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This study analyzed the current state of education for gifted students in Ecuador using the Educational and Learning Capital Model (ELCM) to propose improvements in the development of programs and services. A mixed research approach was employed, addressing two key questions: (a) How is the education of gifted students currently managed in Ecuador? (b) What is the perception of teachers regarding gifted education based on the ELCM? Data sources, such as official documents, primary studies conducted in the country and a survey involving specialized personnel and schoolteachers, were analyzed, focusing on evaluating the Ecuadorian educational system’s strengths and weaknesses concerning gifted students’ education. The results indicated the following: gifted students’ education in Ecuador faces significant challenges due to the lack of adequate teacher training and insufficient infrastructure. Furthermore, existing policies and regulations are poorly implemented, and reliable data on identified students are lacking. Most teachers perceive a lack of training and adequate resources. Only 8.26% believe there is a clear mechanism in the Ministry of Education. Most are dissatisfied with the current programs, which are more recreational than geared toward talent development. The study recommended improvement in the education quality and support for gifted students in Ecuador.

Abstract Pseudomonas aeruginosa is an opportunistic nosocomial pathogen with a pathogenicity that is an important factor in public health and is the result of the functioning of the Quorum Sensing (QS) system. Currently, compounds of natural origin have shown promising biological effects on certain pathogens in recent years. The aim of the present study was to determine the possible inhibitory effect of five naturally occurring molecules on some genes associated with two pathways of the QS system, as well as on elastase protease and pyocyanin production in two resistant strains of P. aeruginosa. For this purpose, RT-qPCR assays were performed to know the expression of some QS-associated genes (lasR, rhlR, lasI, aprA and lasB) and spectrophotometric assays to evaluate the production of elastase, protease and pyocyanin in the presence or absence of the molecules. It was found that sesamin and ferulic acid were the molecules with the highest inhibitory effect, higher than 40 %, on most of the genes evaluated (lasR, rhlR, aprA and lasB) in the two P. aeruginosa strains BAA-47 and 27853. Likewise, ferulic acid was the most active compound on two of the three virulence factors evaluated even though in general the effect of the molecules was not greater than 50 %. Therefore, these compounds are considered to have a possible multitarget effect by inhibiting the expression of genes associated with the two main systems of P. aeruginosa.

Pseudomonas aeruginosa is a Gram-negative bacterium designated by the WHO as a critical priority microorganism due to its virulence, controlled by a quorum sensing (QS) system. QS is regulated through specific subsystems: LasI/LasR, RhlI/RhlR, and PQS/MvfR. Several natural compounds can inhibit these QS mechanisms. In this study, we determined the effect of curcumin, reserpine, and their mixtures with two commercial antibiotics (gentamicin and azithromycin) on P. aeruginosa QS mechanisms: mvfR gene expression and the production of pyocyanin and rhamnolipids. Antibiotic and natural compounds’ minimal inhibitory concentrations (MICs) were determined via microdilution assays. Gentamicin, azithromycin, curcumin, reserpine, and their mixtures exerted variable effects on mvfR gene expression, as assessed via semi-quantitative RT-PCR assays. Curcumin, reserpine, and gentamicin inhibited mvfR gene expression better than azithromycin, and the mixtures curcumin-gentamicin and reserpine-gentamicin outperformed gentamicin alone in inhibiting mvfR gene expression and decreasing pyocyanin and rhamnolipids production, revealing the synergistic effect of these mixture components. The mixtures of curcumin and gentamicin and reserpine and gentamicin may become alternatives to complement or enhance conventional methods currently used to treat P. aeruginosa infections.

The small-molecule iododiflunisal (IDIF) is a transthyretin (TTR) tetramer stabilizer and acts as a chaperone of the TTR-Amyloid beta interaction. Oral administration of IDIF improves Alzheimer’s Disease (AD)-like pathology in mice, although the mechanism of action and pharmacokinetics remain unknown. Radiolabeling IDIF with positron or gamma emitters may aid in the in vivo evaluation of IDIF using non-invasive nuclear imaging techniques. In this work, we report an isotopic exchange reaction to obtain IDIF radiolabeled with 18F. [19F/18F]exchange reaction over IDIF in dimethyl sulfoxide at 160 °C resulted in the formation of [18F]IDIF in 7 ± 3% radiochemical yield in a 20 min reaction time, with a final radiochemical purity of >99%. Biodistribution studies after intravenous administration of [18F]IDIF in wild-type mice using positron emission tomography (PET) imaging showed capacity to cross the blood-brain barrier (ca. 1% of injected dose per gram of tissue in the brain at t > 10 min post administration), rapid accumulation in the liver, long circulation time, and progressive elimination via urine. Our results open opportunities for future studies in larger animal species or human subjects.

Abstract Background Validation of new biomarkers of Alzheimer disease (AD) is crucial for the successful development and implementation of treatment strategies. Additional to traditional AT(N) biomarkers, neuroinflammation biomarkers, such as translocator protein (TSPO) and cystine/glutamine antiporter system (xc -), could be considered when assessing AD progression. Herein, we report the longitudinal investigation of [18F]DPA-714 and [18F]FSPG for their ability to detect TSPO and xc - biomarkers, respectively, in the 5xFAD mouse model for AD. Methods Expression of TSPO and xc - system was assessed longitudinally (2–12 months of age) on 5xFAD mice and their respective controls by positron emission tomography (PET) imaging using radioligands [18F]DPA-714 and [18F]FSPG. In parallel, in the same mice, amyloid-β plaque deposition was assessed with the amyloid PET radiotracer [18F]florbetaben. In vivo findings were correlated to ex vivo immunofluorescence staining of TSPO and xc - in microglia/macrophages and astrocytes on brain slices. Physiological changes of the brain tissue were assessed by magnetic resonance imaging (MRI) in 12-month-old mice. Results PET studies showed a significant increase in the uptake of [18F]DPA-714 and [18F]FSPG in the cortex, hippocampus, and thalamus in 5xFAD but not in WT mice over time. The results correlate with Aβ plaque deposition. Ex vivo staining confirmed higher TSPO overexpression in both, microglia/macrophages and astrocytes, and overexpression of xc - in non-glial cells of 5xFAD mice. Additionally, the results show that Aβ plaques were surrounded by microglia/macrophages overexpressing TSPO. MRI studies showed significant tissue shrinkage and microstructural alterations in 5xFAD mice compared to controls. Conclusions TSPO and xc - overexpression can be assessed by [18F]DPA-714 and [18F]FSPG, respectively, and correlate with the level of Aβ plaque deposition obtained with a PET amyloid tracer. These results position the two tracers as promising imaging tools for the evaluation of disease progression. Graphical abstract Longitudinal in vivo study in the 5xFAD mouse model shows that TSPO and oxidative stress assessment through [18F]DPA-714 and [18F]FSPG-PET imaging, respectively, could serve as a potential tool for the evaluation of Alzheimer disease progression.

Abstract The status of serotonin 5­HT2A receptors (5­HT2ARs) in schizophrenia has been controversial. In vivo positron emission tomography neuroimaging and in vitro post-mortem binding studies have reported conflicting results about 5­HT2AR density. Radiotracers bind different receptor conformations depending on their agonist, antagonist or inverse agonist properties. This study investigates 5­HT2AR density in the post-mortem prefrontal cortex from subjects with schizophrenia and controls using three radiotracers with a different pharmacological profile. The specific binding parameters of the inverse agonist [18F]altanserin, the agonist [3H]lysergic acid diethylamide (LSD) and the antagonist [3H]MDL100907 to brain cortex membranes from 20 subjects with schizophrenia and 20 individually matched controls were evaluated under similar methodological conditions. Ten schizophrenia subjects were antipsychotic-free at death. Saturation curve analyses were performed by non-linear regression to obtain a maximal density of binding sites (B max) and the affinity of the respective radiotracers (K d). In schizophrenia subjects, 5-HT2AR density was decreased when quantified by [18F]altanserin binding, whereas increased when evaluated by [3H]LSD binding. However, [3H]MDL100907 binding was unaltered. A slight loss of affinity (higher K d) was observed exclusively in [3H]LSD binding. The findings were more evident in antipsychotic-free subjects than in antipsychotic-treated subjects. In conclusion, a higher proportion of the 5-HT2AR-active functional conformation, which is rather identified by agonist radiotracers, was observed in schizophrenia patients. A consequent reduction of the inactive 5-HT2AR conformation, which is preferentially identified by inverse agonist radiotracers, was also obtained. Antagonist radiotracers do not distinguish between molecular conformations of the receptor, and accordingly, the absence of changes was shown. These results are compatible with the proposed increased functional activity of brain cortical 5-HT2ARs in schizophrenia.

The microbiota-gut-brain axis is a complex interconnected system altered in schizophrenia. The antioxidant N-acetylcysteine (NAC) has been proposed as an adjunctive therapy to antipsychotics in clinical trials, but its role in the microbiota-gut-brain axis has not been sufficiently explored. We aimed to describe the effect of NAC administration during pregnancy on the gut-brain axis in the offspring from the maternal immune stimulation (MIS) animal model of schizophrenia. Pregnant Wistar rats were treated with PolyI:C/Saline. Six groups of animals were studied according to the study factors: phenotype (Saline, MIS) and treatment (no NAC, NAC 7 days, NAC 21 days). Offspring were subjected to the novel object recognition test and were scanned using MRI. Caecum contents were used for metagenomics 16S rRNA sequencing. NAC treatment prevented hippocampal volume reduction and long-term memory deficits in MIS-offspring. In addition, MIS-animals showed lower bacterial richness, which was prevented by NAC. Moreover, NAC7/NAC21 treatments resulted in a reduction of proinflammatory taxons in MIS-animals and an increase in taxa known to produce anti-inflammatory metabolites. Early approaches, like this one, with anti-inflammatory/anti-oxidative compounds, especially in neurodevelopmental disorders with an inflammatory/oxidative basis, may be useful in modulating bacterial microbiota, hippocampal size, as well as hippocampal-based memory impairments.

Background and objective: The determination of pharmacokinetic properties of new chemical entities is a key step in the process of drug development. Positron emission tomography (PET) is an ideal technique to obtain both biodistribution and pharmacokinetic parameters of new compounds over a wide range of chemical modalities. Here, we use a multi-radionuclide/multi-position labelling approach to investigate distribution, elimination, and metabolism of a triazole-based FKBP12 ligand (AHK2) with potential application in neuromuscular disorders. Methods: Target engagement and stabilizing capacity of the drug candidate (AHK2) towards FKBP12-RyR was evaluated using competitive ligand binding and proximity ligation assays, respectively. Subsequently, AHK2 was labelled either with the positron emitter carbon-11 (11C) via 11C-methylation to yield both [11C]AHK2.1 and [11C]AHK2.2, or by palladium-catalysed reduction of the corresponding 5-iodotriazole derivative using 3H gas to yield [3H]AHK2. Metabolism was first investigated in vitro using liver microsomes. PET imaging studies in rats after intravenous (IV) administration at different doses (1 µg/Kg and 5 mg/Kg) were combined with determination of arterial blood time-activity curves (TACs) and analysis of plasma samples by high performance liquid chromatography (HPLC) to quantify radioactive metabolites. Arterial TACs were obtained in continuous mode by using an in-house developed system that enables extracorporeal blood circulation and continuous measurement of radioactivity in the blood. Pharmacokinetic parameters were determined by non-compartmental modelling of the TACs. Results: In vitro studies indicate that AHK2 binds to FKBP12 at the rapamycin-binding pocket, presenting activity as a FKBP12/RyR stabilizer. [11C]AHK2.1, [11C]AHK2.2 and [3H]AHK2 could be obtained in overall non-decay corrected radiochemical yields of 14 ± 2%, 15 ± 2% and 0.05%, respectively. Molar activities were 60–110 GBq/µmol, 68–122 GBq/µmol and 0.4–0.5 GBq/μmol, respectively. In vitro results showed that oxidation of the thioether group into sulfoxide, demethylation of the CH3O-Ar residue and demethylation of –N(CH3)2 were the main metabolic pathways. Fast metabolism was observed in vivo. Pharmacokinetic parameters obtained from metabolite-corrected arterial blood TACs showed a short half-life (12.6 ± 3.3 min). Dynamic PET imaging showed elimination via urine when [11C]AHK2.2 was administered, probably reflecting the biodistribution of [11C]methanol as the major metabolite. Contrarily, accumulation in the gastrointestinal track was observed after administration of [11C]AKH2.1. Conclusions: AHK2 binds to FKBP12 at the rapamycin-binding pocket, presenting activity as a FKBP12/RyR stabilizer. Studies performed with the 3H- and 11C-labelled FKBP12/RyR stabilizer AHK2 confirm fast blood clearance, linear pharmacokinetics and rapid metabolism involving oxidation of the sulfide and amine moieties and oxidative demethylation of the CH3-O-Ar and tertiary amine groups as the main pathways. PET studies suggest that knowledge about metabolic pathways is paramount to interpret images.

Introduction: Diabetic foot is the infection, ulceration or destruction of the deep tissues of the foot in patients with diabetes mellitus. This pathology occurs when there are high levels of glucose in the blood, as well as other factors such as high blood pressure and hypercholesterolemia. These factors cause damage to the vessels and nerves, producing medium and long-term complications. This is a health problem that affects diabetic patients throughout their lives. Objective: To know the different techniques and strategies that allow to carry out an appropriate management of the diabetic foot. Methodology: A narrative review was carried out between November 2021 and July 2022 in the different databases of Pubmed (Medline), Scielo, Scopus and Web of Science (WOS), with a search string that combined the keywords derived from thesauri, namely Descriptors of Health Sciences (DeCS) and Medical Subject Headings (MeSH), combined with the Boolean operators “AND”, “NOT” and “NOT”. Results: After applying the article selection criteria and evaluating the quality of the methodology, a total of 22 articles were obtained. The results affirm the existence of promising therapies for the treatment of diabetic foot ulcers such as negative-pressure therapy and hyperbaric oxygen therapy. It is highlighted that the use of therapeutic footwear and health education are deficient aspects that must be reinforced. Conclusions: After comparing the different articles, it was possible to determine that negative-pressure therapy and hyperbaric oxygen therapy should be promoted as they are suitable for the treatment of diabetic foot ulcers. In addition, therapeutic footwear is a baseline in the diabetic foot approach. On the other hand, it is necessary to reinforce interdisciplinary work in this area and health education for patients suffering from this disease.

In this paper, we propose a novel Machine Learning Model based on Bayesian Linear Regression intended to deal with the low sample-to-variable ratio typically found in neuroimaging studies and focusing on mental disorders. The proposed model combines feature selection capabilities with a formulation in the dual space which, in turn, enables efficient work with neuroimaging data. Thus, we have tested the proposed algorithm with real MRI data from an animal model of schizophrenia. The results show that our proposal efficiently predicts the diagnosis and, at the same time, detects regions which clearly match brain areas well-known to be related to schizophrenia.

In vivo positron emission tomography of neuroinflammation has mainly focused on the evaluation of glial cell activation using radiolabeled ligands. However, the non-invasive imaging of neuroinflammatory cell proliferation has been scarcely evaluated so far. In vivo and ex vivo assessment of gliogenesis after transient middle cerebral artery occlusion (MCAO) in rats was carried out using PET imaging with the marker of cell proliferation 3′-Deoxy-3′-[18F] fluorothymidine ([18F]FLT), magnetic resonance imaging (MRI) and fluorescence immunohistochemistry. MRI-T2W studies showed the presence of the brain infarction at 24 h after MCAO affecting cerebral cortex and striatum. In vivo PET imaging showed a significant increase in [18F]FLT uptake in the ischemic territory at day 7 followed by a progressive decline from day 14 to day 28 after ischemia onset. In addition, immunohistochemistry studies using Ki67, CD11b, and GFAP to evaluate proliferation of microglia and astrocytes confirmed the PET findings showing the increase of glial proliferation at day 7 after ischemia followed by decrease later on. Hence, these results show that [18F]FLT provides accurate quantitative information on the time course of glial proliferation in experimental stroke. Finally, this novel brain imaging method might guide on the imaging evaluation of the role of gliogenesis after stroke.

Este artículo ofrece una reflexión profunda sobre las implicaciones emocionales y personales que se dan en un proceso de investigación social. A través de la experiencia de la investigadora en el estudio de la discapacidad y el género se ponen de manifiesto las múltiples interacciones e intersecciones que se dan en un proceso de investigación entre lo epistemológico, lo teórico, lo metodológico y lo personal, lo político y lo emocional.

Abstract Background In vivo positron-emission tomography (PET) imaging of transporter protein (TSPO) expression is an attractive and indispensable tool for the diagnosis and therapy evaluation of neuroinflammation after cerebral ischemia. Despite several radiotracers have shown an excellent capacity to image neuroinflammation, novel radiotracers such as [18F] VUIIS1008 have shown promising properties to visualize and quantify the in vivo expression of TSPO. Methods Longitudinal in vivo magnetic resonance (MRI) and PET imaging studies with the novel TSPO radiotracer 2-(5,7-diethyl-2-(4-(2-[18F] fluoroethoxy) phenyl) pyrazolo [1,5-a] pyrimidin-3-yl)-N, N-diethylacetamide ([18F] VUIIS1008), and (N, N-diethyl-2-(2-[4-(2-fluoroethoxy)-phenyl]-5,7-dimethyl-pyrazolo [1,5-a] yrimidin-3-yl)-acetamide ([18F] DPA-714) were carried out before and at days 1, 3, 7, 14, 21, and 28 following the transient middle cerebral artery occlusion (MCAO) in rats. Results MRI images showed the extension and evolution of the brain infarction after ischemic stroke in rats. PET imaging with [18F] VUIIS1008 and [18F] DPA714 showed a progressive increase in the ischemic brain hemisphere during the first week, peaking at day 7 and followed by a decline from days 14 to 28 after cerebral ischemia. [18F] DPA714 uptake showed a mild uptake increase compared to [18F] VUIIS1008 in TSPO-rich ischemic brain regions. In vivo [18F] VUIIS1008 binding displacement with VUIIS1008 was more efficient than DPA714. Finally, immunohistochemistry confirmed a high expression of TSPO in microglial cells at day 7 after the MCAO in rats. Conclusions Altogether, these results suggest that [18F] VUIIS1008 could become a valuable tool for the diagnosis and treatment evaluation of neuroinflammation following ischemic stroke.

Microglia controls the immune system response in the brain. Specifically, the activation and dysregulation of the NLRP3 inflammasome is responsible for the initiation of the inflammatory process through IL-1β and IL-18 release. In this work, we have focused on studying the effect of melatonin on the regulation of the NLRP3 inflammasome through α7 nicotinic receptor (nAChR) and its relationship with autophagy. For this purpose, we have used pharmacological and genetic approaches in lipopolysaccharide (LPS)-induced inflammation models in both in vitro and in vivo models. In the BV2 cell line, LPS inhibited autophagy, which increased NLRP3 protein levels. However, melatonin promoted an increase in the autophagic flux. Treatment of glial cultures from wild-type (WT) mice with LPS followed by extracellular adenosine triphosphate (ATP) produced the release of IL-1β, which was reversed by melatonin pretreatment. In cultures from α7 nAChR knock-out (KO) mice, melatonin did not reduce IL-1β release. Furthermore, melatonin decreased the expression of inflammasome components and reactive oxygen species (ROS) induced by LPS; co-incubation of melatonin with α-bungarotoxin (α-bgt) or luzindole abolished the anti-inflammatory and antioxidant effects. In vivo, melatonin reverted LPS-induced cognitive decline, reduced NLRP3 levels and promoted autophagic flux in the hippocampi of WT mice, whereas in α7 nAChR KO mice melatonin effect was not observed. These results suggest that melatonin may modulate the complex interplay between α7 nAChR and autophagy signaling.

Introducción. Giardia intestinalis es un organismo tempranamente divergente en el que recientemente se demostró la presencia de intrones. La maquinaria responsable de la remoción de intrones en organismos eucariotas superiores es el empalmosoma, el cual está conformado por cinco ribonucleoproteínas, cada una de las cuales tiene un ARN pequeño nuclear, un set de siete proteínas Sm (B, D1, D2, D3, E, F y G) y varias proteínas específicas. En G. intestinalis se han identificado los genes de algunas proteínas del empalmosoma por bioinformática. Aunque se asume que este es el responsable del empalme en el parásito, su caracterización bioquímica no se ha hecho. Objetivo. Inhibir dos genes que codifican para proteínas del empalmosoma de G. intestinalis con el fin de determinar si esta inhibición afecta el crecimiento o el enquistamiento del parásito. Materiales y métodos. En un vector específico para G. intestinalis se clonaron secuencias antisentido de los genes que codifican para las proteínas SmB y SmD3 del empalmosoma del parásito. Posteriormente, se transfectó G. intestinalis con los vectores recombinantes y se seleccionaron aquellos parásitos que lo incorporaron. Se confirmó la disminución del mensajero mediante reacción en cadena de la polimerasa (PCR) en tiempo real, y se evaluaron el crecimiento y el enquistamiento en parásitos silvestres y transfectados. Resultados. Se observó una disminución de 40 y 70 % en el ARNm de SmB y SmD3, respectivamente. El crecimiento y el enquistamiento no se vieron afectados en estos parásitos. Conclusión. La disminución de SmB y SmD3 no afectó al parásito, lo que indica que el empalmosoma sigue siendo funcional, o que el empalme no es una función vital del parásito.

Las personas con discapacidad se convierten en un colectivo organizado, productores de un discurso y una cosmovisión propias a partir de finales de los años 60, cuando surge una nueva visión sociopolítica del fenómeno de la discapacidad y, a su vez, un movimiento social crítico que denuncia la realidad opresora y estigmatizante a la que se enfrentan las personas con discapacidad. Este movimiento, surgido en un principio en Estados Unidos y Gran Bretaña, se da en llamar "Movimiento de Vida Independiente" y se considera propulsor del Modelo Social de la discapacidad, un nuevo paradigma teórico-práctico que se caracteriza por la contundente crítica a la hegemonía del modelo médico en la conceptualización de la discapacidad.Palabras clave: discapacidad, movimiento de vida independiente, movimiento social, feminismo, modelo social._______________________Abstract: Disabled people become a group organized, producing a discourse and worldview own from the late 60s, when a new socio-political vision of the phenomenon of disability and, in turn, critical social movement denounces the oppressive and stigmatizing reality facing the disabled. This movement initially emerged in the United States and Britain, are given called "Independent Living Movement" and is considered propeller Social Model of disability, a new theoretical and practical paradigm is characterized by the strong criticism of the hegemony of the medical model in the conceptualization of disability.Keywords: disability, independent living movement, social movement, feminism, social model of disability.

En 2012 cambió la legislación española que regulaba el copago farmacéutico de la prestación farmacéutica del Sistema Nacional de Salud (SNS). El objetivo fue conocer si este cambio afecta al consumo de los medicamentos para enfermedades crónicas, tales como antidiabéticos, antitrombóticos y fármacos contra padecimientos obstructivos de las vías respiratorias. Método: Estudio observacional longitudinal retrospectivo. Se utiliza - ron modelos de regresión lineal segmentada general para series de tiempo interrumpido. Las variables analizadas fueron el número de dosis diarias definidas (DDDs) y el importe de la facturación de las dispensaciones finan - ciadas y no financiadas por el SNS desde septiembre de 2010 hasta agosto de 2015 (T=60). Resultados: La tasa de variación estimada de las DDDs fue negativa pero decreciente para los 3 subgrupos terapéuticos a los 6, 12, 24 y 38 meses de la intervención: -0,1% para antidiabéticos a los 6 meses y 0,3% a los 38 meses; -3,7% para antitrombóticos a los 6 meses y -4,6% a los 38 meses; -2,7% a los 6 meses para anti-asma y EPOC y -1,3% a los 38 meses. Se estimó una reducción mantenida y significativa del gasto únicamente en el subgrupo para asma y EPOC: -5,2% a los 6 meses, -7,0% a los 12 meses y a los 24 meses y -6,2% a los 38 meses. Conclusiones: La reforma del copago farmacéutico de 2012 ocasionó una reducción inmediata y significativa en el número de dosis diarias de - finidas de los tres grupos terapéuticos estudiados. Este efecto nivel no fue permanente ya que se acompañó de un cambio en la tendencia de crecimiento en los meses post-intervención que, en parte, compensó el efecto sobre el nivel.

Dicarba-closo-dodecaboranes, commonly known as carboranes, possess unique physico-chemical properties and can be used as hydrophobic moieties during the design of new drugs or radiotracers. In this work, we report the synthesis of two analogues of 2-(4-aminophenyl)benzothiazole (a compound that was found to elicit pronounced inhibitory effects against certain breast cancer cell lines in vitro) in which the phenyl ring has been substituted by a m-carborane cage. Two different synthetic strategies have been used. For the preparation of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-benzo-thiazole, the benzothiazole group was first introduced on one of the cluster carbon atoms of m-carborane and the amine group was further attached in three steps. For the synthesis of 1-(9-amino-1,7-dicarba-closo-dodecaboran-1-yl)-6-hydroxybenzothiazole, iodination was performed before introducing the benzothiazole group, and the amino group was subsequently introduced in six steps. Both compounds were radiolabelled with carbon-11 using [11C]CH3OTf as the labelling agent. Radiolabelling yields and radiochemical purities achieved should enable subsequent in vitro and in vivo investigations.

Background: Boron Neutron Capture Therapy (BNCT) is a binary approach to cancer therapy that requires accumulation of boron atoms preferentially in tumour cells. This can be achieved by using nanoparticles as boron carriers and taking advantage of the enhanced permeability and retention (EPR) effect. Here, we present the preparation and characterization of size and shape-tuned gold NPs (AuNPs) stabilised with polyethylene glycol (PEG) and functionalized with the boron-rich anion cobalt bis(dicarbollide), commonly known as COSAN. The resulting NPs were radiolabelled with 124I both at the core and the shell, and were evaluated in vivo in a mouse model of human fibrosarcoma (HT1080 cells) using positron emission tomography (PET). Methods: The thiolated COSAN derivatives for subsequent attachment to the gold surface were synthesized by reaction of COSAN with tetrahydropyran (THP) followed by ring opening using potassium thioacetate (KSAc). Iodination on one of the boron atoms of the cluster was also carried out to enable subsequent radiolabelling of the boron cage. AuNPs grafted with mPEG-SH (5 Kda) and thiolated COSAN were prepared by ligand displacement. Radiolabelling was carried out both at the shell (isotopic exchange) and at the core (anionic absorption) of the NPs using 124I to enable PET imaging. Results: Stable gold nanoparticles simultaneously functionalised with PEG and COSAN (PEG-AuNPs@[4]−) with hydrodynamic diameter of 37.8 ± 0.5 nm, core diameter of 19.2 ± 1.4 nm and ξ-potential of −18.0 ± 0.7 mV were obtained. The presence of the COSAN on the surface of the NPs was confirmed by Raman Spectroscopy and UV-Vis spectrophotometry. PEG-AuNPs@[4]− could be efficiently labelled with 124I both at the core and the shell. Biodistribution studies in a xenograft mouse model of human fibrosarcoma showed major accumulation in liver, lungs and spleen, and poor accumulation in the tumour. The dual labelling approach confirmed the in vivo stability of the PEG-AuNPs@[4]−. Conclusions: PEG stabilized, COSAN-functionalised AuNPs could be synthesized, radiolabelled and evaluated in vivo using PET. The low tumour accumulation in the animal model assayed points to the need of tuning the size and geometry of the gold core for future studies.

Lanthanide-doped upconverting nanoparticles (UCNPs) transform near infrared light (NIR) into higher-energy UV and visible light by multiphotonic processes. Owing to such unique feature, UCNPs have found application in optical imaging and have been investigated for the NIR light activation of prodrugs, including transition metal complexes of interest in photochemotherapy. Besides, UCNPs also function as magnetic resonance imaging (MRI) contrast agents and positron emission tomography (PET) probes when labelled with radionuclides such as 18F. In this contribution, we report on a new series of phosphonate-functionalized NaGdF4:Yb,Er UCNPs that show affinity for hydroxyapatite (inorganic constituent of bones), and we discuss their potential as bone targeting multimodal (MRI/PET) imaging agents. In vivo biodistribution studies of 18F-labelled NaGdF4:Yb,Er UCNPs in rats indicate that surface functionalization with phosphonates favours the accumulation of nanoparticles in bones over time. PET results reveal leakage of 18F− for phosphonate-functionalized NaGdF4:Yb,Er and control nanomaterials. However, Gd was detected in the femur for phosphonate-capped UCNPs by ex vivo analysis using ICP-MS, corresponding to 6−7% of the injected dose.

El homicidio en Medellín, Colombia, se convirtió en la primera causa de muerte desde 1986 y su participación del total de muertes pasó de 3,5% en 1976 a 42% en 1991 y 7% en 2006. Entre 1979 y 2008 hubo 81.166 homicidios (2.706 promedio/año). La tasa de homicidios por 100.000 habitantes fue 44 en 1979 y 47 en 2008, con un máximo de 388 en 1991. Se describen características de los homicidios en 30 años, entre 1979 y 2008, por quinquenios, mediante una muestra aleatoria de 3.414 necropsias médico-legales. Los muertos fueron hombres 92.8% (IC95%: 91,8; 93,6), jóvenes con promedios de edad entre 27 y 33 años, residentes en estratos socio-económicos bajos, con predominó de los móviles ajustes de cuentas, riñas y atracos. Se evidenciaron tres periodos diferentes de la epidemia de homicidios: el primero de incremento acelerado 15 años, el segundo de descenso sostenido hasta 1998 y el tercero ondulante y descenso abrupto en los 10 últimos años. Estos resultados de larga duración de la violencia en la ciudad abren posibilidades analíticas para encontrar políticas más consistentes de intervención.In Medellín, Colombia, homicides have been the leading cause of death since 1986. Their proportion among total deaths increased from 3.5% in 1976 to 42% in 1991 and subsequently decreased to 7% in 2006. From 1979 to 2008, there were 81,166 homicides (annual mean, 2,706). The homicide rates per 100,000 inhabitants were 44 in 1979 and 47 in 2008, with a peak of 388 in 1991. The current article analyzes homicides in 30 years (1979-2008) using a random sample of 3,414 forensic autopsy reports. The vast majority of victims were males, 92.8% (95%CI: 91.8%; 93.6%), mostly low-income young people from 27 to 33 years of age. Most homicides involved revenge, fights, or armed robberies. The study showed different periods in the homicide epidemic: the first 15 years, with a rapid increase, the second, with a steady decline until 1998, and the third, with a fluctuating but overall steep decline in the last 10 years. This long-term study on violence in Medellin opens possibilities for analyzing and identifying more consistent policies for intervention.

The reproductive mechanism of Giardia intestinalis, considered one of the earliest divergent eukaryotes, has not been fully defined yet. Some evidence supports the hypothesis that Giardia is an exclusively asexual organism with a clonal population structure. However, the high genetic variability, the variation in ploidy during its life cycle, the low heterozygosity and the existence of genes involved in the meiotic-like recombination pathway in the parasite's genome cast doubt on exclusively asexual nature of Giardia. In this work, semiquantitative RT-PCR analysis was used to assess the transcription pattern of three meiosis-like-specific genes involved in homologues recombination: dmc1, hop1 and spo11. The mRNAs were amplified during the parasite's differentiation processes, encystation and excystation, and expression was found at each stage of its life cycle. A semiquantitative assessment also suggests that expression of some of the genes is regulated during encystation process.

Se presentan las comparaciones en resistencia a compresión a edades de 3, 7, 28 y 101 días (según NTC-673); durabilidad y análisis petrográficos entre hormigones de 28 MPa de diseño, hechos con cemento Pórtland tipo I y áridos de cinco canteras diferentes de los alrededores de Medellín (rocas ígneas, metamórficas y depósitos aluviales). Los resultados de resistencia a 28 días mostraron que los valores más altos se obtuvieron con áridos de roca ígnea, haciéndose evidente, para este estudio, la influencia de la resistencia, rigidez y dureza del tipo de roca en las propiedades del hormigón. La evaluación de durabilidad fue hecha comparando los testigos de hormigón elaborados con los materiales de cada cantera después de 28 días de curados. Encontrándose que los testigos elaborados con áridos de CC presentaron mejor estabilidad ante los agentes químicos, aún en concentraciones mayores, que los otros tipos de rocas. El análisis petrográfico se hizo mediante el microscopio óptico de luz polarizada y SEM, sobre pulidos hechos de trozos de cilindros fallados a compresión a los 28 días, para comparar la relación entre la pasta de cemento, el árido grueso y el árido fino. Se encontró que las muestras con menores resistencias presentaron mayor cantidad de poros en la pasta y reacciones entre la pasta y los áridos.

Las heridas neoplásicas están relacionadas con el tumor y requieren un abordaje especial y más cuidadoso por los diferentes factores asociados con el cáncer. Se pueden encontrar problemas de difícil manejo como mal olor, exudado, sangrado, dolor, infección, apariencia visual que causa baja autoestima y aislamiento social que conlleva a un marcado deterioro de la calidad de vida de los pacientes y sus familias. Objetivo: determinar cuáles son los aspectos básicos del cuidado de enfermería en heridas neoplásicas. Materiales y métodos: esta revisión documental analiza la epidemiología, clasificación, instrumentos de valoración y las intervenciones de cuidado actual que el profesional de enfermería debe tener al brindar el cuidado a estos pacientes. Conclusión: se requiere un equipo multidisciplinario para el manejo de las heridas neoplásicas. Se deben identificar los problemas o necesidades, acorde con esto se diseñará un plan de manejo personalizado y se evaluarán las intervenciones generando un impacto positivo en el estilo de vida actual y futuro del paciente.

The emergence of resistance to available antimalarials requires the urgent development of new medicines. The recent disclosure of several thousand compounds active in vitro against the erythrocyte stage of Plasmodium falciparum has been a major breakthrough, though converting these hits into new medicines challenges current strategies. A new in vivo screening concept was evaluated as a strategy to increase the speed and efficiency of drug discovery projects in malaria. The new in vivo screening concept was developed based on human disease parameters, i.e. parasitemia in the peripheral blood of patients on hospital admission and parasite reduction ratio (PRR), which were allometrically down-scaled into P. berghei-infected mice. Mice with an initial parasitemia (P0) of 1.5% were treated orally for two consecutive days and parasitemia measured 24 h after the second dose. The assay was optimized for detection of compounds able to stop parasite replication (PRR = 1) or induce parasite clearance (PRR >1) with statistical power >99% using only two mice per experimental group. In the P. berghei in vivo screening assay, the PRR of a set of eleven antimalarials with different mechanisms of action correlated with human-equivalent data. Subsequently, 590 compounds from the Tres Cantos Antimalarial Set with activity in vitro against P. falciparum were tested at 50 mg/kg (orally) in an assay format that allowed the evaluation of hundreds of compounds per month. The rate of compounds with detectable efficacy was 11.2% and about one third of active compounds showed in vivo efficacy comparable with the most potent antimalarials used clinically. High-throughput, high-content in vivo screening could rapidly select new compounds, dramatically speeding up the discovery of new antimalarial medicines. A global multilateral collaborative project aimed at screening the significant chemical diversity within the antimalarial in vitro hits described in the literature is a feasible task.