High-dose versus low-dose corticosteroid treatment strategy in patients hospitalised with COVID-19: effect on ICU admission rate / Estrategia de tratamiento corticoide en altas dosis versus bajas dosis en pacientes COVID-19 hospitalizados: efecto en la tasa de ingreso en UCI

Objective: COVID-19 is associated with lung damage and a high mortality rate in hospitalised patients. Corticoids may reduce the evolution to respiratory failure and death. This study aims to assess the effect on the ICU admission rate of a change in corticosteroid treatment strategy, administering low versus high doses. Methods: A retrospective, observational study was designed. Confirmed COVID-19 patients indicated to start treatment with corticosteroids were enrolled. To study the association between the type of corticosteroid used and admission to the ICU, a binary logistic regression model was constructed. This model included variables that could cause confusion or influence the response: gender, age, comorbidities, and analytical data. Results: From 190 admitted patients, 127 were enrolled in the study. In both groups, patients received a minimum of two doses of corticosteroids during admission. 12.4% (12/97) of the patients who received methylprednisolone (high doses) were subsequently admitted to the ICU, compared to 30.0% (9/30) of the patients who received dexamethasone (low doses). In the logistic regression model constructed, the type of corticosteroid (low-dose dexamethasone) (p=0.002), male gender (p=0.023), age over 50 years (p=0.014) and IL-6 level >70 pg/mL (p=0.004) remained as predictive factors for admission to the ICU.Conclusions: In the studied population of patients hospitalised for COVID-19, the use of high-dose methylprednisolone is associated with a lower rate of admission to the ICU than the administration of low-dose dexamethasone. (AU)

Objetivo: La COVID-19 está asociada a daño pulmonar y alta tasa de mortalidad en pacientes ingresados. Los corticoides pueden reducir la progresión a insuficiencia respiratoria y muerte. El objetivo del presente estudio es evaluar el efecto sobre la tasa de ingreso en UCI tras el cambio de estrategia en el tratamiento con corticoides, administración de bajas dosis frente a altas dosis. Métodos: Se diseñó un estudio retrospectivo observacional en el que se seleccionaron pacientes COVID-19 confirmado con indicación de inicio de tratamiento con corticoides. Para estudiar la asociación entre el tipo de corticoide utilizado y el ingreso en UCI, se construyó un modelo de regresión logística binaria en el que se incluyeron variables que podrían causar confusión o influir en la respuesta: sexo, edad, comorbilidades y datos analíticos. Resultados: De 190 pacientes ingresados, 127 se incluyeron en el estudio. En ambos grupos los pacientes recibieron un mínimo de dos dosis de corticoides durante el ingreso. El 12,4% (12/97) de los pacientes que recibieron metilprednisolona (altas dosis) ingresaron posteriormente en UCI, frente al 30,0% (9/30) de los pacientes que recibieron dexametasona (bajas dosis). En el modelo de regresión logística construido permanecieron como factores predictivos de ingreso en UCI el tipo de corticoide (dexametasona a bajas dosis) (p=0,002), el sexo masculino (p=0,023), edad superior a 50 años (p=0,014) y nivel de IL-6 >70 pg/mL (p=0,004).Conclusiones: En la población estudiada de pacientes hospitalizados por COVID-19, el uso de metilprednisolona a altas dosis se asocia a una menor tasa de ingreso en UCI que dexametasona a bajas dosis. (AU)

Encefalitis y psicosis en la adolescencia: a propósito de un caso / Encephalitis and psychosis in adolescence: report of clinical case

La encefalitis por virus herpes simple es una infección del sistema nervioso central y constituye una emergencia médica por su elevada mortalidad y morbilidad, por lo que requiere una detección y tratamiento tempranos. Se presenta un caso de un adolescente de 16 años sin antecedentes somáticos ni psiquiátricos previos que debuta con un cuadro clínico de aparición brusca caracterizado por sintomatología psicótica productiva. Después de una evaluación exhaustiva se aísla el Virus de Herpes Simple tipo 1 (VHS-1) en líquido cefalorraquídeo (LCR), con buena respuesta al tratamiento con Aciclovir. Este caso ilustra la importancia de descartar las causas orgánicas en pacientes con un primer episodio psicótico y establecer un tratamiento precoz, lo cual va a condicionar el curso y el pronóstico de la enfermedad

Herpes simplex encephalitis is an infection of the central nervous system and is a medical emergency due to its high mortality and morbidity, which requires early detection and treatment. We present a case of a 16-year-old adolescent with no prior somatic and psychiatric history, who debuted with a sudden onset of clinical symptoms characterized by productive psychotic symptoms. After extensive workup, Herpes simplex virus type 1 (HSV1) is detected in cerebrospinal fluid (CSF), with good response to Acyclovir treatment. The case illustrates the importance of ruling out the organic causes in patients with a first psychotic episode and establishing early treatment, which is a determining factor in the course and prognosis of the disease

Performance of different biofilters in a recirculating system for rainbow trout farming / Desempeño de diferentes biofiltros en un sistema de recirculación para cultivo de trucha arcoiris

ABSTRACT Objective. To evaluate the performance of different biofilters in a recirculating aquaculture system (RAS) for trout farming. Materials and methods. It was used a 1m3 plastic tank for fries farming; fabric bags to solids retention; a submersible pump; a constant water level and flow distribution box; six up flow biofilters in 3" PVC tube; sand of D10=0.45mm as carrier. The reactors were operated at local temperature and with hydraulic retention time (HRT) of 11 min, the biofilters were inoculated in the next way: R1-Control: RAS water; R2-Fish culture farm sludges; R3- Water from aerated lagoon of Antanas landfill (AL); R4-Aquarium sediments; R5- Aerated lagoon of AL sludges; R6-Sludges from sulfidogenic reactor of AL. The weight gain (WG) and the food conversion (FC) were evaluated, some physic-chemical parameters were monitored and the nitrogen and suspended solids removal efficiency were evaluated. Results. The WG of the cultured animals was 1.58 g/d and the FC was 1.41. There were no differences for ammonium and nitrite removal between the reactors; the average removal efficiencies were: ammonium 4.78%, nitrite 27.2%, nitrate 32.3%, suspended solids 37.5%; R4 and R5 reactors presented the best performance on nitrate removal, with average efficiencies of 47.4% and 42.8%. R3 presented the best SS removal with an average of 58.2%. Conclusions. The RAS water treatment system guaranteed appropriated liquid quality conditions for trout farming; the most efficient reactor for removal of the different forms of nitrogen was the inoculated with the aerated lagoon of AL sludges.

RESUMEN Objetivo. Evaluar el desempeño de diferentes biofiltros en un sistema de recirculación (SRA) para cultivo de trucha arcoiris. Materiales y métodos. Se utilizó: un tanque de 1m3 para cultivo de alevines, bolsas de lienzo para retención de sólidos, bomba sumergible, caja de nivel constante y distribución de flujo, seis biofiltros en tubo de PVC de 3", arena con D10=0.45mm como medio soporte. Los biofiltros se operaron a temperatura ambiente y con tiempo de retención hidráulica (TRH) de 11 min, se inocularon así: R1-Control: Aguas del SRA; R2-Lodos estación piscícola; R3-Agua Laguna aireada relleno sanitario Antanas (RSA); R4-Sedimentos acuarios; R5-Lodos laguna aireada RSA; R6-Lodos reactor sulfidogénico RSA. Se evaluó la ganancia de peso (GP) y la conversión alimenticia (CA), se monitorearon parámetros físico-químicos y se evaluó la eficiencia de remoción de nitrógeno y sólidos suspendidos. Resultados. La GP de los animales fue de 1.58 g/d y la CA de 1.41. No hubo diferencias para remoción de amonio ni nitritos entre reactores; las eficiencias medias de remoción fueron: amonio 4.78%, nitrito 27.2%, nitrato 32.3%, sólidos suspendidos 37.5%. Los reactores R4 y R5 presentaron mejor remoción de nitratos, con eficiencias medias de 47.4% y 42.8%. El R3 reportó la mejor remoción de SS con promedio del 58.2%. Conclusiones. El sistema de tratamiento del agua en el SRA garantizó condiciones de calidad del líquido, apropiadas para el cultivo de la trucha; el reactor más eficiente para la remoción de las formas de nitrógeno evaluadas fue el inoculado con lodos de la laguna aireada del RSA.

A method to Quantify the Affinity of Cabazitaxel for PLA-PEG Nanoparticles and Investigate the Influence of the Nano-Assembly Structure on the Drug/Particle Association.

PURPOSE: To study the impact of the size and the structure of the nano-assembly on the drug/particle association, determining the intrinsic partition coefficient, in order to better master the encapsulation and release properties of the carrier. METHODS: An experimental methodology is proposed to characterize the drug/nanoparticle association by mean of a partition coefficient between the PLA-PEG nanoparticles and the suspending aqueous medium, referred to as Kp. The determination was made from apparent values (referred to as Kp (ap)) measured in the presence of solubilizing agents (albumin and hydroxypropyl-ßcyclodextrin) and extrapolation to zero concentration. The structure of nanoparticles was investigated by Transmission Electron Microscopy and static light scattering. RESULTS: Depending on the manufacturing process and the PEG length of the copolymer, the nanoparticles structured either as aggregates of copolymer chains or micelles exhibiting significantly different Kp values. CONCLUSION: The methodological tool described here showed that the difference in cabazitaxel/nanoparticle association between aggregates and micelles could be attributed to the difference in PLA-PEG chains packing.

[Transcranial magnetic stimulation, tinnitus and auditory hallucinations]. / Estimulación magnética transcraneal, tinnitus y alucinaciones auditivas.

Transcranial magnetic stimulation (TMS) has been shown to be effective in modulating cerebral cortex activity. Most of the published controlled studies have reported that left temporoparietal area stimulation with 1 Hz frequencies has managed to improve auditory hallucinations at least partially and transiently in patients suffering from schizophrenia. These stimulation parameters have been demonstrated to be useful in otologic patients with tinnitus sensation. The clinical relevance of these findings has already been discussed. However, in spite of the clinical benefit of TMS for these or other patients, it is revealing new data and new questions about the neurobiological basis of mental disorders. For example: which is the common substrate in tinnitus and auditory hallucinations that could explain such a therapeutic coincidence? In this work we present two representative clinic cases and we discuss this question.

Estimulación magnética transcraneal, tinnitus y alucinaciones auditivas / Transcranial magnetic stimulation, tinnitus and auditory hallucinations

La estimulación magnética transcraneal (EMT) se ha demostrado capaz de modular la actividad de la corteza cerebral. La estimulación del área temporoparietal izquierda con frecuencias de 1 Hz ha conseguido mejorar, al menos de forma parcial y transitoria, las alucinaciones auditivas de pacientes con esquizofrenia en la mayoría de los estudios controlados publicados. Lo mismo podemos decir de dichos parámetros de estimulación aplicados a pacientes otológicos con sensación de tinnitus. Se discute todavía la relevancia clínica de estos hallazgos. Sin embargo, aparte del beneficio clínico que pueda aportar en un futuro la EMT a estos u otros pacientes, nos está aportando nuevos datos y nuevas preguntas sobre las bases neurobiológicas de los trastornos mentales. Por ejemplo: ¿qué tienen en común el tinnitus y las alucinaciones auditivas para semejante coincidencia terapéutica? En este trabajo se presentan dos casos clínicos ilustrativos y se discute acerca de la pregunta formulada (AU)

Transcranial magnetic stimulation (TMS) has been shown to be effective in modulating cerebral cortex activity. Most of the published controlled studies have reported that left temporoparietal area stimulation with 1 Hz frequencies has managed to improve auditory hallucinations at least partially and transiently in patients suffering from schizophrenia. These stimulation parameters have been demonstrated to be useful in otologic patients with tinnitus sensation. The clinical relevance of these findings has already been discussed. However, in spite of the clinical benefit of TMS for these or other patients, it is revealing new data and new questions about the neurobiological basis of mental disorders. For example: which is the common substrate in tinnitus and auditory hallucinations that could explain such a therapeutic coincidence? In this work we present two representative clinic cases and we discuss this question (AU)

Design of new mononucleotide prodrugs: aryl (SATE) phosphotriester derivatives.

Synthesis, biological activities and decomposition kinetics of novel phosphotriester derivatives of 3'-azido-2',3'-dideoxythymidine (AZT) bearing a S-tButyl-2-thioethyl (tBuSATE) group and L-tyrosinyl residues are reported. All the derivatives appeared to be potent inhibitors of HIV-1 replication in various cell culture experiments. The proposed decomposition process of these mixed phosphotriesters may involve successively an esterase and then a phosphodiesterase activation.

Rational design of a new series of pronucleotide.

A new pronucleotide series is described involving a two-step degradation process mediated by, respectively, carboxylesterase and phosphoramidase. Taking AZT as nucleosidyl moiety, it is shown that most of the compounds inhibit HIV replication in TK(-) cell line, which proves 5'-AZTMP delivery.

Anti-HIV pronucleotides: SATE versus phenyl as a protecting group of AZT phosphoramidate derivatives.

We comparatively studied the decomposition pathways in CEM cell extract of several PHENYL phosphoramidate diesters of AZT. A correlation between anti-HIV activities in TK- cell lines and pharmacokinetic data has been observed. This study would help to design corresponding SATE phosphoramidate diesters which revealed potent anti-HIV properties.

Rational design of a new series of mixed anti-HIV pronucleotides.

MonoSATE aryl phosphotriesters of AZT are able to deliver intracellularly the corresponding 5'-mononucleotide. This process requires activation by an esterase followed by a phosphodiesterase. This finding opens the way to the design of new pronucleotide series.

Anti-HIV pronucleotides: decomposition pathways and correlation with biological activities.

The purpose of the present study was to compare the decomposition pathways in CEM cell extracts of various phenyl phosphoramidate derivatives of AZT. In addition, the structures of their metabolites were identified. Correlations with their anti-HIV activities in a thymidine kinase deficient (TK-) CEM cell line have been established with a rationale of designing phosphoramidate pronucleotides capable of delivering intracellularly their respective 5'-nucleoside monophosphate derivatives.

Two cases in infantile and familial porphyria cutanea tarda.

In 2 children, both 7 years old, and with an obvious presence of clinical symptoms, the diagnosis of porphyria cutanea tarda was corroborated by the characteristic patterns of urinary and fecal prophyrin excretion. Familial studies allowed us to consider both cases as hereditary.