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Palliative sedation is used to relieve end-of-life refractory symptoms.The objective of this study was to describe the use of palliative sedation in patients who die in internal medicine departments.An observational, cross-sectional, retrospective, and multicenter clinical audit study was conducted in 145 hospitals in Spain and Argentina. Each hospital included the first 10 patients who died in the internal medicine department, starting on December 1, 2015.We included 1447 patients, and palliative sedation was administered to 701 patients (48.4%). Having a terminal illness (odds ratio [OR] 2.469, 95% CI 1.971-3.093, P 0.001) and the length of hospital stay (OR 1.011, 95% CI 1.002-1.021, P = 0.017) were independently associated with the use of palliative sedation. Consent was granted by the families of 582 (83%) patients. The most common refractory symptom was dyspnea, and the most commonly used drugs for sedation were midazolam (77%) and morphine (89.7%). An induction dose was administered in 25.7% of the patients. Rescue doses were scheduled for 70% of the patients, and hydration was maintained in 49.5%. Pain was more common in patients with cancer, whereas dyspnea was more common in those without cancer. Rescue doses were used more often for the patients with cancer (77.8% vs. 67.7%, P = 0.015). Monitoring the palliative sedation with a scale was more frequent in the patients with cancer (23.7% vs. 14.3%, P = 0.008).Palliative sedation is used more often for terminal patients. There are differences in the administration of palliative sedation between patients with and without cancer.

Introduction Meningiomas associating prominent cystic changes (CM) have challenged neurosurgeons since the beginning of this surgical discipline. We present the experience in the diagnostic and therapeutic management of this entity in our institution. Material and methods A review of our patient database was carried out, searching for those CM that were operated on in the last 15 years. Relevant clinical data were recorded and analysed for each case, with special emphasis in the correlation of radiological and pathological findings. Cystic changes were classified according to the scheme proposed by Nauta et al. Results A total of 11 patients were gathered, which represents 1.8% of the meningiomas operated on in our department during the period studied. All were adults, predominantly female patients (8 cases). Among the clinical symptoms a high rate of epileptic seizures was observed while only one patient developed acute intracranial hypertension. Morphologically, most tumours corresponded to type 2 CMs, followed by types 1, 3 and 4. In only five patients an unequivocal radiological diagnosis of meningioma could be made. All neoplasms were surgically removed and there were no records of recurrence (mean follow-up: 52.8 months). Microscopic findings were consistent with the pathological diagnosis of atypical meningioma in 4 cases, while the remaining tumours corresponded to OMS grade I neoplasms with variable microscopic patterns. Conclusions Meningiomas can exceptionally associate cystic changes, both intra and/or extratumoral, in variable number and size. When cystic changes become too prominent (a large number or big-sized cysts), a serious preoperative diagnostic dilemma may arise. The surgical management of those CMs displaying a peripheral, thin-walled cyst (types 2 and 3) is especially complex, as contrast enhancement of the tumour wall did not correlate strictly with neoplastic invasion; even in the absence of this feature free floating islands of meningothelial cells intermixed with cyst fluid can be found. Consequently both surgical biopsy of every suspicious tissue and copious irrigation of the surgical cavity are strongly recommended for these CM types.

Resumen Introduccion Los meningiomas que asocian cambios quisticos prominentes (MQ) han representado un reto diagnostico y terapeutico desde los origenes de la neurocirugia moderna. Presentamos la experiencia en el manejo clinico y quirurgico de esta entidad en nuestro Servicio. Material y metodos En este estudio descriptivo se incluyen los MQ intervenidos en nuestro Servicio en los ultimos 15 anos, evaluando las variables clinicas, diagnosticas y terapeuticas de este subgrupo de meningiomas, con especial enfasis en la correlacion de los hallazgos radiologicos y patologicos. Los tumores se clasificaron siguiendo el esquema propuesto por Nauta y sus colaboradores. Resultados Se identificaron 11 casos, lo que supone un 1,8% de los meningiomas intervenidos en ese periodo. Todos los pacientes eran adultos y 8 de ellos, mujeres. Entre los sintomas, destaco la alta frecuencia de crisis epilepticas, mientras que solo un caso desarrollo hipertension intracraneal aguda. La morfologia predominante fue el tipo 2, seguida de los tipos 1, 3 y 4. En 5 casos pudo establecerse un diagnostico radiologico inequivoco de meningioma. Todos los pacientes fueron tratados mediante cirugia, sin evidenciarse casos de recurrencia durante un seguimiento medio de 52,8 meses. Aunque la mayoria de las neoplasias correspondieron al grado i de la OMS, incluyendo subtipos variados, 4 de ellas fueron diagnosticadas como meningiomas atipicos. Conclusiones De forma excepcional, los meningiomas pueden desarrollar cambios quisticos, intra- o extratumorales, en numero y tamano variable. Estos constituyen hallazgos poco tipicos que pueden dificultar seriamente su diagnostico diferencial radiologico. Los meningiomas con quistes perifericos de capsula fina (tipos 2 y 3) suponen el escenario quirurgico mas complejo, pues el realce capsular en las pruebas de imagen no traduce necesariamente infiltracion tumoral, mientras que el quiste puede contener celulas neoplasicas. Por lo tanto, recomendamos realizar al menos biopsia de la capsula o seudocapsula, y lavado minucioso de la cavidad quirurgica especialmente en estos subtipos.

OBJECTIVESTo investigate the incidence of COVID-19 in a cohort of adult and paediatric patients with rheumatic diseases receiving targeted biologic and synthetic disease modifying anti-rheumatic drugs (tDMARDs) and to explore the possible effect of these treatments in the clinical expression of COVID-19.METHODSA cross-sectional study comprising of a telephone survey and electronic health records review was performed including all adult and paediatric patients with rheumatic diseases treated with tDMARDs in a large rheumatology tertiary centre in Barcelona, Spain. Demographics, disease activity, COVID-19 related symptoms and contact history data were obtained from the start of the 2020 pandemic. Cumulative incidence of confirmed cases (SARS-CoV-2 positive PCR test) was compared to the population estimates for the same city districts from a governmental COVID-19 health database. Suspected cases were defined following WHO criteria and compared to those without compatible symptoms.RESULTS959 patients with rheumatic diseases treated with tDMARDs were included. We identified 11 confirmed SARS-CoV-2 positive cases in the adult cohort and no confirmed positive cases in the paediatric cohort. All patients had a successful recovery and only one patient required admission in the intensive care unit. When using the same classification criteria (only COVID-19 positive cases with pneumonia), COVID-19 incidence rates of the rheumatic patient cohort were very similar to that of the general population [(0.48% (95% CI 0.09 to 8.65%)] and [0.58% (95% CI 5.62 to 5.99%)], respectively. We found significant differences in tDMARDs proportions between the suspected and non-suspected cases (p=0.002).CONCLUSIONAdult and paediatric patients with rheumatic diseases on tDMARDs do not seem to present a higher risk of COVID-19 or a more severe disease outcome when compared to general population. Our exploratory analysis suggests that the proportion of COVID-19 suspected cases differs between tDMARDs.

Introduction Adherence to somatotropin treatment is associated with increased growth velocity and improved adult height. The purpose of this study is to determine the adherence of patients undergoing treatment with an electronic device and its relationship with different variables (age, gender, duration of treatment, diagnosis, height, and growth rate). Material and methods Descriptive, longitudinal and retrospective study of children less than 14 years of age undergoing treatment with somatotropin administered with the Easypod® electronic device in the Paediatric Endocrinology Outpatient Clinic of the General University Hospital of Ciudad Real, Spain. Adherence was monitored for 12 months and was defined according to the equation: (days administered at the prescribed dose/prescribed days) × 100. The data analysis was performed using SPSS software. Results Data were collected from 30 patients, with a predominance of males (57%), a mean age of 6.09 years, with 51% of children less than 5 years old. The most common reasons for the treatment were: small for gestational age (55%) and growth hormone deficiency (38%). The mean duration of treatment was 4.3 years (3.6–5). A mean adherence of 92.3% (87.7–96.9) was observed, and there was a significant correlation with age (Pearson R = −0.384, P = 0.03), and duration of treatment (Pearson R = −0.537; P = 0.003). Conclusions The adherence in our patients with electronic device is high (92.3%), and is inversely associated with age and duration. The use of electronic devices allows monitoring of therapeutic compliance, which affects the optimisation of treatment.

Resumen Introduccion La adherencia al tratamiento con somatotropina se relaciona con el aumento de la velocidad de crecimiento y la mejora de la talla adulta. El objeto de este estudio es conocer la adherencia de pacientes en tratamiento con dispositivo electronico y determinar la relacion con diferentes variables (edad, sexo, duracion del tratamiento, diagnostico, talla y velocidad de crecimiento). Material y metodos Estudio descriptivo, longitudinal y retrospectivo de menores de 14 anos de la consulta de Endocrinologia Pediatrica del Hospital General Universitario de Ciudad Real, en tratamiento con somatotropina administrada con el dispositivo electronico Easypod®. Se realiza seguimiento de la adherencia durante 12 meses. Se define adherencia segun la formula: (dias administrados a la dosis prescrita/dias prescritos) × 100. El analisis de los datos se realizo con el software SPSS. Resultados Se recogio a 30 pacientes: predominio varones (57%), edad media 6,09 anos, menores de 5 anos el 51%. Las causas mas frecuentes de tratamiento: pequeno para la edad gestacional (55%) y deficit de hormona de crecimiento (38%). Tiempo medio de tratamiento 4,3 anos (3,6-5). Se evidencio una adherencia media del 92,3% (87,7-96,9), observandose una correlacion significativa con la edad (R de Pearson = –0,384; p = 0,03) y la duracion del tratamiento (R de Pearson = –0,537; p = 0,003). Conclusiones La adherencia en nuestros pacientes con dispositivo electronico es alta (92,3%), relacionandose inversamente con la edad y la duracion del tratamiento. El uso de dispositivos electronicos permite un seguimiento del cumplimiento terapeutico, lo que repercute en la optimizacion del tratamiento.

Studies in humans and experimental animals have demonstrated the vulnerability of the adolescent brain to actions of ethanol and the long-term consequences of binge drinking, including the behavioral and cognitive deficits that result from alcohol neurotoxicity, and increased risk to alcohol abuse and dependence. Although the mechanisms that participate in these effects are largely unknown, we have shown that ethanol by activating innate immune receptors, toll-like receptor 4 (TLR4), induces neuroinflammation, impairs myelin proteins and causes cognitive dysfunctions in adolescent mice. Since neuroimmune signaling is also involved in alcohol abuse, the aim of this study was to assess whether ethanol treatment in adolescence promotes the long-term synaptic and molecular events associated with alcohol abuse and addiction. Using wild-type (WT) and TLR4-deficient (TLR4-KO) adolescent mice treated intermittently with ethanol (3 g/kg) for 2 weeks, we showed that binge-like ethanol treatment in adolescent mice promotes short- and long-term alterations in synaptic plasticity and epigenetic changes in the promoter region of bdnf and fosb, which increased their expression in the mPFC of young adult animals. These molecular events were associated with long-term rewarding and anxiogenic-related behavioral effects, along with increased alcohol preference. Our results further showed the participation of neuroimmune system activation and the TLR4 signaling response since deficient mice in TLR4 (TLR4-KO) are protected against molecular and behavioral alterations of ethanol in the adolescent brain. Our results highlight a new role of the neuroimmune function and open up new avenues to develop pharmacological treatments that can normalize the immune signaling responsible for long-term effects in adolescence, including alcohol abuse and related disorders. (C) 2015 Elsevier Inc. All rights reserved.

Resumen Introduccion La aparicion de anomalias congenitas a nivel del atlas es frecuente en pacientes con alteraciones neurales, como en el sindrome de Down. La presencia de estenosis clinica por alteracion en el arco posterior de C1 sin que existiera una subluxacion atlantoaxial previa no ha sido descrita en la literatura hasta el momento. Caso clinico Presentamos un caso excepcional de mielopatia por compresion a nivel del atlas en un nino de 5 anos con sindrome de Down provocado por una anomalia del desarrollo del arco posterior de C1. Se realizo una laminectomia posterior a ese nivel con mejoria de la sintomatologia previa. Conclusiones Se debe prestar especial atencion a los ninos con sindromes asociados a alteraciones de la condrogenesis, como es el caso de los que presentan sindrome de Down, para poder beneficiarse de un tratamiento precoz, ya que en la mayoria de las ocasiones son diagnosticados cuando los sintomas son muy severos.

Alcohol drinking during adolescence can induce long-lasting effects on the motivation to consume alcohol. Abnormal plasticity in reward-related processes might contribute to the vulnerability of adolescents to drug addiction. We have shown that binge-like ethanol treatment in adolescent rats induces alterations in the dopaminergic system and causes histone modifications in brain reward regions. Considering that histone acetylation regulates transcriptional activity and contributes to drug-induced alterations in gene expression and behavior, we addressed the hypothesis that ethanol is capable of inducing transcriptional changes by histone modifications in specific gene promoters in adolescent brain reward regions, and whether these events are associated with acquisition of place conditioning. After treating juvenile and adult rats with intermittent ethanol administration, we found that ethanol treatment upregulates histone acetyl transferase (HAT) activity in adolescent prefrontal cortex and increases histone (H3 or H4) acetylation and H3(K4) dimethylation in the promoter region of cFos, Cdk5 and FosB. Inhibition of histone deacetylase by sodium butyrate before ethanol injection enhances both up-regulation of HAT activity and histone acetylation of cFos, Cdk5 and FosB. Furthermore, co-administration of sodium butyrate with ethanol prolongs the extinction of conditioned place aversion and increased the reinstatement effects of ethanol in ethanol-treated adolescents, but not in ethanol-treated adult rats. These results indicate that ethanol exposure during adolescence induces chromatin remodeling, changes histone acetylation and methylation, and modify the effects of ethanol on place conditioning. They also suggest that epigenetic mechanisms might open up avenues to new treatments for binge drinking-induced drug addiction during adolescence. (C) 2012 Elsevier Ltd. All rights reserved.

ResumenEn este estudio se analiza la relación entre algunas dimensiones o activos para el desarrollo en el barrio de residencia, medidos mediante la Escala para la Evaluación de los Activos del Barrio, y el ajuste y la satisfacción vital de adolescentes. La muestra estuvo formada por 2400 adolescentes (1068 chicos y 1332 chicas) con edades comprendidas entre los 12 y los 17 años, que cursaban estudios de Educación Secundaria en centros de Andalucía Occidental. Los resultados mostraron relaciones significativas entre la mayoría de las dimensiones de la escala (empoderamiento de la juventud, apego al barrio, seguridad y control social) y los problemas internalizantes y externalizantes, el consumo de sustancias y la satisfacción vital de los participantes. Por otra parte, los datos aportan evidencias acerca de la validez externa de la escala utilizada. A partir de los resultados se ofrecen algunas sugerencias para la intervención en el entorno comunitario.AbstractThis paper presents the results of a study analyzing the relationship between some dimensions or developmental assets in the neighborhood, as measured by the Scale for the Assessment of Developmental Assets in the Neighborhood, and adjustment and life satisfaction of adolescent boys and girls. The sample consisted of 2400 adolescents (1068 boys and 1332 girls) between ages 12 and 17 who were secondary students in public and private schools in Western Andalusia. The results showed significant relationships between most dimensions of the scale (youth empowerment, attachment to neighborhood safety and social control) and internalizing and externalizing problems, substance use and life satisfaction of participants. Moreover, the data provide evidence about the external validity of the scale used in the study. From the results some suggestions for intervention in the community environment are extracted.

This article provides a definition and description of grief, its characteristics, and the current explanatory models of this phenomenon (the stage model, task model, constructivist model and dual process model). The authors argue that a state of mourning in advance is produced in the process of dementia as a result of significant relational loss before death and describe the risk factors for complicated grief in caregivers: overload, lack of personal and material resources, delegation of care, and complex feelings such as guilt. The need for healthcare organizations to provide professional caregivers with the appropriate means to help with grief and to develop their own measures to prevent burnout is stressed. These measures could include protocols that provide bereavement intervention with the family, the primary caregiver, other patients and/or residents and the professional caregiving team. Finally, losses in persons with dementia must be taken into consideration, avoiding phenomena such as silencing and overprotection and encouraging acceptance and emotional support of their pain so that organic and emotional complications do not occur.

Toll-like receptors (TLRs) response is critical in innate resistance to infection. Alcohol consumption has been shown to suppress the inflammatory response mediated through TLR4, down regulating the production of inflammatory cytokines. We recently reported that low concentrations of ethanol activate TLR4 signaling in astrocytes and triggers neuroinflammation. Because macrophages are important cells in innate immunity, we investigate whether low concentrations of ethanol could stimulate the TLR4 signaling response in murine RAW 264.7 macrophages, and the mechanism involved in the ethanol-induced TLR4 activation. Our results show that while ethanol, at high concentrations (100 mM) or in the presence of the LPS, suppresses the TLR4 response, low to moderate levels (10-50 mM) activate the TLR4 response and triggers the stimulation of the mitogen-activated protein kinases (MAPKs) and the transcription factor NF-kappa B pathways, leading to the production of nitric oxide (NO) and inflammatory cytokines. Pre-treatment with anti-TLR4 Abs abolishes the effects of ethanol on the production of cytokines. We also present evidence that stimulation with either ethanol or LPS induces translocation and clustering of TLR4 and signaling molecules (IRAK and MAPKs) into lipid rafts. Treatment with either streptolysin-O or saponin, lipid rafts disrupting agents, abolishes the ethanol-induced activation of the TLR4/IL-1RI signaling pathway. In summary, the present results demonstrate that low to moderate concentrations of ethanol are capable of stimulating TLR4/IL-1RI response, and provide evidence of a novel mechanism by which ethanol, through its interaction with membrane rafts, can promote TLR4/IL-1RI recruitment and signaling. (C) 2007 Elsevier Ltd. All rights reserved.

Acute lead administration produces a transient increase in brain catalase activity. This effect of lead has been used to assess the involvement of brain ethanol metabolism, and therefore centrally formed acetaldehyde, in the behavioral actions of ethanol. In mice, catalase is involved in ethanol and methanol metabolism, but not in the metabolism of other alcohols such as l-propanol or tert -butanol. In the present study, we assessed the specificity of the effects of lead acetate on catalase-mediated metabolism of alcohols, and the ability of lead to modulate the locomotion and loss of the righting reflex (LRR) induced by 4 different short-chain alcohols. Animals were pretreated IP with lead acetate (100 mg/kg) or saline, and 7 days later were injected IP with ethanol (2.5 or 4.5 g/kg), methanol (2.5 or 6.0 g/kg), 1-propanol (0.5 or 2.5 g/kg) or tert -butanol (0.5 or 2.0 g/kg) for locomotion and LRR, respectively. Locomotion induced by ethanol was significantly potentiated in lead-treated mice, while methanol-induced locomotion was reduced by lead treatment. The loss of righting reflex induced by ethanol was shorter in lead-treated mice, and lead produced the opposite effect in methanol-treated mice. There was no effect of lead on 1-propanol or tert -butanol-induced behaviors. Lead treatment was effective in inducing catalase activity and protein both in liver and brain. These results support the hypothesis that the effects of lead treatment on ethanol-induced behaviors are related to changes in catalase activity, rather than some nonspecific effect that generalizes to all alcohols.

Glial cells and their interactions with neurons play vital roles during the ontogeny of the nervous system and in the adult brain. Alcohol intake during pregnancy can cause mental retardation and neurobehavioral disorders as well as fetal alcohol syndrome (FAS). Clinical and experimental evidence indicate that in utero alcohol exposure induces structural and functional abnormalities in gliogenesis and in glial–neuronal interactions, suggesting a potential role of glial cells on ethanol-induced developmental brain abnormalities. In vivo studies have shown ethanol-associated alterations in the migration of neurons and radial glial as well as in astrogliogenesis and myelin development. In astrocytes in primary culture, ethanol has been found to (1) impair cell growth and differentiation, (2) decrease the levels of glial fibrillary acidic protein or GFAP (an astrocyte marker) and its gene expression and (3) interfere with the stimulatory effect of trophic factors affecting their release and receptor expression. Evidence also suggests that ethanol affects intracellular protein trafficking, which may mediate some effects of ethanol on astroglial cells. These findings suggest that glial cells are target of ethanol toxicity during brain development and may underlie the neurodevelopmental abnormalities observed after in utero alcohol exposure and in FAS.

A selective primary culture of fetal rat hepatocytes was established in our laboratory in order to elucidate the molecular mechanisms of action of different factors and conditions on insulin-like growth factor (IGF)-I and -II gene expression during the perinatal period of the rat. In this model we report that, in a serum-free condition and the presence of non-stimulatory doses of insulin, 5–20 mM glucose evoked an increase of IGF-I and -II mRNA abundance. Glucose regulated in a parallel manner IGF peptide secretion, and an excellent correlation was observed between IGF-I and -II mRNA and IGF-I and -II peptide levels in the conditioned media in response to the carbohydrate. The experiment with 2-deoxyglucose suggests that glucose 6-phosphate, but not its further metabolism, is necessary for the induction of IGF transcript abundance in cultured fetal hepatocytes. Finally, the glucose-induced rise in IGF-II mRNA, the main IGF in fetal stages, was mediated by stimulation of gene transcription and increased transcript stability. The results support the idea that IGFs belong to a family of genes that are positively regulated by glucose., This work was supported by Direccion General de Investigacion, Ciencia y Tecnologia, Ministerio de Educacion y Ciencia, Spain, Grants PB94-0030 and PM 97-0017 and by Comunidad Autonoma de Madrid Grant 08.5/0009/1997.

The effect of the saturable plasma protein binding of ceftriaxone on the elimination of this drug was studied under steady-state conditions in the rat. A concentration-dependent increase in the total, renal and nonrenal clearances of total drug (bound + unbound) was observed, and it was related to the increase in the ex vivo unbound fraction of ceftriaxone as the plasma concentration increased. The nonrenal clearance of the unbound ceftriaxone showed a statistically significant decrease as the plasma concentration of the unbound drug at the steady state increased, which indicates that the nonrenal elimination of the drug (mainly by biliary excretion) is a saturable process. Renal clearance of the unbound ceftriaxone was similar to the glomerular filtration rate, which indicates that glomerular filtration is the principal mechanism involved in the renal excretion of ceftriaxone in the rat.

1. 1. The feeding pattern influences the inhibitory effects of malonyl-CoA on carnitine palmitoyltransferase-I. 2. 2. The sensitivity of liver carnitine palmitoyltransferase-I to malonyl-CoA is increased in rats meal-fed when compared to rats fed ad libitum. 3. 3. Moreover, liver carnitine palmitoyltransferase-I of meal-fed rats remains more sensitive to inhibition by malonyl-CoA during a 24 hour fast than liver carnitine palmitoyltransferase-I of rats previously fed ad libitum.