La fijación externa en el tratamiento de las fracturas de extremidad distal de radio: Revisión de 83 casos

Se presenta un estudio retrospectivo de 83 casos de fractura de extremidad distal de radio tratadas con fijación externa, exclusivamente o asociada a otros métodos de tratamiento, con un seguimiento medio de 15 meses. Se han revisado las indicaciones y se han valorado los resultados mediante el protocolo de evaluación clínica propuesto por Gartland y Werley, modificado por Sarmiento; y la evaluación radiológica según los criterios de Linström, ampliados por Van Der Linden y Ericsson. Se obtuvieron resultados excelentes en 9 casos, buenos en 44 casos, regulares en 24 y malos en 6 casos. La complicación más frecuente hallada fue la osteopenia difusa del carpo (50%) y la causa más común de discapacidad residual, la articulación radiocubital distal. De los resultados concluimos que la fijación externa es un método correcto para el tratamiento de las fracturas de extremidad distal de radio, aunque son necesarias en algunos casos otras técnicas añadidas para conseguir una aceptable congruencia articular y minimizar la cifra de resultados inaceptables.Retrospective study on 83 cases of distal radius fractures in treatment with external fixation, exclusively or associated with other treatment methods, with an average follow-up of 45 months. Indications have been revised and results have been valued through the medical record of clinical evaluation proposed by Gartland and Werley, modified by Sarmiento, and the radiological evaluation accordinf to Linström's criterions, amplified by Van Der Linden and Ericson. Excellent results have been obtained in 9 cases, good ones in 44 cases, not bad ones in 24 cases, bad ones in 6 cases. The most frequent complication found was the carpus wide osteopeny (50%) and the most common cause of residual discapacity, the distal radioulnar joint. We conclude, from the results, that the external fixation is a correct method for the treatment of distal radius fractures, although other added techniques are necessary, in some cases, in order to achieve an acceptable articular congruity and minimize the number of unacceptable results

The impact of Charlson comorbidity index on the functional capacity of COVID-19 survivors: a prospective cohort study with one-year follow-up

Objective: To determine the association between the Charlson comorbidity index (CCI) score after discharge with 6-min walk test (6MWT) 1 year after discharge in a cohort of COVID-19 survivors. Methods: In this prospective study, data were collected from a consecutive sample of patients hospitalized for COVID-19. The CCI score was calculated from the comorbidity data. The main outcome was the distance walked in the 6MWT at 1 year after discharge. Associations between CCI and meters covered in the 6MWT were assessed through crude and adjusted linear regressions. The model was adjusted for possible confounding factors (sex, days of hospitalization, and basal physical capacity through sit-to-stand test one month after discharge). Results: A total of 41 patients were included (mean age 58.8 +/- 12.7 years, 20/21 men/women). A significant association was observed between CCI and 6MWT (meters): (i) crude model: beta = -18.7, 95% CI = -34.7 to -2.6, p < 0.05; (ii) model adjusted for propensity score including sex, days of hospitalization, and sit-to-stand: beta = -23.0, 95% CI = -39.1 to -6.8, p < 0.05. Conclusions: A higher CCI score after discharge indicates worse performance on the 6MWT at 1-year follow-up in COVID-19 survivors. The CCI score could also be used as a screening tool to make important clinical decisions

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Fe d'errates disponible a: http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity

Cognitive impairment induced by delta9-tetrahydrocannabinol occurs through heteromers between cannabinoid CB1 and serotonin 5-HT2A receptors

Delta-9-tetrahydrocannabinol (THC), the main psychoactive compound of marijuana, induces numerous undesirable effects, including memory impairments, anxiety, and dependence. Conversely, THC also has potentially therapeutic effects, including analgesia, muscle relaxation, and neuroprotection. However, the mechanisms that dissociate these responses are still not known. Using mice lacking the serotonin receptor 5-HT2A, we revealed that the analgesic and amnesic effects of THC are independent of each other: while amnesia induced by THC disappears in the mutant mice, THC can still promote analgesia in these animals. In subsequent molecular studies, we showed that in specific brain regions involved in memory formation, the receptors for THC and the 5-HT2A receptors work together by physically interacting with each other. Experimentally interfering with this interaction prevented the memory deficits induced by THC, but not its analgesic properties. Our results highlight a novel mechanism by which the beneficial analgesic properties of THC can be dissociated from its cognitive side effects

Evaluation of the potential association of SOHLH2 polymorphisms with non-obstructive azoospermia susceptibility in a large European population

Non-obstructive azoospermia (NOA) or spermatogenic failure is a complex disease with an important genetic component that causes infertility in men. Known genetic factors associated with NOA include AZF microdeletions of the Y chromosome or karyotype abnormalities; however, most causes of NOA are idiopathic. During the last decade, a large list of associations between single-nucleotide polymorphisms (SNP) and NOA have been reported. However, most of the genetic studies have been performed only in Asian populations. We aimed to evaluate whether the previously described association in Han Chinese between NOA and two SNPs of the SOHLH2 gene (involved in the spermatogenesis process) may also confer risk for NOA in a population of European ancestry. We genotyped a total of 551 NOA patients (218 from Portugal and 333 from Spain) and 1,050 fertile controls (226 from Portugal and 824 from Spain) for the genetic variants rs1328626 and rs6563386 using TaqMan assays. To test for association, we compared the allele and genotype frequencies between cases and controls using an additive model. A haplotype analysis and a meta-analysis using the inverse variance method with our data and those of the original Asian study were also performed. No statistically significant differences were observed in any of the analyses described above. Therefore, considering the high statistical power of our study, it is not likely that the two analysed SOHLH2 genetic variants are related with an increase susceptibility to NOA in the European population.info:eu-repo/semantics/publishedVersio

The splicing modulator sudemycin induces a specific antitumor response and cooperates with ibrutinib in chronic lymphocytic leukemia

Mutations or deregulated expression of the components of the spliceosome can influence the splicing pattern of several genes and contribute to the development of tumors. In this context, we report that the spliceosome modulator sudemycin induces selective cytotoxicity in primary chronic lymphocytic leukemia (CLL) cells when compared with healthy lymphocytes and tumor cells from other B-lymphoid malignancies, with a slight bias for CLL cases with mutations in spliceosome-RNA processing machinery. Consistently, sudemycin exhibits considerable antitumor activity in NOD/SCID/IL2Rγ-/- (NSG) mice engrafted with primary cells from CLL patients. The antileukemic effect of sudemycin involves the splicing modulation of several target genes important for tumor survival, both in SF3B1-mutated and -unmutated cases. Thus, the apoptosis induced by this compound is related to the alternative splicing switch of MCL1 toward its proapoptotic isoform. Sudemycin also functionally disturbs NF-κB pathway in parallel with the induction of a spliced RELA variant that loses its DNA binding domain. Importantly, we show an enhanced antitumor effect of sudemycin in combination with ibrutinib that might be related to the modulation of the alternative splicing of the inhibitor of Btk (IBTK). In conclusion, we provide first evidence that the spliceosome is a relevant therapeutic target in CLL, supporting the use of splicing modulators alone or in combination with ibrutinib as a promising approach for the treatment of CLL patients

Tiges prestades: Poètiques de resistència en temps de pandèmia

[cat] La mostra, combinatòria de formats, tècniques i processos, té un nexe comú: l’exploració –conceptual i formal– que han fet artistes-docents –sols o en companyia– en períodes de confinament –obligat o voluntari– i en els seus espais de treball personal. Compta amb la participació de: Anaïs Civit López, Andrea Martínez Arroyo, Eulàlia Grau i Costa, Jaume R. Vallverdú, Joan Miquel Porquer Rigo, Juancho Pacheco Puig, Julio César Ortega, Laia Moreto i Sara Sánchez, Lucido Petrillo, Pablo Romero i Rafael Romero. Amb la col·laboració de: Grup d’Innovació Docent Consolidat ATESI (Art, Territori, Estratègia docent, Sostenibilitat i Intervenció social, GINDOC-UB/162)

Cosmic CARNage I: on the calibration of galaxy formation models

We present a comparison of nine galaxy formation models, eight semi-analytical, and one halo occupation distribution model, run on the same underlying cold dark matter simulation (cosmological box of comoving width 125h−1 Mpc, with a dark-matter particle mass of 1.24 × 109h−1M) and the same merger trees. While their free parameters have been calibrated to the same observational data sets using two approaches, they nevertheless retain some ‘memory’ of any previous calibration that served as the starting point (especially for the manually tuned models). For the first calibration, models reproduce the observed z = 0 galaxy stellar mass function (SMF) within 3σ. The second calibration extended the observational data to include the z = 2 SMF alongside the z ∼ 0 star formation rate function, cold gas mass, and the black hole–bulge mass relation. Encapsulating the observed evolution of the SMF from z = 2 to 0 is found to be very hard within the context of the physics currently included in the models. We finally use our calibrated models to study the evolution of the stellar-to-halo mass (SHM) ratio. For all models, we find that the peak value of the SHM relation decreases with redshift. However, the trends seen for the evolution of the peak position as well as the mean scatter in the SHM relation are rather weak and strongly model dependent. Both the calibration data sets and model results are publicly available

The new psychoactive substances 5-(2-aminopropyl)indole (5-IT) and 6-(2-aminopropyl)indole (6-IT) interact with monoamine transporters in brain tissue

In recent years, use of psychoactive synthetic stimulants has grown rapidly. 5-(2-Aminopropyl)indole (5-IT) is a synthetic drug associated with a number of fatalities, that appears to be one of the newest 3,4-methylenedioxymethamphetamine (MDMA) replacements. Here, the monoamine-releasing properties of 5-IT, its structural isomer 6-(2-aminopropyl)indole (6-IT), and MDMA were compared using in vitro release assays at transporters for dopamine (DAT), norepinephrine (NET), and serotonin (SERT) in rat brain synaptosomes. In vivo pharmacology was assessed by locomotor activity and a functional observational battery (FOB) in mice. 5-IT and 6-IT were potent substrates at DAT, NET, and SERT. In contrast with the non-selective releasing properties of MDMA, 5-IT displayed greater potency for release at DAT over SERT, while 6-IT displayed greater potency for release at SERT over DAT. 5-IT produced locomotor stimulation and typical stimulant effects in the FOB similar to those produced by MDMA. Conversely, 6-IT increased behaviors associated with 5-HT toxicity. 5-IT likely has high abuse potential, which may be somewhat diminished by its slow onset of in vivo effects, whereas 6-IT may have low abuse liability, but enhanced risk for adverse effects. Results indicate that subtle differences in the chemical structure of transporter ligands can have profound effects on biological activity. The potent monoamine-releasing actions of 5-IT, coupled with its known inhibition of MAO A, could underlie its dangerous effects when administered alone, and in combination with other monoaminergic drugs or medications. Consequently, 5-IT and related compounds may pose substantial risk for abuse and serious adverse effects in human users