De cómo la COVID-19 nos enseñó a reinventarnos / How COVID-19 taught us to reinvent ourselves

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TWEAK favors phosphate-induced calcification of vascular smooth muscle cells through canonical and non-canonical activation of NFκB.

Vascular calcification (VC) is associated with increased cardiovascular mortality in aging, chronic kidney disease (CKD), type 2 diabetes mellitus (T2DM) and atherosclerosis. TNF-like weak inducer of apoptosis (TWEAK) recently emerged as a new biomarker for the diagnosis and prognosis of cardiovascular diseases. TWEAK binding to its functional receptor Fn14 was reported to promote several steps of atherosclerotic plaque progression. However, no information is currently available on the role of TWEAK/Fn14 on the development of medial calcification, which is highly prevalent in aging, CKD and T2DM. This study explored the involvement of TWEAK in human vascular smooth muscle cells (h-VSMCs) calcification in vitro. We report that TWEAK binding to Fn14 promotes inorganic phosphate-induced h-VSMCs calcification, favors h-VSMCs osteogenic transition, decreasing acta2 and myh11 and increasing bmp2 mRNA and tissue non-specific alkaline phosphatase (TNAP), and increases MMP9 activity. Blockade of the canonical NFκB pathway reduced by 80% TWEAK pro-calcific properties and decreased osteogenic transition, TNAP and MMP9 activity. Blockade of non-canonical NFκB signaling by a siRNA targeting RelB reduced by 20% TWEAK pro-calcific effects and decreased TWEAK-induced loss of h-VSMCs contractile phenotype and MMP9 activity, without modulating bmp2 mRNA or TNAP activity. Inhibition of ERK1/2 activation by a MAPK kinase inhibitor did not influence TWEAK pro-calcific properties. Our results suggest that TWEAK/Fn14 directly favors inorganic phosphate-induced h-VSMCs calcification by activation of both canonical and non-canonical NFκB pathways. Given the availability of neutralizing anti-TWEAK strategies, our study sheds light on the TWEAK/Fn14 axis as a novel therapeutic target in the prevention of VC.

Levobupivacaine absorption pharmacokinetics with and without epinephrine during TAP block: analysis of doses based on the associated risk of local anaesthetic toxicity.

PURPOSE: Cases of local anaesthetic systemic toxicity (LAST) periodically occur following transversus abdominal plane (TAP) blocks. The aim of this study was to characterize levobupivacaine absorption pharmacokinetics, with and without epinephrine, and estimate the risk of LAST, based on a previously reported toxic threshold. METHODS: Previously reported data from 11 volunteers receiving ultrasound-guided TAP blocks with and without epinephrine on two independent occasions were analysed. Serial venous concentrations were measured for 90 min. A pharmacokinetic analysis was performed using the NONMEM statistical programme. The use of epinephrine in the solution was included in the analysis of covariates. The associated risk of LAST symptoms associated with different levobupivacaine dose schemes with and without epinephrine was estimated in 1000 simulated subjects. RESULTS: A one-compartment first-order input and elimination model adequately fit the levobupivacaine data. Epinephrine prolonged the levobupivacaine absorption half-life {4.22 [95 % confidence interval (CI) 2.53-6.50] vs. 7.02 [95 % CI 3.74-14.1]; p < 0.05} and reduced its relative bioavailability (0.84; 95 % CI 0.72-0.97; p < 0.05) The derived model predicts that levobupivacaine dose schemes should be halved from 3 mg kg(-1) body weight with epinephrine to 1.5 mg kg(-1) without epinephrine to obtain a comparable risk of anaesthetic toxicity symptoms of approximately 0.1 %. CONCLUSIONS: Our results strongly support the addition of epinephrine to the local anaesthetic solution, especially when doses of levobupivacaine of >1.5 mg kg(-1) are required. Recommendations regarding the maximum allowable doses of local anaesthetics should consider population analysis to determine safer dosage ranges.

Anomalía coronaria congénita, un enemigo silencioso del ejercicio físico / Congenital coronary anomaly, a silent enemy of exercise

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Effect of intravenous fluid therapy on postoperative vomiting in children undergoing tonsillectomy.

BACKGROUND: Postoperative vomiting (POV) is one of the most frequent complications of tonsillectomy in children. The aim of this study was to evaluate the antiemetic effect of super-hydration with lactated Ringer's solution in children undergoing elective otorhinolaryngological surgery. METHODS: One hundred ASA I-II children, aged 1-12 yr, undergoing elective tonsillectomy, with or without adenoidectomy, under general anaesthesia were studied. Induction and maintenance of anaesthesia were standardized with fentanyl, mivacurium, and sevoflurane in N(2)O/O(2). Subjects were assigned to one of the two groups: 10 ml kg(-1) h(-1) lactated Ringer's solution or 30 ml kg(-1) h(-1) lactated Ringer's solution. A multivariable logistic regression was used for assessing the effects of super-hydration on POV (defined as the presence of retching, vomiting, or both). A value of P<0.05 was considered statistically significant. RESULTS: During the first 24 h postoperative, the incidence of POV decreased from 82% to 62% (relative reduction of 24%, P=0.026). In the adjusted logistic regression model, subjects in the 10 ml kg(-1) h(-1) group had an odds ratio of POV that was 2.92 (95% confidence interval: 1.14, 7.51) for POV compared with subjects in the 30 ml kg(-1) h(-1) group. CONCLUSIONS: Intraoperative administration of 30 ml kg(-1) h(-1) lactated Ringer's solution significantly reduced the incidence of POV during the first 24 h postoperative. Our results support the use of super-hydration during tonsillectomy, as an alternative way to decrease the risk of POV in children.

Nitrous oxide (N(2)O) reduces postoperative opioid-induced hyperalgesia after remifentanil-propofol anaesthesia in humans.

BACKGROUND: The aim of this study was to test if intraoperative administration of N(2)O during propofol-remifentanil anaesthesia prevented the onset of postoperative opioid-induced hyperalgesia (OIH). METHODS: Fifty adult ASA I-II patients undergoing elective open septorhinoplasty under general anaesthesia were studied. Anaesthesia was with propofol, adjusted to bispectral index (40-50), and remifentanil (0.30 µg kg(-1) min(-1)). Patients were assigned to one of the two groups: with N(2)O (70%) and without N(2)O (100% oxygen). Mechanical pain thresholds were measured before surgery and 2 and 12-18 h after surgery. Pain measurements were performed on the arm using hand-held von Frey filaments. A non-parametric analysis of variance was used in the von Frey data analysis. P<0.05 was considered statistically significant. RESULTS: Baseline pain thresholds to mechanical stimuli were similar in both groups, with mean values of 69 [95% confidence interval (CI): 50.2, 95.1] g in the group without N(2)O and 71 (95% CI: 45.7, 112.1) g in the group with N(2)O. Postoperative pain scores and cumulative morphine consumption were similar between the groups. The analysis revealed a decrease in the threshold value in both groups. However, post hoc comparisons showed that at 12-18 h after surgery, the decrease in mechanical threshold was greater in the group without N(2)O than the group with N(2)O (post hoc analysis with Bonferroni's correction, P<0.05). CONCLUSIONS: Intraoperative 70% N(2)O administration significantly reduced postoperative OIH in patients receiving propofol-remifentanil anaesthesia.

Prospective evaluation of the time to peak effect of propofol to target the effect site in children.

BACKGROUND: The plasma-effect site equilibration rate constant (k(e0)) of propofol has been determined in children with the use of the time to maximum effect (t(peak)), however, it has not been validated. The objective was to measure the t(peak;) of propofol with two depths of anesthesia monitors in children and to evaluate these measurements with a target-controlled infusion (TCI) system. METHODS: Unpremedicated, ASA I children from 3 to 11 years were studied. In Part 1, children were monitored simultaneously with the bispectral index (BIS) and the A-Line ARX-index (AAI) from the Alaris A-Line auditory-evoked potential monitor/2. The t(peak) after a bolus dose of propofol was measured. In Part 2, the t(peak) measured was used to target the effect site with a TCI system. The median (MD) and the absolute median (MDA) difference between the predicted time of peak concentration at the effect site (Ce) and the measured time of peak effect in the index of depth of anesthesia (t(error)) was used to evaluate the performance of the system. RESULTS: The BIS recordings were of a better quality than the AAI. The mean +/- standard deviation t(peak) was 65 +/- 14 s with the BIS (n=25) and 201 +/- 74 s with the AAI (n=10)(P<0.001). Validation was only performed with the BIS monitor in 40 children, yielding an MD t(error) of -9.5 s and an MDA t(error) of 10.0 s. CONCLUSIONS: The small delay between the evolution of Ce of propofol and the observed effect suggests that this can be a useful model to target the effect site in children.

Flunaricina como tratamiento coadyuvante en epilepsia con crisis parciales / Flunarizine as adjunctive treatment in epilepsy with partial seizures

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Muerte bajo criterios neurológicos. Certificación de la muerte en Argentina / Death according to neurological criteria. Death certification in Argentina

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Retention and phytoavailability of radioniobium in soils.

Radioniobium is present in long-lived nuclear waste as a result of the activation of zirconium pellets associated with the nuclear fuel. The behaviour of niobium (Nb) in the environment and especially its fate in the soil-plant system has not been thoroughly investigated so far. In safety assessment of French long-lived nuclear waste disposal, data concerning the mobility and the bioavailability of Nb in soils are needed as well as general trends of its fate in the specific environment around the site of French underground research laboratory. Therefore, we investigated the mobility of 95Nb in three different soils typical of the area of north-eastern France and its uptake by two plants, rye grass (Lolium perenne L.) and winter wheat (Triticum aestivum L.). Soil:solution distribution of 95Nb was observed in 1:10 batch experiments with deionized water for a 3-day period. Results showed that K(d) values were high (in the order of 10(3) L kg(-1)) and were still significantly increasing after 3 days. A mathematical model, fitted to describe the decrease of the radioactivity after 3 days, is proposed to calculate sorption ratios--SR--(rather than K(d) values as equilibrium was not reached) over longer periods. Soil-to-plant concentration ratios (CR) were measured in shoots and roots of the two plants after cultivation on two soils spiked with (95)Nb (406kBqkg(-1)). Soil-to-root dry weight CR were high (0.30-1.52) and could probably be due to efficient uptake into the roots. However, no transfer of Nb to plant shoots was detected in any of the soils. Nb is thus a rather immobile element in soils and its transfer to plants seems limited to underground parts. It would therefore tend to accumulate in surface horizons of soils in case of long-term continuous surface release.

Technetium species induced in maize as measured by phosphorimager.

Leaves of plants have the ability to accumulate the long-lived fission product (99)Tc. In the present work, an attempt was made to separate and characterize technetium species formed in maize grown on soil contaminated with Tc(VII)O(4)(-) solution. Data obtained from selective extraction, a Phosphorimager and liquid scintillation were employed.

Assessment of plant uptake of radioactive nickel from soils.

As a result of isotopic dilution, the availability to plants of radioisotopes introduced into the soil solution should be directly related to the size of the isotopically exchangeable pool (E(t))-value). This work was undertaken to test this hypothesis for the radionuclide 63Ni. The demonstration was based on pot experiments conducted with seven soils representing a large range of Ni content (from 9.9 mg kg(-1) to 862.6 mg kg(-1)) which were mixed with a 63NiCl2 solution (100 kBq kg(-1)). Three plant species varying in Ni uptake, Triticum aestivum (wheat), Trifolium pratense (clover), and the Ni-hyperaccumulator Alyssum murale, were grown for 90 d, and their total Ni and 63Ni content determined at harvest. In parallel, the isotopically exchangeable kinetics method (IEK) was run on each soil sample to measure the E(t)-value. Results showed that plant uptake of radioactive nickel was negatively correlated with the E(t)-value with wheat and clover as a result of the dilution of 63Ni added in the isotopically exchangeable pool of soil Ni (alpha=5%); correlation was positive with the A. murale (alpha=10%). Hence, this provides a new approach for the assessment of soil-to-plant transfer of 63Ni at larger scale avoiding the carrying out of time consuming experiments.

[Devic's optic neuromyelitis: presentation as an inflammatory spinal tumour]. / Neuromielitis óptica de Devic: forma de presentación como tumor espinal inflamatorio.

INTRODUCTION: Devic s optic neuromyelitis is a clinical syndrome described over 100 years ago and characterized by episodes of severe transverse myelitis, affecting several spinal segments, and simultaneously or otherwise, neuritis of the optic nerve. Both types of disorder may be acute or subacute. In spite of many reviews in recent years, it is still not clear whether it is a distinct clinical entity or whether it is really a form of Multiple Sclerosis. In recent years several authors have drawn up a list of diagnostic criteria to distinguish between Devic s Disease and Multiple Sclerosis. Several aetiologies have been implicated in causing this syndrome, from infectious diseases to demyelinating disorders. However, there is a group of patients who have no associated pathology, in whom it is correct to speak of Devic s Disease. CLINICAL CASE: We studied a patient with a clinical condition compatible with Devic s disease, with an inflammatory tumour in the cervical region, a radiological finding not previously reported. CONCLUSION: When making the diagnosis in patients with inflammatory spinal tumors and no symptoms of demyelination in the rest of the central nervous system, Devic s disease should be borne in mind.

Neuromielitis óptica de Devic: forma de presentación como tumor espinal inflamatorio / Devic's optic neuromyelitis: presentation as an inflammatory spinal tumour

Introducción. La neuromielitis óptica de Devic es un síndrome clínico descrito hace más de 100 años y caracterizado por episodios de una grave mielitis trasversa, con implicación de varios segmentos medulares y, de manera simultánea o no, una neuritis del nervio óptico, ambas de carácter agudo o subagudo. A pesar de las numerosas revisiones llevadas a cabo durante los últimos años, aún es controvertida su distinción como una entidad clínica individual o si se trata, en realidad, de una forma de esclerosis múltiple. En años recientes, varios autores han elaborado una serie de criterios diagnósticos para distinguir entre enfermedad de Devic y esclerosis múltiple. Varias etiologías se han implicado en la génesis de este síndrome, desde enfermedades infecciosas hasta enfermedades desmielinizantes. Sin embargo, existe un grupo de pacientes que no presentan ninguna entidad asociada, por lo que sería correcto, en ellos, hablar de enfermedad de Devic. Caso clínico. Se informa de una paciente con un cuadro compatible con enfermedad de Devic y presencia de un tumor inflamatorio ubicado en zona cervical, hallazgo radiológico no informado hasta ahora. Conclusión. Debemos tener en cuenta el diagnóstico de enfermedad de Devic en pacientes con tumores espinales inflamatorios sin compromiso desmielinizante del resto del sistema nervioso central (AU)

Effect of pH on the sorption of uranium in soils.

This work was undertaken to study the influence of soil type and chemical composition on uranium sorption ratios (SR in 1 kg-1) in order to reduce the uncertainty associated with this parameter in risk assessment models. Thirteen soil samples were collected from three different locations in France under different geological conditions. Clay content varied from 7.0 to 50.0%, pH ranged from 5.5 to 8.8 and organic matter content from 1.0 to 4.6%. Soils were incubated at room temperature in polyethylene packets for 28 days in the presence of 1 mg U kg-1 soil. Sorption ratio values varied from 0.9 to 3198 for all soils with no significant effect of soil texture or of organic matter. However, soil pH was highly linearly correlated with (log SR) as a probable consequence of the existence of different uranium complexes as a function of soil pH. The sorption behaviour differences between UO2(2+) and UO2(2+)-carbonate complexes are so great that any other effect of soil properties on U sorption is hidden. Thus, soil pH should be the focus variable for reduction of the uncertainty associated with the soil Kd value used in environmental risk assessments, even for reducing the uncertainty in site-specific Kd values.