Mancha3D Code: Multipurpose Advanced Nonideal MHD Code for High-Resolution Simulations in Astrophysics.

The Mancha3D code is a versatile tool for numerical simulations of magnetohydrodynamic (MHD) processes in solar/stellar atmospheres. The code includes nonideal physics derived from plasma partial ionization, a realistic equation of state and radiative transfer, which allows performing high-quality realistic simulations of magnetoconvection, as well as idealized simulations of particular processes, such as wave propagation, instabilities or energetic events. The paper summarizes the equations and methods used in the Mancha3D (Multifluid (-purpose -physics -dimensional) Advanced Non-ideal MHD Code for High resolution simulations in Astrophysics 3D) code. It also describes its numerical stability and parallel performance and efficiency. The code is based on a finite difference discretization and a memory-saving Runge-Kutta (RK) scheme. It handles nonideal effects through super-time-stepping and Hall diffusion schemes, and takes into account thermal conduction by solving an additional hyperbolic equation for the heat flux. The code is easily configurable to perform different kinds of simulations. Several examples of the code usage are given. It is demonstrated that splitting variables into equilibrium and perturbation parts is essential for simulations of wave propagation in a static background. A perfectly matched layer (PML) boundary condition built into the code greatly facilitates a nonreflective open boundary implementation. Spatial filtering is an important numerical remedy to eliminate grid-size perturbations enhancing the code stability. Parallel performance analysis reveals that the code is strongly memory bound, which is a natural consequence of the numerical techniques used, such as split variables and PML boundary conditions. Both strong and weak scalings show adequate performance up to several thousands of processors (CPUs).

Serotonin 5-HT2A, 5-HT2c and 5-HT1A receptor involvement in the acute effects of psilocybin in mice. In vitro pharmacological profile and modulation of thermoregulation and head-twich response.

The psychedelic 5-HT2A receptor (5HT2AR) agonist psilocybin (or the active metabolite psilocin) has emerged as potential useful drug for various neuropsychiatric diseases, with a rapid onset of therapeutic activity. However, the mechanisms responsible for such effects remain incompletely characterized. We aimed to study in vitro pharmacological profile and in vivo acute mechanism of psilocin/psilocybin. Competition binding studies with psilocin were performed in brain and cell cultures. The role of 5HT2AR, 5-HT2C receptors (5HT2CR) and 5-HT1A receptors (5HT1AR) on the psychosis-like head-twitch response (HTR) and on body temperature in mice after psilocybin administration were evaluated. Psilocin showed similar affinities for 5HT2AR (Ki: 120-173 nM), 5HT2CR (Ki: 79-311 nM) and 5-HT1AR (Ki: 152-146 nM) in human and mice brain. Psilocybin induced a dose-dependent HTR (maximal effect 17.07 ± 1.31 at 1 mg/kg i.p.) that was completely suppressed by the 5HT2AR antagonist MDL11939 (1 mg/kg). Higher doses of psilocybin (3 mg/kg) induced lower HTR (9.00 ± 0.53). The 5HT2CR antagonist SB242084 (0.1 mg/kg) increased HTR exerted by psilocybin (3 mg/kg). Psilocybin significantly raised core body temperature at low dose (0.125 mg/kg) (Emax=0.67 ± 0.15 °C), whereas a significant decrease was induced by doses over 1 mg/kg (Emax = -1.31 ± 0.16 °C). Pre-treatment with the 5HT1AR antagonist WAY100635 reversed the decrease of body temperature after psilocybin (1 mg/kg), causing hyperthermia (Emax = 0.94 ± 0.26 °C). The present work provides key findings on the 5HT2AR, 5-HT2CR and 5HT1AR involvement in the acute central effects of psilocybin. The results may be relevant for understanding the mechanism of action underlying the therapeutic effects and side effects of this psychedelic drug.

Pure Ormocer vs Methacrylate Composites on Posterior Teeth: A Double-blinded Randomized Clinical Trial.

CLINICAL RELEVANCE: The clinical behavior of pure ormocer composite is reliable when used in class II restorations after 24 months of evaluation.

Targeted DNA sequencing for assessing clonality in multiple lung tumors: A new approach to an old dilemma.

BACKGROUND: The differential diagnosis between multiple primary lung cancer (MPLC) and advanced lung cancer has traditionally relied on conventional radiology and pathology. However, the outcomes of traditional diagnostic workup are often limited, and staging is uncertain. Increasing evidence suggests that next-generation sequencing (NGS) techniques offer the possibility of comparing multiple tumors on a genomic level. OBJECTIVES: The objective of this study is to assess the clinical impact utility of targeted sequencing in patients presenting with multiple synchronous or metachronous lung tumors. MATERIALS AND METHODS: We describe the diagnostic workup conducted in a patient with three lung tumors, where we used a targeted 50-gene DNA sequencing panel (Ion AmpliSeq TM Cancer Hotspot Panel v2) to assess clonality and establish an accurate lung adenocarcinoma stage. Positive results were confirmed by pyrosequencing or Sanger sequencing. RESULTS: Three surgically resected lung tumors were submitted for targeted sequencing. The tumor from the upper right lobe was positive for a TP53 c.659A > G mutation and native for KRAS. The tumor from the upper left lobe was positive for TP53 c.725G > T and KRAS c.35G > T mutations. The tumor from the lower left lobe was positive for TP53 c.1024C > T and KRAS C.34G > T mutations. Results and reviewed literature in the field support the diagnosis of MPLC instead of a single advanced lung cancer. CONCLUSION: Targeted DNA sequencing significantly increases diagnostic accuracy in patients with multiple lung tumors. NGS panels should be available for patients presenting with multiple lung tumors.

Four-dimensional sonographic evaluation of avulsion of the levator ani according to delivery mode.

OBJECTIVE: To determine the frequency of avulsion of the levator ani muscle in primiparous women according to delivery mode, using introital four-dimensional ultrasonography. METHODS: We performed a prospective observational study at a tertiary obstetric unit. One hundred and eighty primiparous women were included and divided into three groups: normal vaginal delivery without episiotomy, forceps delivery and Cesarean section groups. Between 40 and 120 days after delivery, four-dimensional ultrasonography was performed in order to evaluate the integrity of the levator ani muscle. The operator was blinded to all clinical data and was not aware of delivery mode. The influence of other variables associated with delivery such as birth weight, body mass index, maternal age and use of epidural anesthesia was also studied. RESULTS: Avulsion of the puborectalis component of the levator ani muscle was detected on ultrasonography in 61.7% of women who had undergone a forceps delivery, compared with 13.3% of those who had had a normal vaginal delivery and 0% of those who had had a Cesarean section. Bilateral avulsion was observed in 12/60 (20.0%) of the forceps group and in 2/60 (3.3%) of the normal vaginal delivery group (P < 0.001). Other variables did not seem to influence prevalence. CONCLUSIONS: Forceps delivery is associated with an increased rate of avulsion of the puborectalis component of the levator ani muscle. The effect of forceps use is independent of other delivery-related variables.

Paraplejía aguda y trombosis segmentaria de aorta infrarrenal / Acute paraplegia, and segmental thrombosis of the infrarenal aorta

Introducción. La oclusión aórtica aguda es un evento raro asociado a elevadas cifras de morbimortalidad. Lalesión neurológica directa con paraplejía aguda es muy poco frecuente. Caso clínico. Varón de 72 años de edad, hipertensoe hipercolesterolémico, sufrió dolor súbito de extremidades inferiores y paraplejía completa a la altura de L2. Unatomografía computarizada mostró trombosis segmentaria corta de la aorta infrarrenal, a la altura de L3, donde se situabauna placa calcificada posterior. Realizamos una trombectomía aórtica transfemoral y una angioplastia transluminalde la estenosis aórtica con balón 10 × 40 mm. El paciente recuperó pulsos distales normales y revascularización completade ambas extremidades inferiores (tiempo evento-reperfusión: 8 horas). A pesar del tratamiento intensivo, el pacientedesarrolló un síndrome de reperfusión grave, fracaso multiorgánico, y falleció 48 horas después de la intervención. Laautopsia reveló una placa ateromatosa calcificada y fisurada en la aorta infrarrenal e infarto no hemorrágico de la médulaespinal lumbar. Conclusión. Describimos un caso poco habitual de paraplejía aguda secundaria a una trombosissegmentaria corta de la aorta infrarrenal, que tratamos mediante técnicas endovasculares y discutimos los pocos casossimilares publicados anteriormente

Introduction. Acute aortic occlusion is a rare event associated with high morbidity and mortality rates.Direct neurological lesion with acute paraplegia is very uncommon. Case report. A 72-year-old hypertensive andhypercholesterolemic man suffered sudden lower limb pain and complete paraplegia at L2 level. An abdominal CT scanshowed a short thrombosis of the infrarenal aorta, at the level of L3, where a posterior calcified plaque was located. Weperformed a transfemoral aortic thrombectomy and a PTA of the aortic stenosis with a 10 × 40 mm balloon. The patientrecovered normal distal pulses and complete revascularization of both lower limbs (time event-reperfusion: 8 hours).Despite intensive treatment, the patient developed a severe reperfusion syndrome, multiorgan failure, and he died 48hours after the procedure. The autopsy revealed a fisured and calcified atheromatous plaque in the infrarenal aorta anda non-hemorrhagic infarction of the lumbar spinal cord. Conclusion. We report an unusual case of acute paraplegiasecondary to a short infrarenal aortic thrombosis, treated with an innovative endovascular approach, and we discuss thefew previously published cases

Empleo del NMP22 bladder chek en el diagnóstico y seguimiento del cáncer de vejiga / The use of NMP22 Bladder-Check for the diagnosis and follow-up of bladder cancer

Objetivo: Evaluar la utilidad del NMP22 BladderChek para el diagnóstico y el seguimiento del tumor vesical comparándolo con la citología y la cistoscopia. Métodos: Grupo 1 formado por 109 pacientes asintomáticos en seguimiento por cáncer de vejiga a los que realizamos citología, cistoscopia y el test NMP22. Grupo 2 constituido por 15 pacientes que consultan por hematuria. Se realiza cistoscopia y el test NMP22. Resultados: Grupo1, 9 pacientes presentaron recidiva vesical. La sensibilidad fue del 25% para el NMP22 BladderChek, del 50% para la citología y del 100% para la cistoscopia. La especificidad fue del 91.1% para el NMP22, del 94.1% para la citología y del 95% para la cistoscopia. Grupo 2, de los 15 pacientes 12 (80%) presentaron tumoración vesical. La sensibilidad del NMP22 fue del 83.3% y del 100% para la cistoscopia. La especificidad fue del 100% para el NMP22 y del 66.7% para la cistoscopia. Conclusiones: El NMP22 BladderChek no nos permite distanciar la realización de las cistoscopias en el seguimiento de los tumores vesicales, ya que presenta una baja sensibilidad. Recomendamos sin embargo su uso como screening de tumor vesical en pacientes de riesgo (aquellos que presentan hematuria, disuria y son fumadores) (AU)

Objectives: The goal of this work is to evaluate the usefulness of NMP22 BladderChek in the diagnosis and follow-up of bladder cancer, comparing it with cystoscopy and urine cytology. Methods: Group 1: 109 asymptomatic patients on follow up for bladder cancer underwent cystoscopy, cytology and NMP22 BladderChek. Group 2: 15 patients with history of hematuria underwent cystoscopy and NMP22 BladderChek. Results: Group 1: 9 patients had tumor relapse. Sensitivity was 25% for NMP22 test, 50% for citology and 100% for cystoscopy. Specificity was 91.1%, 94.1% and 95% respectively. Group 2: 12 patients had bladder cancer. The sensitivity was of 83.3% for NMP22 BladderChek and 100% for cystoscopy. The specificity was of 100% for NMP22 BladderChek and 66.7% for cystoscopy. Conclusions: The low sensitivity of NMP22 BladderChek invalidates it as alternative method to cystoscopy in the follow-up of bladder cancer. But it can be recommended for screening in patients without history of bladder cancer but with an increased risk (smokers, patients with dysuria and hematuria) (AU)

Urgencias/emergencias: ¿una especialidad médica? / Urgent care/emergency care: a medical speciality?

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Manejo del dolor posoperatorio en cirugía radical urológica con anestesia epidural / No disponible

La analgesia epidural lumbar posoperatoria es una técnica muy útil en el manejo del dolor posoperatorio (D.P.O.) tras cirugía radical urológica (C.R.U.). Presentamos los resultados del análisis de nuestra experiencia con el manejo de ropivacaína 0,2%, vía epidural, con bomba de perfusión continua. Por el grado de analgesia y confort posoperatorio conseguimos, así como la reducción del trabajo del equipo de enfermería, pensamos que la analgesia posoperatoria epidural con ropivacaína es una técnica idónea y de fácil manejo en planta para la enfermería de urología

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Genetics and molecular disorders in severe secondary hyperparathyroidism: lessons from rna and microarray studies.

Secondary hyperparathyroidism-related disorders begin in the pre-dialysis period and progressively worsen during dialysis. In a high proportion of cases, therapeutic failure in the control of PTH secretion is related to a late start in medical treatment. This may happen because recovery of the functional control of the parathyroid gland, once some irreversible molecular and genetic changes have occurred, can be only partial. These irreversible changes include promotion of cell proliferation and failure of several pathways affecting the metabolism of DNA, RNA and proteins.

A novel mutation in the calcium-sensing receptor responsible for autosomal dominant hypocalcemia in a family with two uncommon parathyroid hormone polymorphisms.

A novel missense activating mutation in the extracellular calcium-sensing receptor (CaSR) is reported in this work. It was identified in three related subjects with the phenotypic features of autosomal dominant hypocalcemia (ADH). The proband, a 27-year-old woman, diagnosed as having hypoparathyroidism at 7 years of age and a history of seizures, showed the highest penetrance of the mutation. The remaining two affected members presented asymptomatic chronic hypocalcemia despite severe hypoparathyroidism associated with high levels of serum phosphate and calcium urinary excretion. The missense mutation (Glu(604)Lys) affected an amino acid residue in the C terminus of the cysteine-rich domain of the extracellular amino-terminal domain, which seems to be required for the coupling of ligand binding to the activation of intracellular signaling pathways. This genetic change cosegregated with hypocalcemia in all the individuals where the mutation was found. As parathyroid hormone (PTH) secretion is the regulatory target of the CaSR, polymorphism analysis of the PTH gene was carried out. PTH polymorphisms were analyzed in the kindred studied. Affected members for the Glu(604)Lys CaSR mutation which also carried the uncommon PTH alleles showed higher penetrance of the mutation, with more severe autosomal dominant hypocalcemia. These results suggested that the PTH gene could act as a modifier locus of ADH, affecting the penetrance of the activating CaSR mutation described.

[Chromosome abnormalities in hyperparathyroidism: utility of comparative genomic hybridization in the study of parathyroid hyperplasias]. / Anomalías cromosómicas en el hiperparatiroidismo: utilidad de la hibridación genómica comparada en el estudio de las hiperplasias paratiroideas.

Genetic abnormalities responsible for primary (pHPT) and secondary hyperparathyroidism (sHPT) are not well described, especially those underlying the autonomous and refractory behaviour of glands from uremic patients with glandular hyperplasia and nodular growth. Comparative Genomic Hybridization (CGH) is a molecular cytogenetic technique based on a double-color in situ fluorescent analysis, allowing a global description of gains and losses of genomic material. It is a useful tool that localizes unstable genetic areas whose alteration could modify the expression of one or several genes related to the pathology in study. Results on primary hyperparathyroidism adenomas have shown a series of genetic changes correlating with areas where genes related to pHPT are located, such as MEN1 and cyclin D1. A large number of chromosomal aberrations in glands from patients with secondary hyperparathyroidism have also been found, and although some of them are common with those described for primary hyperparathyroidism, most of them are located in different areas or in a different proportion. These results confirm that although severe sHPT hyperplasias can evolve into neoplasias similar to pHPT adenomas, both parathyroid alterations must be considered, from a genetic point of view, as unrelated.

Anomalías cromosómicas en el hiperparatiroidismo: utilidad de la hibridación genómica comparada en el estudio de las hiperplasias paratiroideas / Genetic abnormalities on hyperparathyroidism: comparative genomic hybridization in the study of parathyroid hyperplasias

Las anomalías genéticas responsables de la patogenia del hiperparatiroidismo primario y secundario se desconocen casi por completo, sobre todo las que subyacen al comportamiento autónomo y refractario a tratamiento de las glándulas paratiroides de pacientes urémicos con hiperplasia glandular y crecimiento nodular. La hibridación genómica comparada, una técnica de citogenética molecular basada en técnicas de hibridación in situ fluorescente de doble color, permite realizar un análisis global de las ganancias y pérdidas de material genómico, siendo así una potente herramienta de estudio al permitir identificar zonas inestables genéticamente y cuya alteración podría modificar la expresión de uno o varios genes responsables de la patogenia en estudio. Los resultados sobre glándulas con hiperparatiroidismo primario han permitido establecer una serie de cambios cromosómicos, que se corresponden en gran medida a zonas en las que se localizan genes cuya implicación en el hiperparatiroidismo primario ya había sido demostrada. Se han podido detectar también una gran acumulación de aberraciones cromosómicas en glándulas provenientes de enfermos con hiperparatiroidismo secundario severo, y si bien en algunos casos estas aberraciones son comunes a las descritas en el hiperparatiroidismo primario, una gran parte de ellas aparecen en regiones específicas para esta patogenia y en distinta proporción (AU)

Genetic abnormalities responsible for primary (pHPT) and secondary hyperparathyroidism (sHPT) are not well described, especially those underlying the autonomous and refractory behaviour of glands from uremic patients with glandular hyperplasia and nodular growth. Comparative Genomic Hybridization (CGH) is a molecular citogenetic technique based on a doble-color in situ fluorescent analysis, allowing a global description of gains and losses of genomic material. It is a useful tool that localizes instable genetic areas whose alteration could modify the expression of one or several genes related to the pathology in study. Results on primary hyperparathyroidism adenomas have shown a series of genetic changes correlating with areas where genes related to pHPT are located, such as MEN1 and cyclin D1. A large number of chromosomal aberrations in glands from patients with secondary hyperparathyroidism have also been found, and although some of them are common with those described for primary hyperparathyroidism, most of them are located in different areas or in a different proportion. These results confirm that although severe sHPT hyperplasias can evolve into neoplasias similar to pHPT adenomas, both parathyroid alterations must be considered, from a genetic point of view, as unrelated (AU)

Etiopatogenia del hiperparatiroidismo primario, secundario y terciario: implicaciones de los cambios moleculares en el fracaso terapéutico

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Lesión focal esplénica / Focal spleen lesions

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Factores de riesgo de ingreso hospitalario en mayores de 64 años / Risk factors for hospitalization among the elderly

Objetivo: Determinar los factores asociados al ingreso hospitalario en una muestra representativa de la población mayor de 64 años. Diseño y participantes: Estudio de cohorte sobre una muestra de 3.214 sujetos representativa de la población de 65 y más años del partido judicial de Toledo (Castilla-La Mancha).Método: Entrevista personal en el domicilio del sujeto donde se recogen: datos sociodemográficos, carga de enfermedad, situación funcional en actividades de autocuidado e instrumentales, presencia de deterioro cognitivo y trastorno del ánimo, salud autopercibida y utilización previa de recursos sanitarios. Se analiza la presencia de ingreso hospitalario en los 12 meses que siguen a la entrevista en cualquiera de los tres hospitales que atienden el mencionado área. Resultados: 342 (10,6 por ciento) de los sujetos ingresaron en una ocasión al menos en el año siguiente a la realización de la entrevista. En el modelo logístico resultaron factores de riesgo de ingreso hospitalario: la edad avanzada (OR: 1,02), el sexo masculino (OR: 1,37), la presencia de cardiopatía (OR: 1,97) o broncopatía (OR: 1,57), el déficit visual incapacitante (OR: 1,88), la pobre salud autopercibida (OR: 1,37), la dependencia en actividades de autocuidado (OR: 1,45) y haber utilizado previamente el hospital (OR: 3,45). La ingesta de alcohol resultó un factor protector (OR: 0,70). Conclusiones: Las circunstancias asociadas a precisar ingreso hospitalario son multifactoriales. El ingreso anterior es el factor de riesgo de mayor magnitud a la hora de predecir una nueva admisión (AU)

[Risk factors for hospital admission in persons older than 64-years of age]. / Factores de riesgo de ingreso hospitalario en mayores de 64 años.

OBJECTIVE: To determine factors associated with hospitalization in a representative sample of population older than 64 years. DESIGN AND PARTICIPANTS: Cohort study on a sample of 3,214 representative subjects of the population 65 years and older from the judicial district of Toledo (Spain). METHOD: Personal home interview collecting data on: sociodemographic factors, comorbidity, basic and instrumental activities of daily life, conigitive decline and depressive disorder, self-rated health and previous use of health services. Hospital discharge in the 12-month period after the interview in anyone of the three hospitals in the study area were analyzed. RESULTS: 342 (10.6%) of the subjects spent at least one night in the hospital in the year after the accomplishment of the interview. Risk factors for hospitalization in the logistical model were: advanced age (OR: 1.02), male sex (OR: 1.37), presence of cardiopathy (OR: 1.97) or chronic obstruction to airflow (OR: 1.57), visual deficit (OR: 1.88), worse self-rated health (OR: 1.37) and having used the hospital previously (OR: 3.45). Alcohol consumption was a protective factor (OR: 0.70). CONCLUSIONS: Risk factors for hospitalization are of diverse origin. The previous admission is the strongest predictive factor for new hospitalization.