Endosonographic radial tumor thickness after neoadjuvant chemoradiation therapy to predict response and survival in patients with locally advanced esophageal cancer: a prospective multicenter phase ll study by the Swiss Group for Clinical Cancer Research (SAKK 75/02)

EUS response assessment in patients with locally advanced esophageal cancer undergoing neoadjuvant chemoradiation therapy (CRT) is limited by disintegration of the involved anatomic structures.

A case report of Clarkson's disease: If you don't know it, you'll miss it

The systemic capillary leak syndrome (SCLS), also known as Clarkson's disease, is a rare disorder characterized by paroxysmal capillary hyperpermeability with a shift of plasma fluid from the intravascular to the interstitial space. A 35-year-old previously healthy woman was admitted with rapidly developing hypovolemic shock syndrome, rhabdomyolysis, and diffuse edema. Laboratory analysis revealed a severe hemoconcentration, renal insufficiency, and paraproteinemia. After exclusion of infection, allergy, burning or drug-induced conditions, the clinical presentation was consistent with the diagnosis of SCLS. Though this is a rare entity, the substantial morbidity and mortality associated with it necessitate the physician's awareness in order to provide timely therapy. This report is meant to enhance awareness of SCLS.

Role of glial cells in the functional expression of LL-37/rat cathelin-related antimicrobial peptide in meningitis

Antimicrobial peptides are intrinsic to the innate immune system in many organ systems, but little is known about their expression in the central nervous system. We examined cerebrospinal fluid (CSF) and serum from patients with active bacterial meningitis to assess antimicrobial peptides and possible bactericidal properties of the CSF. We found antimicrobial peptides (human cathelicidin LL-37) in the CSF of patients with bacterial meningitis but not in control CSF. We next characterized the expression, secretion, and bactericidal properties of rat cathelin-related antimicrobial peptide, the homologue of the human LL-37, in rat astrocytes and microglia after incubation with different bacterial components. Using real-time polymerase chain reaction and Western blotting, we determined that supernatants from both astrocytes and microglia incubated with bacterial component supernatants had antimicrobial activity. The expression of rat cathelin-related antimicrobial peptide in rat glial cells involved different signal transduction pathways and was induced by the inflammatory cytokines interleukin 1beta and tumor necrosis factor. In an experimental model of meningitis, infant rats were intracisternally infected with Streptococcus pneumoniae, and rat cathelin-related antimicrobial peptide was localized in glia, choroid plexus, and ependymal cells by immunohistochemistry. Together, these results suggest that cathelicidins produced by glia and other cells play an important part in the innate immune response against pathogens in central nervous system bacterial infections.

Lack of cathelicidin processing in Papillon-Lefèvre syndrome patients reveals essential role of LL-37 in periodontal homeostasis.

BACKGROUND Loss-of-function point mutations in the cathepsin C gene are the underlying genetic event in patients with Papillon-Lefèvre syndrome (PLS). PLS neutrophils lack serine protease activity essential for cathelicidin LL-37 generation from hCAP18 precursor. AIM We hypothesized that a local deficiency of LL-37 in the infected periodontium is mainly responsible for one of the clinical hallmark of PLS: severe periodontitis already in early childhood. METHODS To confirm this effect, we compared the level of neutrophil-derived enzymes and antimicrobial peptides in gingival crevicular fluid (GCF) and saliva from PLS, aggressive and chronic periodontitis patients. RESULTS Although neutrophil numbers in GCF were present at the same level in all periodontitis groups, LL-37 was totally absent in GCF from PLS patients despite the large amounts of its precursor, hCAP18. The absence of LL-37 in PLS patients coincided with the deficiency of both cathepsin C and protease 3 activities. The presence of other neutrophilic anti-microbial peptides in GCF from PLS patients, such as alpha-defensins, were comparable to that found in chronic periodontitis. In PLS microbial analysis revealed a high prevalence of Aggregatibacter actinomycetemcomitans infection. Most strains were susceptible to killing by LL-37. CONCLUSIONS Collectively, these findings imply that the lack of protease 3 activation by dysfunctional cathepsin C in PLS patients leads to the deficit of antimicrobial and immunomodulatory functions of LL-37 in the gingiva, allowing for infection with A. actinomycetemcomitans and the development of severe periodontal disease.

ll "Pasquillus extaticus" di Celio Secondo Curione: eresia, censura, tradizione a stampa e manoscritta del testo

The essay examines the print and manuscript traditions of the "Pasquillus extaticus" by Celio Secondo Curione with a particular focus on their relation with censorship. At first, the essay investigates into the redactional evolution and into the editorial history of the dialogue and of its vernacular versions, e.g. the relation between some editions of the "Pasquillus extaticus" and of the "Pasquino in estasi" (which appeared anonymously and without typographical information) and the provisions of political and ecclesiastical censorship in the 16th century. Finally, analysing the manuscript tradition, the essay discusses Carlos Gilly’s identification of «Coelii Secundi Pasquillus, emendatus impress[us]», registered in the inventory of the private library of the Basel typographer Johannes Oporinus, with the copy preserved at the Herzog August Bibibliothek Wolfenbüttel [hab: p 1811. 8º Helmst. (1)]). The author refutes Gilly’s hypothetical attribution to Curione’s handwriting of the many marginalia present in this copy.

Impact de la fabrication de charbon de bois sur la production et la disponibilité fourragère de pâturage en zone subaride, cas de la commune de Soalara-Sud, Toliara ll: Rapport final

Ce projet a pour objectif de (1) décrire la filière charbon dans un terroir de la commune de Soalara, (2) d’identifier les effets des activités de fabrication de charbon de bois sur la végétation des pâturages qui est un fourré épineux et (3) d’estimer la quantité maximale de charbon pouvant être produite sans causer sa dégradation irréversible. Pour ce faire, des enquêtes auprès de la population locale et des relevés écologiques ont été entrepris. La majorité des ménages enquêtés (>80% ; N=56) pratiquent la fabrication de charbon de bois. Environ 41 000 sacs de charbons ont été produits dans le terroir en 2009. L’impact socio-économique de la filière charbon est positif puisqu’elle génère des revenus importants pour ses agents (producteur, transporteur et collecteur). Par contre, l’impact écologique est plutôt négatif puisque les activités charbonnières contribuent à réduire la densité d’arbres et d’arbustes de la végétation des fourrés épineux et sa richesse spécifique même si elles n’affectent pas trop sa disponibilité fourragère. De plus, la quantité de charbon produite (environ 820 t en 2009) dépasse la productivité de la végétation, estimée à 218 t.an-1. Par conséquent, une dégradation du site de production actuel, se traduisant par la disparition des espèces charbonnières, arriverait dans 17 ans au plus tard, si le rythme de production actuel continue. Des mesures de réduction des pressions sur la végétation (professionnalisation des éleveurs, amélioration des rendements de carbonisation et réglementation et contrôle plus strict de la filière charbon) et d’augmentation de sa production et productivité (restauration) doivent être prises pour éviter cette dégradation irréversible qui à terme pourrait être dommageable à l’élevage de petits ruminants même si ce n’est pas encore le cas actuellement.

Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37.

Vitamin D has immunomodulatory properties in the defence against pathogens. Its insufficiency is a widespread feature of cystic fibrosis (CF) patients, which are repeatedly suffering from rhinovirus (RV)-induced pulmonary exacerbations.To investigate whether vitamin D has antiviral activity, primary bronchial epithelial cells from CF children were pre-treated with vitamin D and infected with RV16. Antiviral and anti-inflammatory activity of vitamin D was assessed. RV and LL-37 levels were measured in bronchoalveolar lavage (BAL) of CF children infected with RV.Vitamin D reduced RV16 load in a dose-dependent manner in CF cells (10(-7 )M, p<0.01). The antiviral response mediated by interferons remained unchanged by vitamin D in CF cells. Vitamin D did not exert anti-inflammatory properties in RV-infected CF cells. Vitamin D increased the expression of the antimicrobial peptide LL-37 up to 17.4-fold (p<0.05). Addition of exogenous LL-37 decreased viral replication by 4.4-fold in CF cells (p<0.05). An inverse correlation between viral load and LL-37 levels in CF BAL (r=-0.48, p<0.05) was observed.RV replication in primary CF bronchial cells was reduced by vitamin D through the induction of LL-37. Clinical studies are needed to determine the importance of an adequate control of vitamin D for prevention of virus-induced pulmonary CF exacerbations.