RESUMEN
Plants accumulate hundreds of thousands of specialized metabolites that participate in their interactions with the environment. Among these compounds, phenolics represent a large class, and they play important physiological roles, such as providing a first barrier against pathogens, cues to pollinators, and radiation protection. Maize is one of the most important crops worldwide for food, animal feed, and biofuels, and it has the potential to accumulate different phenolics in vegetative tissues as well as in seeds. Recent studies have identified a large number of phenolic compounds-with a diversity of chemical decorations-in different maize tissues, but these likely represent just a fraction of the metabolic diversity of maize. In this protocol, we describe a specific method for the extraction and quantification of maize phenolic compounds by ultra-high-pressure liquid chromatography-tandem multiple reaction monitoring mass spectrometry (UHPLC-MRM-MS/MS) analysis. We provide detailed instructions for the extraction of phenolics using acidic methanol, and for the quantification of 33 different compounds in maize stems, including flavonoids, phenolic acids, and lignin precursors.
RESUMEN
Anthocyanins are flavonoid pigments that accumulate in fruits and flowers that serve as attractants for pollinators and seed-dispersing organisms. Anthocyanins exhibit diverse chemical structures, characterized both by different anthocyanidin core structures and numerous chemical modifications of the anthocyanidin core. Here, we describe a protocol for the extraction and quantification of total anthocyanins, as well as for the characterization of anthocyanidin core structures and specific anthocyanins, using a spectrophotometer, high-performance liquid chromatography (HPLC), and ultra-high-performance liquid chromatography-two-dimensional mass spectrometry (UHPLC-MS/MS). The method involves anthocyanin extraction using acidic methanol, anthocyanin quantification using a spectrophotometer, determination of anthocyanidin core structure from hydrolyzed anthocyanin extracts using UHPLC-MS/MS, separation of different anthocyanins using HPLC, and characterization of specific anthocyanins using UHPLC-MS/MS. As an example, we describe how we have used this protocol to extract and quantify total anthocyanins from maize leaves, identify cyanidin as the core anthocyanidin structure, and characterize three specific anthocyanins that accumulate in maize leaves, each having a cyanidin core with decorations of a hexose group, and a malonyl or coumaroyl moiety.
RESUMEN
Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by the aggregation of α-Synuclein (αSYN) building up intraneuronal inclusions termed Lewy pathology. Mounting evidence suggests that neuron-released αSYN aggregates could be central to microglial activation, which in turn mounts and orchestrates neuroinflammatory processes potentially harmful to neurons. Therefore, understanding the mechanisms that drive microglial cell activation, polarization and function in PD might have important therapeutic implications. Here, using primary microglia, we investigated the inflammatory potential of pure αSYN fibrils derived from PD patients. We further explored and characterized microglial cell responses to a chronic-type inflammatory stimulation combining PD patient-derived αSYN fibrils (FPD), Tumor necrosis factor-α (TNFα) and prostaglandin E2 (PGE2) (TPFPD). We showed that FPD hold stronger inflammatory potency than pure αSYN fibrils generated de novo. When combined with TNFα and PGE2, FPD polarizes microglia toward a particular functional phenotype departing from FPD-treated cells and featuring lower inflammatory cytokine and higher glutamate release. Whereas metabolomic studies showed that TPFPD-exposed microglia were closely related to classically activated M1 proinflammatory cells, notably with similar tricarboxylic acid cycle disruption, transcriptomic analysis revealed that TPFPD-activated microglia assume a unique molecular signature highlighting upregulation of genes involved in glutathione and iron metabolisms. In particular, TPFPD-specific upregulation of Slc7a11 (which encodes the cystine-glutamate antiporter xCT) was consistent with the increased glutamate response and cytotoxic activity of these cells toward midbrain dopaminergic neurons in vitro. Together, these data further extend the structure-pathological relationship of αSYN fibrillar polymorphs to their innate immune properties and demonstrate that PD-derived αSYN fibrils, TNFα and PGE2 act in concert to drive microglial cell activation toward a specific and highly neurotoxic chronic-type inflammatory phenotype characterized by robust glutamate release and iron retention.
Asunto(s)
Síndromes de Neurotoxicidad , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/patología , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Microglía/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Señales (Psicología) , Inflamación/metabolismo , Neuronas Dopaminérgicas/patología , Síndromes de Neurotoxicidad/metabolismo , Glutamatos/metabolismo , Hierro/metabolismoRESUMEN
BACKGROUND: The burden of disease of diabetes in Colombia have increased in the last decades. Secondary prevention is crucial for diabetes control. Many patients already treated remain with poor glycemic control and without timely and appropriate treatment intensification. This has been called in the literature as Clinical Inertia. Updated information regarding clinical inertia based on the Colombian diabetes treatment guidelines is needed. OBJECTIVE: To measure the prevalence of clinical inertia in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients in healthcare institutions in Colombia, based on the recommendations of the current official guidelines. METHODS: An observational and retrospective cohort study based on databases of two Health Medical Organizations (HMOs) in Colombia (one from subsidized regimen and one from contributory regimen) was conducted. Descriptive analysis was performed to summarize demographic and clinical information. Chi-square tests were used to assess associations between variables of interest. RESULTS: A total of 616 patients with T2DM (308 for each regimen) were included. Median age was 61 years. Overall clinical inertia was 93.5% (87.0% in contributory regimen and 100% in subsidized regimen). Patients with Hb1Ac ≥ 8% in the subsidized regimen were more likely to receive monotherapy than patients in the contributory regimen (OR 2.33; 95% CI 1.41-3.86). CONCLUSIONS: In this study, the prevalence of overall clinical inertia was higher in the subsidized regime than in the contributory regime (100% vs 87%). Great efforts have been made to equalize the coverage between the two systems, but this finding is worrisome with respect to the difference in quality of the health care provided to these two populations. This information may help payers and clinicians to streamline strategies for reducing clinical inertia and improve patient outcomes.
RESUMEN
Several studies have examined the association of externalizing polygenic scores (PGS) with externalizing symptoms in samples of European ancestry. However, less is known about the associations of externalizing polygenic vulnerability in relation to phenotypic externalizing disorders among individuals of different ancestries, such as Mexican youth. Here, we leveraged the largest genome-wide association study on externalizing behaviors that included over 1 million individuals of European ancestry to examine associations of externalizing PGS with a range of externalizing disorders in Mexican adolescents, and investigated whether adversity exposure in childhood moderated these associations. Participants (N = 1064; age range 12-17 years old; 58.8% female) were adolescents recruited for a general population survey on adolescent mental health in the Mexico City Metropolitan region and were genotyped. Childhood adversity exposure and externalizing disorders, specifically attention-deficit hyperactivity disorder (ADHD), conduct disorder, oppositional defiant disorder, and substance use disorder, were assessed via the computer-assisted World Mental Health Composite International Diagnostic Interview for adolescents. A greater externalizing PGS was associated with a greater odds of any externalizing disorder (OR = 1.29 [1.12, 1.48]; p < 0.01) and ADHD (OR = 1.40 [1.15, 1.70]; p < 0.01) in the whole sample, and in females in particular. There were no main effects of the externalizing PGS on conduct disorder, oppositional defiant disorder, or substance use disorder, nor did adversity exposure moderate these associations. Our results suggest that greater genetic propensity for externalizing disorders is associated with increased odds of any externalizing disorders and ADHD among Mexican adolescents, furthering our understanding of externalizing disorder manifestation in this population.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastorno de la Conducta , Trastornos Relacionados con Sustancias , Humanos , Adolescente , Femenino , Niño , Masculino , Estudio de Asociación del Genoma Completo , México , Trastorno de la Conducta/epidemiología , Trastorno de la Conducta/genética , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/genética , Trastornos Relacionados con Sustancias/complicacionesRESUMEN
To evaluate the osteogenic potential of platelet-rich fibrin (PRF) and low-level laser therapy (LLLT) on human stem cells from the apical papilla (SCAP) we isolated, characterized, and then cultured in an osteogenic medium cells with PRF and/or LLLT (660 nm, 6 J/m2-irradiation). Osteogenic differentiation was assessed by bone nodule formation and expression of bone morphogenetic proteins (BMP-2 and BMP-4), whereas the molecular mechanisms were achieved by qRT-PCR and RNA-seq analysis. Statistical analysis was performed by ANOVA and Tukey's post hoc tests (p < 0.05* and p < 0.01**). Although PRF and LLLT increased bone nodule formation after 7 days and peaked at 21 days, the combination of PRF + LLLT led to the uppermost nodule formation. This was supported by increased levels of BMP-2 and -4 osteogenic proteins (p < 0.005). Furthermore, the PRF + LLLT relative expression of specific genes involved in osteogenesis, such as osteocalcin, was 2.4- (p = 0.03) and 28.3- (p = 0.001) fold higher compared to the PRF and LLLT groups, and osteopontin was 22.9- and 1.23-fold higher, respectively (p < 0.05), after 7 days of interaction. The transcriptomic profile revealed that the combination of PRF + LLLT induces MSX1, TGFB1, and SMAD1 expression, after 21 days of osteogenic differentiation conditions exposition. More studies are required to understand the complete cellular and molecular mechanisms of PRF plus LLLT on stem cells. Overall, we demonstrated for the first time that the combination of PRF and LLLT would be an excellent therapeutic tool that can be employed for dental, oral, and craniofacial repair and other tissue engineering applications.
Asunto(s)
Osteogénesis , Fibrina Rica en Plaquetas , Humanos , Fibrina Rica en Plaquetas/metabolismo , Proliferación Celular , Células Cultivadas , Células Madre , Diferenciación Celular , Rayos LáserRESUMEN
The recruitment of participants for research studies may be subject to bias. The Prospective Imaging Study of Ageing (PISA) aims to characterize the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). Participants approached to take part in PISA were selected from existing cohort studies with available genomewide genetic data for both successfully and unsuccessfully recruited participants, allowing us to investigate the genetic contribution to voluntary recruitment, including the genetic predisposition to AD. We use a polygenic risk score (PRS) approach to test to what extent the genetic risk for AD, and related risk factors predict participation in PISA. We did not identify a significant association of genetic risk for AD with study participation, but we did identify significant associations with PRS for key causal risk factors for AD, IQ, household income and years of education. We also found that older and female participants were more likely to take part in the study. Our findings highlight the importance of considering bias in key risk factors for AD in the recruitment of individuals for cohort studies.
Asunto(s)
Enfermedad de Alzheimer , Envejecimiento Cognitivo , Adulto , Humanos , Femenino , Enfermedad de Alzheimer/genética , Predisposición Genética a la Enfermedad , Estudios Prospectivos , Australia/epidemiología , FenotipoRESUMEN
Objective: Intestinal failure refers to a reduction in intestinal function that necessitates intravenous supplementation of macronutrients, water, or electrolytes due to the intestine's inability to absorb these substances adequately to maintain health and growth. This study aims to explore the experiences and challenges faced by patients enrolled in the intestinal rehabilitation program at Hospital Pablo Tobón Uribe in Medellín. Methodology: This qualitative study adopts a hermeneutic approach and utilizes grounded theory techniques. The sampling process involved both selective and theoretical sampling. A total of 20 semi-structured interviews were conducted, with eight interviews including contributions from family members. The data analysis commenced with open coding, followed by the grouping of codes into descriptive categories. Dimensions and properties were identified within these categories, and analytical categories were subsequently developed through axial and selective coding. This iterative process led to the emergence of the final paradigm matrix. Results: The study revealed that the healthcare system inadequately addresses the needs and expectations of patients with intestinal failure, leading to increased uncertainty about the disease's origin and future prognosis. Intestinal failure and its treatment disrupt various aspects of patients' lives, including personal, family, and work domains. Social stigmatization and rejection are prominent, underscoring the importance of support from family and close individuals in facilitating adaptation and revaluing life. Conclusions: Coping with the challenges of intestinal failure entails embracing the necessity of relying on parenteral nutrition, which is perceived as a prison that paradoxically enables survival.
Objetivo: la insuficiencia intestinal es la reducción de la función intestinal que requiere la suplementación intravenosa de macronutrientes, agua o electrolitos, pues el intestino no logra la absorción mínima para mantener la salud y el crecimiento. El objetivo es comprender el significado que tiene afrontar la condición de insuficiencia intestinal en pacientes que pertenecen al programa de rehabilitación intestinal del Hospital Pablo Tobón Uribe de Medellín. Metodología: estudio cualitativo con enfoque hermenéutico que utilizó técnicas de la teoría fundamentada. El muestreo fue primero selectivo y luego teórico. Se realizó un total de 20 entrevistas semiestructuradas; 8 de las cuales tuvieron el aporte de familiares. El análisis inició por la codificación abierta. Los códigos obtenidos se agruparon en categorías descriptivas, y en ellas se identificaron dimensiones y propiedades que se utilizaron para elaborar categorías analíticas mediante la codificación axial y selectiva que permitió emerger la matriz del paradigma final. Resultados: las necesidades y expectativas de los pacientes con insuficiencia intestinal no son suficientemente atendidas por el sistema de salud, lo que genera mayor incertidumbre sobre el origen de la enfermedad y aún más sobre su futuro. La insuficiencia intestinal y su tratamiento trastornan la vida personal, familiar y laboral. El rechazo social es marcado, por lo que el apoyo familiar y de las personas cercanas es fundamental para lograr la adaptación que les permite revalorar la vida. Conclusiones: afrontar la condición de insuficiencia intestinal representa la experiencia de requerir necesariamente de nutrición parenteral, la cual se percibe como una prisión que paradójicamente permite sobrevivir.
Asunto(s)
COVID-19 , SARS-CoV-2 , Niño , Humanos , Salud Pública , COVID-19/epidemiología , Estudios Retrospectivos , Colombia/epidemiologíaRESUMEN
Samples can be prone to ascertainment and attrition biases. The Australian Genetics of Depression Study is a large publicly recruited cohort (n = 20,689) established to increase the understanding of depression and antidepressant treatment response. This study investigates differences between participants who donated a saliva sample or agreed to linkage of their records compared to those who did not. We observed that older, male participants with higher education were more likely to donate a saliva sample. Self-reported bipolar disorder, ADHD, panic disorder, PTSD, substance use disorder, and social anxiety disorder were associated with lower odds of donating a saliva sample, whereas anorexia was associated with higher odds of donation. Male and younger participants showed higher odds of agreeing to record linkage. Participants with higher neuroticism scores and those with a history of bipolar disorder were also more likely to agree to record linkage whereas participants with a diagnosis of anorexia were less likely to agree. Increased likelihood of consent was associated with increased genetic susceptibility to anorexia and reduced genetic risk for depression, and schizophrenia. Overall, our results show moderate differences among these subsamples. Most current epidemiological studies do not search for attrition biases at the genetic level. The possibility to do so is a strength of samples such as the AGDS. Our results suggest that analyses can be made more robust by identifying attrition biases both on the phenotypic and genetic level, and either contextualising them as a potential limitation or performing sensitivity analyses adjusting for them.
Asunto(s)
Anorexia , Depresión , Humanos , Masculino , Depresión/epidemiología , Depresión/genética , Australia , Consentimiento Informado , ADNRESUMEN
INTRODUCTION: Assisted suicide and euthanasia are controversial issues today and have been throughout the history of humanity, mainly because there are individuals for and against them. Currently, the legalization of these practices is being discussed in Chile, and the perception of physicians regarding this issue is unknown. Therefore, this study aimed to assess physicians' perception of Chile's euthanasia and assisted suicide. METHODS: A nationwide cross-sectional study was carried out in Chile. A questionnaire of physicians' attitudes and opinions on assisted suicide and euthanasia was used. The population was the doctors who work in Chile, and the sample was convenient with a sample calculation of 384 physicians. About 20 variables were considered and included in a form created through the Google forms option, which was distributed through social networks: LinkedIn, Facebook, Twitter, and WhatsApp. To guarantee the anonymity of the participants, the option to request and remember the participant's email was deactivated. A generated database allowed the quantitative analysis of the variables and their expression through frequencies, percentages, and graphs. The European University of the Atlantic's research ethics committee approved this study as stated in the document CE-55 of March 2021. RESULTS: A total of 410 physicians were surveyed. 50.7% (n = 208) of the participants identified themselves as men, and 69.8% (n = 286) were Chilean. The city of Santiago was the area of residence of 72.9% (n = 299) of the participants. About 34.6% (n = 142) of participants were general practitioners, and 39.3% (n = 161) of the physicians had more than 20 years of experience. About 68.7% had favorable attitudes toward euthanasia and 54.4% toward assisted suicide; However, although the majority favored legalizing euthanasia and assisted suicide, approximately 48.8% stated that they would not participate in an assisted suicide procedure. CONCLUSIONS: There was evidence of support for the implementation and legalization of euthanasia and assisted suicide by physicians in Chile. However, there are still professionals who have not yet decided on a definitive position on these practices.
Asunto(s)
Eutanasia , Médicos , Suicidio Asistido , Actitud del Personal de Salud , Chile , Estudios Transversales , Humanos , Masculino , PercepciónRESUMEN
The persistence of erythrocytes infected with Plasmodium falciparum gametocytes in the bloodstream is closely related to the modulation of their mechanical properties. New drugs that increase the stiffness of infected erythrocytes may thus represent a novel approach to block malaria parasite transmission. The phosphodiesterase inhibitor tadalafil has been shown to impair the ability of infected erythrocytes to circulate in an in vitro model for splenic retention. Here, we used a humanized mouse model to address in vivo the effect of tadalafil on the circulation kinetics of mature gametocyte-infected erythrocytes. We show that stiff immature gametocyte-infected erythrocytes are retained in the spleen of humanized mice at rates comparable to that of the in vitro model. Accordingly, tadalafil-induced stiffening of mature gametocyte-infected erythrocytes impairs their circulation in the bloodstream and triggers their retention by the spleen. These in vivo results validate that tadalafil is a novel drug lead potentially capable of blocking malaria parasite transmission by targeting GIE mechanical properties.
Asunto(s)
Malaria Falciparum , Plasmodium falciparum , Animales , Malaria Falciparum/tratamiento farmacológico , Malaria Falciparum/parasitología , Ratones , Inhibidores de Fosfodiesterasa , Bazo , Tadalafilo/farmacologíaRESUMEN
El avance en materia de derechos humanos es indispensable durante el desarrollo de políticas públicas en salud y marcos legales que garanticen el cuidado integro de la salud; la eutanasia y suicidio asistido siguen siendo conceptos ampliamente discutidos desde la medicina, y especialmente en la bioética por el peso que poseen en la toma de decisiones del paciente terminal y cuidados paliativos. Estos términos, su uso, aprobación y regulación legal dependen de la influencia de diversos determinantes como la investigación biomédica, las creencias religiosas, los aspectos socioculturales, entre otros. Sin embargo, lo que permite la interpretación y observación de resultados son las practicas soportadas por las legislaciones de cada país; Colombia es el único país que ha despenalizado la eutanasia en la región y que progresa activamente en temas relacionados. En este orden de ideas, el objetivo de esta revisión consiste en analizar los marcos legales internacionales sobre la definición y uso de la eutanasia y el suicidio asistido, que permitan comprender la evolución de la normatividad sobre el cuidado al final de la vida.
Advances in human rights are indispensable during the development of public policies in health and legal frameworks that guarantee integral health care; euthanasia and assisted suicide continue to be concepts widely discussed in medicine, and especially in bioethics due to the weight they have in the decision-making process of the terminal patient and palliative care. These terms, their use, approval, and legal regulation depend on the influence of various determinants such as biomedical research, religious beliefs, and sociocultural aspects. However, what allows the interpretation and observation of results are the practices supported by the legislation of each country; Colombia is the only country that has decriminalized euthanasia in the region and is actively progressing in related issues. In this order of ideas, the objective of this review is to analyze the international legal frameworks on the definition and use of euthanasia and assisted suicide to understand the evolution of regulations on end-of-life care.
Os avanços nos direitos humanos são indispensáveis para o desenvolvimento de políticas públicas de saúde e marcos legais que garantam a atenção integral à saúde. A eutanásia e o suicídio assistido continuam sendo conceitos amplamente discutidos na medicina e, principalmente, na bioética, devido ao peso que têm no processo de tomada de decisão de pacientes terminais e nos cuidados paliativos. Esses termos, seu uso, aprovação e regulamentação legal dependem da influência de vários determinantes, como pesquisas biomédicas, crenças religiosas, aspectos socioculturais, entre outros. No entanto, o que permite a interpretação e a observação dos resultados são as práticas apoiadas pela legislação de cada país; a Colômbia é o único país que descriminalizou a eutanásia na região e está avançando ativamente em questões relacionadas. O objetivo desta revisão é analisar as estruturas jurídicas internacionais sobre a definição e o uso da eutanásia e do suicídio assistido a fim de compreender a evolução das regulamentações de cuidados no fim da vida.
Asunto(s)
Humanos , Autonomía PersonalRESUMEN
End-of-life care is an increasingly relevant topic due to advances in biomedical research and the establishment of new disciplines in evidence-based medicine and bioethics. Euthanasia and assisted suicide are two terms widely discussed in medicine, which cause displeasure on many occasions and cause relief on others. The evolution of these terms and the events associated with their study have allowed the evaluation of cases that have established useful definitions for the legal regulation of palliative care and public policies in the different health systems. However, there are still many aspects to be elucidated and defined. Based on the above, this review aimed to compile relevant historical aspects on the evolution of euthanasia and assisted suicide, which will allow understanding the use and research of these terms.
RESUMEN
Resumen El exantema intertriginoso y flexural simétrico por fármacos (SDRIFE) es una toxicodermia que se presenta con exantema limitado a pliegues, sobretodo en región glútea y genital, y representa una reacción a la exposición sistémica a un medicamento sin sensibilización previa. Presentamos el caso de una paciente mujer adulta previamente sana, que consulta por este tipo de reacción medicamentosa asociada al uso de piroxicam intramuscular, manejada de forma exitosa con antihistamínicos, esteroides tópicos y sistémicos.
Abstract Symmetrical drug related intertriginous and flexural exanthema is a cutaneous drug eruption that is characterized by exanthema limited to creases, buttocks and the upper inner thighs. It represents a reaction to systemic exposure to a drug, without previous sensitization. We present the case of a woman, previously healthy, who consulted due to this drug reaction after being injected with piroxicam, who was successfully treated with antihistamines, topical and systemic corticosteroids.
RESUMEN
INTRODUCTION: A burn injury is a very painful experience, with subsequent emotional problems, which have been gaining relevance to the extent that survival from burns has improved. Among the alterations of the mental sphere in this population is Acute Stress Disorder (ASD) that has been described in up to one-third of patients with major burns. METHODOLOGY: A nested case-control study was carried out in a cohort of hospitalized patients in a burn referral unit, in patients over 16 years of age. A total of 135 patients, 41 cases, and 94 controls were included. All of them underwent a psychiatric interview, a standardized form was filled out on sociodemographic and clinical information, and the PID-5-BF scale was applied to evaluate associated personality elements. The diagnosis of acute stress was made with the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria. RESULTS: The incidence of acute stress was 23.4%. When the clinical and sociodemographic characteristics of both the cases and the controls were compared, the risk factors were subsidized insurance, flame burn, burn in a special area, third-degree burn, high pain, stay in the Intensive Care Unit (ICU), peritraumatic amnesia and life threat. Patients also had a higher percentage of burned body surface, higher average pulse, longer hospital length of stay, higher average in the negative affect variable and in the psychoticism variable of the PID-5-BF scale. But for the multivariate analysis using logistic regression, the model that best explains the presence of acute stress only includes the variables life threat (Odds Ratio adjusted (ORa): 117.0; Confidence Interval (CI): 10.9-1258.5), severe pain (ORa: 9.9; CI: 1.8-52.8), electrical burn (ORa: 20.8; CI: 17.2-250), burn in a special area (ORa: 8.9; CI: 1, 0-76.8), third-degree burn (ORa: 10.4; CI: 0.7-166.7). CONCLUSION: Acute stress disorder is frequent in the hospitalised burn population, and is more frequent than in other types of trauma. Associated factors with the presentation of Acute Stress Disorder are the feeling of life threat at the time of the burn, having pain classified as strong (Visual Analog Scale (VAS) 5-10), electrical burn, and burns in special areas.
Asunto(s)
Quemaduras por Electricidad , Quemaduras , Trastornos de Estrés Traumático Agudo , Quemaduras/complicaciones , Quemaduras/epidemiología , Quemaduras por Electricidad/complicaciones , Estudios de Casos y Controles , Humanos , Tiempo de Internación , Dolor/complicaciones , Estudios Retrospectivos , Trastornos de Estrés Traumático Agudo/epidemiologíaRESUMEN
Introducción. La presencia de neumomediastino secundario a un trauma contuso es un hallazgo común, especialmente con el uso rutinario de la tomografía computarizada. Aunque en la mayoría de los casos es secundario a una causa benigna, la posibilidad de una lesión aerodigestiva subyacente ha llevado a que se recomiende el uso rutinario de estudios endoscópicos para descartarla. El propósito de este estudio fue determinar la incidencia de neumomediastino secundario a trauma contuso y de lesiones aerodigestivas asociadas y establecer la utilidad de la tomografía computarizada multidetector en el diagnóstico de las lesiones aerodigestivas. Métodos. Mediante tomografía computarizada multidetector se identificaron los pacientes con diagnóstico de neumomediastino secundario a un trauma contuso en un periodo de 4 años en un Centro de Trauma Nivel I. Resultados. Fueron incluidos en el estudio 41 pacientes con diagnóstico de neumomediastino secundario a un trauma contuso. Se documentaron en total tres lesiones aerodigestivas, dos lesiones traqueales y una esofágica. Dos de estas fueron sospechadas en tomografía computarizada multidetector y confirmadas mediante fibrobroncoscopia y endoscopia digestiva superior, respectivamente, y otra fue diagnosticada en cirugía. Conclusión. El uso rutinario de estudios endoscópicos en los pacientes con neumomediastino secundario a trauma contuso no está indicado cuando los hallazgos clínicos y tomográficos son poco sugestivos de lesión aerodigestiva.
Introduction.The presence of pneumomediastinum secondary to blunt trauma is a common finding, especially with the use of computed tomography. Although in most cases the presence of pneumomediastinum is secondary to a benign etiology, the possibility of an underlying aerodigestive injuries has led to the recommendation of the routine use of endoscopic studies to rule them out. The purpose of this study was to determine the incidence of pneumomediastinum secondary to blunt trauma and associated injuries and to establish the role of multidetector computed tomography in the diagnosis of aerodigestive injuries. Methods.Using multidetector computed tomography, patients with a diagnosis of pneumomediastinum secondary to blunt trauma were identified over a period of 4 years in a Level 1 Trauma Center. Results. Forty-one patients diagnosed with pneumomediastinum secondary to blunt trauma, were included in this study. Two airway ruptures were documented: two tracheal injuries and one esophageal injury. Two of them suspected on multidetector computed tomography and confirmed on bronchoscopy and esophagogastroduodenoscopy, respectively, and another was diagnosed in surgery. Conclusion.The routine use of endoscopic studies in patients with pneumomediastinum secondary to blunt trauma is not indicated when the clinical and tomographic findings are not suggestive of aerodigestive injury.
Asunto(s)
Humanos , Tórax , Perforación del Esófago , Tráquea , Heridas y Lesiones , MediastinoRESUMEN
Human malaria infection begins with a one-time asymptomatic liver stage followed by a cyclic symptomatic blood stage. For decades, the research for novel antimalarials focused on the high-throughput screening of molecules that only targeted the asexual blood stages. In a search for new effective compounds presenting a triple action against erythrocytic and liver stages in addition to the ability to block the transmission of the disease via the mosquito vector, 2-amino-thienopyrimidinone derivatives were synthesized and tested for their antimalarial activity. One molecule, named gamhepathiopine (denoted as "M1" herein), was active at submicromolar concentrations against both erythrocytic (50% effective concentration [EC50] = 0.045 µM) and liver (EC50 = 0.45 µM) forms of Plasmodium falciparum. Furthermore, gamhepathiopine efficiently blocked the development of the sporogonic cycle in the mosquito vector by inhibiting the exflagellation step. Moreover, M1 was active against artemisinin-resistant forms (EC50 = 0.227 µM), especially at the quiescent stage. Nevertheless, in mice, M1 showed modest activity due to its rapid metabolization by P450 cytochromes into inactive derivatives, calling for the development of new parent compounds with improved metabolic stability and longer half-lives. These results highlight the thienopyrimidinone scaffold as a novel antiplasmodial chemotype of great interest to search for new drug candidates displaying multistage activity and an original mechanism of action with the potential to be used in combination therapies for malaria elimination in the context of artemisinin resistance. IMPORTANCE This work reports a new chemical structure that (i) displays activity against the human malaria parasite Plasmodium falciparum at 3 stages of the parasitic cycle (blood stage, hepatic stage, and sexual stages), (ii) remains active against parasites that are resistant to the first-line treatment recommended by the World Health Organization (WHO) for the treatment of severe malaria (artemisinins), and (iii) reduces transmission of the parasite to the mosquito vector in a mouse model. This new molecule family could open the way to the conception of novel antimalarial drugs with an original multistage mechanism of action to fight against Plasmodium drug resistance and block interhuman transmission of malaria.
Asunto(s)
Antimaláricos/farmacología , Malaria Falciparum/tratamiento farmacológico , Plasmodium cynomolgi/efectos de los fármacos , Plasmodium falciparum/efectos de los fármacos , Plasmodium yoelii/efectos de los fármacos , Pirimidinonas/farmacología , Animales , Antimaláricos/química , Artemisininas/farmacología , Línea Celular Tumoral , Modelos Animales de Enfermedad , Perros , Resistencia a Medicamentos/fisiología , Femenino , Células Hep G2 , Humanos , Hígado/parasitología , Macaca fascicularis , Células de Riñón Canino Madin Darby , Masculino , Ratones , Ratones Endogámicos BALB C , Pirimidinonas/químicaRESUMEN
BACKGROUND: Platelet-rich fibrin (PRF) is a biomaterial widely used in the field of regenerative medicine. The purpose of this work was to analyze the structure and biomolecular characteristics of PRF through nine centrifugation parameters (CP) for its preparation, using a pool of blood samples of five volunteers. METHODS: The PRF obtained was analyzed by morphological and histological characteristics, as well as electronic and atomic force microscopy and growth factors determinations. RESULTS: A longer time of centrifugation showed taller clots and denser mesh fibrin in comparison with a short time (p < 0.05). The protocols with higher speed of centrifugation showed higher levels of PDGF-BB and VEGF. Higher levels of TGFß1 were found in protocols with a shorter centrifuge time. The mean platelet count (916.05 ± 23.73 cells x 103 cells x cm3) and its roughness (Ra) (616.5 ± 45.2 nm) did not show significant differences between different CP (p > 0.05). A significant correlation between fibrin density and levels of PDGF (r = 0.57) and VEGF (r = 0.52) was found. Additionally, the size of the clot had a significant correlation (r = -0.47) with TGFß1 levels. CONCLUSIONS: Different centrifugation parameters to obtain PRF have been reported. These results indicate that changes in the conditions to obtain PRF have a significant impact on their fibrin structure, cellular distribution, and biomolecular content, which can be decisive for its choice in the different clinical applications to be used. It is necessary to use a standardized centrifuge and protocol to guarantee high-quality PRF and clinical outcomes with less variability.