The vacuolar transporter chaperone (VTC) complex is required for microautophagy.

Microautophagy involves direct invagination and fission of the vacuolar/lysosomal membrane under nutrient limitation. This occurs by an autophagic tube, a specialized vacuolar membrane invagination that pinches off vesicles into the vacuolar lumen. In this study we have identified the VTC (vacuolar transporter chaperone) complex as required for microautophagy. The VTC complex is present on the ER and vacuoles and at the cell periphery. On induction of autophagy by nutrient limitation the VTC complex is recruited to and concentrated on vacuoles. The VTC complex is inhomogeneously distributed within the vacuolar membranes, showing an enrichment on autophagic tubes. Deletion of the VTC complex blocks microautophagic uptake into vacuoles. The mutants still form autophagic tubes but the production of microautophagic vesicles from their tips is impaired. In line with this, affinity-purified antibodies to the Vtc proteins inhibit microautophagic uptake in a reconstituted system in vitro. Our data suggest that the VTC complex is an important constituent of autophagic tubes and that it is required for scission of microautophagic vesicles from these tubes.

Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer

BACKGROUND: Mediastinal lymph-node dissection was compared to systematic mediastinal lymph-node sampling in patients undergoing complete resection for non-small cell lung cancer with respect to morbidity, duration of chest tube drainage and hospitalization, survival, disease-free survival, and site of recurrence. METHODS: A consecutive series of one hundred patients with non-small-cell lung cancer, clinical stage T1-3 N0-1 after standardized staging, was divided into two groups of 50 patients each, according to the technique of intraoperative mediastinal lymph-node assessment (dissection versus sampling). Mediastinal lymph-node dissection consisted of removal of all lymphatic tissues within defined anatomic landmarks of stations 2-4 and 7-9 on the right side, and stations 4-9 on the left side according to the classification of the American Thoracic Society. Systematic mediastinal lymph-node sampling consisted of harvesting of one or more representative lymph nodes from stations 2-4 and 7-9 on the right side, and stations 4-9 on the left side. RESULTS: All patients had complete resection. A mean follow-up time of 89 months was achieved in 92 patients. The two groups of patients were comparable with respect to age, gender, performance status, tumor stage, histology, extent of lung resection, and follow-up time. No significant difference was found between both groups regarding the duration of chest tube drainage, hospitalization, and morbidity. However, dissection required a longer operation time than sampling (179 +/- 38 min versus 149 +/- 37 min, p < 0.001). There was no significant difference in overall survival between the two groups; however, patients with stage I disease had a significantly longer disease-free survival after dissection than after sampling (60.2 +/- 7 versus 44.8 +/- 8 months, p < 0.03). Local recurrence was significantly higher after sampling than after dissection in patients with stage I tumor (12.5% versus 45%, p = 0.02) and in patients with nodal tumor negative mediastinum (N0/N1 disease) (46% versus 13%, p = 0.004). CONCLUSION: Our results suggest that mediastinal lymph-node dissection may provide a longer disease-free survival in stage I non-small cell lung cancer and, most importantly, a better local tumor control than mediastinal lymph-node sampling after complete resection for N0/N1 disease without leading to increased morbidity.

Fibrinogen binds to nontoxigenic and toxigenic Corynebacterium diphtheriae strains

The production of fibrinous exudates may play an important role in determining the outcome of bacterial infection. Although pseudomembrane formation is a characteristic feature of diphtheria, little is known about the fibrinogen (Fbn)-binding properties of Corynebacterium diphtheriae strains and the influence of the gene that codes for diphtheria toxin (tox gene) in this process. In this study we demonstrated the ability of C. diphtheriae strains to bind to Fbn and to convert Fbn to fibrin. Bacterial interaction with rabbit plasma was evaluated by both slide and tube tests. Interaction of microorganisms with human Fbn was evaluated by both enzyme linked immunosorbent assay (ELISA) and fluorescein isothiocyanate-conjugated (FITC) Fbn binding assays. Nontoxigenic and toxigenic strains formed bacterial aggregates in the presence of plasma in the slide tests. The ability to convert Fbn to a loose web of fibrin in the plasma solution in the tube tests appeared to be a common characteristic of the species, including strains that do not carry the tox gene. Fbn binding to C. diphtheriae strains occurred at varying intensities, as demonstrated by the FITC-Fbn and ELISA binding assays. Our data suggest that the capacity to bind to Fbn and to convert Fbn to fibrin may play a role in pseudomembrane formation and act as virulence determinants of both nontoxigenic and toxigenic strains.

Properties of ideal composite knots.

The shortest tube of constant diameter that can form a given knot represents the 'ideal' form of the knot. Ideal knots provide an irreducible representation of the knot, and they have some intriguing mathematical and physical features, including a direct correspondence with the time-averaged shapes of knotted DNA molecules in solution. Here we describe the properties of ideal forms of composite knots-knots obtained by the sequential tying of two or more independent knots (called factor knots) on the same string. We find that the writhe (related to the handedness of crossing points) of composite knots is the sum of that of the ideal forms of the factor knots. By comparing ideal composite knots with simulated configurations of knotted, thermally fluctuating DNA, we conclude that the additivity of writhe applies also to randomly distorted configurations of composite knots and their corresponding factor knots. We show that composite knots with several factor knots may possess distinct structural isomers that can be interconverted only by loosening the knot.

Prevalencia y factores asociados a desnutrición entre pacientes ingresados en un hospital de media-larga estancia

OBJECTIVES To determine the prevalence of hyponutrition at admission at a mid- to long-term stay hospital. To analyze the possible factors associated to hyponutrition; the possible relationship with mortality at one month, and the treatments for hyponutrition performed. MATERIALS AND METHOD Descriptive study from the laboratory data obtained in 140 patients. For diagnosing hyponutrition, a tool based on albumin, total cholesterol, and lymphocytes levels was used. Demographical (age and gender) and clinical data (presence of pressure soars, nasogastric tube, dementia, neoplasm, previous admission to the ICU, and main diagnosis) were gathered at admission as well as the mortality at the first month. The treatments used for hyponutrition were reviewed. RESULTS patients' age was 77.1 years and 63% were females. 17.1% of the patients presented normal nutritional status, 50.7% met the criteria for mild hyponutrition, 26.4% of moderate hyponutrition, and 5.7% of severe hyponutrition. We found no association between hyponutrition and gender, nasogastric tube, soars, dementia or neoplasm, but we did so with age (P = 0.033). We found a relationship between moderate-severe hyponutrition and pressure soars (P = 0.036). We found an association between hyponutrition and mortality at one month (OR = 1.357, 95% CI 1.121 to 1.643; P = 0.02). 35.6% of the patients with moderate-severe hyponutrition received therapy for this condition (28.9% with protein supplements and 6.7% with enteral diet). CONCLUSIONS hyponutrition affects most of the patients admitted to a mid to long-term stay hospitals and is associated with higher mortality. One third of hyponutrition patients receive nutritional therapy.

Lipofilling : rôle de la centrifugation

Introduction : Le lipofilling s'est développé au cours du 20ème siècle, mais nécessite encore d'être amélioré, notamment à cause de sa grande variabilité. Dans cette revue de littérature, nous tenterons de déterminer les caractéristiques et les rôles de la centrifugation dans le transfert graisseux autologue. Méthodes : La discussion est fondée sur les 14 articles (Pubmed) qui traitent directement ou non de la centrifugation et ses implications. Discussion : Quelques auteurs s'accordent à penser que la centrifugation crée un gradient de cellules stromales le long du tube centrifugé et statuent que cette sous-couche dense de la phase graisseuse est la plus viable. La centrifugation apparaît donc délétère pour la partie peu dense du tissu prélevé, mais semble, pour certains, améliorer la survie de la sous-couche dense, puisqu'elle est enrichie en ADSC's/MSC's. Conclusion : Dans la mesure où le prélèvement est traumatique pour le tissu graisseux, son taux de survie est relativement faible. Mais si toutes les mesures sont prises en influant sur les déterminants de la prise de greffe, la survie s'optimise et les résultats sont meilleurs.

Costes frente a beneficios de los suplementos nutricionales orales.

Health economics pretends to assign resources that are short in essence and that may be used for other purposes. Health costs analysis pretends to compare the pros and cons of several options among which an election can be made in order to obtain greater benefits with lower costs. The current legislation on prescription of enteral nutrition entails confusing definitions about the administration route and the requirements of home-based enteral nutrition, without a specific regulation comprising the prescription of oral supplements (OS). From the year 2000 to 2007, the consumption of homebased enteral nutrition in Andalusia increased considerably; the costs generated being multiplied by 37. Although the number of persons that daily consumed supplements was higher than the number of diets through nasogastric tube (DT) during the years evaluated, the costs derived from OS surpassed those of DT from the year 2005 due to the combination of two factors: a progressive increase in the number of persons to whom supplements were prescribed, and on the other hand the incorporation of more expensive specific formulations. The use of oral supplements seems to be cost/effective in hospitalized surgical patients (during the pre- and postsurgical period) and possibly in hospitalized malnourished elderly, especially after performing a hyponutrition screening. Although they may be effective, under other circumstances, such as ambulatory patients, studies with an adequate methodology are necessary in order to adopt clinical decisions based on evidence and cost analysis.

Nutrición, fibrosis quística y aparato digestivo

The prevalence of hyponutrition in cystic fibrosis is high although it may vary according to the different studies. Detection of hyponutrition should be done by combining different methods, depending on their availability. However, the simplest and most validated criterion is to measure at each visit the weight (and height in children) in order to calculate the body mass index and categorizing hyponutrition according to absolute criteria: in adults < 18.5 kg/m(2), and in children as percentiles of the body mass index. Worsening of the nutritional status is directly related with the decrease in lung function parameters and it has been proposed as a morbidity (and even mortality) predictive factor in people with cystic fibrosis, independently of the level of pulmonary dysfunction. Exocrine pancreatic insufficiency is present is approximately 70-90% of the patients with cystic fibrosis and the genotype-phenotype correlation is high. Most of the patients with exocrine pancreatic insufficiency tolerate a high-fat diet provided that they are treated with pancreatic enzymes at appropriate doses. The prevalence of diabetes increases with age, reaching up 40% of the cases in patients older than 30 years. Clinical liver involvement is less prevalent (it approximately affects 1/3 of the patients). Other intestinal complications such as meconial ileus, gastroesophageal reflux, obstruction of the distal intestine, or fibrosing colon disease may also condition malnourishment. In patients with cystic fibrosis, a usual high-fat diet providing 120%-150% of the recommended calories is advised. If the nutritional goals are not achieved or maintained with diet modifications, artificial supplements may be added, although the recommendation for their use has not been endorsed by solid scientific evidences. The most frequently used preparations usually are polymeric or hypercaloric. The indications for enteral (through a tube, especially gastrostomy) or parenteral nutritional support are similar to those used in other pathologies. Dietary and nutritional control should be included in a multidisciplinary program allowing the improvement of the functional capacity and the quality of life and reducing, at least from a theoretical viewpoint, the morbimortality associated to malnourishment in these patients.

Objective comparison of image quality and dose between conventional and synchrotron radiation mammography.

The shape of the energy spectrum produced by an x-ray tube has a great importance in mammography. Many anode-filtration combinations have been proposed to obtain the most effective spectrum shape for the image quality-dose relationship. On the other hand, third generation synchrotrons such as the European Synchrotron Radiation Facility in Grenoble are able to produce a high flux of monoenergetic radiation. It is thus a powerful tool to study the effect of beam energy on image quality and dose in mammography. An objective method was used to evaluate image quality and dose in mammography with synchrotron radiation and to compare them to standard conventional units. It was performed systematically in the energy range of interest for mammography through the evaluation of a global image quality index and through the measurement of the mean glandular dose. Compared to conventional mammography units, synchrotron radiation shows a great improvement of the image quality-dose relationship, which is due to the beam monochromaticity and to the high intrinsic collimation of the beam, which allows the use of a slit instead of an anti-scatter grid for scatter rejection.

Multiple insecticide resistance in Aedes aegypti (Diptera: Culicidae) populations compromises the effectiveness of dengue vector control in French Guiana

In French Guiana, pyrethroids and organophosphates have been used for many years against Aedes aegypti. We aimed to establish both the resistance level of Ae. aegypti and the ultra low volume spray efficacy to provide mosquito control services with practical information to implement vector control and resistance management. Resistance to deltamethrin and fenitrothion was observed. In addition, the profound loss of efficacy of AquaK'othrine® and the moderate loss of efficacy of Paluthion® 500 were recorded. Fenitrothion remained the most effective candidate for spatial application in French Guiana until its removal in December 2010. Further investigation of the mechanism of resistance to deltamethrin demonstrated the involvement of mixed-function oxidases and, to a lesser extent, of carboxylesterases. However, these observations alone cannot explain the level of insecticide resistance we observed during tube and cage tests.

Evaluation of rapid techniques for the detection of mycobacteria in sputum with scanty bacilli or clinically evident, smear negative cases of pulmonary and extra-pulmonary tuberculosis

The objective of the current study was to compare two rapid methods, the BBL Mycobacteria Growth Indicator Tube (MGIT TM) and Biotec FASTPlaque TB TM (FPTB) assays, with the conventional Löwenstein-Jensen (LJ) media assay to diagnose mycobacterial infections from paucibacillary clinical specimens. For evaluation of the clinical utility of the BBL MGIT TM and FPTB assays, respiratory tract specimens (n = 208), with scanty bacilli or clinically evident, smear negative cases and non-respiratory tract specimens (n = 119) were analyzed and the performance of each assay was compared with LJ media. MGIT and FPTB demonstrated a greater sensitivity (95.92% and 87.68%), specificity (94.59% and 98.78%), positive predictive value (94.91% and 99.16%) and negative predictive value (96.56% and 90.92%), respectively, compared to LJ culture for both respiratory tract and non-respiratory tract specimens. However, the FPTB assay was unable to detect nontuberculous mycobacteria and few Mycobacterium tuberculosis complex cases from paucibacillary clinical specimens. It is likely that the analytical sensitivity of FPTB is moderately low and may not be useful for the direct detection of tuberculosis in paucibacillary specimens. The current study concluded that MGIT was a dependable, highly efficient system for recovery of M. tuberculosis complexes and nontuberculous mycobacteria from both respiratory and non-respiratory tract specimens in combination with LJ media.

Use of active personal dosemeters in interventional radiology and cardiology: Tests in hospitals - ORAMED project

Although active personal dosemeters (APDs) are not used quite often in hospital environments, the possibility to assess the dose and/or dose rate in real time is particularly interesting in interventional radiology and cardiology (IR/IC) since operators can receive relatively high doses while standing close to the primary radiation field.A study concerning the optimization of the use of APDs in IR/IC was performed in the framework of the ORAMED project, a Collaborative Project (2008-2011) supported by the European Commission within its 7th Framework Program. This paper reports on tests performed with APDs on phantoms using an X-ray facility in a hospital environment and APDs worn by interventionalists during routine practice in different European hospitals.The behaviour of the APDs is more satisfactory in hospitals than in laboratories with respect to the influence of the tube peak high voltage and pulse width, because the APDs are tested in scattered fields with dose equivalent rates generally lower than 1 Sv.h(-1).

Fístula gastrocolocutánea: una infrecuente complicación de la gastrostomía endoscópica percutánea

Endoscopic percutaneous gastrostomy is a safe technique although with potential complications before which the clinician has to be on alert in order to early detect them even after a long period of normal functioning. Most of them represent minor problems. Gastrocolocutaneous fistula is a rare but severe complication favored by some risk factors such as previous post-surgical adherences, deformities of the spine, or excessive gastric inflation at the time of performing the technique. We present the case of a patient with PEG with this complication that occurred after the first tube replacement. Our goal was in two senses: on the one hand, to analyze the preventive aspects and basic guidelines for a safe PEG placement to minimize the risks; on the other hand, to alert on the possible presence of this entity to prevent a progressive nutritional impairment. This complication ought to be included in the differential diagnosis of the diarrhea syndrome in the patient carrying a PEG. The diagnostic techniques of choice are radiologic tests such as CT scan and contrast media administration through the tube. Surgical therapy should be reserved to patients with acute peritonitis in order to perform a new gastrostomy.

Database resources for the tuberculosis community.

Access to online repositories for genomic and associated "-omics" datasets is now an essential part of everyday research activity. It is important therefore that the Tuberculosis community is aware of the databases and tools available to them online, as well as for the database hosts to know what the needs of the research community are. One of the goals of the Tuberculosis Annotation Jamboree, held in Washington DC on March 7th-8th 2012, was therefore to provide an overview of the current status of three key Tuberculosis resources, TubercuList (tuberculist.epfl.ch), TB Database (www.tbdb.org), and Pathosystems Resource Integration Center (PATRIC, www.patricbrc.org). Here we summarize some key updates and upcoming features in TubercuList, and provide an overview of the PATRIC site and its online tools for pathogen RNA-Seq analysis.

Real-time recording of circadian liver gene expression in freely moving mice reveals the phase-setting behavior of hepatocyte clocks.

The mammalian circadian timing system consists of a master pacemaker in the suprachiasmatic nucleus (SCN) in the hypothalamus, which is thought to set the phase of slave oscillators in virtually all body cells. However, due to the lack of appropriate in vivo recording technologies, it has been difficult to study how the SCN synchronizes oscillators in peripheral tissues. Here we describe the real-time recording of bioluminescence emitted by hepatocytes expressing circadian luciferase reporter genes in freely moving mice. The technology employs a device dubbed RT-Biolumicorder, which consists of a cylindrical cage with reflecting conical walls that channel photons toward a photomultiplier tube. The monitoring of circadian liver gene expression revealed that hepatocyte oscillators of SCN-lesioned mice synchronized more rapidly to feeding cycles than hepatocyte clocks of intact mice. Hence, the SCN uses signaling pathways that counteract those of feeding rhythms when their phase is in conflict with its own phase.