A Phase I/IIa Prospective, Randomized, Open-Label Study on the Safety and Efficacy of Nebulized Liposomal Amphotericin for Invasive Pulmonary Aspergillosis.

Although nebulized liposomal amphotericin B (NLAB) is being used in invasive pulmonary aspergillosis (IPA) prophylaxis, no clinical trial has shown its efficacy as a therapeutic strategy. NAIFI is the inaugural randomized, controlled clinical trial designed to examine the safety and effectiveness of NLAB (dosage: 25 mg in 6 mL, three times per week for 6 weeks) against a placebo, in the auxiliary treatment of IPA. Throughout the three-year clinical trial, thirteen patients (six NLAB, seven placebo) were included, with 61% being onco-hematological with less than 100 neutrophils/µL. There were no significant differences noted in their pre- and post-nebulization results of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and oxygen saturation between the groups. Neither bronchospasm nor serum amphotericin B levels were reported in any patients given NLAB. 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET-TC) was carried out at the baseline and after 6 weeks. A notable decrease in median SUV (standardized uptake value) was observed in NLAB patients after 6 weeks (-3.6 vs. -0.95, p: 0.039, one tail). Furthermore, a reduction in serum substance galactomannan and beta-D-Glucan was identified within NLAB recipients. NLAB is well tolerated and safe for patients with IPA. Encouraging indirect efficacy data have been derived from image monitoring or biomarkers. However, further studies involving more patients are necessary.

A critical view on the current use of daptomycin in Spain: The daptomise study.

BACKGROUND: The Study on the Clinical Use of DAPTOMycin in Spain (DAPTOMISE Study) is a national surveillance program of daptomycin use. The objectives of this study are to evaluate the current variability in daptomycin consumption across the different hospitals and the adequacy of therapy, specially focused on underdosing. METHODS: All adult and pediatric patients who received, at least, one dose of daptomycin in a single week in 98 institutions in Spain were included. The adequacy of daptomycin use was evaluated with respect to the indication, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. RESULTS: A total of 615 patients received daptomycin during the study week. The prevalence use was 2.3 patients / 100,000 inhabitants per week, 12.4 patients / 1000 admissions and 9.2 Days of Therapy (DOT) / 1000 hospital stays. These rates varied between hospitals: from 0 to 13.9 patients / 100,000 inhabitants, from 0 to 76.1 patients / 1000 admissions and from 0 to 49.4 DOT / 1000 hospital stays. The most frequent infections were bacteremia (31.6 %) and skin and soft tissue infections (17.9 %). Microbiological results were available in only 65.4 % of infections. The most frequent microorganisms were Staphylococcus aureus (192 isolates, of which 87 were resistant to methicillin) and coagulase-negative staphylococci (124 isolates). A total of 136 prescriptions (22.1 %) were underdosed. Dosages < 8 mg/kg were used for 35.6 % of endovascular infections and for 26.2 % of osteoarticular infections. Overall, 57.2 % of prescriptions were not optimal in, at least, one item. Clinical cure rate was 76.1% and mortality attributable to the infection 8.1%. CONCLUSION: This is the first registry that identifies the prevalence of use of daptomycin in Spain and shows a high variability in the consumption between the different hospitals. Daptomycin underdosing was present in more than 20 % of cases.

Necrosis, netosis, and apoptosis in pulmonary tuberculosis and type-2 diabetes mellitus. Clues from the patient's serum.

Pulmonary tuberculosis (PTB) and type 2 diabetes mellitus (T2DM) are two inflammatory diseases whose pathology involves neutrophils (NEU) as key participants. Countless inflammatory elements produced at the lesion sites leak into the blood and are distributed systemically. The study aimed to investigate the effect of the serum of patients with PTB, T2DM, and PTB + T2DM on the cellular and nuclear morphology of healthy NEU. Monolayers of NEU were prepared and incubated with sera from PTB (n꓿ 10), T2DM (n꓿10), PTB + T2DM (n꓿ 10) patients, or sera from healthy people (n = 10). Monolayers were stained for histones, elastase, and myeloperoxidase for NETosis, annexin V for apoptosis, and Iris fuchsia for necrosis. Hoechst stain (DNA) was used to identify the nuclear alterations. Necrosis was the predominant alteration. Sera from PTB + T2DM were the most potent change inducers. Normal sera did not induce cell alterations. The blood of TBP and T2DM patients carries a myriad of abnormal elements that induce necrosis of NEU in normal people, thus reflecting what might occur in the neutrophils of the patients themselves. These findings reinforce the participation of NEU in the pathology of these diseases. Necrosis is expected to be the most frequent neutrophil-induced alteration in tuberculosis and diabetes mellitus.

A neutrophil-based test as an auxiliary tool for substantiating the diagnosis of bovine tuberculosis.

Background: Bovine tuberculosis (bTB) is still a prominent threat to animal health; lacking an efficient vaccine, other than BCG to get rid of tuberculosis, the most effective way for this is culling and slaughtering the infected animals. There are several cellular, serological, and molecular tests for the diagnosis of the disease but the most practical one at the field level is the double skin testing with bovine and aviary tuberculins. This is not a very specific test but is sensitive enough to identify most diseased animals; adjunct practical tests are desirable to strengthen the utility of skin tests. All lymphoid and myeloid cells participate, in diverse grades, in the immune response to tuberculosis with neutrophils playing an unintended pathologic role. The study aimed to investigate the response of neutrophils to agents present in the sera of tuberculous cows. Methods: We have developed a neutrophil-based test (N BT) to identify diseased cows within a herd suspected of having tuberculosis; a positive N BT correlates with a positive double skin test. In this test, healthy neutrophils are incubated with the sera of healthy or tuberculous cows for 3 and 6 h, and the nuclear morphologic changes are recorded and analyzed. Results: Sera from tuberculous but not from healthy cows induce nuclear alterations including pyknosis, swelling, apoptosis, and sometimes NETosis, in healthy neutrophils, and CFP 10 and ESAT 6 participate in the phenomenon. Conclusion: We propose the N BT as an auxiliary tool for substantiating the diagnosis of bTB reinforcing the PPD test outcome to help decide whether or not a cow should be sacrificed.

NeuroImmunoEndocrinology: A brief historic narrative.

Although no precise moment or unique event marks its birth, neuroimmunoendocrinology arguably shares a great deal of history with other medical and biologic disciplines. It originated from empirical observations and suppositions that failed to prevail upon the existing axioms. Despite the widespread resistance to embracing novel ideas, the seeming defeats inspired visionary researchers. Those pioneers managed to systematize the emerging knowledge and were able to contribute to science with real foundations. In consequence, new concepts and ideas arose in physiology, anatomy, endocrinology and early immunology. Together, they gave rise to a budding approach on the integration between the nervous, immune and endocrine systems. Then, neuroimmunoendocrinology emerged as a discipline integrating an intricate system with multidirectional functions and interactions that allow for responding to internal and external threats. Such response is mediated by cytokines, hormones and neurotransmitters, involved in different physiologic mechanisms of the organism homeostasis. Neuroimmunoendocrinology is no longer an area of scientific skepticism; on the contrary, it has cemented its position as a biomedical discipline worldwide for the past 70 years. Now, it offers a better understanding of pathologic processes.

Sera from patients with tuberculosis increase the phagocytic-microbicidal activity of human neutrophils, and ESAT-6 is implicated in the phenomenon.

Background: It has been reported that sera from patients with active pulmonary tuberculosis (APT) induced nuclear changes in normal neutrophils that included pyknosis, swelling, apoptosis, and production of extracellular traps (NETs). Similar changes were observed with some sera from their household contacts but not with sera from healthy, unrelated individuals. It was suggested that those sera from household contacts that induced neutrophil nuclear changes might correspond to people with subclinical tuberculosis. Thus, our experimental approach might serve to identify individuals with early, ongoing disease. Methods: Nuclear changes in neutrophils were fully evident by 3 h of contact and beyond. Circulating mycobacterial antigens were the most likely candidates for this effect. We wanted to know whether the nuclear changes induced on neutrophils by the sera of APT patients would negatively affect the phagocytic/microbicidal ability of neutrophils exposed to APT sera for short periods. Results: We now provide evidence that short-term contact (30 min) with sera from patients with pulmonary tuberculosis increases several phagocytic parameters of normal neutrophils, including endocytosis, myeloperoxidase levels, production of free reactive oxygen species, phagolysosome fusion, and microbicidal activity on Staphylococcus aureus, with these effects not being observed with sera from healthy donors. We also give evidence that suggests that ESAT-6 and CFP-10 are involved in the phenomenon. Conclusion: We conclude that activation is a stage that precedes lethal nuclear changes in neutrophils and suggests that autologous neutrophils must circulate in an altered state in the APT patients, thus contributing to the pathology of the disease.

Effect of dialyzable leukocyte extract, sodium butyrate, and valproic acid in the development of anergy in murine leprosy.

Background: Murine leprosy is a chronic granulomatous disease caused by Mycobacterium lepraemurium (MLM) in mice and rats. The disease evolves with the development of cellular anergy that impedes the production of interferon gamma (IFNγ), tumor necrosis factor-alpha (TNFα), and nitric oxide (NO) required to kill the microorganism. In this study we investigated whether histone deacetylase inhibitors (HDACi) (valproic acid and sodium butyrate [NaB]) and the immunomodulator transfer factor in dialyzable leukocyte extracts (DLE) can prevent anergy in murine leprosy. Methods: Five groups of six Balb/c mice were intraperitoneally inoculated with 2 × 107 MLM. Thirty-days post inoculation, treatment was started; one group received no treatment, one was treated with rifampicin-clofazimine (R-C), one with sodium valproate (VPA), one with NaB, and one with DLE. The animals were monitored for the evidence of disease for 96 days. After euthanasia, their spleens were removed and processed for histologic, bacteriologic, and cytokine studies. Results: R-C completely controlled the ongoing disease. DLE and NaB significantly reduced the development of lesions, including granuloma size and the number of bacilli; VPA was less effective. DLE, NaB, and VPA reverted the anergic condition in diverse grades and allowed the expression of IFNγ, TNFα, and inducible NO synthase, also in diverse grades. Conclusion: Anergy in leprosy and murine leprosy allows disease progression. In this study, anergy was prevented, in significant degree, by DLE (an immunomodulator) and NaB (HDACi). VPA was less effective. These results suggest potential beneficial effects of DLE and NaB in the ancillary treatment of leprosy.

Anti-inflammatory effect of omega unsaturated fatty acids and dialysable leucocyte extracts on collagen-induced arthritis in DBA/1 mice.

Rheumatoid arthritis is a disabling autoimmune disease with a high global prevalence. Treatment with disease-modifying anti-arthritic drugs (DIMARDs) has been routinely used with beneficial effects but with adverse long-term consequences; novel targeted biologics and small-molecule inhibitors are promising options. In this study, we investigated whether purified omega unsaturated fatty acids (ω-UFAs) and dialysable leukocyte extracts (DLEs) prevented the development of arthritis in a model of collagen-induced arthritis (CIA) in mice. We also investigated whether the transcription factor NF-κB and the NLRP3 inflammasome were involved in the process and whether their activity was modulated by treatment. The development of arthritis was evaluated for 84 days following treatment with nothing, dexamethasone, DLEs, docosahexaenoic acid, arachidonic acid, and oleic acid. Progression of CIA was monitored by evaluating clinical manifestations, inflammatory changes, and histological alterations in the pads' articular tissues. Both DLEs and ω-UFAs led to an almost complete inhibition of the inflammatory histopathology of CIA and this was concomitant with the inhibition of NF-kB and the inhibition of the activation of NLRP3. These data suggest that ω-UFAs and DLEs might have NF-κB as a common target and that they might be used as ancillary medicines in the treatment of arthritis.

Sleep characteristics of the parents of children admitted to a pediatric intensive care unit: risk factors and repercussion on their daily life activities.

OBJECTIVE: to analyze the sleep characteristics of the parents of children admitted to a pediatric intensive care unit (PICU), the possible risk factors and impact of sleep quality on their daily life activities. METHODS: Parents of children admitted to PICU for at least 48 h filled in a survey. Demographic data, sleep characteristics before and during admission and its impact on daily life activities measured by the FOSQ-10 questionnaire, were collected. RESULTS: 100 surveys from parents of 53 children admitted to the PICU were collected. Most children (74%) were cardiac patients. 55% of them had had previous PICU admissions. 45% of parents lived in a different city. They spent a median of 14 h a day (IQR 12-16) at the hospital and 89.2% did not attend work. Parents had significantly worse subjective sleep quality (p = 0.001), less sleeping hours/day (p = 0.001), more difficulty falling asleep (p = 0.001) and more night arousals (p = 0.001) during PICU admission than before. 77% of parents also had a bad FOSQ-10 score. Perceived sleep quality and FOSQ-10 score had a good correlation (p = 0.00, Kappa 0.43). Significant risk factors were living in a different city (p = 0.03), programmed admissions (p = 0.001), previous PICU admissions (p = 0.001), prolonged PICU length of stay (p = 0.03) and longer distance from home (p = 0.03). CONCLUSIONS: Three quarters of the parents of children admitted to PICU suffer from sleep disorders, which negatively affects their personal lives. Perceived sleep quality had a good correlation with FOSQ-10 score. Institutional support is needed to optimize parents' resting conditions during their child's hospitalization.

Análisis de la laparoscopía diagnóstica y estudios de imagen en el manejo del dolor en fosa ilíaca derecha de etiología incierta / Analysis of diagnostic laparoscopy and imaging studies for the handling of pain in undetermined etiology right iliac fossa / Análise da laparoscopia diagnóstica e estudos de imagem no manejo da dor na fossa ilíaca direita de etiologia incerta

Introducción: el dolor en la fosa ilíaca derecha (FID) es un motivo de consulta habitual en los servicios de urgencias. El principal desafío es diferenciar si es un cuadro quirúrgico o no. Objetivo: conocer qué rol ocupa la laparoscopía diagnóstica (LD), la ecografía de abdomen y la tomografía computada (TC) en el algoritmo de estudio de los pacientes con dolor en FID con diagnóstico incierto en Uruguay. Método: estudio observacional, descriptivo, prospectivo, multicéntrico, sobre pacientes que consultaron por dolor en FID desde el 1º de junio al 31 de agosto de 2017 en centros asistenciales de Uruguay. Se recolectaron los siguientes datos en una planilla electrónica: sexo, edad, sintomatología, hallazgos físicos, exámenes solicitados, conducta tomada, hallazgos intraoperatorios, complicaciones. Resultados: se completaron 159 planillas. Luego de una valoración primaria se planteó duda diagnóstica en 69 (43,4%) pacientes. La TC se solicitó en 29 (42%) pacientes. Se realizó TC al 78% de los mayores de 50 años versus 18% entre los de 15 y 29 años. Del total, 13 (44,8%) se informaron como normales, confirmando en el intraoperatorio cuatro (30,7%) apendicitis agudas. Se realizaron 29 LD en los casos con duda diagnóstica, dos tercios fueron en pacientes de 15 a 29 años. En 22 (76%) casos se arribó a un diagnóstico. No hubo complicaciones. Conclusiones: la LD permitió realizar diagnóstico y tratamiento en la mayoría de los casos. La sensibilidad de la TC fue baja en comparación con datos internacionales. El algoritmo diagnóstico debe ser individualizado, basado en protocolos adaptados a los recursos de cada institución. (AU)

Introduction: right iliac fossa (RIF) pain is a frequent reason for consultation at the Emergency Units. The main challenge lies in defining whether it is a surgical condition or not. Objective: to learn about the role of diagnostic laparoscopy, abdominal ultrasound and CT scan in the studies algorithm of patients with RIF pain of unknown etiology in Uruguay. Method: observational, descriptive, prospective, multi-center study of patients who consulted for RIF from June 1st to August 31, 2017 in Health Institutions in Uruguay. The following data were gathered in an excel sheet: sex, age, symptoms, physical findings, tests requested, conduct adopted, intraoperative findings and complications. Results: 159 sheets were completed. Upon a primary assessment a diagnostic doubt was arose in 69 patients (43.4%). A CT scan was requested to 29 patients, and a CT was performed to 78% of patients older than 50 years old vs 18% of those between 15 and 29 years. Conclusions: the diagnostic laparoscopy allowed for diagnosis in most cases. Sensitivity of the CT scan was low when compared to international data. The diagnostic algorithm needs to me individualized, based on protocols adapted to the resources of every institution.

Introdução: a dor na fossa ilíaca direita (FID) é um motivo habitual de consulta habitual nos Serviços de Urgências. O principal desafio é diferenciar entre um quadro cirúrgico e um não cirúrgico. Objetivo: conhecer o papel da laparoscopia diagnóstica (LD), do ultrassom de abdômen e da tomografia computada (TC) no algoritmo de estudo dos pacientes com dor na FID com diagnóstico incerto no Uruguai. Método: estudo observacional, descritivo, prospectivo, multicêntrico sobre pacientes que consultaram por dor na FID no período 1º de junho - 31 de agosto del 2017 em Centros Assistenciais no Uruguai. Em una planilha electrónica foram incluídos os seguintes dados: sexo, idade, sintomatologia, achados físicos, exames solicitados, conduta tomada, achados intra-operatórios e complicações. Resultados: foram preenchidas 159 planilhas. Depois de uma avaliação primaria foram definidas dúvidas diagnósticas em 69 (43,4%) pacientes. Foram solicitadas TC a 29 (42%) pacientes; 78% dos pacientes com mais de 50 anos vs 18% dos pacientes com idades entre 15 e 29 anos. 13 (44,8% do total) tiveram laudo "normal", confirmando apendicite aguda em 4 (30,7%) durante cirurgia. Foram realizadas 29 LD nos casos com dúvida diagnóstica sem dos terços em pacientes de 15 a 29 anos. Em 22 (76%) casos foi possível definir um diagnóstico. Não se registraram complicações. Conclusões: a LD permitiu realizar diagnóstico e tratamento na maioria dos casos. A sensibilidade da TC foi baixa em comparação com dados internacionais. O algoritmo diagnóstico deve ser individualizado, baseado em protocolos adaptados aos recursos de cada instituição.

Bullying entre adolescentes, una problemática creciente / Bullying among adolescents, an growing problem

El bullying en la actualidad es un verdadero problema de salud creciente que ha ganado espacio,pero sin embargo es poco denunciado, a pesar de existir leyes en el Ecuador que lo estipulan como delito;la forma de maltrato en la actualidad se ha intensificado debido a la utilización de redes sociales y discriminación de clase. En Ambato, en una unidad educativa privada, se realizó el presente estudio transversal descriptivo en jóvenes de 13 a 18 años deedad, mediante la aplicación de una encuesta, y los resultados mostraron que el 49 % de adolescentes admite ser acosado, identificándosea la provocación, el maltrato verbal como formas frecuentes de intimidación, seguido del maltrato físico y psicológico; el lugar donde se produce el mayor número de intimidaciones es fuera de la unidad educativa y en ausencia del docente; el adolescente intimidado en alto porcentaje no comparte su problema, lo que hace que esta modalidad de intimidación no sea resuelta deforma inmediata y no se tome el correctivo necesario, tanto para el acosador como para el intimidado,lo cual en el futuro traerá graves consecuencias, dentro de las cuales se pueden citar trastornos psicológicos, de conducta, bajo rendimiento escolar, distimia y en el peor de los casos llegar a autolisis. Por todo aquello es necesario realizar campañas de concienciación dirigidas a docentes, padres de familia y estudiantes, con el fin de detectar y corregir a tiempo esta problemática social, evitando consecuencias fatales.

Bullying is in the actuality a real and silent health problem, that has gained ground, however it is little denounced, despite of the existence of laws in Ecuador that report it as a crime, the way to abuse today has been intensified due to the use of social networks and class discrimination. In Ambato, in a private education unit, was made this descriptive cross-sectional study in teenagers between 13-18 years old, and the results showed that 49 % of teenagers admit being bullied, as the main factor was identified the provocation, and as more frequent the verbal abuse, followed by physical and psychological abuse; the place the most number of intimidations where made is in the around of the educational unit and in the absence of teachers; the teenager who is bullied in high percentage does not share their problem, what makes this type of intimidation not be resolved immediately and they do not take the necessary corrective measures, for both the bully as the aggressed, this will bring serious consequences in the future within which we can cite psychological disorders, behavioral, poor school performance, dysthymias and in the worst of case to the autolysis, For this reason, it is necessary to conduct awareness campaigns aimed at teachers, parents and students, in order to detect and correct as soon as possible this social problem, avoiding fatal consequences.

Sera from patients with active pulmonary tuberculosis and their household contacts induce nuclear changes in neutrophils.

BACKGROUND: Resident alveolar macrophages, dendritic cells, and immigrating neutrophils (NEU) are the first cells to contact Mycobacterium tuberculosis in the lung. These cells, and additional lymphoid cells in the developing granuloma, release a series of components that may concentrate in the serum and affect disease progression. PURPOSE: The aim of this study was to investigate the effect of the serum from tuberculosis (TB) patients and their household contacts (HHC) on the nuclear morphology of NEU. MATERIALS AND METHODS: NEU from healthy (HLT) people were incubated with sera from patients with active pulmonary TB, their HHC, and unrelated people. Changes in the nuclear morphology of NEU were analyzed by light and electron microscopy. RESULTS: Sera from patients with TB induced changes in the nuclear morphology of NEU that included pyknosis, swelling, apoptosis, and netosis in some cases. Sera from some HHC induced similar changes, while sera from HLT people had no significant effects. Bacteria did not appear to participate in this phenomenon because bacteremia is not a recognized feature of nonmiliary TB, and because sera from patients that induced nuclear changes maintained their effect after filtration through 0.22 µm membranes. Neither anti-mycobacterial antibodies, TNFα, IL-6, IFNγ, or IL-8 participated in the phenomenon. In contrast, soluble mycobacterial antigens were likely candidates, as small quantities of soluble M. tuberculosis antigens added to the sera of HLT people led to the induction of nuclear changes in NEU in a dose-dependent manner. CONCLUSION: These results might help to detect subclinical TB within HHC, thus leading to a recommendation of prophylactic treatment.

Etiological identification of viral agents in acute encephalitis in Guadalajara, México, 2011-2015

Introduction: Viral encephalitis is a well-known inflammatory process associated with neurological dysfunction that might derive into severe brain damage or a fatal outcome. In México there is no epidemiological data that describes the prevalence of viral agents responsible for acute encephalitis. Objective: To identify the main viral agents by real time PCR involved in acute encephalitis in Mexico. Materials and methods: We obtained cerebral spinal fluid (CSF) samples from all patients with suspected viral encephalitis admitted to the emergency service of the Hospital Civil de Guadalajara "Fray Antonio Alcalde". To identify pathogens, we performed nucleic acid extraction using real-time PCR and RT-PCR. Results: Sixty-six patients were diagnosed with acute encephalitis from 2011 to 2014. A definitive viral etiological diagnosis was established in 16 patients (24%); the main causative agents were enteroviruses in 50% of the 16 positive samples, followed by herpes simplex virus (37%) and cytomegaloviruses (12.5%). Patients with encephalitis were predominantly male (63.3%) and a seasonal predominance was observed during autumn (37.5%). The main clinical characteristics in the acute encephalitis phase were fever (48.45) and cephalea (36.3), followed by seizures, disorientation, and muscular weakness (30.3%). Kerning sign was present in two cases (3%) and other two cases presented Brudzinski's sign (3%). Conclusions: CSF PCR is a suitable diagnostic technique for the identification of viral encephalitis caused by viral infections that allows an appropriate antiviral therapeutic treatment.

Identificación etiológica de agentes virales de la encefalitis aguda en Guadalajara, México, 2011-2015 / Etiological identification of viral agents in acute encephalitis in Guadalajara, México, 2011-2015

Resumen Introducción. La encefalitis viral aguda se define como un proceso inflamatorio asociado a disfunción neurológica con desenlace fatal o daño grave permanente. En México no se han hecho estudios de identificación directa de los agentes etiológicos causales de la encefalitis viral aguda. Objetivo. Identificar mediante PCR en tiempo real los principales agentes virales causantes de encefalitis viral aguda en México. Materiales y métodos. Se obtuvo el líquido cefalorraquídeo de pacientes con sospecha de encefalitis viral que ingresaron al servicio de urgencias del Hospital Civil Fray Antonio Alcalde. Se extrajeron ácidos nucleicos para identificar los patógenos mediante PCR y PCR con transcripción inversa en tiempo real. Resultados. Se captaron un total de 66 pacientes entre el 2011 y el 2014. En 16 de los casos (24 %) se identificó el agente viral y se encontró que el principal agente causal fue el enterovirus, con ocho casos (50 %), seguido del virus del herpes simple (HSV: 37 %), con seis casos, y el citomegalovirus (CMV: 12,5 %), con dos casos. El promedio de edad fue de 25 años (0-70 años). Los casos positivos predominaron en los varones (63,3 %) y se estableció un predominio estacional en otoño (37,5 %). La mayoría de los pacientes presentó fiebre (48,4 %) o cefalea (36,3 %) y, en menor proporción, convulsiones, confusión y debilidad muscular (30,3 %) seguidas de desorientación (28,75 %) y apatía (25,7 %). En dos de los casos se observó el signo de Kerning (3 %) y en otros dos, el signo de Brudzinski (3 %). Conclusiones. La PCR en líquido cefalorraquídeo es una técnica de diagnóstico adecuada para la identificación de virus causales de encefalitis viral, lo cual permite prescribir los medicamentos específicos.

Abstract Introduction: Viral encephalitis is a well-known inflammatory process associated with neurological dysfunction that might derive into severe brain damage or a fatal outcome. In México there is no epidemiological data that describes the prevalence of viral agents responsible for acute encephalitis. Objective: To identify the main viral agents by real time PCR involved in acute encephalitis in Mexico. Materials and methods: We obtained cerebral spinal fluid (CSF) samples from all patients with suspected viral encephalitis admitted to the emergency service of the Hospital Civil de Guadalajara "Fray Antonio Alcalde". To identify pathogens, we performed nucleic acid extraction using real-time PCR and RT-PCR. Results: Sixty-six patients were diagnosed with acute encephalitis from 2011 to 2014. A definitive viral etiological diagnosis was established in 16 patients (24%); the main causative agents were enteroviruses in 50% of the 16 positive samples, followed by herpes simplex virus (37%) and cytomegaloviruses (12.5%). Patients with encephalitis were predominantly male (63.3%) and a seasonal predominance was observed during autumn (37.5%). The main clinical characteristics in the acute encephalitis phase were fever (48.45) and cephalea (36.3), followed by seizures, disorientation, and muscular weakness (30.3%). Kerning sign was present in two cases (3%) and other two cases presented Brudzinski's sign (3%). Conclusions: CSF PCR is a suitable diagnostic technique for the identification of viral encephalitis caused by viral infections that allows an appropriate antiviral therapeutic treatment.

Validación de la batería de instrumentos para la evaluación de factores de riesgo psicosocial / Validation of the battery of instruments for the evaluation of psychosocial risk factors

Objetivo: El presente estudio tuvo el objetivo de adaptar y validar los resultados de la Batería de Instrumentos para la Evaluación de Factores de Riesgo Psicosocial desarrollado por el Ministerio de la Protección Social de Colombia en el 2010. Materiales y métodos: Se realizó un estudio instrumental con los trabajadores que pasaron examen médico ocupacional de marzo a setiembre 2014, con un total de 478 personas. Se procedió al análisis de propiedades psicométricas mediante criterio de jueces, análisis de validez mediante el coeficiente V de Aiken, análisis de validez de constructo mediante análisis factorial de tipo exploratorios y el análisis de confiabilidad mediante la consistencia interna con el coeficiente Alpha de Cronbach. Resultados: Como resultados del análisis de la validez de contenido, al aplicar el criterio de jueces, se consideraron solo aquellos ítems con V = 1 (p = 0,032), quedando en la Forma A, 108 reactivos, en la Forma B, 96 y en Extralaborales, 29 ítems. Se evidenciaron índices de homogeneidad de los ítems mayor al criterio (rit > 0,20) e índices adecuados de confiabilidad por el método de consistencia interna con el estadístico Alfa de Cronbach en las escalas Intralaboral Forma A, Forma B, Extralaboral y Estrés. Para el grado de validez convergente, se obtuvieron correlaciones estadísticamente significativas en la mayoría de dimensiones entre las escalas Extralaboral y Estrés, y entre la Forma A y Estrés. Conclusiones: Se determinó la validez de criterio y validez convergente en las escalas Intralaboral A, Intralaboral B y Extralaboral, encontrándose evidencias empíricas de mediciones coherentes al constructo de Riesgos Psicosociales; asimismo, se calcularon los coeficientes de consistencia interna, obteniéndose en las dimensiones evaluadas adecuados índices de acuerdo al criterio mínimo sugerido para la investigación

Objective: This study aimed to adapt and validate the results of the Batería de Instrumentos para la Evaluación de Factores de Riesgo Psicosocial (Battery of Instruments for the Evaluation of Psychosocial Risk Factors) developed by the Ministry of Health and Social Protection of Colombia in 2010. Materials and methods: An instrumental study was conducted with a total of 478 workers who underwent an occupational medical examination from March to September 2014. The following analyses were performed: psychometric properties by judges' criteria, validity by Aiken's V coefficient, construct validity by exploratory factor analysis, and reliability and internal consistency by Cronbach's Alpha. Results: In the content validity analysis using judges' criteria, only items with V = 1 (p = 0.032) were considered, resulting in 108 items in the Inside-Work scale form A, 96 items in the Inside-Work scale form B, and 29 items in the Outside-Work scale. A higher-than-standard item homogeneity level (rit > 0.20), and adequate reliability and internal consistency levels were demonstrated by Cronbach's Alpha in the Inside-Work scale form A, Inside-Work scale form B, Outside-Work scale and Stress scale. In the convergent validity analysis, statistical significant correlations were obtained in most of the dimensions between the Outside-Work scale and Stress scale, and the Inside-Work scale form A and Stress scale. Conclusions: Criteria validity and convergent validity were determined in the Inside-Work scale form A, Inside-Work scale form B and Outside-Work scale, with empiric evidence of measurements consistent with the psychosocial risk construct being found. Moreover, internal consistency coefficients were estimated, with adequate levels being obtained in the assessed dimensions, according to the minimum level suggested for the research

Colitis pseudomembranosa por Clostridium difficile: Reporte de un caso en paciente pediátrico. [Reporte de Caso] / Pseudomembranous colitis by Clostridium difficile infection: a case report in pediatric patient. [Case Report]

Clostridium difficile es un bacilo Gram positivo esporulado, anaerobio estricto, resistente a condiciones adversas y transmitido por vía oral-fecal, se describió por primera vez en 1930; sin embargo, se asoció a enfermedad en humanos en la década de los setenta al identificarse como agente causal de colitis pseudomembranosa. Esta infección se ha relacionado con diversas manifestaciones clínicas que van desde diarrea sin complicaciones hasta sepsis e incluso la muerte. Se presenta un caso clínico de un paciente masculino de 1 año 8 meses, con antecedentes de hipertermia y deposiciones líquidas abundantes, tras varios días de tratamiento antibiótico los síntomas se incrementaron con eliminación de resto membranoso en heces, se refiere a un hospital; donde se realiza el estudio de toxinas de Clostridium difficile, resultando positivo, por lo cual, se establece el diagnostico de colitis pseudomembranosa. Se administra metronidazol y vancomicina por 7 días, con una evolución favorable. El uso de antibióticos es un factor predisponente de colitis pseudomembranosa por la afectación de la microbiota intestinal; además de la estancia hospitalaria y factores intrínsecos. En la literatura se describe un número reducido de estudios sobre esta infección en pacientes pediátricos de allí la importancia del reporte de caso.

Clostridium difficile is a bacillus Gram positive and spore form, anaerobic strictly, resistant to adverse conditions and transmitted by oral - fecal route, it was described by the first time in 1930, nevertheless it's has been associated to disease in human beings in the decade of the seventies it identified as causal agent of pseudomembranous colitis. Its infection has related to diverse clinical manifestations such as diarrhea without complications, which lead to sepsis and inclusive the death. In the following clinical case we have a male infant 1 year old and 18 months patient, with precedents of hyperthermia and liquid depositions, after several days of antibiotics treatment, the symptoms increased with elimination of membranous rest in the faeces; reason why he is transferred to a hospital, in which the Clostridium difficile toxins test is realized, yielding positive results, therefore the diagnosis of pseudomembranous colitis is established metronidazole and vancomycin is given for 7 days having a favorable development. The use of antibiotics is a predisposing factor of pseudomembranous colitis for the affectation of the intestinal microbiota, in addition hospital stays and intrinsic factors. The literature describes a limited number of studies about this infection in pediatric patients, hence the importance of the case report

In vivo induction of neutrophil extracellular traps by Mycobacterium tuberculosis in a guinea pig model.

In 2004, a novel mechanism of cellular death, called 'NETosis', was described in neutrophils. This mechanism, different from necrosis and apoptosis, is characterized by the release of chromatin webs admixed with microbicidal granular proteins and peptides (NETs). NETs trap and kill a variety of microorganisms. Diverse microorganisms, including Mycobacterium tuberculosis, are NET inducers in vitro. The aim of this study was to examine whether M. tuberculosis can also induce NETs in vivo and if the NETs are bactericidal to the microorganism. Guinea pigs were intradermally inoculated with M. tuberculosis H37Rv, and the production of NETs was investigated at several time points thereafter. NETs were detected as early as 30 min post-inoculation and were clearly evident by 4 h post-inoculation. NETs produced in vivo contained DNA, myeloperoxidase, elastase, histones, ROS and acid-fast bacilli. Viable and heat-killed M. tuberculosis, as well as Mycobacterium bovis BCG were efficient NET inducers, as were unilamellar liposomes prepared with lipids from M. tuberculosis. In vitro, guinea pig neutrophils also produced NETs in response to M. tuberculosis. However, neither the in vivo nor the in vitro-produced NETs were able to kill M. tuberculosis. Nevertheless, in vivo, neutrophils might propitiate recruitment and activation of more efficient microbicidal cells.

Mycobacterium lepraemurium uses TLR-6 and MR, but not lipid rafts or DC-sign, to gain access into mouse macrophages.

OBJECTIVE/BACKGROUND: Mycobacterium lepraemurium (MLM), the etiologic agent of murine leprosy, is an intracellular parasite of macrophages; the mechanism used by this bacterium to enter macrophages is not known. The fate of the MLM phagosome inside macrophages is also unknown. This study was conducted to investigate how MLM enters macrophages and to define the maturation process of MLM phagosome inside macrophages. MATERIALS AND METHODS: Peritoneal macrophages were incubated in the presence of mannan-bovine serum albumin (BSA), and antibodies to known macrophage receptors, including, anti-FcγRIII/RII (anti-CD16/32), anti-CD35 (anti-CR1), anti-TLR2, anti-TLR4, anti-TLR6, anti-CD14, and anti-dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN). Then, macrophages were challenged with Iris Fuchsia-stained MLM, at a multiplicity of infection of 50:1. The blocking effect of the antibodies (and mannan-BSA) used was analyzed using direct microscopy and flow cytometry. The maturation process of MLM phagosomes was visualized by their interaction with antibodies to Rab5, Rab7, proton ATPase, and cathepsin D, by confocal microscopy. RESULTS: Only mannan-BSA and anti-TLR6 antibody significantly blocked the entry of MLM into macrophages. None of the other antibodies, including that for DC-SIGN, meaningfully inhibited the endocytic process. We also found that MLM is a fusiogenic mycobacterium. This was deduced from the orderly association of MLM phagosomes with Rab5, Rab7, Proton ATPase, and lysosomes (cathepsin D). CONCLUSION: Fusion of MLM phagosomes with lysosomes seems to be a necessary event for the intracellular multiplication of MLM; similar to Mycobacterium leprae, this microorganism hardly grows on artificial, synthetic, bacteriologic media.

Estrongiloidosis como causa de hemorragia digestiva baja

Intestinal parasites are a common pathology in the pediatric practice, constituting a major public health problem. Currently their epidemiology, especially in countries like Ecuador where there are populations and communities where health services are scarce or difficult to access. We report the case of a child with chronic grade 3 malnutrition, from Sarayacu province of Pastaza, Ecuador an endemic area in several parasitosis. The clinical features were lower gastrointestinal bleeding added to chronic anemia and eosinophilia. The patient underwent surgery, colectomy right after finding at colonoscopy mass at the small intestine and colon, which ends with the symptoms. We get to the subsequent diagnosis histopathological analysis in which found peritoneal invasion of Strongyloides stercoralis larvae filariform. This article shows a general perspective on the gastrointestinal bleeding in pediatrics and relevant data about the strongyloidiasis.

Las parasitosis intestinales son una patología frecuente en la consulta pediátrica, constituyendo un problema importante de salud pública. Actualmente, su epidemiología ha variado en países como Ecuador en el que existen poblaciones y comunidades en las que los servicios de salud son escasos o de difícil acceso. Comunicamos el caso de un niño de tres años con desnutrición crónica, proveniente de Sarayacu, provincia de Pastaza, Ecuador, área endémica de parasitosis, que presentó una hemorragia digestiva baja asociado a anemia crónica y eosinofilia. Se realizó una hemicolectomía derecha tras encontrar en la colonoscopia múltiples masas en intestino delgado y de colon. El análisis histopatológico demostró una invasión peritoneal de larvas filariformes de Strongyloides stercoralis.