Novel mid-infrared dispersive wave generation in gas-filled PCF by transient ionization-driven changes in dispersion

Gas-filled hollow-core photonic crystal fibre (PCF) is being used to generate ever wider supercontinuum spectra, in particular via dispersive wave (DW) emission in the deep and vacuum ultraviolet, with a multitude of applications. DWs are the result of the resonant transfer of energy from a self-compressed soliton, a process which relies crucially on phase matching. It was recently predicted that, in the strong-field regime, the additional transient anomalous dispersion introduced by gas ionization would allow phase-matched DW generation in the mid-infrared (MIR)-something that is forbidden in the absence of free electrons. Here we report for the first time the experimental observation of such MIR DWs, embedded in a 4.7-octave-wide supercontinuum that uniquely reaches simultaneously to the vacuum ultraviolet, with up to 1.7 W of total average power

Celiac disease in older persons: A case of seronegative disease

A 68-year-old man with a history of smoking (former smoker of 40 cigarettes per day), euthyroid goiter, deep vein thrombosis and depression, came to our attention for weakness, cachexia, abdominal bloating and diarrhea lasting for almost six months. Furthermore, he had lost about 25 kilograms of weight in the last year and was bedridden for three months. Combining the results of serological, histopathological and genetic tests, he was diagnosed with a seronegative celiac disease. Gluten-free diet, combined with nutritional supplements and physical therapy, improved his clinical condition and allowed the recovery of weight and the walking ability. Celiac disease might be suspected in elderly patients with diarrhea, malabsorption, malnutrition and cachexia, but also with other symptoms such as anemia, micronutrients' deiciency, fragility fractures and neurological symptoms

An Oral Vaccine Based on U-Omp19 Induces Protection against B. abortus Mucosal Challenge by Inducing an Adaptive IL-17 Immune Response in Mice

As Brucella infections occur mainly through mucosal surfaces, the development of mucosal administered vaccines could be radical for the control of brucellosis. In this work we evaluated the potential of Brucella abortus 19 kDa outer membrane protein (U-Omp19) as an edible subunit vaccine against brucellosis. We investigated the protective immune response elicited against oral B. abortus infection after vaccination of mice with leaves from transgenic plants expressing U-Omp19; or with plant-made or E. coli-made purified U-Omp19. All tested U-Omp19 formulations induced protection against Brucella when orally administered without the need of adjuvants. U-Omp19 also induced protection against a systemic challenge when parenterally administered. This built-in adjuvant ability of U-Omp19 was independent of TLR4 and could be explained at least in part by its capability to activate dendritic cells in vivo. While unadjuvanted U-Omp19 intraperitoneally administered induced a specific Th1 response, following U-Omp19 oral delivery a mixed specific Th1-Th17 response was induced. Depletion of CD4+ T cells in mice orally vaccinated with U-Omp19 resulted in a loss of the elicited protection, indicating that this cell type mediates immune protection. The role of IL-17 against Brucella infection has never been explored. In this study, we determined that if IL-17A was neutralized in vivo during the challenge period, the mucosal U-Omp19 vaccine did not confer mucosal protection. On the contrary, IL-17A neutralization during the infection did not influence at all the subsistence and growth of this bacterium in PBS-immunized mice. All together, our results indicate that an oral unadjuvanted vaccine based on U-Omp19 induces protection against a mucosal challenge with Brucella abortus by inducing an adaptive IL-17 immune response. They also indicate different and important new aspects i) IL-17 does not contribute to reduce the bacterial burden in non vaccinated mice and ii) IL-17 plays a central role in vaccine mediated anti-Brucella mucosal immunity

A disordered region retains the full protease inhibitor activity and the capacity to induce CD8+ T cells in vivo of the oral vaccine adjuvant U-Omp19

U-Omp19 is a bacterial protease inhibitor from Brucella abortus that inhibits gastrointestinal and lysosomal proteases, enhancing the half-life and immunogenicity of co-delivered antigens. U-Omp19 is a novel adjuvant that is in preclinical development with various vaccine candidates. However, the molecular mechanisms by which it exerts these functions and the structural elements responsible for these activities remain unknown. In this work, a structural, biochemical, and functional characterization of U-Omp19 is presented. Dynamic features of U-Omp19 in solution by NMR and the crystal structure of its C-terminal domain are described. The protein consists of a compact C-terminal beta-barrel domain and a flexible N-terminal domain. The latter domain behaves as an intrinsically disordered protein and retains the full protease inhibitor activity against pancreatic elastase, papain and pepsin. This domain also retains the capacity to induce CD8+ T cells in vivo of U-Omp19. This information may lead to future rationale vaccine designs using U-Omp19 as an adjuvant to deliver other proteins or peptides in oral formulations against infectious diseases, as well as to design strategies to incorporate modifications in its structure that may improve its adjuvanticity.Fil: Darriba, María Laura. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Pueblas Castro, Celeste. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Coria, Lorena M. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Bruno, Laura. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Cerutti, María Laura. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Chemes, Lucía B. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Cassataro, Juliana. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Pasquevich, Karina A. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Darriba, María Laura. Universidad Nacional de San Martín. Escuela de Bio y Nanotecnologías (EByN); Argentina.Fil: Pueblas Castro, Celeste. Universidad Nacional de San Martín. Escuela de Bio y Nanotecnologías (EByN); Argentina.Fil: Coria, Lorena M. Universidad Nacional de San Martín. Escuela de Bio y Nanotecnologías (EByN); Argentina.Fil: Bruno, Laura. Universidad Nacional de San Martín. Escuela de Bio y Nanotecnologías (EByN); Argentina.Fil: Cerutti, María Laura. Universidad Nacional de San Martín. Escuela de Bio y Nanotecnologías (EByN); Argentina.Fil: Chemes, Lucía B. Universidad Nacional de San Martín. Escuela de Bio y Nanotecnologías (EByN); Argentina.Fil: Cassataro, Juliana. Universidad Nacional de San Martín. Escuela de Bio y Nanotecnologías (EByN); Argentina.Fil: Pasquevich, Karina A. Universidad Nacional de San Martín. Escuela de Bio y Nanotecnologías (EByN); Argentina.Fil: Otero, Lisandro H. Fundación Instituto Leloir. Plataforma Argentina de Biología Estructural y Metabolómica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Klinke, Sebastián. Fundación Instituto Leloir. Plataforma Argentina de Biología Estructural y Metabolómica. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina.Fil: Rasia, Rodolfo M. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario. Plataforma Argentina de Biología Estructural y Metabolómica; Argentina

Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as Nasal Adjuvant Induces a Th1 Immune Response and Modulates the Th2 Allergic Response to Cow's Milk Proteins

The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA) increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow's Milk Protein (CMP), decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations.Laboratorio de Investigaciones del Sistema Inmun

Unlipidated Outer Membrane Protein Omp16 (U-Omp16) from Brucella spp. as Nasal Adjuvant Induces a Th1 Immune Response and Modulates the Th2 Allergic Response to Cow's Milk Proteins

The discovery of novel mucosal adjuvants will help to develop new formulations to control infectious and allergic diseases. In this work we demonstrate that U-Omp16 from Brucella spp. delivered by the nasal route (i.n.) induced an inflammatory immune response in bronchoalveolar lavage (BAL) and lung tissues. Nasal co-administration of U-Omp16 with the model antigen (Ag) ovalbumin (OVA) increased the amount of Ag in lung tissues and induced OVA-specific systemic IgG and T helper (Th) 1 immune responses. The usefulness of U-Omp16 was also assessed in a mouse model of food allergy. U-Omp16 i.n. administration during sensitization ameliorated the hypersensitivity responses of sensitized mice upon oral exposure to Cow's Milk Protein (CMP), decreased clinical signs, reduced anti-CMP IgE serum antibodies and modulated the Th2 response in favor of Th1 immunity. Thus, U-Omp16 could be used as a broad Th1 mucosal adjuvant for different Ag formulations.Laboratorio de Investigaciones del Sistema Inmun

Photoionization-Induced Emission of Tunable Few-Cycle Midinfrared Dispersive Waves in Gas-Filled Hollow-Core Photonic Crystal Fibers

We propose a scheme for the emission of few-cycle dispersive waves in the midinfrared using hollow-core photonic crystal fibers filled with noble gas. The underlying mechanism is the formation of a plasma cloud by a self-compressed, subcycle pump pulse. The resulting free-electron population modifies the fiber dispersion, allowing phase-matched access to dispersive waves at otherwise inaccessible frequencies, well into the midinfrared. Remarkably, the pulses generated turn out to have durations of the order of two optical cycles. In addition, this ultrafast emission, which occurs even in the absence of a zero dispersion point between pump and midinfrared wavelengths, is tunable over a wide frequency range simply by adjusting the gas pressure. These theoretical results pave the way to a new generation of compact, fiber-based sources of few-cycle midinfrared radiation

MALNUTRIZIONE E FRAGILITÀ NELL’ANZIANO: UN CASO COMPLESSO DI MULTIMORBILITÀ E COMORBILITÀ

La malnutrizione è un problema di rilevante importanza nell’anziano. Numerosi studi hanno dimostrato che la prevalenza della malnutrizione è compresa tra il 20 e il 60% nei pazienti anziani al momento dell’ammissione in un reparto ospedaliero e tra il 30 e il 50% nei pazienti che accedono alle nursing-home; alcuni studi hanno stimato un dato di prevalenza di malnutrizione pari all’85% nei pazienti anziani confinati in casa, ospedalizzati o istituzionalizzati. Nell’anziano lo stato di nutrizione influenza notevolmente l’evoluzione del quadro clinico e condiziona l’esito dei trattamenti e dei programmi di riabilitazione. Il cambiamento più frequente delle abitudini alimentari dell’anziano è rappresentato dall’anoressia: patologie a carico del cavo orale e dei denti, disordini della masticazione e della deglutizione, declino cognitivo, depressione del tono dell’umore, alterazione dei neurotrasmettitori che agiscono sul centro della fame e della sete a livello del sistema nervoso centrale, polipatologia, polifarmacoterapia possono esserne la causa. Si realizza un processo a cascata che conduce alla mal-nutrizione e alla fragilità. Descriviamo il caso clinico di un paziente di sesso maschile, di 89 anni, giunto alla nostra osservazione per grave stato di malnutrizione con cachessia e sindrome da immobilizzazione

RUOLO DEL PLASMA ARRICCHITO IN PIASTRINE (PRP) IN FORMA GELIFICATA NEL TRATTAMENTO DELLE ULCERE DA DECUBITO: PRESENTAZIONE DI UN CASO CLINICO

Le ulcere da decubito rappresentano una condizione frequente in popolazioni ad alto rischio quali gli anziani e i soggetti con compromissione dell’autonomia funzionale, dall’ipomobilità sino all’allettamento. Esse si con-figurano come un indicatore negativo dell’assistenza sanitaria erogata in quanto potenzialmente prevenibili attraverso l’applicazione di alcune regole fondamentali per la cura e la corretta gestione del paziente non autonomo. L’invecchiamento della popolazione, con il conseguente aumento dei soggetti con deficit funzionali, multimorbilità e comorbilità complesse e, quindi, in ultima analisi, fragili, ha contribuito e continuerà a determinare un aumento dell’incidenza e della prevalenza delle ulcere da pressione. Definire le dimensioni del fenomeno sul piano epidemiologico, tuttavia, è difficile; la stima delle ulcere da decubito, inoltre, varia nei diversi setting assistenziali (reparto per acuti, reparti di area medica o chirurgica, lungodegenza, residenze sanitarie assistenziali). È necessaria una gestione multidisciplinare del fenomeno con particolare attenzione rivolta non solo alla diagnosi e alla cura, ma anche e soprattutto alla prevenzione. Descriviamo il caso di un paziente di sesso maschile, di 66 anni, con ulcera da decubito giunto alla nostra osservazione per la necessità di riattivazione funzionale geriatrica