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1.
J Educ Teach Emerg Med ; 9(2): I1-I6, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38707943

RESUMEN

Audience: This airway trainer modification is designed to instruct all levels of training in emergency medicine in order to familiarize trainees with airway anatomy and obtain superior views of the glottic inlet. Introduction: During intubation with a standard geometry laryngoscope, such as the Macintosh blade, placement of the distal end of the blade within the vallecula and engagement of the median glossoepiglottic fold, also referred to as the midline vallecular fold (MVF), has long been championed by experts in airway management for its ability to improve glottic inlet visualization. This notion was further supported by the recent publication of a retrospective video review by Driver et al.1 Unfortunately, airway anatomy, including engagement of the MVF, does not receive the emphasis it deserves during intubation training of emergency medicine residents. Emergency physicians often have limited time to perform complete airway examinations, but a sound recognition and appreciation of the laryngeal inlet can serve as a roadmap to optimal laryngoscopy.2Recent advancements in airway education emphasize visualization of airway anatomy with review of video laryngoscopy (VL) recordings to identify routine VL errors in vallecula manipulation, such as failure to engage the MVF. 3 Simulation can continue to play an essential role in enhancing trainees' airway skills. Current airway trainers lack functional fidelity components, such an engageable MVF, resulting in a missed opportunity to teach airway skills and anatomy in a safe and controlled setting.4, 5 To address these concerns, we modified an existing airway task trainer with the addition of a simulated MVF to expose trainees to airway anatomy and adequate MVF engagement resulting in epiglottic elevation. Educational Objectives: By the end of this education session, participants should be able to:Identify relevant airway anatomy during intubation, including base of the tongue, epiglottis, midline vallecular fold, anterior arytenoids.Appreciate the value of a stepwise anatomically guided approach to intubation.Become familiar with the midline vallecular fold and underlying anatomy, including the hyoepiglottic ligament, and how proper placement of the laryngoscope can result in improved glottic visualization. Educational Methods: The TrueCorp AirSim airway task trainer was modified with the addition of a simulated MVF. Prior to the modification described here, there were no dynamic trainers with the functional fidelity needed to teach trainees how to engage the MVF with proper placement of the distal tip of the laryngoscope. Once the trainer was created, learners are introduced to relevant anatomy through the initial lecture to unsure baseline knowledge. During the lecture, videos and images are reviewed to demonstrate the importance of an anatomical roadmap to successful intubation. Learners then practiced with the modified task trainer to gain hands-on experience with laryngoscope placement and improved glottic visualization. A short verbal debriefing was performed at the end of the skills session to address any remaining questions. Research Methods: Pre- and post-simulation surveys were completed by attendees of a weekly didactic session, ranging from medical students, PGY 1-4 emergency medicine residents, and emergency medicine attending physicians. Pre- and post-simulation familiarity with airway anatomy and comfortability with MVF engagement was assessed using a 5-point Likert scale. Results: Twenty-six participants ranging from medical students to attending physicians completed a pre- and post-simulation survey. Overall, feedback from leaners was positive. Learners were excited to learn new airway management techniques and requested an expansion of current airway curriculum based on the success of this implementation. Discussion: This modified task trainer places an emphasis on teaching airway anatomy to trainees with the addition of functional fidelity by adding an engageable element providing the trainee with feedback on successful placement of the laryngoscope. This simple and cost-effective modification can add value to existing airway management curriculums by serving as a visual cue of airway anatomy and instructing trainees on proper placement of the laryngoscope. Our results showed participants experienced increased comfort with airway anatomy recognition and engagement of MVF for difficult intubations. Participants found the trainer effective with the simulated MVF resulting in glottic elevation and recommended this for future simulation. Participants were eager to learn additional airway techniques to improve their laryngoscopy skills, suggesting an area of growth for emergency medicine didactic curriculums. Topics: Airway, midline vallecular fold, anatomy, difficult airway, education.

2.
Int J Biomed Imaging ; 2024: 3655327, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38665417

RESUMEN

Purpose: The Gram-positive Staphylococcus aureus bacterium is one of the leading causes of infection in humans. The lack of specific noninvasive techniques for diagnosis of staphylococcal infection together with the severity of its associated complications support the need for new specific and selective diagnostic tools. This work presents the successful synthesis of an immunotracer that targets the α-toxin released by S. aureus. Methods: [89Zr]Zr-DFO-ToxAb was synthesized based on radiolabeling an anti-α-toxin antibody with zirconium-89. The physicochemical characterization of the immunotracer was performed by high-performance liquid chromatography (HPLC), radio-thin layer chromatography (radio-TLC), and electrophoretic analysis. Its diagnostic ability was evaluated in vivo by positron emission tomography/computed tomography (PET/CT) imaging in an animal model of local infection-inflammation (active S. aureus vs. heat-killed S. aureus) and infective osteoarthritis. Results: Chemical characterization of the tracer established the high radiochemical yield and purity of the tracer while maintaining antibody integrity. In vivo PET/CT image confirmed the ability of the tracer to detect active foci of S. aureus. Those results were supported by ex vivo biodistribution studies, autoradiography, and histology, which confirmed the ability of [89Zr]Zr-DFO-ToxAb to detect staphylococcal infectious foci, avoiding false-positives derived from inflammatory processes. Conclusions: We have developed an immuno-PET tracer capable of detecting S. aureus infections based on a radiolabeled antibody specific for the staphylococcal alpha toxins. The in vivo assessment of [89Zr]Zr-DFO-ToxAb confirmed its ability to selectively detect staphylococcal infectious foci, allowing us to discern between infectious and inflammatory processes.

3.
Psychol Med ; : 1-8, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38623694

RESUMEN

BACKGROUND: Suicide is one of the main external causes of death worldwide. People who have already attempted suicide are at high risk of new suicidal behavior. However, there is a lack of information on the risk factors that facilitate the appearance of reattempts. The aim of this study was to calculate the risk of suicide reattempt in the presence of suicidal history and psychosocial risk factors and to estimate the effect of each individual risk factor. METHODS: This systematic review and meta-analysis were conducted following the PRISMA-2020 guidelines. Studies on suicide reattempt that measured risk factors were searched from inception to 2022. The risk factors studied were those directly related to suicide history: history of suicide prior to the index attempt, and those that mediate the transition from suicidal ideation to attempt (alcohol or drug misuse, impulsivity, trauma, and non-suicidal self-injury). RESULTS: The initial search resulted in 11 905 articles. Of these, 34 articles were selected for this meta-analysis, jointly presenting 52 different effect sizes. The pooled effect size across the risk factors was significant (OR 2.16). Reattempt risk may be increased in presence of any of the following risk factors: previous history, active suicidal ideation, trauma, alcohol misuse, and drug misuse. However, impulsivity, and non-suicidal self-injury did not show a significant effect on reattempt. CONCLUSION: Most of the risk factors traditionally associated with suicide are also relevant when talking about suicide reattempts. Knowing the traits that define reattempters can help develop better preventive and intervention plans.

4.
Cryst Growth Des ; 23(8): 5658-5670, 2023 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-37547875

RESUMEN

The synthesis of ZSM-5 zeolites by hydrothermal crystallization of protozeolitic nanounits functionalized with amphiphilic organosilanes of different chain length (Cn-N(CH3)2-(CH2)3-Si-(OCH3)3, n = 10, 14, 18 and 22) has been investigated. Well-developed dendritic nanoarchitectures were achieved when using C14 and C18 organosilanes, exhibiting a radial and branched pattern of zeolitic nanounits aggregates. In contrast, although C10 and C22 organosilanes led to materials with hierarchical porosity, they lack of dendritic features. These differences have been linked to the formation of an amorphous mesophase at the gel preparation stage for the C14 and C18 samples, in which the surfactant micelles are covalently connected with the protozeolitic nanounits through siloxane bonds. The presence of the dendritic nanostructure positively impacts both the textural and catalytic properties of ZSM-5 zeolite. Thus, ZSM-5 (C14) and ZSM-5 (C18) samples exhibit the largest contribution of mesoporosity in terms of both surface area and pore volume. On the other hand, when tested as catalysts in the aldol condensation of furfural with cyclopentanone, which is an interesting reaction for the production of sustainable jet fuels, the highest catalytic activity is attained over the dendritic ZSM-5 materials due to their remarkable accessibility and balanced Brønsted/Lewis acidity.

5.
Gen Hosp Psychiatry ; 81: 51-56, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36805332

RESUMEN

OBJECTIVES: To estimate the risk of suicide attempt repetition among individuals with an index attempt. It also aims to study the role of risk factors and prevention programme in repetition. METHODS: This systematic review and meta-analysis was conducted in keeping with the PRISMA 2020 guidelines. Studies on attempt repetition (both cohort studies and intervention studies) were searched from inception to 2022. RESULTS: A total of 110 studies comprising 248,829 attempters was reviewed. The overall repetition rate was 0.20 (0.17, 0.22). Repetition risk linearly increased over time. A higher risk of attempt repetition was associated with female sex and index attempts in which self-cutting methods were used. Moreover, a mental disorder diagnosis was associated with an increasing repetition risk (OR = 2.02, p < .01). The delivery of a preventive programme reduced the repetition risk, OR = 0.76, p < .05; however, this effect was significant for psychotherapy interventions, OR = 0.38, p < .01. CONCLUSION: One in five suicide attempters will engage in a new suicide attempt. An elevated repetition risk is associated with being female, more severe index methods and psychiatric disorder diagnosis. Preventive programmes, particularly psychotherapy, may contribute to reducing repetition risk and eventually save lives.


Asunto(s)
Psicoterapia , Intento de Suicidio , Humanos , Femenino , Masculino , Intento de Suicidio/prevención & control , Factores de Riesgo
6.
Br J Pharmacol ; 180(4): 459-478, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36181002

RESUMEN

BACKGROUND AND PURPOSE: Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil ß1 adrenoceptors (ß1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that ß1AR blockade will improve stroke outcomes. EXPERIMENTAL APPROACH: Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective ß1AR blocker metoprolol (12.5 mg·kg-1 ) when injected i.v. 10 min before reperfusion. KEY RESULTS: Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1+ ). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via ß1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil-depleted rats upon stroke. In patients suffering an ischaemic stroke, ß1AR blockade by metoprolol reduced circulating neutrophil-platelet co-aggregates. CONCLUSIONS AND IMPLICATIONS: Our findings describe that ß1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratas , Animales , Metoprolol/farmacología , Metoprolol/uso terapéutico , Metoprolol/metabolismo , Neutrófilos/metabolismo , Enfermedades Neuroinflamatorias , Isquemia Encefálica/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Receptores Adrenérgicos/metabolismo
7.
Artículo en Inglés | MEDLINE | ID: mdl-35836474

RESUMEN

Introduction: Paediatric and adult psychiatric emergency department (ED) visits decreased during the initial COVID-19 outbreak. Long-term consequences of the COVID-19 pandemic will include increases in mental healthcare needs, especially among vulnerable groups such as children and adolescents. Aim: This study examined changes in the number of overall and diagnosis-specific mental health ED visits among patients aged <18 years following the onset of the COVID-19 pandemic in Madrid, Spain. Methods: Using clinical records from all psychiatric ED visits at a major teaching hospital between October 2018 and April 2021, we conducted interrupted time-series analyses and compared trends before and after the day of the first ED COVID-19 case (1st March 2020). Results: A total of 663 patients were included. In March 2020, there was a marked initial decrease of -12.8 (95% CI -21.9, - 7.9) less monthly mental health ED visits. After April 2020, there was a subsequent increasing trend of 3.4 (95% CI 2.6, 4.2) additional monthly mental health ED visits. Conclusion: After the onset of the COVID-19 pandemic, there was an increase in paediatric psychiatric ED visits, especially due to suicide-related reasons. These data reinforce the crucial role of the ED in the management of acute mental health problems among youth and highlight the need for renovated efforts to enhance access to care outside of and during acute crises during the pandemic and its aftermath.

8.
BMC Geriatr ; 22(1): 114, 2022 02 10.
Artículo en Inglés | MEDLINE | ID: mdl-35144558

RESUMEN

BACKGROUND: Although medication poisoning in older adults is considered an increasingly important, but preventable cause of death, it has received relatively little attention. We explored recent trends and correlates of suicidal and accidental fatal drug poisonings among older and working-age individuals using nationwide data from Spain. METHODS: We identified all 15,353 fatal drug poisonings involving decedents aged ≥15 years in Spain between 2000 and 2018 and divided them by age into older adults (≥65 years) and working-age (15-64 years) individuals. For each age group, we analyzed time trends in suicidal and accidental fatal drug poisoning rates (overall and by ICD-10 drug categories) using joinpoint regressions. To understand the specific drugs classified as "Non-psychotropic/non-specified", we used 2018 data including substance-specific ICD-10 supplementary codes. We explored relevant sociodemographic correlates of suicidal and accidental fatal poisoning rates using multivariable negative binomial regressions. RESULTS: Between 2000 and 2018, suicidal fatal poisonings increased faster among older (from 0.19 to 0.63 per 100,000 - average annual change: 7.7%) than working-age individuals (from 0.40 to 0.72 per 100,000 - average annual change: 3.8%). Accidental fatal poisonings increased among older adults (from 0.25 to 2.67 per 100,000 - average annual change: 16.2%) but decreased among working-age counterparts (from 2.38 to 1.42 per 100,000 - average annual change: - 1.9%). Anticoagulants and cardiac-stimulants glycosides accounted for 70% of the 223 accidental fatal poisonings due to non-psychotropic/non-specified drugs registered among older adults in 2018. Roles of gender and urban dwelling in suicidal and accidental poisonings were heterogeneous across age groups. CONCLUSION: Increases in suicidal drug poisonings were faster among older than working-age individuals. Accidental fatal poisonings increased only among older adults. Our findings that (i) sociodemographic correlates were heterogeneous across age groups and (ii) anticoagulant and cardiac-stimulant glycosides were particularly salient drivers of accidental poisonings among older adults have implications for prevention.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Ideación Suicida , Anciano , Humanos , Clasificación Internacional de Enfermedades , Psicotrópicos , España/epidemiología
9.
J Colloid Interface Sci ; 613: 447-460, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35051720

RESUMEN

Stimuli-responsive nanomaterials are very attractive for biomedical applications. They can be activated through external stimuli or by the physico-chemical conditions present in cells or tissues. Here, we describe the preparation of hybrid iron oxide-manganese oxide core-satellite shell nanostructures that change their contrast mode in magnetic resonance imaging (MRI) from T2 to T1, after being internalized by cells. This occurs by the dissolution of the MnO2 of the shell, preserving intact the iron oxide at the core. First, we study the seeded-growth synthesis of iron oxide-manganese oxide nanoparticles studying the effect of varying the core size of the magnetic seeds and the concentration of the surfactant. This allows tuning the size and shape of the final hybrid nanostructure. Then, we show that the shell can be removed by a redox reaction with glutathione, which is naturally present inside the cells at much higher concentrations than outside the cells. Finally, the dissolution of the MnO2 shell and the change in the contrast mode is confirmed in cell cultures. After this process, the iron oxide nanoparticles at the core remain intact and are still active as heating mediators when an alternating magnetic field is applied.


Asunto(s)
Compuestos de Manganeso , Nanopartículas , Compuestos Férricos , Imagen por Resonancia Magnética , Óxidos
10.
J Affect Disord ; 300: 532-539, 2022 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-34998806

RESUMEN

BACKGROUND: Suicide rates in Spain remained stable during the early 21st century. Suicide rates among specific socially vulnerable groups, however, remain unknown, and there are no data on suicide mortality rates and trends among migrants living in Spain. METHODS: We analyzed Spain's 2000-2019 suicide mortality data by migration status (native- vs. foreign-born), examining crude and age-standardized rates and trends overall and by sex, age-group, suicide method, Spanish citizenship status, and country of origin, using joinpoint regression models. RESULTS: Annual crude suicide mortality rates were higher among native- than foreign-born individuals (9.2 versus 6.2 por 100.000 inhabitants, respectively). While suicide rates decreased among native-born men and remained roughly stable among native-born women - with slight decreases among older native-born women, they increased after 2010 among foreign-born men aged 15-44 and ≥65 years and foreign-born women aged ≥65 years. Increases in suicide trends among foreign-born residents in Spain were largely driven by increases specific to individuals without Spanish citizenship. LIMITATIONS: Suicide mortality data are subject to potential errors due to underreporting of suicide in death certificates CONCLUSIONS: Between 2010-2019, suicide in Spain increased only among foreign-born residents. These findings should enhance our understanding of the dynamics and potential actionable causes of suicide among migrants living in Spain.


Asunto(s)
Emigrantes e Inmigrantes , Mortalidad , Suicidio , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Adulto Joven , Emigrantes e Inmigrantes/estadística & datos numéricos , Internacionalidad , Mortalidad/tendencias , España/epidemiología , Suicidio/estadística & datos numéricos , Pueblo Europeo/estadística & datos numéricos , Ciudadanía
11.
Mol Genet Metab ; 133(3): 242-249, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-34083144

RESUMEN

CONTEXT: The clinical and laboratory features of dominant acute hepatic porphyrias (AHPs) in prepubertal children and adolescents have not been well established. OBJECTIVE: To evaluate clinical and laboratory features of AHPs in prepubertal children and adolescents compared to adults. DATA SOURCES: OVID (Embase Classic+Embase and MEDLINE), Scopus, and Google Scholar. STUDY SELECTION: Studies describing symptomatic children or adolescents (<18 years old) with increased urinary porphobilinogen were included. DATA EXTRACTION: Two reviewers independently extracted the data, with a third reviewer arbitrating discrepancies. RESULTS: 100 studies were included describing 112 patients (26 prepubertal children and 86 adolescents). Differences were found between prepubertal children and adolescents regarding sex distribution (female-to-male ratio: 1:2 vs. 4:1), clinical manifestations, and concomitant clinical manifestations. LIMITATIONS: There was variation in the methods used to diagnose porphyria attacks across studies, and some elements of the quality of individual studies were unclear. CONCLUSIONS: Prepubertal children with AHPs and porphyria attacks presented with distinct demographic and clinical characteristics from adolescents and adults. Nearly two-thirds of the affected children were males, and about half had a concomitant medical condition that can constitutively upregulate hepatic δ-aminolevulinic acid synthase-1. Adolescents were comparable to adults in almost all respects.


Asunto(s)
Porfobilinógeno Sintasa/deficiencia , Porfirias Hepáticas/diagnóstico , Porfirias Hepáticas/fisiopatología , Adolescente , Adulto , Niño , Femenino , Humanos , Hígado/patología , Masculino , Distribución por Sexo
12.
PLoS One ; 16(5): e0251454, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33984015

RESUMEN

In both clinical and preclinical scenarios, 2-deoxy-2[18F]fluoro-D-glucose ([18F]FDG) is the radiotracer most widely used to study brain glucose metabolism with positron emission tomography (PET). In clinical practice, there is a worldwide standardized protocol for preparing patients for [18F]FDG-PET studies, which specifies the room lighting. However, this standard is typically not observed in the preclinical field, although it is well known that animal handling affects the biodistribution of [18F]FDG. The present study aimed to evaluate the effect of ambient lighting on brain [18F]FDG uptake in mice. Two [18F]FDG-PET studies were performed on each animal, one in light and one in dark conditions. Thermal video recordings were acquired to analyse animal motor activity in both conditions. [18F]FDG-PET images were analysed with the Statistical Parametric Mapping method. The results showed that [18F]FDG uptake is higher in darkness than in light condition in mouse nucleus accumbens, hippocampus, midbrain, hindbrain, and cerebellum. The SPM analysis also showed an interaction between the illumination condition and the sex of the animal. Mouse activity was significantly different (p = 0.01) between light conditions (632 ± 215 s of movement) and dark conditions (989 ± 200 s), without significant effect of sex (p = 0.416). We concluded that room illumination conditions during [18F]FDG uptake in mice affected the brain [18F]FDG biodistribution. Therefore, we highlight the importance to control this factor to ensure more reliable and reproducible mouse brain [18F]FDG-PET results.


Asunto(s)
Encéfalo/metabolismo , Fluorodesoxiglucosa F18/metabolismo , Iluminación , Tomografía de Emisión de Positrones , Animales , Transporte Biológico , Femenino , Fluorodesoxiglucosa F18/análisis , Luz , Masculino , Ratones , Ratones Endogámicos C57BL , Tomografía de Emisión de Positrones/métodos , Distribución Tisular
13.
Cardiovasc Res ; 117(3): 876-889, 2021 02 22.
Artículo en Inglés | MEDLINE | ID: mdl-32346730

RESUMEN

AIMS: Human influenza A virus (hIAV) infection is associated with important cardiovascular complications, although cardiac infection pathophysiology is poorly understood. We aimed to study the ability of hIAV of different pathogenicity to infect the mouse heart, and establish the relationship between the infective capacity and the associated in vivo, cellular and molecular alterations. METHODS AND RESULTS: We evaluated lung and heart viral titres in mice infected with either one of several hIAV strains inoculated intranasally. 3D reconstructions of infected cardiac tissue were used to identify viral proteins inside mouse cardiomyocytes, Purkinje cells, and cardiac vessels. Viral replication was measured in mouse cultured cardiomyocytes. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to confirm infection and study underlying molecular alterations associated with the in vivo electrophysiological phenotype. Pathogenic and attenuated hIAV strains infected and replicated in cardiomyocytes, Purkinje cells, and hiPSC-CMs. The infection was also present in cardiac endothelial cells. Remarkably, lung viral titres did not statistically correlate with viral titres in the mouse heart. The highly pathogenic human recombinant virus PAmut showed faster replication, higher level of inflammatory cytokines in cardiac tissue and higher viral titres in cardiac HL-1 mouse cells and hiPSC-CMs compared with PB2mut-attenuated virus. Correspondingly, cardiac conduction alterations were especially pronounced in PAmut-infected mice, associated with high mortality rates, compared with PB2mut-infected animals. Consistently, connexin43 and NaV1.5 expression decreased acutely in hiPSC-CMs infected with PAmut virus. YEM1L protease also decreased more rapidly and to lower levels in PAmut-infected hiPSC-CMs compared with PB2mut-infected cells, consistent with mitochondrial dysfunction. Human IAV infection did not increase myocardial fibrosis at 4-day post-infection, although PAmut-infected mice showed an early increase in mRNAs expression of lysyl oxidase. CONCLUSION: Human IAV can infect the heart and cardiac-specific conduction system, which may contribute to cardiac complications and premature death.


Asunto(s)
Alphainfluenzavirus/patogenicidad , Sistema de Conducción Cardíaco/virología , Miocarditis/virología , Infecciones por Orthomyxoviridae/virología , Animales , Conexinas/genética , Citocinas/metabolismo , Modelos Animales de Enfermedad , Perros , Matriz Extracelular/metabolismo , Matriz Extracelular/virología , Femenino , Fibrosis , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Sistema de Conducción Cardíaco/metabolismo , Sistema de Conducción Cardíaco/patología , Interacciones Huésped-Patógeno , Humanos , Mediadores de Inflamación/metabolismo , Alphainfluenzavirus/genética , Alphainfluenzavirus/crecimiento & desarrollo , Cinética , Pulmón/virología , Células de Riñón Canino Madin Darby , Ratones Endogámicos BALB C , Ratones Transgénicos , Mutación , Miocarditis/metabolismo , Miocarditis/patología , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/virología , Infecciones por Orthomyxoviridae/metabolismo , Infecciones por Orthomyxoviridae/patología , Ramos Subendocárdicos/metabolismo , Ramos Subendocárdicos/virología , Carga Viral , Virulencia , Replicación Viral , Proteína alfa-5 de Unión Comunicante
15.
Int J Mol Sci ; 21(20)2020 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-33092303

RESUMEN

Mutations in the EPM2A and EPM2B genes, encoding laforin and malin proteins respectively, are responsible for Lafora disease, a fatal form of progressive myoclonus epilepsy with autosomal recessive inheritance. Neuroimaging studies of patients with Lafora disease have shown different degrees of brain atrophy, decreased glucose brain uptake and alterations on different brain metabolites mainly in the frontal cortex, basal ganglia and cerebellum. Mice deficient for laforin and malin present many features similar to those observed in patients, including cognitive, motor, histological and epileptic hallmarks. We describe the neuroimaging features found in two mouse models of Lafora disease. We found altered volumetric values in the cerebral cortex, hippocampus, basal ganglia and cerebellum using magnetic resonance imaging (MRI). Positron emission tomography (PET) of the cerebral cortex, hippocampus and cerebellum of Epm2a-/- mice revealed abnormal glucose uptake, although no alterations in Epm2b-/- mice were observed. Magnetic resonance spectroscopy (MRS) revealed significant changes in the concentration of several brain metabolites, including N-acetylaspartate (NAA), in agreement with previously described findings in patients. These data may provide new insights into disease mechanisms that may be of value for developing new biomarkers for diagnosis, prevention and treatment of Lafora disease using animal models.


Asunto(s)
Encefalopatías/metabolismo , Encéfalo/anomalías , Modelos Animales de Enfermedad , Enfermedad de Lafora/metabolismo , Proteínas Tirosina Fosfatasas no Receptoras/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Atrofia , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/metabolismo , Ganglios Basales/patología , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Encefalopatías/genética , Encefalopatías/patología , Cerebelo/diagnóstico por imagen , Cerebelo/metabolismo , Cerebelo/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Glucosa/metabolismo , Hipocampo/diagnóstico por imagen , Hipocampo/metabolismo , Hipocampo/patología , Humanos , Enfermedad de Lafora/genética , Enfermedad de Lafora/patología , Imagen por Resonancia Magnética/métodos , Ratones Noqueados , Mutación , Tomografía de Emisión de Positrones/métodos , Proteínas Tirosina Fosfatasas no Receptoras/genética , Ubiquitina-Proteína Ligasas/genética
17.
Curr Top Behav Neurosci ; 46: 1-23, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32860592

RESUMEN

Suicide, a major public health concern, takes around 800,000 lives globally every year and is the second leading cause of death among adolescents and young adults. Despite substantial prevention efforts, between 1999 and 2017, suicide and nonfatal self-injury rates have experienced unprecedented increases across the United States - as well as in many other countries in the world. This chapter reviews the existing evidence on the causes behind increased suicide rates and critically evaluates the impact of a range of innovative approaches to suicide prevention. First, we briefly describe current trends in suicide and suicidal behaviors and relate them to recent time trends in relevant suicide risk markers. Then, we review the existing evidence in suicide prevention at the individual and the population levels, including new approaches that are currently under development. Finally, we advocate for a new generation of suicide research that examines causal factors beyond the proximal and clinical and fosters a socially conscious reimagining of suicidal prevention. To this end, we emphasize the need for the conceptualization of suicide and suicidal behaviors as complex phenomena with causes at several levels of organization. Future interdisciplinary research and interventions should be developed within a multilevel causal framework that can better capture the social, economic, and political settings where suicide, as a process, unfolds across the life course.


Asunto(s)
Conducta Autodestructiva , Prevención del Suicidio , Adolescente , Humanos , Estados Unidos/epidemiología , Adulto Joven
19.
Top Curr Chem (Cham) ; 378(1): 15, 2020 Jan 14.
Artículo en Inglés | MEDLINE | ID: mdl-31938922

RESUMEN

Nowadays, biomaterials have become a crucial element in numerous biomedical, preclinical, and clinical applications. The use of nanoparticles entails a great potential in these fields mainly because of the high ratio of surface atoms that modify the physicochemical properties and increases the chemical reactivity. Among them, carbon nanotubes (CNTs) have emerged as a powerful tool to improve biomedical approaches in the management of numerous diseases. CNTs have an excellent ability to penetrate cell membranes, and the sp2 hybridization of all carbons enables their functionalization with almost every biomolecule or compound, allowing them to target cells and deliver drugs under the appropriate environmental stimuli. Besides, in the new promising field of artificial biomaterial generation, nanotubes are studied as the load in nanocomposite materials, improving their mechanical and electrical properties, or even for direct use as scaffolds in body tissue manufacturing. Nevertheless, despite their beneficial contributions, some major concerns need to be solved to boost the clinical development of CNTs, including poor solubility in water, low biodegradability and dispersivity, and toxicity problems associated with CNTs' interaction with biomolecules in tissues and organs, including the possible effects in the proteome and genome. This review performs a wide literature analysis to present the main and latest advances in the optimal design and characterization of carbon nanotubes with biomedical applications, and their capacities in different areas of preclinical research.


Asunto(s)
Nanomedicina/métodos , Nanotecnología/métodos , Nanotubos de Carbono/análisis , Animales , Humanos , Modelos Moleculares , Nanotubos de Carbono/toxicidad , Nanotubos de Carbono/ultraestructura
20.
J Cancer Surviv ; 14(3): 377-385, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-31933151

RESUMEN

PURPOSE: To compare the differences in lifestyle behaviours between cancer survivors (CSs) and cancer-free participants in a large and representative population-based cohort. METHODS: We included 115,257 adults from the Lifelines cohort. Cancer status was self-reported, and health behaviours were measured (e.g. body mass index [BMI]) or assessed by questionnaire (e.g. physical activity, smoking, alcohol consumption, sedentary behaviour and diet). The data were then categorised for logistic regression analysis, stratified and adjusted by sex and age (< 55 vs ≥ 55 years). RESULTS: CSs (5473; 4.7%) were diagnosed 9 ± 8.5 years before data collection, were older (mean age 55.4 vs 44.4 years) and more often female (66.6% vs 33.4%) than the cancer-free participants. They were also more likely to be physically active and to have a better diet, and also less likely to be alcohol drinkers; but, were more likely to have a higher BMI, be former smokers and to be sedentary. After adjustment for sex and age, however, BMI was more likely to be normal, physical activity was more likely to be higher and smoking to be prevalent in CSs. Current smoking was also significantly higher among females and those aged < 55 years who were CSs than for those with no history of cancer. CONCLUSIONS: In this population-based cohort, CSs have health behaviour comparable to those without a cancer diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Smoking cessation strategies should target all CSs, but efforts could yield greatest benefit if they target females and those younger than 55 years.


Asunto(s)
Supervivientes de Cáncer/estadística & datos numéricos , Conductas Relacionadas con la Salud/fisiología , Neoplasias/mortalidad , Adulto , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad
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