Evaluación de la efectividad y seguridad del tratamiento con adalimumab y tocilizumab en pacientes con artritis reumatoide atendidos en el Hospital P.N.P. “Luis N. Sáenz”- Período 2015-2017

Plantea evaluar la efectividad y seguridad de adalimumab (ADA) y tocilizumab (TCZ) en pacientes con AR atendidos en el Hospital P.N.P. “Luis N. Sáenz” en el período 2015-2017. El diseño fue observacional, analítico y retrospectivo; se revisaron las historias clínicas de pacientes que recibieron ADA y TCZ. Para evaluar la efectividad se registró Disease Activity Score 28 y velocidad de sedimentación globular (DAS28-VSG) reportado al inicio de la terapia biológica y luego en las semanas 12, 24 y 52; y se observó una disminución estadísticamente significativa del DAS28-VSG basal hasta la semana 52 (P<0.001) en ADA, para TCZ no hubo disminución significativa (P=0.814), cuyo porcentaje de remisión fue 47.8 y 33.3 respectivamente. Para evaluar la seguridad se identificó las reacciones adversas a medicamentos (RAMs) reportadas en las historias clínicas; y se obtuvo que 15 pacientes (55.6%) presentaron RAM con ADA, y 5 (62.6%) con TCZ; se registraron 27 RAMs para ADA y 12 para TCZ. Las infecciones urinarias, respiratorias entre otras fueron las RAMs (48.6%) más frecuentes. Fueron 6 RAMs (22.2%) catalogadas como serias para el ADA (tuberculosis pulmonar, trombocitopenia, leucopenia, neumonía) y 1 (8.3%) para el TCZ (anemia aplásica). Se concluyó que ADA disminuyó significativamente el DAS28-VSG con un 47.8% de remisión; ADA y TCZ resultaron ser seguros para el tratamiento de la AR.Tesi

Mejora de la gestión del proceso de sistema de anclajes temporales con inyección única para asegurar la producción en suelos gravosos en Lima – Perú

Esta investigación es de enfoque cuantitativo que surge ante la necesidad de asegurar la producción en los procesos constructivos del sistema de anclajes temporales. A fin de lograr esta finalidad, se tiene como objetivo mejorar la gestión del proceso de sistema de anclajes temporales para sostenimiento de muro anclado con la finalidad de asegurar la producción en suelos gravosos a través de documentos técnicos propuestos, para esto se analizarán las causas de interrupción en los procesos de movilización, perforación, inyección, tensado, destensado, con la finalidad de proponer soluciones a estos percances. Para esta investigación se recogieron todos los datos corporativos, la documentación, los planos y los cronogramas de la empresa utilizados en la ejecución del proyecto de anclaje temporal de un edificio de viviendas multifamiliares. Obteniendo como resultado que la mejora de la gestión del sistema de anclajes temporales con inyección única incrementa la producción ya que al levantar las observaciones que interrumpían el flujo de la continuidad se pudo reducir el incremento de gasto que hubo en mano de obra ya que al asegurar la continuidad no se incrementaron los plazos, respetando el presupuesto inicial

Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease

The oral antidiabetic drug metformin is known to exhibit anti-inflammatory properties through activation of AMP kinase, thus protecting various brain tissues as cortical neurons, for example. However, the effect of metformin on the substantia nigra (SN), the main structure affected in Parkinson’s disease (PD), has not yet been studied in depth. Inflammation is a key feature of PD and it may play a central role in the neurodegeneration that takes place in this disorder. The aim of this work was to determine the effect of metformin on the microglial activation of the SN of rats using the animal model of PD based on the injection of the pro-inflammogen lipopolysaccharide (LPS). In vivo and in vitro experiments were conducted to study the activation of microglia at both the cellular and molecular levels. Our results indicate that metformin overall inhibits microglia activation measured by OX-6 (MHCII marker), IKKβ (pro-inflammatory marker) and arginase (anti-inflammatory marker) immunoreactivity. In addition, qPCR experiments reveal that metformin treatment minimizes the expression levels of several pro- and anti-inflammatory cytokines. Mechanistically, the drug decreases the phosphorylated forms of mitogen-activated protein kinases (MAPKs) as well as ROS generation through the inhibition of the NADPH oxidase enzyme. However, metformin treatment fails to protect the dopaminergic neurons of SN in response to intranigral LPS. These findings suggest that metformin could have both beneficial and harmful pharmacological effects and raise the question about the potential use of metformin for the prevention and treatment of PD.España MINECO SAF2015-64171-

Con esta fecha comunicó á los M. RR. Arzobispos, RR. Obispos y demas Prelados eclesiásticos la órden del Consejo, que dice asi: El Escmo. Sr. D. Tomas Moyano, Secretario de Estado y del Despacho de Gracia y Justicia, comunicó al Consejo con fecha de 12 de Abril de este año

Al final del text: "Es copia de su original, de que certifico"Còpia datada a Segovia el 27 de juliol de 1815 signada per Esteban Valenciano y QuintanaText datat a Madrid el 18 de juliol de 1815 certificat per Bartolomé MuñozTítol obtingut de les 1eres línies del text"Real Orden por la que se resuelve que los predicadores en los púlpitos, no deben exponer a los oyentes más que las doctrinas evangélicas exclusivamente" --Catàleg manual de la Biblioteca Econòmica CarandellOrdre Reial per la que es resol que els predicadors en els púlpits, no han d'exposar als oients més que les doctrines evangèliques exclusivament.

Nasal cannula use during polysomnography in children aged under three with suspected sleep apnea

Nasal cannula; Pediatric sleep apnea; PolysomnographyCánula nasal; Apnea del sueño pediátrica; PolisomnografíaCànula nasal; Apnea del son pediàtrica; PolisomnografiaObjective Early diagnosis of obstructive sleep apnea (OSA) in children is important. The use of a nasal cannula as an airflow sensor during polysomnography has not been evaluated in younger children. The study aims to evaluate the use of nasal cannula in detecting respiratory events in children under three with suspected OSA during daytime nap studies. Methods A total of 185 patients were prospectively included. Respiratory events were scored using nasal cannula alone, thermistor alone, and both methods simultaneously as the airflow sensor. Agreement and diagnostic accuracy were assessed. Results One hundred and seventy-two children were finally analyzed and 110 (64.0%) presented OSA. Total sleep time with an uninterpretable signal was longer with the nasal cannula than with the thermistor (17.8% vs 1.9%; p < 0.001), and was associated with poor sensor tolerance and adenotonsillar hypertrophy. In the estimation of the apnea-hypopnea index, the nasal cannula showed lower agreement than the thermistor with the joint use of the two sensors (intraclass correlation coefficient: 0.79 vs 0.996 with thermistor). Compared with the thermistor, the nasal cannula presented lower sensitivity for detecting OSA (82.7% vs 95.5%) and a lower negative predictive value (76.5% vs 92.4%). Overall, fewer children were diagnosed with severe OSA with the nasal cannula (19.8% vs 30.8% with the thermistor, and 32.6% with both). Conclusions In children under the age of three, the ability of the nasal cannula to detect obstructive events was relatively low. Therefore, other non-invasive measurements for identifying respiratory events during sleep may be of additional value

End-tidal and transcutaneous CO2 monitoring during sleep in children aged under three with suspected sleep apnea

Monitorización transcutánea de CO2; Niños; Apnea del sueñoTranscutaneous CO2 monitoring; Children; Sleep apneaMonitorització transcutània de CO2; Nens; Apnea del so

El Excmo. Sr. D. Tomas Moyano, Secretario de Estado y del Despacho de Gracia y Justicia, ha comunicado al Consejo por medio del Excmo. Sr. Duque del Infantado, su Presidente, con fecha 1º de este mes

Al final del text: "Es copia á la letra de su original, de que certifico como Secretario del Ayuntamiento"Còpia datada a Segovia el 18 de febrer de 1815 signada per Esteban Valenciano y QuintanaText datat a Madrid el 10 de febrer de 1815 certificat per Bartolomé MuñozTítol obtingut de les 1eres línies del textÚltima p. en blanc"Real Decreto por el que se reforma el plan de la Enseñanza, en Universidades y demás centros, con objeto de elevar el nivel cultural del Reyno" --Catàleg manual de la Biblioteca Econòmica CarandellDecret Reial pel que es reforma el pla d'ensenyament, a Universitats i altres centres, amb l'objectiu d'elevar el nivell cultural del Regne.

Effect of adjunctive perampanel on the quality of sleep and daytime somnolence in patients with epilepsy

Epilèpsia; Somnolència diürna; Fàrmacs antiepilèpticsEpilepsia; Somnolencia diurna; Fármacos antiepilépticosEpilepsy; Daytime somnolence; Antiepileptic drugsThis prospective uncontrolled study evaluated the effect of low-dose adjunctive perampanel therapy (4 mg/day for 3 months) on the sleep-wake cycle and daytime somnolence in adult patients (n = 10) with focal seizures. A > 50% reduction in the number of seizures was reported in 80% of the study patients; treatment had no significant effect on any sleep parameters as evident by the Maintenance of Wakefulness Test, Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale scores. Two patients reported dizziness with treatment. In conclusion, low-dose perampanel may improve seizure control without affecting the sleep characteristics or daytime somnolence in patients with epilepsy.This work was supported by Eisai Pharmaceuticals, Spain

Developing and validating an individualized breast cancer risk prediction model for women attending breast cancer screening

Several studies have proposed personalized strategies based on women's individual breast cancer risk to improve the effectiveness of breast cancer screening. We designed and internally validated an individualized risk prediction model for women eligible for mammography screening. Retrospective cohort study of 121,969 women aged 50 to 69 years, screened at the long-standing population-based screening program in Spain between 1995 and 2015 and followed up until 2017. We used partly conditional Cox proportional hazards regression to estimate the adjusted hazard ratios (aHR) and individual risks for age, family history of breast cancer, previous benign breast disease, and previous mammographic features. We internally validated our model with the expected-to-observed ratio and the area under the receiver operating characteristic curve. During a mean follow-up of 7.5 years, 2,058 women were diagnosed with breast cancer. All three risk factors were strongly associated with breast cancer risk, with the highest risk being found among women with family history of breast cancer (aHR: 1.67), a proliferative benign breast disease (aHR: 3.02) and previous calcifications (aHR: 2.52). The model was well calibrated overall (expected-to-observed ratio ranging from 0.99 at 2 years to 1.02 at 20 years) but slightly overestimated the risk in women with proliferative benign breast disease. The area under the receiver operating characteristic curve ranged from 58.7% to 64.7%, depending of the time horizon selected. We developed a risk prediction model to estimate the short- and long-term risk of breast cancer in women eligible for mammography screening using information routinely reported at screening participation. The model could help to guiding individualized screening strategies aimed at improving the risk-benefit balance of mammography screening programs