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Tocopherols are lipophilic antioxidants known as vitamin E and synthesized from the condensation of two metabolic pathways leading to the formation of homogentisate and phytyl diphosphate. While homogentisate is derived from tyrosine metabolism, phytyl diphosphate may be formed from geranylgeranyl diphosphate or phytol recycling from chlorophyll degradation. Here, we hypothesized that abscisic acid (ABA) could induce tocopherol biosynthesis in sweet cherries by modifying the expression of genes involved in vitamin E biosynthesis, including those from the phytol recycling pathway. Hence, the expression of key tocopherol biosynthesis genes was determined together with vitamin E and chlorophyll contents during the natural development of sweet cherries on the tree. Moreover, the effects of exogenously applied ABA on the expression of key tocopherol biosynthesis genes were also investigated during on-tree fruit development, and tocopherols and chlorophylls contents were analyzed. Results showed that the expression of tocopherol biosynthesis genes, including VTE5, VTE6, HPPD and HPT showed contrasting patterns of variation, but in all cases, increased by 2- and 3-fold over time during fruit de-greening. This was not the case for GGDR and VTE4, the first showing constitutive expression during fruit development and the second with marked down-regulation at ripening onset. Furthermore, exogenous ABA stimulated the production of both α- and γ-tocopherols by 60% and 30%, respectively, promoted chlorophyll degradation and significantly enhanced VTE5 and VTE6 expression, and also that of HPPD and VTE4, altogether increasing total tocopherol accumulation. In conclusion, ABA increases promote the transcription of phytol recycling enzymes, which may contribute to vitamin E biosynthesis during fruit development in stone fruits like sweet cherries.
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Difosfatos , Prunus avium , Vitamina E , Vitamina E/metabolismo , Frutas , Prunus avium/metabolismo , Ácido Abscísico/metabolismo , Tocoferoles/metabolismo , Clorofila/metabolismo , Fitol/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
Phytohormones are naturally occurring small organic molecules found at low concentrations in plants. They perform essential functions in growth and developmental processes, from organ initiation to senescence, including fruit ripening. These regulatory molecules are studied using different experimental approaches, such as performing exogenous applications, evaluating endogenous levels, and/or obtaining genetically modified lines. Here, we discuss the advantages and limitations of current experimental approaches used to study active biomolecules modulating fruit ripening, focusing on melatonin. Although melatonin has been implicated in fruit ripening in several model fruit crops, current knowledge is affected by the different experimental approaches used, which have given different and sometimes even contradictory results. The methods of application and the doses used have produced different results in studies based on exogenous applications, while different measurement methods and ways of expressing results explain most of the variability in studies using correlative analyses. Furthermore, studies on genetically modified crops have focused on tomato (Solanum lycopersicum L.) plants only. However, TILLING and CRISPR methodologies are becoming essential tools to complement the results from the experimental approaches described above. This will not only help the scientific community better understand the role of melatonin in modulating fruit ripening, but it will also help develop technological advances to improve fruit yield and quality in major crops. The combination of various experimental approaches will undoubtedly lead to a complete understanding of the function of melatonin in fruit ripening in the near future, so that this knowledge can be effectively transferred to the field.
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Frutas , Melatonina , Proteínas de Plantas , Productos Agrícolas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Solanum lycopersicum/genéticaRESUMEN
Sublethal exposure to imidacloprid and other neonicotinoid insecticides may affect the neurological functions of birds. As such, behavior may be compromised. Here, we tested experimentally the effects of 1 and 6 mg/kg bw of imidacloprid on the antipredator behavioral responses of the red-legged partridge (Alectoris rufa) to simulated predator threats. Sixty-six partridges were challenged in groups or individually to intra- and interspecific alarm calls, to a raptor silhouette (aerial predation risk), and to a fox model (terrestrial predation risk). Antipredator behaviors were recorded as active (escape, active vigilance) and passive (passive vigilance, crouching, and freezing) responses. Latency in response to the stimuli, percentage of individuals who responded, response duration, speed of active responses, and vocalizations were measured. In experiments with partridges in the group, crouching against simulated predation risk lasted less time in birds treated with 6 mg a.i./kg bw than in control birds. In the experiments with individual partridges, passive vigilance against the intraspecific alarm lasted longer in birds treated with 6 mg a.i./kg bw than in control birds. The observed hyperreactivity to the predatory threat after a sublethal imidacloprid exposure can have consequences on survival under field conditions, where predation is a main driver of population dynamics.
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OBJECTIVE: This study aimed to investigate the influence of sarcopenic obesity on anastomotic leak following elective colon resection for non-metastatic colon cancer. Secondary outcomes included overall morbidity, mortality and length of hospital stay. METHODS: This retrospective observational study, conducted at a colorectal surgery referral centre, spanned from January 1, 2015, to January 1, 2020. A total of 544 consecutive patients who underwent elective colon resection were included in the analysis, excluding patients with rectal cancer, urgent surgery, absence of anastomosis, lack of imaging, multivisceral resections and synchronic tumours. RESULTS: Postoperative complications were observed in 177 (32.3%) patients, with 51 (9.31%) classified as severe (Clavien-Dindo > II). Sarcopenic obesity was identified in 9.39% of the sample and emerged as an independent predictor of increased overall morbidity [OR 2.15 (1.14-3.69); p = 0.016] and 30-day mortality [OR 5.07 (1.22-20.93); p = 0.03] and was significantly associated with the development of anastomotic leak [OR 2.95 (1.41-6.18); p = 0.007]. Furthermore, it increased the risk of reoperation and was linked to a prolonged length of hospital stay. CONCLUSIONS: CT-measured sarcopenic obesity demonstrates a discernible correlation with an elevated risk of postoperative morbidity and mortality in the context of colon cancer surgery.
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Neoplasias del Colon , Sarcopenia , Humanos , Fuga Anastomótica/diagnóstico por imagen , Fuga Anastomótica/etiología , Colectomía , Neoplasias del Colon/cirugía , Obesidad/complicaciones , Sarcopenia/complicaciones , Sarcopenia/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Estudios RetrospectivosRESUMEN
Political trust is an important predictor of compliance with government policies, especially in the face of natural disasters or public health emergencies. During the COVID-19 pandemic, for example, multiple studies related political trust to increased compliance with mobility restrictions. Yet these findings come mostly from high-income countries where political trust and wealth correlate positively. In Latin America, both variables correlate negatively, allowing for better testing of competing explanations. Using a difference-in-differences design, we find that in Latin America wealth and, counterintuitively, low political trust predict increased compliance. To understand mechanisms, we decompose political trust and wealth into underlying predictors (social protection, corruption, and education) and reinsert them into the model. While education, as a wealth proxy, predicts decreased mobility across all periods, social protection, which was the strongest predictor of political trust, relates significantly to increased mobility, but only at the beginning of the lockdown prior to distribution of emergency support. This suggests the existence of a public health moral hazard early in the pandemic, whereby citizens who benefited previously from government benefits may have been more risk tolerant in the face of the COVID-19 threat. We interpret these findings within the context of the region's recent "inclusionary turn." Future studies should explore the distinct relationships between political trust, risk perception, and compliance, especially in low- and middle-income countries, and their implications for policy responses to national emergencies.
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OBJECTIVES: In-hospital acute ischemic stroke (HIS) accounts for 2-17% of all acute ischemic strokes (AIS) seen in hospital and they have worse prognosis. In this study we aimed to identify the frequency of HIS and their characteristics in our center. MATERIALS AND METHODS: Retrospective analysis of a prospective register of patients with AIS seen at Clínica Alemana de Santiago, between January 2017 and January 2019. HIS and community onset ischemic strokes patients (CIS) were compared, univariate analysis was performed, covariates with p < 0.25 were selected for multivariate analysis. Differences between, proportion of strokes treated with thrombolytic therapy, door to needle time were compared between HIS and CIS patients, as also mortality rates at 90 days. RESULTS: During the study period 369 patients with AIS were seen; of these 20 (5.4%, 95 CI%, 3.5-8.2) corresponded to HIS. In univariate analysis, HIS compared to patients arriving form the community to the emergency room, suffered more frequently from, heart failure (p = 0.04), and active malignancies (p < 0.001). HIS patients had longer times from symptom onset to non-contrast brain tomography (540 ±150 minutes); they were also less frequently treated with intravenous thrombolysis compared to community AIS: 15% versus 30% respectively (p = 0.08). Mortality rates at 90 days were higher in HIS: 30 versus 5% (p = 0.001). CONCLUSIONS: In this cohort, HIS patients suffered delays in their neuroimaging studies and received less intravenous thrombolysis; this underscores the need for a standardized approach to the recognition and management of inhospital acute ischemic stroke.
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Disparidades en Atención de Salud , Hospitalización , Pacientes Internos , Accidente Cerebrovascular Isquémico/terapia , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Chile , Comorbilidad , Femenino , Mortalidad Hospitalaria , Humanos , Accidente Cerebrovascular Isquémico/diagnóstico por imagen , Accidente Cerebrovascular Isquémico/mortalidad , Masculino , Persona de Mediana Edad , Neuroimagen , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/mortalidad , Factores de Tiempo , Tiempo de Tratamiento , Resultado del TratamientoRESUMEN
BACKGROUND: The worst Ebola virus disease (EVD) outbreak in history has resulted in more than 28,000 cases and 11,000 deaths. We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)-based vaccine candidate designed to prevent EVD. METHODS: We conducted two phase 1, placebo-controlled, double-blind, dose-escalation trials of an rVSV-based vaccine candidate expressing the glycoprotein of a Zaire strain of Ebola virus (ZEBOV). A total of 39 adults at each site (78 participants in all) were consecutively enrolled into groups of 13. At each site, volunteers received one of three doses of the rVSV-ZEBOV vaccine (3 million plaque-forming units [PFU], 20 million PFU, or 100 million PFU) or placebo. Volunteers at one of the sites received a second dose at day 28. Safety and immunogenicity were assessed. RESULTS: The most common adverse events were injection-site pain, fatigue, myalgia, and headache. Transient rVSV viremia was noted in all the vaccine recipients after dose 1. The rates of adverse events and viremia were lower after the second dose than after the first dose. By day 28, all the vaccine recipients had seroconversion as assessed by an enzyme-linked immunosorbent assay (ELISA) against the glycoprotein of the ZEBOV-Kikwit strain. At day 28, geometric mean titers of antibodies against ZEBOV glycoprotein were higher in the groups that received 20 million PFU or 100 million PFU than in the group that received 3 million PFU, as assessed by ELISA and by pseudovirion neutralization assay. A second dose at 28 days after dose 1 significantly increased antibody titers at day 56, but the effect was diminished at 6 months. CONCLUSIONS: This Ebola vaccine candidate elicited anti-Ebola antibody responses. After vaccination, rVSV viremia occurred frequently but was transient. These results support further evaluation of the vaccine dose of 20 million PFU for preexposure prophylaxis and suggest that a second dose may boost antibody responses. (Funded by the National Institutes of Health and others; rVSV∆G-ZEBOV-GP ClinicalTrials.gov numbers, NCT02269423 and NCT02280408 .).
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Vacunas contra el Virus del Ébola/inmunología , Ebolavirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Adulto , Anticuerpos Antivirales/sangre , Método Doble Ciego , Vacunas contra el Virus del Ébola/administración & dosificación , Vacunas contra el Virus del Ébola/efectos adversos , Ebolavirus/genética , Ebolavirus/aislamiento & purificación , Ensayo de Inmunoadsorción Enzimática , Femenino , Fiebre Hemorrágica Ebola/inmunología , Humanos , Masculino , Persona de Mediana Edad , Proteínas Recombinantes , Seroconversión , Vacunas Atenuadas/inmunología , Virus de la Estomatitis Vesicular Indiana , Proteínas del Envoltorio Viral/aislamiento & purificación , ViremiaRESUMEN
OBJECTIVES: The prevalence of fibromyalgia (FM) differs depending on the population studied. The main objective of the EPISER2016 study was to estimate the prevalence of FM in adults in Spain. The secondary objective was to evaluate the association with sociodemographic and anthropometric characteristics and smoking. METHODS: This is a population-based cross-sectional multicentre study. The random selection was based on multistage stratified cluster sampling. The final sample comprised 4916 persons aged ≥20 years. Participants were contacted by telephone for completion of a screening survey. Investigating rheumatologists evaluated positive results (review of medical records and/or telephone interview, with medical visit if needed) to confirm the diagnosis. Prevalence and 95% confidence interval were calculated, taking into account the sample design. Weighing was applied based on age, sex, and geographic origin. Predictive models were constructed to analyse which sociodemographic, anthropometric and lifestyle variables in the call centre questionnaire were associated with the presence of FM. RESULTS: 602 subjects (12.25%) had a positive screening result for FM, of which 24 were missing (3.99%). A total of 141 cases of FM were recorded. The estimated prevalence was 2.45% (95% CI, 2.06-2.90). Female sex was the variable most associated with FM, with an odds ratio (OR) of 10.156 (95% CI, 5.068-20.352). Peak prevalence was at 60-69 years (p=0.009, OR=6.962). FM was 68% more frequent in obese individuals (OR, 1.689; 95% CI, 1.036-2.755). CONCLUSIONS: The prevalence of FM in adults in Spain barely changed between 2000 and 2016 and it is similar to that observed in Europe as a whole.
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Fibromialgia/epidemiología , Adulto , Estudios Transversales , Femenino , Humanos , Obesidad/complicaciones , Prevalencia , Factores Sexuales , España/epidemiología , Adulto JovenRESUMEN
BACKGROUND: Intravenous thrombolysis (IT) in acute ischemic stroke (AIS) is time dependent. The time elapsed from hospital admission to the thrombolytic bolus is named door to needle time (DNT) and is recommend to be of less than 60 min. AIM: To describe the DNT in our center and determine those factors associated with a DNT longer than 60 min. MATERIAL AND METHODS: Prospective analysis of patients treated with IT at a private hospital between June 2016 and June 2019. The percentage of patients with DNT exceeding 60 min, and the causes for this delay were evaluated. RESULTS: IT was used in 205 patients. DNT was 43.6 ± 23.8 min. Forty patients (19.5% (95% CI, 14.4-25.7), had a DNT longer than 60 min. Uni-varied analysis demonstrated that AIS with infratentorial symptomatology (ITS), was significantly associated with DNTs exceeding 60 min. A history of hypertension, a higher NIH Stroke Scale score, the presence of an hyperdense sign in brain tomography (p = 0.001) and the need for endovascular therapy (p = 0.019), were associated with DNT shorter than 60 min. Multivariate analysis ratified the relationship between ITS and DNT longer than 60 min (Odds ratio: 3.19, 95% confidence intervals 1.26-8). CONCLUSIONS: The individual elements that correlated with a DNT longer than 60 min were the failure to detect the AIS during triage and doubts about its diagnosis.
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Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Terapia Trombolítica , Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Humanos , Estudios Prospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Tiempo de Tratamiento , Activador de Tejido Plasminógeno/uso terapéuticoRESUMEN
BACKGROUND: Echocardiography (ECO) is frequently used as a screening test in patients with acute ischemic brain disease. We aimed to evaluate the additional information and therapeutic impact resulting from ECO in these patients. METHODS: We conducted a prospective study performing ECO on consecutive patients with ischemic stroke or transient ischemic attacks, admitted to our centre between February 2013 and May 2017. RESULTS: A total of 696 patients were included (female, 57.3%; mean age, 70 ± 15.3 years). Seven hundred thirty two echocardiographic examinations were performed (696 transthoracic and 36 transesophageal). Echocardiography yielded findings judged of clinical importance in 142 patients (20.4%, 95% CI 17.5-23.5). The most frequent of these were left atrial volume enlargement or a normal evaluation. Echocardiography findings resulted in changes in the management of 76 patients (10.7% 95% CI 8.8-13.4); initiation of anticoagulation therapy, administration of IV antibiotic therapy, cardiac surgeries, or other pharmacological therapies occurring in 42 cases (6%). The presence of coronary heart disease (OR: 2.64 95% CI 1.34-5.25), atrial fibrillation (OR: 0.24; 95% CI, 0.2-0.69), and admission NIHSS (OR: 1.04; 95% CI, 1.01-1.09), were the variables associated with changes in management. CONCLUSIONS: In unselected patients with acute ischemic stroke ECO had a low yield of additional information, and it changed management in a small percentage of patients.
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Isquemia Encefálica/diagnóstico por imagen , Ecocardiografía Transesofágica , Cardiopatías/diagnóstico por imagen , Ataque Isquémico Transitorio/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/etiología , Isquemia Encefálica/terapia , Chile , Toma de Decisiones Clínicas , Femenino , Cardiopatías/complicaciones , Cardiopatías/terapia , Humanos , Ataque Isquémico Transitorio/terapia , Masculino , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapiaRESUMEN
AIMS: The aims of the present study were to assess the safety, tolerability and pharmacokinetics of radavirsen following single ascending doses and multiple doses given as intravenous infusions in healthy adults. METHODS: A phase I safety and pharmacokinetic study of radavirsen was performed in healthy volunteers. The study was divided into two parts. The first was a single-ascending-dose study of five cohorts of eight subjects each, randomized 6:2 to receive single intravenous doses of radavirsen ranging from 0.5 mg kg-1 to 8 mg kg-1 or placebo. The second was a multiple-dose study of 16 subjects randomized 12:4 to receive 8 mg kg-1 or placebo once daily for 5 days. RESULTS: A total of 66 subjects were screened, and 56 subjects were dosed between 2013 and 2015. At least one adverse event occurred in 31/42 (74%) who received radavirsen, and 13/14 (93%) receiving placebo. The most common adverse events were headache and proteinuria, and were similar in incidence and severity among those receiving radavirsen or placebo. Single-dose pharmacokinetics demonstrated relatively linear and dose-proportional increases in maximal concentration and in area under the concentration-time curve from zero to 24 h (AUC0-24 ). At 8 mg kg-1 in the multiple-dose cohort, the day 4 geometric mean AUC0-24 was 57.9 µg*h ml-1 . CONCLUSION: Single infusions of radavirsen up to 8 mg kg-1 , and multi-dosing at 8 mg kg-1 once daily for 5 days, appear to be safe and well tolerated in healthy subjects. The multi-dose day 4 AUC0-24 in the present study was comparable with that associated with protection from viral infection in a preclinical ferret influenza model. Further evaluation of radavirsen for the treatment of influenza infections is warranted.
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Antivirales/farmacología , Gripe Humana/tratamiento farmacológico , Morfolinos/farmacología , Oligonucleótidos Antisentido/farmacología , Adulto , Antivirales/uso terapéutico , Método Doble Ciego , Esquema de Medicación , Femenino , Cefalea/inducido químicamente , Cefalea/epidemiología , Voluntarios Sanos , Humanos , Incidencia , Virus de la Influenza A/genética , Gripe Humana/virología , Infusiones Intravenosas , Masculino , Persona de Mediana Edad , Morfolinos/genética , Morfolinos/uso terapéutico , Oligonucleótidos Antisentido/genética , Oligonucleótidos Antisentido/uso terapéutico , Placebos , Biosíntesis de Proteínas/genética , Proteinuria/inducido químicamente , Proteinuria/epidemiología , Proteínas de la Matriz Viral/genética , Adulto JovenRESUMEN
INTRODUCTION: Graft-versus-host disease (GVHD) is caused by a pathologic and destructive response of the organism as a result of the interaction between donor immunocompetent T lymphocytes and the recipient tisular antigens. It's considered the most serious complication of hematopoietic stem cell transplantation, most frequently described after bone marrow transplantation (BMT). The skin is usually the first and most commonly affected organ, in both acute and chronic, with a variable clinical spectrum of presentation. OBJECTIVE: To report a case of vitiligo as a manifestation of cutaneous chronic GVHD, a low prevalence sign, which recognition could help to suspect this severe compli cation. CASE REPORT: 8 years old male, diagnosed with acute lymphoblastic leukemia (ALL) at 3 years old, had a combined medullary and central nervous system (NCS) relapse with minimal positive disease 3 years afterwards. After 4 years ALL was diagnosed, he received an allogeneic bone marrow transplant. Seven months after the BMT he presented multiple melanocytic nevi with peripheral hypopigmentation, and some isolated asymptomatic, confluent achromic macules on the face, trunk and limbs. The skin biopsy was compatible with chronic vitiligo and sclerodermiform type GVHD. He received topical treatment with Tacrolimus, achieving clinical stabilization. CONCLUSIONS: GVHD leads to the appearance of autoantibodies that could act as a trigger in the onset of autoimmune diseases, such as vitiligo. Consequently it could explain this poorly described manifestation in the literature of chronic cutaneous GVHD.
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Enfermedad Injerto contra Huésped/diagnóstico , Vitíligo/etiología , Trasplante de Médula Ósea , Niño , Enfermedad Crónica , Enfermedad Injerto contra Huésped/complicaciones , Humanos , MasculinoRESUMEN
Trypanosomatids are the etiologic agents of various infectious diseases in humans. They diverged early during eukaryotic evolution and have attracted attention as peculiar models for evolutionary and comparative studies. Here, we show a meticulous study comparing the incorporation and detection of the thymidine analogs BrdU and EdU in Leishmania amazonensis, Trypanosoma brucei, and Trypanosoma cruzi to monitor their DNA replication. We used BrdU- and EdU-incorporated parasites with the respective standard detection approaches: indirect immunofluorescence to detect BrdU after standard denaturation (2 M HCl) and "click" chemistry to detect EdU. We found a discrepancy between these two thymidine analogs due to the poor detection of BrdU, which is reflected on the estimative of the duration of the cell cycle phases G1, S, and G2. To solve this discrepancy, we increase the exposure of incorporated BrdU using different concentrations of HCl. Using a new value for HCl concentration, we re-estimated the phases G1, S, G2 + M, and cytokinesis durations, confirming the values found by this approach using EdU. In conclusion, we suggest that the studies using BrdU with standard detection approach, not only in trypanosomatids but also in others cell types, should be reviewed to ensure an accurate estimation of DNA replication monitoring.
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Bromodesoxiuridina/análisis , Ciclo Celular , Replicación del ADN , Desoxiuridina/análogos & derivados , Leishmania/crecimiento & desarrollo , Trypanosoma/crecimiento & desarrollo , Desoxiuridina/análisis , Leishmania/metabolismo , Coloración y Etiquetado , Trypanosoma/metabolismoRESUMEN
BACKGROUND: The effectiveness of intravenous thrombolysis (IVT) in cerebral ischemia is time dependent. Stroke mimics (SM) are frequent in emergency rooms. The effort to reduce door to needle time, can lead to administer thrombolytics to SM. AIM: To describe the frequency and prognosis of SM treated with IVT. MATERIAL AND METHODS: Prospective analysis of all patients evaluated in a Chilean private clinic between December 2004 and July 2015 with a suspected acute ischemic stroke (AIS). We calculated the number of SM that were treated with IVT. In these patients, we analyzed the presence of symptomatic cerebral hemorrhage defined as the presence of a neurological deterioration of four points or more on the National Institute of Health Stroke Scale, the presence of extracranial bleeding according to Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries criteria and the patient's functional status at three months by modified Rankin scale (MRS). RESULTS: We evaluated 1,417 patients with suspected AIS, of which 240 (16.9%) were finally diagnosed as SM. A total of 197 patients were treated with IVT, of these 10 (5%) corresponded to SM. All SM patients treated with thrombolytic drugs were functionally independent at 3 months and showed no bleeding complications. CONCLUSIONS: Occasionally SM patients were treated with IVT. This treatment was not associated with bleeding complications and the prognosis of these patients at three months was favorable.
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Isquemia Encefálica/tratamiento farmacológico , Fibrinolíticos/administración & dosificación , Accidente Cerebrovascular/tratamiento farmacológico , Administración Intravenosa , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/complicaciones , Femenino , Hemorragia/etiología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Accidente Cerebrovascular/complicaciones , Centros de Atención Terciaria , Terapia Trombolítica , Factores de Tiempo , Tiempo de TratamientoAsunto(s)
Flores/efectos de la radiación , Frutas/efectos de la radiación , Luz , Estrés Oxidativo/efectos de la radiación , Hojas de la Planta/efectos de la radiación , Cloroplastos/genética , Cloroplastos/metabolismo , Cloroplastos/efectos de la radiación , Flores/genética , Flores/crecimiento & desarrollo , Frutas/genética , Frutas/crecimiento & desarrollo , Regulación del Desarrollo de la Expresión Génica/efectos de la radiación , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMEN
BACKGROUND: Sonothrombolysis (ST) is an emerging modality for the treatment of stroke. AIM: To assess the feasibility to perform ST in a Chilean hospital. MATERIAL AND METHODS: Patients attended at a private clinic with an acute ischemic stroke, between September 2002 and May 2013 and eligible for endovenous thrombolysis, were studied with a transcranial Doppler (Spencer PMD 100 or 150®). Those with an adequate sonographic window and a demonstrated arterial occlusion were monitored continuously with transcranial Doppler at the site of worst residual flow following the CLOTBUST study protocol. RESULTS: One thousand twenty six patients were studied, of whom 136 received intravenous thrombolysis (rt-PA) and 61, aged 66 ± 18 years (59% males), were subjected to ST (7% of total). Their median National Institutes of Health Stroke Scale score was 14, the lapse from symptom onset to rt-PA was 127 minutes (43-223). Middle cerebral artery (MCA) occlusion was found in 88.5% of patients. Complete recanalization was achieved in 44.3% of patients. Sixty percent had Modified Rankin Scale of 0 to 2 at 3 months (95% confidence intervals (CI) 48.1 to 72). Case fatality was 9.8% and asymptomatic intracranial hemorrhage occurred in 9.8% (95% CI: 4.3 to 20.2). CONCLUSIONS: ST can be carried out in a complex medical center and is safe.
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Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapia , Terapia Trombolítica/métodos , Terapia por Ultrasonido/métodos , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/terapia , Estudios de Factibilidad , Femenino , Humanos , Masculino , Factores de Riesgo , Terapia Trombolítica/instrumentación , Ultrasonografía Doppler TranscranealRESUMEN
Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have demonstrated their impact on disease-free survival (DFS) and overall survival (OS) of patients with peritoneal metastases (PM). However, prior literature lacks evidence regarding any follow-up beyond 5 years. In this study, we analyse long-term OS and DFS (more than 10 years of follow-up) of patients undergoing CRS + HIPEC in a specialized unit. We conducted a retrospective study that included only patients who underwent CRS + HIPEC from January 2001 to May 2012. Data collection was conducted by reviewing medical records and telephone calls to patients or relatives. A total of 86 patients were included. The mean PCI was nine (range 0-39) and complete cytoreduction (CC-0) was reached in 80% of patients. Postoperative complications Clavien-Dindo III-IV occurred in 27.9% of patients and the 30-day mortality rate was 2.3%. After 10 years of actual follow-up, OS was 33.7% and DFS was 31.4%. Considering the historical context in which the standard of care for patients with PM was palliation, the results obtained show that CRS + HIPEC was a valid option, with morbimortality comparable to other major abdominal surgeries and encouraging survival results, since, after 10 years of follow-up, almost one-third of patients are still alive and disease-free.
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Salmonella enterica serovar Typhimurium expresses two type III secretion systems, T3SS1 and T3SS2, which are encoded in Salmonella pathogenicity island 1 (SPI1) and SPI2, respectively. These are essential virulent factors that secrete more than 40 effectors that are translocated into host animal cells. This study focuses on three of these effectors, SlrP, SspH1, and SspH2, which are members of the NEL family of E3 ubiquitin ligases. We compared their expression, regulation, and translocation patterns, their role in cell invasion and intracellular proliferation, their ability to interact and ubiquitinate specific host partners, and their effect on cytokine secretion. We found that transcription of the three genes encoding these effectors depends on the virulence regulator PhoP. Although the three effectors have the potential to be secreted through T3SS1 and T3SS2, the secretion of SspH1 and SspH2 is largely restricted to T3SS2 due to their expression pattern. We detected a role for these effectors in proliferation inside fibroblasts that is masked by redundancy. The generation of chimeric proteins allowed us to demonstrate that the N-terminal part of these proteins, containing the leucine-rich repeat motifs, confers specificity towards ubiquitination targets. Furthermore, the polyubiquitination patterns generated were different for each effector, with Lys48 linkages being predominant for SspH1 and SspH2. Finally, our experiments support an anti-inflammatory role for SspH1 and SspH2.
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Salmonella typhimurium , Ubiquitina-Proteína Ligasas , Animales , Salmonella typhimurium/genética , Ubiquitina-Proteína Ligasas/genética , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Serogrupo , UbiquitinaciónRESUMEN
Background: Staphylococcus aureus infections are a significant cause of morbidity and mortality in pediatric populations worldwide. The Staphylo Research Network conducted an extensive study on pediatric patients across Colombia from 2018 to 2021. The aim of this study was to describe the epidemiological and microbiological characteristics of S. aureus in this patient group. Methods: We analyzed S. aureus isolates from WHONET-reporting centers. An "event" was a positive culture isolation in a previously negative individual after 2 weeks. We studied center characteristics, age distribution, infection type, and antibiotic susceptibilities, comparing methicillin sensitive (MSSA) and resistant S. aureus (MRSA) isolates. Results: Isolates from 20 centers across 7 Colombian cities were included. Most centers (80%) served both adults and children, with 55% offering oncology services and 85% having a PICU. We registered 8,157 S. aureus culture isolations from 5,384 events (3,345 MSSA and 1,961 MRSA) in 4,821 patients, with a median age of 5 years. Blood (26.2%) and skin/soft tissue (18.6%) were the most common infection sources. Most isolates per event remained susceptible to oxacillin (63.2%), clindamycin (94.3%), and TMP-SMX (98.3%). MRSA prevalence varied by city (<0.001), with slightly higher rates observed in exclusively pediatric hospitals. In contrast, the MRSA rate was somewhat lower in centers with Antimicrobial Stewardship Program (ASP). MRSA was predominantly isolated from osteoarticular infections and multiple foci, while MSSA was more frequently associated with recurrent infections compared to MRSA. Conclusions: This is the largest study of pediatric S. aureus infections in Colombia. We found MSSA predominance, but resistance have important regional variations. S. aureus remains susceptible to other commonly used antibiotics such as TMP-SMX and clindamycin. Ongoing monitoring of S. aureus infections is vital for understanding their behavior in children. Prospective studies within the Staphylored LATAM are underway for a more comprehensive clinical and genetic characterization.
RESUMEN
BACKGROUND AND PURPOSE: The accuracy of diffusion-weighted imaging (DWI) for the diagnosis of acute cerebral ischemia among patients with suspected ischemic stroke arriving to an emergency room has not been studied in depth. METHODS: DWI was performed in 712 patients with acute or subacute focal symptoms that suggested an acute ischemic stroke (AIS), 609 of them with AIS. RESULTS: DWI demonstrated a sensitivity of 90% and specificity of 97%, a positive likelihood ratio of 31 and a negative likelihood ratio of 0.1 for detecting AIS. The overall accuracy was 95%. Of those patients who demonstrated abnormal DWI studies, 99.5% were AIS patients, and of those patients with normal DWI studies 63% were stroke mimics. CONCLUSIONS: DWI is accurate in detecting AIS in unselected patients with suspected AIS; a negative study should alert for nonischemic conditions.