Tromboembolismo pulmonar como posible reacción adversa a Quetiapina Reporte de caso / Pulmonary thromboembolism as a possible adverse reaction to Quetiapine Case report

Resumen Algunos estudios sugieren que existe una relación entre el uso de antipsicóticos y el riesgo de tromboembolismo venoso (TEV) y embolia pulmonar (EP). Sin embargo, los resultados siguen sin ser concluyentes. Se trata del caso de un Masculino de 23 años con antecedentes de Esquizofrenia y Depresión tratado quetiapina 800 mg, el cual es encontrado muerto en la cama de un hotel. En la necropsia sin lesiones traumáticas visibles, hallazgos histológicos de tromboembolismo pulmonar masivo con infartos pulmonares secundarios. Laboratorio de Toxicología detectó la presencia de quetiapina, no se detectó alcohol o drogas de abusos. Mediante el Algoritmo De Karch & Lasagna Modificado el tromboembolismo pulmonar fue una reacción adversa con una probabilidad de relación causal posible. Se han informado muchos casos de muerte súbita causada por EP con la exposición a antipsicóticos, pero la relación de su uso y el riesgo de TEV y EP sigue siendo controvertida.

Abstract Some studies suggest a relationship between antipsychotic use and the risk of venous thromboembolism (VTE) and pulmonary embolism (PE). However, the results remain inconclusive. This is the case of a 23-year-old male with a history of schizophrenia and depression treated with quetiapine 800 mg, who was found dead in a hotel bed. At necropsy with no visible traumatic lesions, histological findings of massive pulmonary thromboembolism with secondary pulmonary infarcts. Toxicology laboratory detected the presence of quetiapine, no alcohol or drugs of abuse were detected. Using the Modified Karch & Lasagna Algorithm, pulmonary thromboembolism was an adverse reaction with a probable causal relationship. Many cases of sudden death caused by PE have been reported with exposure to antipsychotics, but the relationship of their use and the risk of VTE and PE remains controversial.

Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome.

Importance: Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established. Objective: To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments. Design, Setting, and Participants: This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia, Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia. Exposures: Neurological and neuropsychological assessments. Main Outcomes and Measures: The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test. Results: A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age <40 years; 21.1% [95% CI, 8.0%-32.5%] for age 40-44 years; 41.4% [95% CI, 23.1%-55.3%] for age 45-49 years; 57.5% [95% CI, 38.2%-70.8%] for age ≥50 years; P < .001), and 94.1% (95% CI, 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline. Conclusions and Relevance: This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD.

Performance of the artificial urinary sphincter implantation in men with urinary incontinence: Results from a contemporary long-term real-world nationwide analysis.

PURPOSE: The artificial urinary sphincter (AUS) is one of the most effective surgical treatments for male urinary incontinence regardless of its severity. Current knowledge comes from high-volume centers, but little is known about the performance of this surgery from community practices. This study aims to report contemporary AUS performance in a nationwide observational study in Colombia. METHODS: Male patients who underwent AUS surgery with AMS 800™ between 2000 and 2020 in more than 17 centers and four cities were identified. Pre, intra, and postoperative characteristics were evaluated, mainly addressing patient reported outcomes measurements in the postoperative period. Retrospective and prospective data collection and descriptive analysis were completed. Kaplan-Meier analysis was used to determine AUS survival rate. RESULTS: Out of an initial 667 cases, a total of 215 patients met inclusion and exclusion criteria and were included. Mean age was 67 ± 9.4 years, and mean follow-up was 6.0 ± 4.4 years with maximum range of 14 years. The etiology of urinary incontinence was prostate cancer surgery in 141 (81%) of the cases. The rest of the cases were related to benign prostatic disease or spinal cord injury. It is noteworthy that out of 115 patients, only 59 (51.3%) reported previous formal pelvic floor rehabilitation. Subjective severity of urinary incontinence determined by a visual analog scale showed a decrease in 4.5 points after sphincter implantation. Sphincter removal was required in 50 (23.2%) cases. The main reasons for implant removal were urethral erosion and infection. The sphincter survival rate at 2, 5, 8, 10, and 14 years was 76%, 70%, 60%, 57%, and 17%, respectively. Of the subjects at the last follow-up with the device still in place, 80.7% defined their urinary condition as "does not cause or causes minor discomfort," and 99% would recommend the device to a friend or relative in the same condition. CONCLUSIONS: This series from a community-based practice shows the lack of adherence to clinical practice guidelines and the lack of standardized data collection. In contrast, this study provides real-world data on explantation and revision rates, allows physicians to inform patients and to have clear metrics for a shared decision-making process before the procedure.

Catheter-related bloodstream infection due to Acinetobacter ursingii in a hemodialysis patient: case report and literature review.

Acinetobacter ursingii is an anaerobic gram negative opportunistic coccobacillus, rarely isolated in bacteremic patients. It is mainly found in immunocompromised and severely ill patients with no identifiable source of infection. When isolated into the bloodstream, it usually displays resistance to at least two antimicrobial agents. To date only seven cases of bacteremia due to this microorganism have been reported in adults, of which, this accounts for the second one associated to renal replacement therapy and the first case of a documented catheter-related bloodstream infection (CRBSI) in a patient with a hemodialysis catheter. A 78-year-old male presented into the emergency department with acute kidney injury requiring hemodialysis, later developing bacteremia due to Acinetobacter ursingii.

Phosphorylated tau181 in plasma as a potential biomarker for Alzheimer's disease in adults with Down syndrome.

Plasma tau phosphorylated at threonine 181 (p-tau181) predicts Alzheimer's disease (AD) pathology with high accuracy in the general population. In this study, we investigated plasma p-tau181 as a biomarker of AD in individuals with Down syndrome (DS). We included 366 adults with DS (240 asymptomatic, 43 prodromal AD, 83 AD dementia) and 44 euploid cognitively normal controls. We measured plasma p-tau181 with a Single molecule array (Simoa) assay. We examined the diagnostic performance of p-tau181 for the detection of AD and the relationship with other fluid and imaging biomarkers. Plasma p-tau181 concentration showed an area under the curve of 0.80 [95% CI 0.73-0.87] and 0.92 [95% CI 0.89-0.95] for the discrimination between asymptomatic individuals versus those in the prodromal and dementia groups, respectively. Plasma p-tau181 correlated with atrophy and hypometabolism in temporoparietal regions. Our findings indicate that plasma p-tau181 concentration can be useful to detect AD in DS.

Evaluation of biochemical and hematological parameters in adults with Down syndrome.

Down syndrome (DS) is the most common worldwide cause of intellectual disability of genetic origin and the most common chromosomal disorder affecting live-born infants. In addition to intellectual disability, individuals with DS have other comorbidities and complex medical conditions. The increase in the life expectancy of patients with DS requires expanding the knowledge about their clinical characteristics and related laboratory parameters. Several studies exploring laboratory tests in DS patients exist, but their focus is limited to specific areas of metabolism. Therefore, our main goal was to describe the biochemical and hematological findings in a DS cohort and to compare the values to those of a control population. A total of 248 DS individuals and 84 control subjects were enrolled. DS individuals had a higher frequency of several clinical conditions compared to control individuals and presented with significant differences with respect to the controls in both biochemical and hematological parameters. We found age- and sex-related differences in several of the parameters. A good understanding of the differences in our cohort might be of aid in the clinical follow-up of adults with DS, especially considering that the lifespan of DS individuals may reach 60 years of age in developed countries.

Diagnosis of prodromal and Alzheimer's disease dementia in adults with Down syndrome using neuropsychological tests.

INTRODUCTION: We aimed to define prodromal Alzheimer's disease (AD) and AD dementia using normative neuropsychological data in a large population-based cohort of adults with Down syndrome (DS). METHODS: Cross-sectional study. DS participants were classified into asymptomatic, prodromal AD and AD dementia, based on neurologist's judgment blinded to neuropsychological data (Cambridge Cognitive Examination for Older Adults with Down's syndrome [CAMCOG-DS] and modified Cued Recall Test [mCRT]). We compared the cutoffs derived from the normative data in young adults with DS to those from receiver-operating characteristic curve (ROC) analysis. RESULTS: Diagnostic performance of the CAMCOG-DS and modified Cued Recall Test (mCRT) in subjects with mild and moderate levels of intellectual disability (ID) was high, both for diagnosing prodromal AD and AD dementia (area under the curve [AUC] 0.73-0.83 and 0.90-1, respectively). The cutoffs derived from the normative data were similar to those derived from the ROC analyses. DISCUSSION: Diagnosing prodromal AD and AD dementia in DS with mild and moderate ID using population norms for neuropsychological tests is possible with high diagnostic accuracy.

Tumors defective in homologous recombination rely on oxidative metabolism: relevance to treatments with PARP inhibitors.

Mitochondrial metabolism and the generation of reactive oxygen species (ROS) contribute to the acquisition of DNA mutations and genomic instability in cancer. How genomic instability influences the metabolic capacity of cancer cells is nevertheless poorly understood. Here, we show that homologous recombination-defective (HRD) cancers rely on oxidative metabolism to supply NAD+ and ATP for poly(ADP-ribose) polymerase (PARP)-dependent DNA repair mechanisms. Studies in breast and ovarian cancer HRD models depict a metabolic shift that includes enhanced expression of the oxidative phosphorylation (OXPHOS) pathway and its key components and a decline in the glycolytic Warburg phenotype. Hence, HRD cells are more sensitive to metformin and NAD+ concentration changes. On the other hand, shifting from an OXPHOS to a highly glycolytic metabolism interferes with the sensitivity to PARP inhibitors (PARPi) in these HRD cells. This feature is associated with a weak response to PARP inhibition in patient-derived xenografts, emerging as a new mechanism to determine PARPi sensitivity. This study shows a mechanistic link between two major cancer hallmarks, which in turn suggests novel possibilities for specifically treating HRD cancers with OXPHOS inhibitors.

Influence of Hyrax screw position on dental movement and cortical bone: A study of finite elements.

BACKGROUND: Rapid maxillary expansion (RME) has effects on the dental and periodontal structures of the parts involved, which vary according to the design and position of the expansion screw. The purpose of the study was to determine the optimal three-dimensional position of the Hyrax screw to obtain precise control of the dental movement and effect on the bone cortex using the finite element method (FEM). MATERIAL AND METHODS: RME was performed from the patient whom two Cone-Beam computerized tomography scans (CBCT) were obtained: T1 before expansion, and T2 three months after stabilization of RME. The FEM model was designed with T1 and of Hyrax photographs. FEM was obtained by comparing the simulation, T2, and clinical results. Three sagittal screw positions (anterior-middle-posterior) and vertical (upper-medium-low) were evaluated. RESULTS: A coronal- buccal displacement of premolars and first molars was found which decreased in the occlusal-apical direction, presenting different types of dental movement in the screw positions; besides, a tendency of translational movement in the posterior-high location was observed. In the posterior-high position a higher concentration of efforts and homogeneous deformations in the periodontal ligament and vestibular cortex of the cervical area of first molars, first and second premolars were observed, with variations according to the screw position and the distribution of stresses. CONCLUSIONS: The ideal location of the expansion screw for controlling dental movement and periodontal side effects was the high-posterior position. Key words:Maxillary expansion, dental movement, finite element analysis, orthodontic appliances.

Validación del programa de intervención para el consumo abusivo de alcohol: pactos por la vida / Validation of an intervention program against alcohol abuse: pacts for life

Resumen El objetivo de este estudio era evaluar los alcances de la aplicación del programa de prevención del consumo abusivo y la dependencia alcohólica "Pactos por la Vida" propuesto por Flórez-Alarcón y Vélez (2012), en la modificación de factores asociados al consumo de drogas en un Municipio Pequeño. Los instrumentos usados para la evaluación cuantitativa y cualitativa de los alcances del programa fueron: entrevista en profundidad, diarios de campo, mapeo, encuestas y registros de observación directa. Se realizaron análisis cualitativos del material obtenido y comparaciones de medias de las medidas asociadas con el consumo de alcohol; además de incluir un cuadro de análisis de la eficacia del programa. Se concluye que la estrategia es probablemente efectiva, y que en su aplicación a Municipios pequeños requiere de un ajuste.

Abstract The aim of this study was to assess the scope of the implementation of the "Pacts for Life" program, designed to prevent alcohol abuse and dependence (Flórez-Alarcón & Velez, 2012), in modifying factors associated to drug use in a small municipality. Instruments used for the quantitative and qualitative assessment were: in-depth interview, field notes, mapping, surveys and direct observation records. Qualitative analysis of the material obtained and comparison of means of measurements associated with alcohol consumption were performed; and an analysis of the effectiveness of the program is included. We conclude that the strategy is probably effective, and that its application to small municipalities requires adjustment.

In contrast to other species, α-Galactosylceramide (α-GalCer) is not an immunostimulatory NKT cell agonist in horses.

α-GalCer is a potent immunomodulatory molecule that is presented to NKT cells via the CD1 antigen-presenting system. We hypothesized that when used as an adjuvant α-GalCer would induce protective immune responses against Rhodococcus equi, an important pathogen of young horses. Here we demonstrate that the equine CD1d molecule shares most features found in CD1d from other species and has a suitable lipid-binding groove for presenting glycolipids to NKT cells. However, equine CTL stimulated with α-GalCer failed to kill cells infected with R. equi, and α-GalCer did not increase killing by CTL co-stimulated with R. equi antigen. Likewise, α-GalCer did not induce the lymphoproliferation of equine PBMC or increase the proliferation of R. equi-stimulated cells. Intradermal injection of α-GalCer in horses did not increase the recruitment of lymphocytes or cytokine production. Furthermore, α-GalCer-loaded CD1d tetramers, which have been shown to be broadly cross-reactive, did not bind equine lymphocytes. Altogether, our results demonstrate that in contrast to previously described species, horses are unable to respond to α-GalCer. This raises questions about the capabilities and function of NKT cells and other lipid-specific T lymphocytes in horses.

Efficient Characterization of Protein Cavities within Molecular Simulation Trajectories: trj_cavity.

Protein cavities and tunnels are critical in determining phenomena such as ligand binding, molecular transport, and enzyme catalysis. Molecular dynamics (MD) simulations enable the exploration of the flexibility and conformational plasticity of protein cavities, extending the information available from static experimental structures relevant to, for example, drug design. Here, we present a new tool (trj_cavity) implemented within the GROMACS ( www.gromacs.org ) framework for the rapid identification and characterization of cavities detected within MD trajectories. trj_cavity is optimized for usability and computational efficiency and is applicable to the time-dependent analysis of any cavity topology, and optional specialized descriptors can be used to characterize, for example, protein channels. Its novel grid-based algorithm performs an efficient neighbor search whose calculation time is linear with system size, and a comparison of performance with other widely used cavity analysis programs reveals an orders-of-magnitude improvement in the computational cost. To demonstrate its potential for revealing novel mechanistic insights, trj_cavity has been used to analyze long-time scale simulation trajectories for three diverse protein cavity systems. This has helped to reveal, respectively, the lipid binding mechanism in the deep hydrophobic cavity of a soluble mite-allergen protein, Der p 2; a means for shuttling carbohydrates between the surface-exposed substrate-binding and catalytic pockets of a multidomain, membrane-proximal pullulanase, PulA; and the structural basis for selectivity in the transmembrane pore of a voltage-gated sodium channel (NavMs), embedded within a lipid bilayer environment. trj_cavity is available for download under an open-source license ( http://sourceforge.net/projects/trjcavity ). A simplified, GROMACS-independent version may also be compiled.

Dynamics of the antigen-binding grooves in CD1 proteins: reversible hydrophobic collapse in the lipid-free state.

CD1 proteins mediate the presentation of endogenous and foreign lipids on the cell surface for recognition by T cell receptors. To sample a diverse antigen pool, CD1 proteins are repeatedly internalized and recycled, assisted, in some cases, by lipid transfer proteins such as saposins. The specificity of each CD1 isoform is, therefore, conferred in part by its intracellular pathway but also by distinct structural features of the antigen-binding domain. Crystal structures of CD1-lipid complexes reveal hydrophobic grooves and pockets within these binding domains that appear to be specialized for different lipids. However, the mechanism of lipid loading and release remains to be characterized. Here we gain insights into this mechanism through a meta-analysis of the five human CD1 isoforms, in the lipid-bound and lipid-free states, using all-atom molecular dynamics simulations. Strikingly, for isoforms CD1b through CD1e, our simulations show the near-complete collapse of the hydrophobic cavities in the absence of the antigen. This event results from the spontaneous closure of the binding domain entrance, flanked by two α-helices. Accordingly, we show that the anatomy of the binding cavities is restored if these α-helices are repositioned extrinsically, suggesting that helper proteins encountered during recycling facilitate lipid exchange allosterically. By contrast, we show that the binding cavity of CD1a is largely preserved in the unliganded state because of persistent electrostatic interactions that keep the portal α-helices at a constant separation. The robustness of this binding groove is consistent with the observation that lipid exchange in CD1a is not dependent on cellular internalization.

The simulation approach to lipid-protein interactions.

The interactions between lipids and proteins are crucial for a range of biological processes, from the folding and stability of membrane proteins to signaling and metabolism facilitated by lipid-binding proteins. However, high-resolution structural details concerning functional lipid/protein interactions are scarce due to barriers in both experimental isolation of native lipid-bound complexes and subsequent biophysical characterization. The molecular dynamics (MD) simulation approach provides a means to complement available structural data, yielding dynamic, structural, and thermodynamic data for a protein embedded within a physiologically realistic, modelled lipid environment. In this chapter, we provide a guide to current methods for setting up and running simulations of membrane proteins and soluble, lipid-binding proteins, using standard atomistically detailed representations, as well as simplified, coarse-grained models. In addition, we outline recent studies that illustrate the power of the simulation approach in the context of biologically relevant lipid/protein interactions.

Diseño y validación de la Escala de Optimismo Disposicional/Pesimismo-EOP / Design and Validation of the Dispositional Optimism/Pesimism Scale-EOP

Este estudio tuvo como objetivo principal el diseño y validación de una escala que permitiera la evaluar la tendencia optimista/pesimista en adolescentes y jóvenes universitarios. La muestra estuvo conformada 617 estudiantes de educación superior, de ambos géneros, con una edad entre 18 y 31 años, provenientes de cuatro instituciones educativas ubicadas en dos ciudades colombianas. El análisis psicométrico mostró que la prueba cuenta con las condiciones de confiabilidad y validez necesarias para ser utilizada en poblaciones similares a la de validación. Las conclusiones muestran diferencias de género en los puntajes de optimismo y pesimismo, la presencia de sesgo optimista no realista en los adolescentes y la existencia de diferencias en la tendencia optimista según la procedencia. Se discuten las limitaciones del presente estudio.

This study's main objective was the design and validation of a scale that allowed the evaluate trend of optimistic / pessimistic in adolescents and university young. The sample consisted of 617 university students aged between 18 and 31 years, from 4 educational institutions located in two Colombian cities. The psychometric analysis showed that the scale meets the conditions of reliability and validity for use in related populations . The conclusions show differences between genders in scores of optimism and pessimism trends; the presence of unrealistically optimistic bias in adolescents and the differences in the optimistic trend according to city. Limitations of this study are discussed.

Natural variations at position 93 of the invariant Vα24-Jα18 α chain of human iNKT-cell TCRs strongly impact on CD1d binding.

Human invariant natural killer T (NKT) cell TCRs bind to CD1d via an "invariant" Vα24-Jα18 chain (iNKTα) paired to semi-invariant Vß11 chains (iNKTß). Single-amino acid variations at position 93 (p93) of iNKTα, immediately upstream of the "invariant" CDR3α region, have been reported in a substantial proportion of human iNKT-cell clones (4-30%). Although p93, a serine in most human iNKT-cell TCRs, makes no contact with CD1d, it could affect CD1d binding by altering the conformation of the crucial CDR3α loop. By generating recombinant refolded iNKT-cell TCRs, we show that natural single-nucleotide variations in iNKTα, translating to serine, threonine, asparagine or isoleucine at p93, exert a powerful effect on CD1d binding, with up to 28-fold differences in affinity between these variants. This effect was observed with CD1d loaded with either the artificial α-galactosylceramide antigens KRN7000 or OCH, or the endogenous glycolipid ß-galactosylceramide, and its importance for autoreactive recognition of endogenous lipids was demonstrated by the binding of variant iNKT-cell TCR tetramers to cell surface expressed CD1d. The serine-containing variant showed the strongest CD1d binding, offering an explanation for its predominance in vivo. Complementary molecular dynamics modeling studies were consistent with an impact of p93 on the conformation of the CDR3α loop.

Colombian lay people’s willingness to forgive different actors of the armed conflict: results from a pilot study

A pilot study examined lay people’s willingness to forgive acts that were committed by actors of the armed conflicts in Colombia. The participants (100 persons living in Bogota) were shown vignettes describing cases in which a member of the guerilla or a member of the former paramilitary forces asks for forgiveness to a victim’s family, and were instructed to judge of the degree to which they would be willing to forgive if they were a family member. The concrete cases were constructed using a 3 x 3 x 3 orthogonal design: Degree of Responsibility x Severity of the Negative Acts Committed x Apologies. In half of the cases, the actor was a former member of the guerilla, whereas in the other half the actor was a former member of the paramilitary forces. The four factors had an impact on willingness to forgive, and several meaningful interactions were detected. Overall, a former member of the paramilitary forces has a reasonable chance of being forgiven (a) if he did not directly take part to offenses to people (e.g., killings) or offenses to property perpetrated by his companions, and (b) if he has sincerely begged for forgiveness and offered to partly compensate the harm done. A former member of the guerilla has few chance of being forgiven(AU)

The 2.5 Å structure of CD1c in complex with a mycobacterial lipid reveals an open groove ideally suited for diverse antigen presentation.

CD1 molecules function to present lipid-based antigens to T cells. Here we present the crystal structure of CD1c at 2.5 Å resolution, in complex with the pathogenic Mycobacterium tuberculosis antigen mannosyl-ß1-phosphomycoketide (MPM). CD1c accommodated MPM's methylated alkyl chain exclusively in the A' pocket, aided by a unique exit portal underneath the α1 helix. Most striking was an open F' pocket architecture lacking the closed cavity structure of other CD1 molecules, reminiscent of peptide binding grooves of classical major histocompatibility complex molecules. This feature, combined with tryptophan-fluorescence quenching during loading of a dodecameric lipopeptide antigen, provides a compelling model by which both the lipid and peptide moieties of the lipopeptide are involved in CD1c presentation of lipopeptides.

Riesgo suicida y factores relacionados en estudiantes de 6º a 11º grado en colegios de la ciudad de Manizales (Colombia): 2007- 2008 / Suicide risk and related factors at students of 6º to 11º grades in different schools of Manizales City (Colombia): 2007-2008

Introducción: En los últimos 45 años las tasas de suicidio se han incrementado un 60 por ciento en el mundo. A escala mundial, el suicidio se ha ubicado como una de las cinco primeras causas de muerte en el grupo de edad de 15 a 19 años. Factores de riesgo identificados: ser mujer, antecedentes personales o familiares de intento suicida, presentar trastornos del ánimo, ansiedad, depresión y consumir sustancias psicoactivas; se considera que más del 50 por ciento de los adolescentes sufren depresión mayor. El objetivo de este estudio fue medir el riesgo suicida en adolescentes escolarizados de la ciudad de Manizales (Colombia) y establecer un perfil sociodemográfico y epidemiológico.Materiales y Métodos: Estudio de corte transversal, en el cual se seleccionó una muestra probabilí­stica de 339 alumnos de los colegios participantes, y se aplicaron diversos instrumentos para la medición del riesgo suicida y de las variables asociadas.Resultados: El 56,8 por ciento de los participantes fueron hombres y 43,2 por ciento mujeres; 10,2 por ciento habían efectuado un intento suicida, 12,8 por ciento presentaron riesgo suicida y 19,9 por ciento tení­an antecedentes familiares de intento suicida; solo el 31,6 por ciento gozaban de buena función familiar, disfunción familiar severa en el 11,4 por ciento. 16,6 por ciento presentaban ansiedad y 2,9 por ciento depresión; 39,2 por ciento son dependientes del alcohol, 8,8 por ciento consumen drogas y 15,3 por ciento fuman.Conclusiones: se concluyó que ser mujer, tener una disfunción familiar severa, una decepción amorosa, antecedentes personales o familiares de intento suicida, fumar y consumir sustancias psicoactivas o padecer algún trastorno psiquiátrico como la ansiedad y la depresión mayor, aumentan el riesgo de suicidio...

Predicted structural basis for CD1c presentation of mycobacterial branched polyketides and long lipopeptide antigens.

CD1 proteins mediate the trafficking and presentation of a diverse range of lipid antigens to T-cell receptors, and thus play a key role in our adaptive immune system. Crystal structures of several CD1 isoforms reveal a highly conserved tertiary structure, but also great variability in the anatomy of their binding pockets, reflecting their distinct ligand specificity. The structure of one important member of the family, CD1c, remains unknown. CD1c is of great interest as it can present an unusual and potent lipid antigen, mannosyl-beta(1)-phosphomycoketide (MPM) from Mycobacterium tuberculosis, the causative agent of tuberculosis. CD1c has also been reported to present acetylated 12-amino-acid-long peptides (lipo-12), an observation with broad immunological implications but difficult to rationalize on structural grounds. To gain insights into the structural basis for the ligand specificity of CD1c, we have generated an atomic model of its binding domain using a detailed position-specific multiple-template homology modeling approach. This model reveals structural features unique to this isoform, particularly with regard to the so-called pocket F', which provide a compelling rationale for the ability of CD1c to bind not only branched alkyl chains such as in MPM, but also long lipopeptides comparable to those presented by MHC proteins. A model of CD1c with bound MPM was constructed and analyzed through molecular dynamics simulations, showing marked structural stability in the time-scale of 100 ns. A model of CD1c in complex with lipo-12 is also presented.