Tau filaments are tethered within brain extracellular vesicles in Alzheimer's disease.

The abnormal assembly of tau protein in neurons is the pathological hallmark of multiple neurodegenerative diseases, including Alzheimer's disease (AD). In addition, assembled tau associates with extracellular vesicles (EVs) in the central nervous system of patients with AD, which is linked to its clearance and prion-like propagation between neurons. However, the identities of the assembled tau species and the EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from AD patients. We found filaments of truncated tau enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD.

Utilidad de la Determinación de CD25 Soluble en Pacientes con sospecha de Síndrome de Activación Macrofágica / Usefulness of the determination of soluble CD25 in patients with suspected macrophage activation syndrome

El síndrome de activación macrofágica (SAM) presenta criterios clínicos y de laboratorio establecidos. Presentamos el caso de un adolescente varón con debut de Lupus eritematoso generalizado pediátrico grave, donde su manifestación principal fue un SAM y el receptor de interleucina 2 soluble en suero (IL-2rs) o CD25 soluble (CD25s) aumentado resultó clave en la confirmación diagnóstica, en el tratamiento y pronóstico de su enfermedad. Sin embargo, este receptor de citocinas no se mide habitualmente en la práctica clínica.

Macrophage activation syndrome (MAS) presents established clinical and laboratory criteria. We present the case of a male adolescent with the onset of severe pediatric systemic Lupus erythematosus, manifested mainly by MAS and how a laboratory marker, serum soluble interleukin-2 receptor (IL-2rs) or altered soluble CD25(CD25s), played a key role in treatment and prognosis of the disease. However, this cytokine receptor is rarely measured in clinical practice.

Beer effects on postprandial digestive symptoms and gastroesophagic physiology.

BACKGROUND: Beer has been related to gastroesophageal reflux (GER) and dyspepsia, based on its alcohol and gas content. The aim of this study is to evaluate the association between moderate consumption of traditional and alcohol-free beer and upper digestive symptoms, gastric accommodation and GER. METHODS: Healthy adults without frequent gastrointestinal symptoms and GER disease were included. The intervention involved administration of traditional beer to 10 subjects (substudy 1) and alcohol-free beer to 20 (substudy 2); control intervention entailed administration of water. Study duration was 2 weeks (control/intervention). Postprandial gastric accommodation was assessed through the maximum tolerated volume during a nutrient drink test after the ingestion of water (day 1) and beer (day 8), in which symptoms of dyspepsia were evaluated every 5 minutes. An impedance-pH monitoring assessed 24 hours and post-NDT GER (days 1 and 8). Symptoms were evaluated daily during the study. The defined variables were compared between visits and weeks using a nonparametric test for paired data. KEY RESULTS: Dyspepsia symptoms showed a progressive increase during the NDT for both interventions in the 2 substudies, though no significant differences were detected in the MTV analysis. No differences were detected in the sum of weekly symptoms. The analysis of impedance-pH monitoring did not show any differences between intervention and control visits for both interventions. CONCLUSIONS AND INFERENCES: Moderate consumption of traditional and alcohol-free beer does not increase dyspeptic symptoms or GER in healthy subjects, whether in a controlled-intake or real-life situation. Neither gastric accommodation nor reflux episodes are modified in this context.

IFPA Meeting 2010 Workshop Report I: Immunology; ion transport; epigenetics; vascular reactivity; epitheliochorial placentation; proteomics.

Workshops are an important part of the IFPA annual meeting. At IFPA Meeting 2010 there were twelve themed workshops, six of which are summarized in this report. 1. The immunology workshop focused on normal and pathological functions of the maternal immune system in pregnancy. 2. The transport workshop dealt with regulation of ion and water transport across the syncytiotrophoblast of human placenta. 3. The epigenetics workshop covered DNA methylation and its potential role in regulating gene expression in placental development and disease. 4. The vascular reactivity workshop concentrated on methodological approaches used to study placental vascular function. 5. The workshop on epitheliochorial placentation covered current advances from in vivo and in vitro studies of different domestic species. 6. The proteomics workshop focused on a variety of techniques and procedures necessary for proteomic analysis and how they may be implemented for placental research.

Flegmasia cerulea dolens: reporte de un caso y revisión de la literatura / Flegmasia cerulea dolens: case report and literature review

Phlegmasia Caerulea Dolens is a rare complication of deep vein thrombosis. It presents with a sudden onset of pain, swelling, discoloration and arterial compromise of the affected limb. There’s usually history of prothrombotic events such as malignancy, femoral vein catheterism, antiphospholipid syndrome, recent surgery, pregnancy, etc. Left without treatment, it can evolvein to gangrene, septic shock and death. Diagnosis usually only requires clinical appreciation.Confirmation can be done with ultrasonographic studies with doppler. Treatment can be both medical and surgically based. Medical therapy can be done with heparin and elevation of the affected limb or the use of thrombolytic, whilst surgical therapy can be either venous thrombectomy or amputation. We present the case of a 57-year old smoker, diabetic, and with systemic lupus erythematosus history female patient, that goes to the emergency room with sudden left leg pain, with cyanosis and absence of distal pulses. Besides she presented with lower respiratory symptoms. Diagnosis was confirmed with ultrasound and CT pulmonary angiography was performed showing pulmonary embolism. Medical treatment was initiated with good response.

Metástasis cutáneas en cáncer de ovario: [revisión] / Skin metastases of ovarian cancer: [review]

El cáncer de ovario es la segunda neoplasia maligna ginecológica más común, pero la principal causa de muerte entre las mujeres que padecen algún cáncer ginecológico. El hallazgo de metástasis a distancia en cáncer de ovario tanto en el diagnostico como durante el seguimiento, se encuentra en cerca del 18 por ciento de las pacientes. Las metástasis en piel se han reportado en cifras menores a un 4 por ciento. El compromiso cutáneo se ha descrito como un fenómeno tardío en la historia natural de la, enfermedad, reportándose una sobrevida promedio de 4 meses, posterior al hallazgo de la metástasis en piel. En éste trabajo se reporta el caso de una paciente con éste tipo de diseminación metastásica en piel, junto con una revisión bibliográfica del tema.

Ovarian carcinoma is the second most common gynecologic neoplasm, but it is still the main cause of death among the gynecologic tumors in women. Distant metastases are found in 18 percent of the patients with ovarian carcinoma. Skin metastases of ovarian carcinoma are very rare. It has been reported in almost 4 percent and in some cases as the first manifestation of the disease. Skin metastases have been described as a late manifestation during the natural history of the disease, reporting an average of 4 month survival after the finding of skin lesions. In this paper a case of a patient with this type of metastatic dissemination on skin is reported, including a bibliographic review of the literature.

Reparación laparoscópica de fístula vesicovaginal mediante técnica retrovesical: una serie de 6 pacientes / Laparoscopic repair of vesicovaginal fistula: a serie of 6 patients

Antecedentes: La fístula vesicovaginal (FVV) es una enfermedad frecuente en países no desarrollados y afecta la calidad de vida de mujeres en edad media, siendo la causa más habitual la histerectomía previa. Las técnicas quirúrgicas disponibles para su reparación presentan resultados variables. Objetivos: Presentar nuestra experiencia en la reparación de FVV por vía laparoscópica con abordaje retrovesical, en una serie consecutiva de 6 pacientes. Método: análisis prospectivo descriptivo de 6 pacientes sometidos a reparación laparoscópica retrovesical de FVV supratrigonales secundarias a histerectomías. Resultados: El tiempo operatorio promedio fue de 191 minutos. Ningún paciente requirió transfusiones y el tiempo de hospitalización promedio fue de 2,5 días. No se presentaron complicaciones ni recidivas, con un seguimiento promedio de 15 meses. Conclusión: La reparación laparoscópica de FVV mediante técnica retrovesical es una técnica segura, poco invasiva y reproducible en manos entrenadas, que podría convertirse en la técnica de elección a futuro. De acuerdo a nuestra revisión, esta comunicación es la primera serie de reparación laparoscópica de FVV publicada en Chile.

Background: Vesicovaginal fistula (VVF) is a fairly common condition in underdeveloped countries affecting mainly young women. Its most prevalent cause is prior hysterectomy. Surgical techniques for repairing VVF have widespread results. Objective: To present our results with a retrovesical laparoscopical repair of VVF in a 6 consecutive patient case series. Method: It is a descriptive prospective analysis of 6 consecutive patients with a retrovesical laparoscopical repair of supratrigonal VVF after hysterectomy. Results: Average surgical time was 191 minutes. No blood transfusion was required. Average hospital stay was 2.5 days. None of them had postoperatory complications nor relapse whatsoever, after a minimum of 15 months follow-up. Conclusion: Retrovesical laparoscopic repair of VVF is a feasible, simple, reproducible and less invasive technique. In trained hands it is the election technique for this condition. To the best of our knowledge this is the first publication of laparoscopic management for VVF in Chile.

[Atrioventricular conduction disorders following total correction of tetralogy of Fallot. Analysis of the electrogram of the bundle of His]. / Trastornos de conducción auriculoventricular post-corrección total de la tetralogía de Fallot. Análisis mediante el electrograma del haz de His

A study was made of the electric activity of the atrioventricular (AV) conduction system in basal conditions and with atrial stimulation in order to discover the type, severity and prognosis of the AV disturbance in cases of total correction of tetralogy of Fallot. The authors studied thirteen patients from the Paediatric Department of the National Institute of Cardiology who had undergone such surgery, 7 males, 6 females from 3 to 22 years old. All presented advanced RBBB and sinus rhythm; in the immediate postoperative period, one presented complete transitory A-V block which required a stand by pacemaker; in 2 cases there was a first degree AV block; in two other, LAH and LPH. In 5 cases atrial stimulation was made with single charges and progressive frequency. Measurements were taken at the customary intervals. In basal conditions, prolongation of the AH interval was only found in 2 patients, both with first degree AV block in the peripheral EKG; both patients were taking digitalis. The HV interval was longer than normal in 3 cases, with one of these showing also a lengthened AH interval. The atrial stimulation showed prolonged ventricular activation in 2 cases, one of them with normal basal HV interval. The authors conclude that this procedure permits: 1) The discovery of alterations in the AV conduction system which could not be found in a peripheral EKG. 2) Localization of the site of the lesion. 3) The finding of disturbances of the ventricular conduction by atrial stimulation. 4) Identification of those patients who, after a complete correction of tetralogy of Fallot, show a potential high risk of developing complete complete AV block or of sudden death. 5) The establishment of a real prognosis in these patients.