Preparation of carboxylic arylphosphines by hydrolysis of the trifluoromethyl group.

Triarylphosphines substituted with carboxylic and trifluoromethlyl groups have been prepared by the hydrolysis of trifluoromethyl groups using fuming sulfuric acid and boric acid. The reaction has been studied in a set of homoleptic and heteroleptic trifluoromethylated triarylphosphines and offers a new synthetic procedure for the preparation of carboxylic phosphines with a relatively simple methodology. The degree of carboxylation is modulated by the reaction conditions and is sensitive to the substitution pattern of the starting trifluoromethylated phosphines. A pH-dependent procedure based on the amphiphilic character of these phosphines was developed for their separation and purification. The electronic properties of the synthesized carboxylic-trifluoromethylated phosphines have been analyzed by 31P NMR of the corresponding selenide derivatives. Finally, the structures of two palladium complexes, containing the para and meta carboxylic-trifluoromethylated phosphines are also described, showing different dimeric structures.

The consequences of implementing non-invasive prenatal testing with cell-free foetal DNA for the detection of Down syndrome in the Spanish National Health Service: a cost-effectiveness analysis.

BACKGROUND: DNA-based non-invasive prenatal testing (NIPT) using maternal blood constitutes an emerging technology for the detection of Down syndrome (DS). The aim of the study was to conduct a cost-effectiveness analysis to evaluate the economic costs and health implications of the introduction of NIPT based on cell-free foetal DNA analysis through different screening strategies for the detection of DS. METHODS: An analytical short-term decision model was developed, from the payer´s perspective (Spanish National Health Service). The main outcome measure was the number of DS cases detected. Secondary measures included associated miscarriages, women undergoing current screening, women undergoing NIPT, positive NIPT and invasive procedures performed. The study setting was the Spanish National Health Service. Three strategies were compared: (a) first- and second-trimester screening (current screening); (b) NIPT as contingent testing; and (c) NIPT as first-line testing. Modelling was based on a hypothetical cohort of 100,000 Spanish pregnant women. Population data were obtained from the database of the Basque Antenatal Screening Programme. Deterministic sensitivity analyses were performed to assess variations in the cost of NIPT, screening risk cut-off, screening uptake-rate and rate of failure of NIPT. RESULTS: NIPT as contingent testing (strategy b) led to fewer miscarriages following invasive procedures and a slight reduction in the number of DS cases detected compared to current screening. However, lowering the screening cut-off to ≥ 1:500 would improve the overall effectiveness of NIPT as contingent testing, increasing the number of DS cases detected and decreasing foetal losses as compared to the current screening, despite there would be an extra-cost of 3.5%. When NIPT was used as first-line testing (strategy c), the screening would be more effective but also more expensive, with incremental cost-effectiveness ratios (ICERs) per additional case of DS detected of €1,299,763 and €1,232,763, compared with strategies a and b, respectively. Results were sensitive to the different parameters considered in the analysis. CONCLUSIONS: Both, as first-line testing and as contingent testing when screening cut-off was lowered ≥ 1:500, NIPT would lead to more favourable outcomes as compared to the current screening (both in terms of DS cases detected and miscarriages avoided), but at a greater cost.

Antimicrobial activity of ceftolozane-tazobactam against multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa clinical isolates from a Spanish hospital.

OBJECTIVE: Our objective was to evaluate the in vitro activity of ceftolozane-tazobactam against multidrug resistant (MDR) and extensively drug-resistant (XDR) non metallo-ß-lactamase producing Pseudomonas aeruginosa clinical isolates at Hospital Universitario Miguel Servet (Zaragoza, Spain) from February 2016 to October 2017. METHODS: We evaluated the in vitro activity of ceftolozane-tazobactam and other antipseudomonal antibiotics against 12 MDR and 117 XDR non metallo-ß-lactamase producing P. aeruginosa isolates. Ceftolozane-tazobactam minimal inhibitory concentrations (MICs) were determined by MIC gradient diffusion test strip. RESULTS: Among the 129 MDR/XDR isolates included, 119 (92.2%) were susceptible to ceftolozane-tazobactam, and ten (7.8%) were resistant. MIC50 was 2 mg/L, and MIC90 4 mg/L. Ceftolozane-tazobactam was the second most active antibiotic after colistin, overtaking amikacin. CONCLUSIONS: Ceftolozane-tazobactam is a valuable treatment option for MDR and XDR P. aeruginosa infections in our setting.

Eye lens dose levels in interventional rooms using simple phantom simulation, dose management software and Monte Carlo method of uncertainty assessment.

This paper presents a fast method to estimate the annual eye lens dose levels for interventional practitioners applying the Monte Carlo method of uncertainty assessment. The estimation was performed by placing an anthropomorphic phantom in the typical working position, and applying the habitually employed protocol. No radiation protection devices were considered in the simulation. The results were compatible with the measurements performed during interventions by placing dosimeters in the vicinity of the eyes of two paediatric interventional cardiologists working with a fluoroscopic biplane system.

Eye lens dose correlations with personal dose equivalent and patient exposure in paediatric interventional cardiology performed with a fluoroscopic biplane system.

PURPOSE: To analyse the correlations between the eye lens dose estimates performed with dosimeters placed next to the eyes of paediatric interventional cardiologists working with a biplane system, the personal dose equivalent measured on the thorax and the patient dose. METHODS: The eye lens dose was estimated in terms of Hp(0.07) on a monthly basis, placing optically stimulated luminescence dosimeters (OSLDs) on goggles. The Hp(0.07) personal dose equivalent was measured over aprons with whole-body OSLDs. Data on patient dose as recorded by the kerma-area product (PKA) were collected using an automatic dose management system. The 2 paediatric cardiologists working in the facility were involved in the study, and 222 interventions in a 1-year period were evaluated. The ceiling-suspended screen was often disregarded during interventions. RESULTS: The annual eye lens doses estimated on goggles were 4.13±0.93 and 4.98±1.28mSv. Over the aprons, the doses obtained were 10.83±0.99 and 11.97±1.44mSv. The correlation between the goggles and the apron dose was R2=0.89, with a ratio of 0.38. The correlation with the patient dose was R2=0.40, with a ratio of 1.79µSvGy-1cm-2. The dose per procedure obtained over the aprons was 102±16µSv, and on goggles 40±9µSv. The eye lens dose normalized to PKA was 2.21±0.58µSvGy-1cm-2. CONCLUSIONS: Measurements of personal dose equivalent over the paediatric cardiologist's apron are useful to estimate eye lens dose levels if no radiation protection devices are typically used.

Psychometric validation of the behavioral indicators of pain scale for the assessment of pain in mechanically ventilated and unable to self-report critical care patients / Validación psicométrica de la Escala de Conductas Indicadoras de Dolor para la medición de dolor en pacientes críticos, no comunicativos y sometidos a ventilación mecánica

OBJECTIVE: To assess the psychometric properties of the behavioral indicators of pain scale (ESCID) when applied to a wide range of medical and surgical critical patients. DESIGN: A multicentre, prospective observational study was designed to validate a scale measuring instrument. SETTING: Twenty Intensive Care Units of 14 hospitals belonging to the Spanish National Health System. PARTICIPANTS: A total of 286 mechanically ventilated, unable to self-report critically ill medical and surgical adult patients. Procedure: Pain levels were measured by two independent evaluators simultaneously, using two scales: ESCID and the behavioral pain scale (BPS). Pain was observed before, during, and after two painful procedures (turning, tracheal suctioning) and one non-painful procedure. MAIN VARIABLES: ESCID reliability was measured on the basis of internal consistency using the Cronbach-_ coefficient. Inter-rater and intra-rater agreement were measured. The Spearman correlation coefficient was used to assess the correlation between ESCID and BPS. RESULTS: A total of 4386 observations were made in 286 patients (62% medical and 38% surgical). High correlation was found between ESCID and BPS (r=0.94-0.99; p < 0.001), together with high intra-rater and inter-rater concordance. ESCID was internally reliable, with a Cronbach-_ value of 0.85 (95%CI 0.81-0.88). Cronbach-_ coefficients for ESCID domains were high: facial expression 0.87 (95%CI 0.84-0.89), calmness 0.84 (95%CI 0.81-0.87), muscle tone 0.80 (95%CI 0.75-0.84), compliance with mechanical ventilation 0.70 (95%CI 0.63-0.75) and consolability 0.85 (95%CI 0.81-0.88). CONCLUSION: ESCID is valid and reliable for measuring pain in mechanically ventilated unable to self-report medical and surgical critical care patients

OBJETIVO: Evaluar las propiedades psicométricas de la Escala de Conductas Indicadoras de Dolor (ESCID), aplicada a una muestra amplia de pacientes críticos de patología médica y posquirúrgica. DISEÑO: Estudio multicéntrico, observacional, prospectivo de validación de una escala como instrumento de medida. Ámbito: Veinte Unidades de Cuidados Intensivos de 14 hospitales del Sistema Nacional de Salud español. PARTICIPANTES: Doscientos ochenta y seis pacientes críticos adultos, sometidos a ventilación mecánica, sin capacidad de comunicación, de patología médica y posquirúrgica. Intervención: Se midió el nivel de dolor de los pacientes por 2 observadores de manera simultánea y utilizando dos escalas: ESCID y la Behavoiral Pain Scale. El dolor fue medido antes, durante y después de la aplicación de dos procedimientos dolorosos (movilización y aspiración endotraqueal) y un procedimiento no doloroso. Variables de interés: La fiabilidad de ESCID se midió mediante la consistencia interna determinada con el coeficiente alfa de Cronbach. Se midió la concordancia inter- e intraobservadores. Se determinó la correlación entre las escalas ESCID y Behavoiral Pain Scale mediante el coeficiente de Spearman. RESULTADOS: Se realizaron 4.386 observaciones de dolor en 286 pacientes (62% patología médica y 38% posquirúrgica). Se evidencia una alta correlación entre ESCID y Behavoiral Pain Scale(r = 0,94-0,99; p < 0,001) así como una alta concordancia inter- e intraobservador. La escala ESCID presenta buena consistencia interna, con un valor de α-Cronbach de 0,85 (IC 95% 0,81-0,88). Los 5 dominios de ESCID presentan alta consistencia interna con α-Cronbach: musculatura facial 0,87 (IC 95% 0,84-0,89), tranquilidad 0,84 (IC 95% 0,81-0,87), tono muscular 0,80 (IC 95% 0,75-0,84), adaptación a ventilación mecánica 0,70 (IC 95% 0,63-0,75) y confortabilidad 0,85 (IC 95% 0,81-0,88). CONCLUSIÓN: ESCID es válida y fiable para medir el dolor en pacientes críticos médicos y posquirúrgicos, no comunicativos y sometidos a ventilación mecánica

Psychometric validation of the behavioral indicators of pain scale for the assessment of pain in mechanically ventilated and unable to self-report critical care patients.

OBJECTIVE: To assess the psychometric properties of the behavioral indicators of pain scale (ESCID) when applied to a wide range of medical and surgical critical patients. DESIGN: A multicentre, prospective observational study was designed to validate a scale measuring instrument. SETTING: Twenty Intensive Care Units of 14 hospitals belonging to the Spanish National Health System. PARTICIPANTS: A total of 286 mechanically ventilated, unable to self-report critically ill medical and surgical adult patients. PROCEDURE: Pain levels were measured by two independent evaluators simultaneously, using two scales: ESCID and the behavioral pain scale (BPS). Pain was observed before, during, and after two painful procedures (turning, tracheal suctioning) and one non-painful procedure. MAIN VARIABLES: ESCID reliability was measured on the basis of internal consistency using the Cronbach-α coefficient. Inter-rater and intra-rater agreement were measured. The Spearman correlation coefficient was used to assess the correlation between ESCID and BPS. RESULTS: A total of 4386 observations were made in 286 patients (62% medical and 38% surgical). High correlation was found between ESCID and BPS (r=0.94-0.99; p<0.001), together with high intra-rater and inter-rater concordance. ESCID was internally reliable, with a Cronbach-α value of 0.85 (95%CI 0.81-0.88). Cronbach-α coefficients for ESCID domains were high: facial expression 0.87 (95%CI 0.84-0.89), calmness 0.84 (95%CI 0.81-0.87), muscle tone 0.80 (95%CI 0.75-0.84), compliance with mechanical ventilation 0.70 (95%CI 0.63-0.75) and consolability 0.85 (95%CI 0.81-0.88). CONCLUSION: ESCID is valid and reliable for measuring pain in mechanically ventilated unable to self-report medical and surgical critical care patients. CLINICALTRIALS.GOV: NCT01744717.

Síndrome de implantación del cemento óseo: a propósito de un caso / Bone cement implantation syndrome: a case report

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Diazoxide enhances excitotoxicity-induced neurogenesis and attenuates neurodegeneration in the rat non-neurogenic hippocampus.

Diazoxide, a well-known mitochondrial KATP channel opener with neuroprotective effects, has been proposed for the effective and safe treatment of neuroinflammation. To test whether diazoxide affects the neurogenesis associated with excitotoxicity in brain injury, we induced lesions by injecting excitotoxic N-methyl-d-aspartate (NMDA) into the rat hippocampus and analyzed the effects of a daily oral administration of diazoxide on the induced lesion. Specific glial and neuronal staining showed that NMDA elicited a strong glial reaction associated with progressive neuronal loss in the whole hippocampal formation. Doublecortin immunohistochemistry and bromo-deoxyuridine (BrdU)-NeuN double immunohistochemistry revealed that NMDA also induced cell proliferation and neurogenesis in the lesioned non-neurogenic hippocampus. Furthermore, glial fibrillary acidic protein (GFAP)-positive cells in the injured hippocampus expressed transcription factor Sp8 indicating that the excitotoxic lesion elicited the migration of progenitors from the subventricular zone and/or the reprograming of reactive astrocytes. Diazoxide treatment attenuated the NMDA-induced hippocampal injury in rats, as demonstrated by decreases in the size of the lesion, neuronal loss and microglial reaction. Diazoxide also increased the number of BrdU/NeuN double-stained cells and elevated the number of Sp8-positive cells in the lesioned hippocampus. These results indicate a role for KATP channel activation in regulating excitotoxicity-induced neurogenesis in brain injury.

Análisis de las traqueotomías en cuidados intensivos pediátricos durante el periodo 2003-2013 / Analysis of tracheostomies in a pediatric intensive care unit during the period 2003-2013

INTRODUCCIÓN: La traqueotomía es un procedimiento poco frecuente en la Unidad de cuidados intensivos pediátricos (UCIP). Analizamos las complicaciones derivadas de la técnica, la mortalidad atribuible a la misma y la mortalidad global de los pacientes traqueotomizados. PACIENTES Y MÉTODOS: Estudio retrospectivo descriptivo durante el periodo comprendido entre enero del 2003 y diciembre del 2013 de los pacientes ingresados en la UCIP a los que se realiza una traqueotomía a lo largo de su ingreso. RESULTADOS: Durante el periodo analizado se recoge a 25 pacientes. La media de edad es de 31,3 meses (rango 1-144, mediana 14 meses) y la media de estancia en UCIP es de 53 días (rango 1-338 días, mediana 37 días). En su mayoría (68%) son pacientes con comorbilidades previas a su ingreso, destacando en frecuencia las anomalías craneofaciales/síndromes polimalformativos (32%) y problemas asociados a la prematuridad (12%). Las patologías más frecuentes que motivaron la realización del procedimiento fueron la obstrucción congénita de la vía aérea y diversas causas de lesión medular, seguido de traqueobroncomalacia y estenosis subglótica. Se detectaron complicaciones en el 40% de los pacientes, siendo la más frecuente la decanulación accidental. Presentaron durante el curso evolutivo una decanulación accidental el 20% de los pacientes, principalmente en las primeras 24 h del postoperatorio, motivo por el que falleció uno de los pacientes. CONCLUSIONES: La realización de la traqueotomía es un procedimiento poco frecuente en la UCIP, aunque no exento de complicaciones, algunas de ellas de riesgo vital

INTRODUCTION: Tracheotomy in pediatric patients is a rare procedure. In this pediatric series, perioperative complications, mortality related to surgical procedure and overall mortality are analyzed. PATIENTS AND METHODS: This is a retrospective study conducted from January 2003 to December 2013. Data were retrieved from patients who were tracheotomized and admitted to our PICU in the postoperative period. RESULTS: Data were collected from 25 tracheotomized patients admitted during the study period. The mean age was 3.3 months (median 14 months, range 1-144 months), and PICU length of stay was 53 days (median 37 days, range 1-338 days). Most patients (68%) had comorbidities before their admission, with a higher prevalene of craniofacial anomalies/polymalformative syndromes (32%) and prematurity related disorders (12%) being obserevd. The most common etiologies related to the procedure were congenital airway obstruction (16%) and several types of spinal cord injury (16%), followed by tracheobronchomalacia (12%) and subglottic stenosis (12%). Some kind of complication was detected in 40% of patients, with accidental decannulation being the most frequent. Accidental or unexpected decannulation was present in a percentage as high as 20% of our patients, mainly in the first 24hours after surgery. One of the patients died as a result of this. CONCLUSIONS: The postoperative course of a tracheotomy is associated with a high rate of complications, some of them related to life-threatening events

[Analysis of tracheostomies in a pediatric intensive care unit during the period 2003-2013]. / Análisis de las traqueotomías en cuidados intensivos pediátricos durante el periodo 2003-2013.

INTRODUCTION: Tracheotomy in pediatric patients is a rare procedure. In this pediatric series, perioperative complications, mortality related to surgical procedure and overall mortality are analyzed. PATIENTS AND METHODS: This is a retrospective study conducted from January 2003 to December 2013. Data were retrieved from patients who were tracheotomized and admitted to our PICU in the postoperative period. RESULTS: Data were collected from 25 tracheotomized patients admitted during the study period. The mean age was 3.3 months (median 14 months, range 1-144 months), and PICU length of stay was 53 days (median 37 days, range 1-338 days). Most patients (68%) had comorbidities before their admission, with a higher prevalene of craniofacial anomalies/polymalformative syndromes (32%) and prematurity related disorders (12%) being obserevd. The most common etiologies related to the procedure were congenital airway obstruction (16%) and several types of spinal cord injury (16%), followed by tracheobronchomalacia (12%) and subglottic stenosis (12%). Some kind of complication was detected in 40% of patients, with accidental decannulation being the most frequent. Accidental or unexpected decannulation was present in a percentage as high as 20% of our patients, mainly in the first 24 hours after surgery. One of the patients died as a result of this. CONCLUSIONS: The postoperative course of a tracheotomy is associated with a high rate of complications, some of them related to life-threatening events.

[Pulmonary reperfusion syndrome after pulmonary stent implants in a patient with vascular tortuosity syndrome]. / Síndrome de reperfusión pulmonar tras implante de stents pulmonares en un paciente con síndrome de tortuosidad vascular.

Vascular tortuosity syndrome is a rare genetic disorder that causes tortuosity and stenosis of the pulmonary, systemic and / or coronary circulations. As a result of treatment of pulmonary stenosis, symptoms of pulmonary edema, known as lung reperfusion syndrome, may occur. The case is presented of an adolescent patient with vascular tortuosity syndrome who presented with a pulmonary reperfusion syndrome after multiple stent implants in the left pulmonary artery. After the procedure, the patient immediately developed an acute pulmonary edema with severe clinical deterioration, which required assistance with extracorporeal membrane oxygenation for recovery.

Glucose pathways adaptation supports acquisition of activated microglia phenotype.

With its capacity to survey the environment and phagocyte debris, microglia assume a diversity of phenotypes to respond specifically through neurotrophic and toxic effects. Although these roles are well accepted, the underlying energetic mechanisms associated with microglial activation remain largely unclear. This study investigates microglia metabolic adaptation to ATP, NADPH, H(+) , and reactive oxygen species production. To this end, in vitro studies were performed with BV-2 cells before and after activation with lipopolysaccharide + interferon-γ. Nitric oxide (NO) was measured as a marker of cell activation. Our results show that microglial activation triggers a metabolic reprogramming based on an increased glucose uptake and a strengthening of anaerobic glycolysis, as well as of the pentose pathway oxidative branch, while retaining the mitochondrial activity. Based on this energy commitment, microglial defense capacity increases rapidly as well as ribose-5-phosphate and nucleic acid formation for gene transcription, essential to ensure the newly acquired functions demanded by central nervous system signaling. We also review the role of NO in this microglial energy commitment that positions cytotoxic microglia within the energetics of the astrocyte-neuron lactate shuttle.

Inicio, dosificación y balance de líquidos en las técnicas de depuración extrarrenal / Initiation, dosage and fluid balance in the extrarenal depuration techniques

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Mycobacterium africanum, an emerging disease in high-income countries?

BACKGROUND: Mycobacterium africanum is a cause of tuberculosis (TB) that has mainly been described in Africa, but immigration and travel patterns have contributed to the spread of the disease to other countries. METHODS: We retrospectively reviewed TB cases due to M. africanum during 2000-2010 in seven Spanish hospitals. Selected clinical charts were reviewed using a predefined protocol that included demographical, clinical and microbiological data and outcome. RESULTS: Although 57 cases were diagnosed, only 36 clinical charts were available for review: 82.8% were men and the mean age was 31.6 years (range 12-81). Forty-four cases were from Africa, 1 from the Philippines, 1 from India, and 4 from Spain, while the country of origin was unknown in 7 cases. The most frequent site of infection was the lung (58.3%). Four cases (6.9%) were resistant to at least one first-line anti-tuberculosis drug. CONCLUSIONS: Disease due to M. africanum in industrialised countries is mainly associated with immigration from endemic areas, although some cases also occur among native-born populations.

ATP-dependent potassium channel blockade strengthens microglial neuroprotection after hypoxia-ischemia in rats.

Stroke causes CNS injury associated with strong fast microglial activation as part of the inflammatory response. In rat models of stroke, sulphonylurea receptor blockade with glibenclamide reduced cerebral edema and infarct volume. We postulated that glibenclamide administered during the early stages of stroke might foster neuroprotective microglial activity through ATP-sensitive potassium (K(ATP)) channel blockade. We found in vitro that BV2 cell line showed upregulated expression of K(ATP) channel subunits in response to pro-inflammatory signals and that glibenclamide increases the reactive morphology of microglia, phagocytic capacity and TNFα release. Moreover, glibenclamide administered to rats 6, 12 and 24h after transient Middle Cerebral Artery occlusion improved neurological outcome and preserved neurons in the lesioned core three days after reperfusion. Immunohistochemistry with specific markers to neuron, astroglia, microglia and lymphocytes showed that resident amoeboid microglia are the main cell population in that necrotic zone. These reactive microglial cells express SUR1, SUR2B and Kir6.2 proteins that assemble in functional K(ATP) channels. These findings provide that evidence for the key role of K(ATP) channels in the control of microglial reactivity are consistent with a microglial effect of glibenclamide into the ischemic brain and suggest a neuroprotective role of microglia in the early stages of stroke.

Design and construction of an experimental pervious paved parking area to harvest reusable rainwater.

Pervious pavements are sustainable urban drainage systems already known as rainwater infiltration techniques which reduce runoff formation and diffuse pollution in cities. The present research is focused on the design and construction of an experimental parking area, composed of 45 pervious pavement parking bays. Every pervious pavement was experimentally designed to store rainwater and measure the levels of the stored water and its quality over time. Six different pervious surfaces are combined with four different geotextiles in order to test which materials respond better to the good quality of rainwater storage over time and under the specific weather conditions of the north of Spain. The aim of this research was to obtain a good performance of pervious pavements that offered simultaneously a positive urban service and helped to harvest rainwater with a good quality to be used for non potable demands.

Performance of pervious pavement parking bays storing rainwater in the north of Spain.

Pervious pavements are drainage techniques that improve urban water management in a sustainable manner. An experimental pervious pavement parking area has been constructed in the north of Spain (Santander), with the aim of harvesting good quality rainwater. Forty-five pervious pavement structures have been designed and constructed to measure stored water quantity and quality simultaneously. Ten of these structures are specifically constructed with different geotextile layers for improving water storage within the pavements. Following the confirmation in previous laboratory experiments that the geotextile influenced on water storage, two different geosynthetics (Inbitex and a One Way evaporation control membrane) and control pervious pavements with no geotextile layers were tested in the field. Weather conditions were monitored in order to find correlations with the water storage within the pervious pavement models tested. During one year of monitoring the three different pervious pavement types tested remained at their maximum storage capacity. The heavy rain events which occurred during the experimental period caused evaporation rates within the pervious pavements to be not significant, but allowed the researchers to observe certain trends in the water storage. Temperature was the most closely correlated weather factor with the level of the water stored within the pervious pavements tested.

Embolia aérea pulmonar como complicación de punción venosa central / Pulmonary air embolism as a complication of central venous catheter

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