi-institutional retrospective study comparing neoadjuvant chemoradiotherapy or chemotherapy plus surgery (CRTS) to definitive chemoradiotherapy (dCRT). MATERIAL AND METHODS: A total of 247 patients with potentially resectable stage T1-T3N2M0 NSCLC treated with either CRTS or dCRT between January 2005 and December 2014 at 15 hospitals in Spain were identified. A centralized review was performed to ensure resectability. A propensity score matched analysis was carried out to balance patient and tumor characteristics (n = 78 per group). RESULTS: Of the 247 patients, 118 were treated with CRTS and 129 with dCRT. In the CRTS group, 62 patients (52.5%) received neoadjuvant CRT and 56 (47.4%) neoadjuvant chemotherapy. Surgery consisted of either lobectomy (97 patients; 82.2%) or pneumonectomy (21 patients; 17.8%). In the matched samples, median overall survival (OS; 56 vs 29 months, log-rank p = .002) and progression-free survival (PFS; 46 vs 15 months, log-rank p < 0.001) were significantly higher in the CRTS group. This survival advantage for CRTS was maintained in the subset comparison between the lobectomy subgroup versus dCRT (OS: 57 vs 29 months, p < 0.001; PFS: 46 vs 15 months, p < 0.001), but not in the comparison between the pneumonectomy subgroup and dCRT. CONCLUSION: The findings reported here indicate that neoadjuvant chemotherapy or chemoradiotherapy followed by surgery (preferably lobectomy) yields better OS and PFS than definitive chemoradiotherapy in patients with resectable stage IIIA-N2 NSCLC.

Long-term survival (>25 years) of deceased donor kidney transplant recipients: a single-center experience.

INTRODUCTION: The aim of this preliminary work is to analyze the clinical features of 52 patients with a functional transplanted kidney for >25 years (all first transplant and all deceased donor recipients) and to compare with a similar though more complete study from Hôpital Necker-Paris 2012. METHODS: The mean graft survival at 25 years is 12.7% and at 30 years is 10%. The actual mean serum creatinine concentration is 1.3 mg/L. We analyzed recipient age (mean, 35.9 years) and gender (29 men and 23 women). Donor age was 26.7 ± 10.3 years. Seven patients (13.4%) were transplanted with 1 HLA mismatch, 42.3% with 2 mismatches, and 44.2% with 3 mismatches. Mean cold ischemia time was 15.45 ± 7.7 hours. Of the recipients, 76% had immediate graft function; 38% experienced 1 acute rejection episode and 4 patients had 2 rejection crises. The initial immunosuppressive regimen was azathioprine (AZA) + prednisolone (Pred) in 14 patients, cyclosporin (CSA) + Pred in 13 patients, and CSA + AZA + Pred in 25 patients. Of these patients, 19% maintained their initial regimen, and 54% (28 patients) were very stable on a mixed CSA regimen for >25 years. RESULTS: We present the major complications (diabetes, neoplasia, and hepatitis C virus positivity). CONCLUSION: Our results in deceased donor kidney recipients for >25 years are similar to the mixed population (deceased donors and living donors) presented by the Necker group, although 54% of our patients remain on CSA immunosuppression, contradicting the idea that its use is not compatible with good long-term kidney function in transplant recipients.

Low-temperature phase transformation studies in the stearic acid: C form.

This paper reports the temperature-dependent measurements in the C form of stearic acid. Raman scattering, X-ray diffraction, and differential scanning calorimetry measurements were performed at low temperatures. The polarized Raman spectra were measured for temperatures ranging from 8 to 300 K over the spectral range of 30-3000 cm(-1). The spectral changes observed in both the lattice vibrational modes and the internal vibrational modes regions of the Raman spectrum, allowed to identify a phase transition undergone by the stearic acid crystal occurring between 210 and 170 K and a change in the structure continues to be observed down to 8 K. The anharmonicity of some vibrational modes and the possible space groups presented by the crystal at low temperatures were also discussed. Low-temperature X-ray diffraction measurements were performed from 290 to 80 K and the results showed slight changes in the lattice parameters at ∼200 K. Furthermore, the evidence of the phase transformation was provided by the differential scanning calorimetry measurements, which identified an enthalpic anomaly at about 160 K.

Energy dispersive x-ray spectroscopy evaluation of demineralized human enamel after titanium tetrafluoride application.

OBJECTIVE: Evaluate the presence of a titanium dioxide layer after application of titanium tetrafluoride on human permanent tooth enamel. STUDY DESIGN: The sample consisted of unerupted third molars. After the removal of the roots, each tooth was mesiodistally divided into 2 fragments, one reserved for the experimental group and the other for the control group. Before the treatments the fragments were artificially demineralized. The experimental group (n=5) received an application of 4% titanium tetrafluoride, for one minute and the control group (n=5) did not receive any treatment. The samples were sputter-coated with a 20-30nm gold layer as the energy dispersive x-ray spectrometer analysis was carried out in a scanning electron microscope and the results were descriptively analyzed. RESULTS: The titanium dioxide layer was present on all experimental samples with a titanium peak varying between 6.82 and 26.37%. This layer was not found in the control group. Fluoride and calcium fluoride precipitates were present in the samples treated with titanium tetrafluoride. CONCLUSION: Titanium dioxide layer was formed after one titanium tetrafluoride application, but it was not uniform. Further studies should be carried out so that both the morphology and thickness of such layers can be better understood.

Events supposedly attributable to vaccination or immunization during pandemic influenza A (H1N1) vaccination campaigns in Latin America and the Caribbean.

As part of the vaccination activities against influenza A[H1N1]pdm vaccine in 2009-2010, countries in Latin American and the Caribbean (LAC) implemented surveillance of events supposedly attributable to vaccines and immunization (ESAVI). We describe the serious ESAVI reported in LAC in order to further document the safety profile of this vaccine and highlight lessons learned. We reviewed data from serious H1N1 ESAVI cases from LAC countries reported to the Pan American Health Organization/World Health Organization. We estimated serious ESAVI rates by age and target group, as well as by clinical diagnosis, and completed descriptive analyses of final outcomes and classifications given in country. A total of 1000 serious ESAVI were reported by 18 of the 29 LAC countries that vaccinated against A[H1N1]pdm. The overall reporting rate in LAC was 6.91 serious ESAVI per million doses, with country reporting rates ranging from 0.77 to 64.68 per million doses. Rates were higher among pregnant women (16.25 per million doses) when compared to health care workers (13.54 per million doses) and individuals with chronic disease (4.03 per million doses). The top three most frequent diagnoses were febrile seizures (12.0%), Guillain-Barré Syndrome (10.5%) and acute pneumonia (8.0%). Almost half (49.1%) of the serious ESAVI were reported among children aged <18 years of age; within this group, the highest proportion of cases was reported among those aged <2 years (53.1%). Of all serious ESAVI reported, 37.8% were classified as coincidental, 35.3% as related to vaccine components, 26.4% as non-conclusive and 0.5% as a programmatic error. This regional overview of A[H1N1]pdm vaccine safety data in LAC estimated the rate of serious ESAVI at lower levels than other studies. However, the ESAVI diagnosis distribution is comparable to the published literature. Lessons learned can be applied in the response to future pandemics.

Adipose tissue-derived factors as potential biomarkers in cachectic cancer patients.

Cachexia, a paraneoplastic syndrome markedly associated with worsened prognosis in cancer patients, provokes profound wasting of both lean and adipose mass in an association with a state of metabolic "chaos". The white adipose tissue responds to cachexia with marked local inflammation and may be thus a relevant contributor to systemic inflammation. To address this hypothesis we examined the correlation between tissue expression of adipokines and plasma concentration in cachectic and stable weight patients with or without cancer. Adiponectin and liver-derived CRP concentration were significantly higher in the cachectic groups when compared with stable weight patients (P<0.01). The concentration of plasma IL-6 was higher (11.4-fold) in the cancer cachectic group when compared with weight-stable controls, and presented a significant correlation with the presence of cancer (P<0.001). A marked increase (5-fold) in IL-6 as a result of the interaction between the presence of cachexia and the presence of tumour was observed in the subcutaneous tissue of the patients, yet not in the visceral depot. Plasma adiponectin levels were higher in cachectic cancer patients, compared with stable weight cancer patients individually matched by age, sex, and BMI, and the subcutaneous depot was found to be the main contributing tissue, rather than the visceral pad. Based on the results we concluded that the subcutaneous adipose tissue is associated with plasma changes that may function as markers of cachexia.

Asma agudo severo en niños: ¿fenotipo diferente? / Severe asthma in children: a different phenotype?

Background: The magnitude of response to treatment of asthma exacerbations is variable and a significant proportion of them need hospitalization. Objectives: to define the profile of children that were hospitalized for severe asthma and the possible indicators and determinants of their poor responsiveness. Methods: a prospective study in 60 children 4 years or more of age with a search of the ethiology of the exacerbation and a study of the inflammatory profile in sputum. Results: 60 children between 4 and 15 years. 50 percent had a previous diagnosis of asthma without regular use of inhaled corticosteroids in two thirds. 40 percent had previous admissions for asthma. Etiology of the exacerbation was identified in 52 percent with Rhinovirus, human Metapneumovirus, RSV and Mycoplasma pneumoniae as the most frequent agents. Inflammatory profile was determined in 33 children: eosinophilic in 36 percent, eosinophilic/ neutrophilic in 64 percent. Conclusions: Severe asthma with serious exacerbations may be a phenotype whose outstanding aspects in this cohort were: previous hospitalizations, lack of prophylactic treatment, viral infections as frequent trigger, and combined inflammatory cell profile in sputum.

La magnitud de la respuesta al tratamiento de una exacerbación de asma es variable entre los pacientes y una proporción significativa de ellos debe hospitalizarse. Objetivos: Definir el perfil de los niños que se hospitalizaron por asma grave y los posibles indicadores y determinantes de la respuesta desfavorable al tratamiento. Método: Estudio prospectivo en niños de 4 años o más, con búsqueda etiológica de la exacerbación y estudio de perfil inflamatorio en esputo. Resultados: 60 niños entre 4 y 15 años. El 50 por ciento tenía diagnóstico previo de asma sin uso regular de corticoesteroides inhalados en dos tercios. Hospitalizaciones previas por asma en el 40 por ciento. La etiología de la exacerbación fue identificada en el 52 por ciento siendo los agentes más frecuentes Rhinovirus, Metapneumovius, VRS y Mycoplasma pneumoniae. El perfil inflamatorio fue determinado en 33 niños: eosinofílico en 36 por ciento y eosinoflico/neutroflico en 64 por ciento. Comentario: El asma severa con exacerbaciones graves sería un fenotipo cuyos aspectos destacados en esta cohorte serían: niños con hospitalizaciones previas, falta de tratamiento profiláctico, infección viral como desencadenante frecuente, patrón inflamatorio combinado del esputo y rinitis atópica.

Guía clínica: consenso para Chile en enfermedad de Fabry / Clinical guidelines: Chilean consensus in Fabry disease

Fabry's disease is an X-linked recessive inborn error of metabolism of glycosphingolipids, caused by the deficiency of the lisosomal enzyme alpha-galactosidase. It is a rare disease with an estimated incidence rate of approximately 1:80.000 to 1:117,000 births in the general population. Recently, the growing knowledge about this disease has permitted the development of enzyme replacement therapy, which has modified the prognosis and quality of life of these patients. In Chile, the real incidence is unknown, but the increase in the number of patients diagnosed during the last five years, mainly in the north of the country. This guide was prepared with the intention of establishing a consensus for the diagnosis, treatment and monitoring of the patients with Fabry disease based on the present available scientific evidence.

La enfermedad de Fabry es un error innato del catabolismo de los glucoesfingolipidos, de herencia recesiva ligada al cromosoma X, causado por la deficiencia de la enzima lisosomal alfa-galactosidasa A (alfa-gal A). Es un defecto poco frecuente, con una incidencia estimada de 1:80.000 a 1:117.000, entre la población general. Recientemente, el creciente conocimiento acerca de esta enfermedad, ha permitido el desarrollo de la terapia de reemplazo enzimático, la cual ha modificado el pronóstico y calidad de vida de los pacientes. En Chile, se desconoce la incidencia real, pero el aumento del número de pacientes diagnosticados durante los últimos cinco años, principalmente en la zona norte del país, ha generado un mayor interés por esta enfermedad. Esta guía fue elaborada con la intención de establecer un consenso para el diagnóstico, tratamiento y seguimiento de los pacientes con enfermedad de Fabry, basado en la evidencia científica, actualmente disponible.

Adipose tissue inflammation and cancer cachexia: possible role of nuclear transcription factors.

Cancer cachexia is a multifaceted syndrome whose aetiology is extremely complex and is directly related to poor patient prognosis and survival. Changes in lipid metabolism in cancer cachexia result in marked reduction of total fat mass, increased lipolysis, total oxidation of fatty acids, hyperlipidaemia, hypertriglyceridaemia, and hypercholesterolaemia. These changes are believed to be induced by inflammatory mediators, such as tumour necrosis factor-α (TNF-α) and other factors. Attention has recently been drawn to the current theory that cachexia is a chronic inflammatory state, mainly caused by the host's reaction to the tumour. Changes in expression of numerous inflammatory mediators, notably in white adipose tissue (WAT), may trigger several changes in WAT homeostasis. The inhibition of adipocyte differentiation by PPARγ is paralleled by the appearance of smaller adipocytes, which may partially account for the inhibitory effect of PPARγ on inflammatory gene expression. Furthermore, inflammatory modulation and/or inhibition seems to be dependent on the IKK/NF-κB pathway, suggesting that a possible interaction between NF-κB and PPARγ is required to modulate WAT inflammation induced by cancer cachexia. In this article, current literature on the possible mechanisms of NF-κB and PPARγ regulation of WAT cells during cancer cachexia are discussed. This review aims to assess the role of a possible interaction between NF-κB and PPARγ in the setting of cancer cachexia as well as its significant role as a potential modulator of chronic inflammation that could be explored therapeutically.

Effects of depot growth hormone replacement on thyroid function and volume in adults with congenital isolated growth hormone deficiency.

BACKGROUND: Conflicting data exist on the effects of GH replacement therapy (GHRT) on thyroid function and thyroid volume (TV) in GH-deficient (GHD) patients. AIM: The aim of this study was to assess the effects of GHRT on thyroid function and TV in adults with congenital lifetime isolated GHD (IGHD). SUBJECTS AND METHODS: We studied 20 GH-naïve adults with IGHD due to a homozygous mutation of the GHRH-receptor gene at baseline, after 6-month depot- GH replacement therapy (pGH), and 6-month washout (6mo). Total T(3), free T(4) (FT(4)), reverse T(3) (rT(3)), TSH, IGF-I, SHBG, and TV were measured; body surface area-corrected TV (CTV) was calculated. RESULTS: IGF-I and T(3) increased pGH. T(3) levels remained elevated at 6mo. GHRT did not significantly change FT(4), rT(3), TSH, and SHBG. TV and CTV increased pGH and remained elevated at 6mo. CONCLUSIONS: GHRT in IGHD adults caused an increase in serum T(3) levels and TV, suggesting an important role of the GH-IGF-I axis in thyroid function.

Calidad de vida en pacientes portadores de cardiopatías congénitas / Quality of life in patients with congenital heart disease

Antecedentes: La corrección de las Cardiopatías Congénitas (CC) tiene como fin mejorar la calidad de vida de los pacientes portadores de ellas, pero no existen en nuestro medio estudios sobre ésta, ni su comparación con niños sanos. Objetivos: Estudiarla calidad de vida de los CC, objetivando tres áreas, en tres grupos de pacientes de complejidad diferente, y compararlos con un grupo sano. Método: Se escogieron 4 grupos de niños del área sur oriente de Santiago; 3 grupos de CC: comunicación interventricular (CIV), Tetralogía de Fallot(T4F), Ventrículo único (VU), y un grupo de niños sanos (S). Se sometieron a encuesta de calidad de vida ellos y sus padres, se evaluaron tres áreas especificas; actividad escolar, actividades cotidianas (actividad física y generales) y vida familiar. Se objetivó capacidad física con Test de Esfuerzo (TE), con protocolo de Bruce modificado, en todos. El análisis estadístico incluyó análisis de varianza y chi cuadrado. Resultados: Se seleccionaron 65 niños, 12 con CIV, 18 con T4F, 15 con VU,y 20 sanos. Treinta y cuatro de ellos son hombres (52 por ciento). En escolaridad no existen diferencias significativas en edad/curso, promedio de notas (5.7), repetición (24.8 por ciento), en percepción de notas y rendimiento escolar los pacientes con VU tanto ellos como sus padres perciben peor rendimiento que sus pares. Con relación a actividades físicas generales el TE reveló concordancia con percepción cualitativa y diferencias de rendimientos de acuerdo a la gravedad de la patología, estadísticamente significativa sólo VU en esfuerzos mayores (S: 11:75min CIV: 12:2min, T4F:10min y VU: 7:3min). Con relación a actividades cotidianas, no perciben limitación de la vida diaria en forma significativa, excepto en algunas actividades, los pacientes con VU. Los padres de niños con CC tienen percepción de mayor limitación. Con relación a la vida familiar no hay diferencias significativas entre los 4 grupos...

Background: Surgical correction of congenital heart diseases (CHD) intends to improve quality of life (QL) in affected patients. In Chile this aspect has not been objectively evaluated, especially through comparison with normal children. Aim: to compare the quality of life in three groups of CHD patients with that of normal controls. Three aspects of QL were evaluated. Methods: three groups of patients with CHD (Ventricular septal defect, Tetralogy of Fallot, Single Ventricle) were compared to a group of healthy children from the south east area of Santiago. A standard QL questionnaire was used to evaluate school performance, physical and general daily activities and family life . A treadmill test with a modified Bruce protocol was used to evaluate physical capacity Results: There were 12 patients in the VSD, 12 in the Fallot, 15 in the Single Ventricle and 20 in the normal groups. 52 percent were males. Age at each school level, school performance (grades and failure rates) were similar across groups except for a lower performance in patients with Single Ventricle. Physical capacity (duration of stress test) was lower in patients with Single Ventricle (7.3 min average) compared to normal (11.75min), VSD (12.2min) and Tetralogy of Fallot (10.0 min). The results of these test correlated with subjective performance of physical capacity. Similarly patients with Single Ventricle perceived a greater limitation for daily activities (60 percent) compared to VSD (100 percent), Fallot's (89 percent) and healthy controls (89 percent). In general, parents of CHD patients perceived a greater limitation compared to their children. Family life was not different among groups. Conclusions: The perception of QL in these patients with corrected CHD did not differ compared to healthy controls. Objective evaluation showed a lower physical capacity in patients with a more severe type of CHD.

Purification of a beta-galactosidase from cotyledons of Hymenaea courbaril L. (Leguminosae). Enzyme properties and biological function.

Beta-galactosidases are enzymes that can be found in most living beings and in the plant kingdom its activity and genes have been detected in several tissues such as ripening fruits, developing leaves and flowers and storage tissues such as cotyledons. In plants, their activities are usually associated with the secondary metabolism or with oligosaccharide or polysaccharide degradation. Polysaccharide specific beta-galactosidases include beta-galactanases, which attack pectic polymers and beta-galactosidases that attack xyloglucans (XG). In the present work we purified an XG-specific beta-galactosidase (named hcbetagal) from cotyledons of developing seedlings of Hymenaea courbaril, a legume tree from the Neotropical region of the world. The enzyme has a molecular weight of 52-62 kDa and was shown to attack specifically xyloglucan oligosaccharides (XGOs) but not the polymer. It has a pH optimum between 3 and 4 and at this pH range the enzyme increases activity linearly up to 50 degrees C. Kinetic studies showed that hcbetagal is inhibited competitively by free galactose (K(i) = 3.7). The biochemical properties of hcbetagal as a whole suggest that it is involved in storage xyloglucan mobilisation during seedling development. Its high specificity towards XGOs, the low pH optimum and the fact that it is inhibited by its product (galactose) suggest that hcbetagal might be one of the biochemical control points in xyloglucan catabolism in vivo. A possible relationship with functional stability of the wall during cell death as cotyledons undergo senescence is discussed.

Cytochrome P450 1A1 (CYP1A1) T6325C polymorphism might modulate essential hypertension-associated stroke risk.

Stroke is a serious complication associated with hypertension. Because cytochrome P450 1A1 (CYP1A1) is involved in the production of arachidonic acid-derived vasoactive substances, we hypothesized that CYP1A1 functional polymorphisms (linked to changes in enzyme activity) might be related to pathological conditions associated with essential hypertension. We genotyped 32 patients with hypertension for three CYP1A1 polymorphisms, and individuals with or without history of previous stroke were compared. These results were also compared with a control population sample of 152. The distributions of T6235C (m1) CYP1A1 genotypes in patients with (TT: 44.4%; TC/CC: 55.6%; n = 9) and without stroke (TT: 82.6%; TC/CC: 17.4%; n = 23) indicate that the C allele is associated with stroke (OR = 5.94; 95% C = 1.46 - 24.23). No association was found between the polymorphism studied and essential hypertension. Our results suggest a relationship between CYP1A1 activity and incidence of stroke in patients with essential hypertension, but no conclusion can be drawn regarding an association with essential hypertension.

A2A receptor and striatal cellular functions: regulation of gene expression, currents, and synaptic transmission.

A2A receptor is highly coexpressed with enkephalin and D2 receptor in striatopallidal neurons. A2A antagonists acutely enhance motor behavior in animal models of Parkinson's disease (PD) and are therefore considered potential PD therapeutic agents. Analysis of gene expression regulation using pharmacologic tools or A2A receptor-deficient mice (A2A-/-) shows that the A2A receptor positively and tonically controls the expression of enkephalin and immediate early genes in striatopallidal neurons. Because this regulation strictly mirrors the effect of D2 receptor, these data strongly support the hypothesis that A2A antagonists reduce the activity of striatopallidal neurons in models of PD. However, analysis of A2A-/- mice suggests additional effects of A2A receptor in the control of striatal physiology. Unexpectedly, these animals exhibited a reduction in exploratory activity and a 50% reduction in substance P expression. This was associated with a 45% decrease in the striatal extracellular dopamine concentration, suggesting that chronic absence of A2A receptor results in a functional hypodopaminergic state in the striatum. The A2A receptor controls inhibitory synaptic transmission negatively in the striatum and positively in the globus pallidus; this further supports the efficacy of A2A antagonists in reducing the activity of striatopallidal neurons in PD. The A2A receptor does not modulate basal alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)-mediated excitatory corticoaccumbal synaptic transmission during normal physiologic conditions. However, genetic inactivation or pharmacologic blockade of the A2A receptor significantly reduced long-term potentiation (LTP) at this synapse. Therefore, this receptor is implicated in the induction of corticoaccumbal LTP, an effect that could be related to its involvement in long-term behavioral sensitization to repeated dopaminergic treatment.

Health Science students' attitude to dying.

Health care professionals must be prepared, both as scientists and as humans, to treat, accompany and help anyone in the difficult moments prior to their death. The following study aims to identify the attitude of Health Sciences students to their own death process and the circumstances surrounding it, so as to be able to give them appropriate training in caring for those in this situation. 666 Health Sciences students at the University of Murcia were given a questionnaire dealing with different aspects of what would cause them peace or anxiety during their death process. We can see from the results that the thing that would most help them to die peacefully would be knowing that their life would not be prolonged artificially, and what worries them most is pain and suffering. We have reached the following conclusions from these results: we must train future health care professionals on a personal and professional level so that they are able to provide quality care and comfort in those situations and aspects that are associated with death in order to preclude wanting a quick death.

Inactivation of adenosine A2A receptor impairs long term potentiation in the accumbens nucleus without altering basal synaptic transmission.

The nucleus accumbens is considered to be critically involved in the control of complex motivated behaviors. By modulating its glutamatergic excitatory input, mesolimbic dopaminergic afferents have been implicated in the reinforcing properties of drugs of abuse. However, they might not represent the only path for influencing the accumbens output. The aim of this study was to investigate possible modulation of synaptic transmission at this glutamatergic synapse by adenosine receptors. The standard field potential recording technique was used on brain slices from wild-type and A2A receptor-deficient mice. Neither the stimulus-response relationship nor paired-pulse facilitation was altered in the mutant mice. In both genotypes, the activation of A1 receptors by 2-chloro-N6-cyclopentyladenosine reduced the field excitatory postsynaptic potential (fEPSP) slope to a similar extent. In wild-type slices, activation or blockade of A2A receptors by 2-[4-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosine and 4-(2-[7-amino-2-(2-furyl)[1,2,4]-triazolo-[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol, respectively, did not modify the synaptic transmission. Moreover, a long lasting pre-activation of these A2A receptors did not influence the A1 receptor-mediated reduction in fEPSP slope. Long term potentiation (LTP) of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate (AMPA) receptor-mediated synaptic transmission could be elicited in both wild-type and A2A receptor-deficient mice. However, LTP appeared to be quantitatively modulated by the A2A receptor pathway since the level of potentiation was reduced in A2A receptor-deficient mice as well as in slices of wild-type mice in which the A2A receptor pathway was blocked. The involvement of the cAMP-dependent protein kinase was supported by the reduction in potentiation level in slices of wild-type mice treated with adenosine 3',5'-cyclic monophosphorothiotate, 8-(4-chlorophenylthio)-Rp isomer, an inhibitor of this enzyme. These data provide evidence that the adenosine acting at the A2A receptor is implicated in events directly or indirectly related to LTP induction in the accumbens whereas it is not involved in the regulation of the basal AMPA receptor-mediated excitatory synaptic transmission.