Violacein, an indole-derived purple-colored natural pigment produced by Janthinobacterium lividum, inhibits the growth of head and neck carcinoma cell lines both in vitro and in vivo

Violacein (VIO; 3-[1,2-dihydro-5-(5-hydroxy-1H-indol-3-yl)-2-oxo-3H-pyrrol-3-ylidene]-1,3-dihydro-2H-indol-2-one), an indole-derived purple-colored pigment, produced by a limited number of Gram-negative bacteria species, including Chromobacterium violaceum and Janthinobacterium lividum, has been demonstrated to have anti-cancer activity, as it interferes with survival transduction signaling pathways in different cancer models. Head and neck carcinoma (HNC) represents the sixth most common and one of the most fatal cancers worldwide. We determined whether VIO was able to inhibit head and neck cancer cell growth both in vitro and in vivo. We provide evidence that VIO treatment of human and mouse head and neck cancer cell lines inhibits cell growth and induces autophagy and apoptosis. In fact, VIO treatment increased PARP-1 cleavage, the Bax/Bcl-2 ratio, the inhibition of ERK1 and ERK2 phosphorylation, and the expression of light chain 3-II (LC3-II). Moreover, VIO was able to induce p53 degradation, cytoplasmic nuclear factor kappa B (NF-κB) accumulation, and reactive oxygen species (ROS) production. VIO induced a significant increase in ROS production. VIO administration was safe in BALB/c mice and reduced the growth of transplanted salivary gland cancer cells (SALTO) in vivo and prolonged median survival. Taken together, our results indicate that the treatment of head and neck cancer cells with VIO can be useful in inhibiting in vivo and in vitro cancer cell growth. VIO may represent a suitable tool for the local treatment of HNC in combination with standard therapies

Formyl-peptide Receptor Agonists and Amorphous SiO2-NPs Synergistically and Selectively Increase the Inflammatory Responses of Human Monocytes and PMNs

We tested whether amorphous SiO2-NPs and formyl-peptide receptor (FPRs) agonists synergistically activate human monocytes and neutrophil polymorphonuclear granulocytes (PMNs). Peptide ligands specifically binding to FPR1 (f-MLP) and to FPR2 (MMK-1, WKYMVM and WKYMVm) human isoforms did not modify the association of SiO2-NPs to both cell types or their cytotoxic effects. Similarly, the extent of CD80, CD86, CD83, ICAM-1 and MHCII expression in monocytes treated with SiO2-NPs was not significantly altered by any FPRs agonist. However, FPR1 stimulation with f-MLP strongly increased the secretion of IL-1β, IL-6 and IL-8 by human monocytes, and of IL-8 by PMNs in the presence of SiO2-NPs, due to the synergic stimulation of gene transcription. FPR2 agonists also up-modulated the production of IL-1β induced by monocytes treated with SiO2-NPs. In turn, SiO2-NPs increased the chemotaxis of PMNs toward FPR1-specific ligands, but not toward FPR2-specific ones. Conversely, the chemotaxis of monocytes toward FPR2-specific peptides was inhibited by SiO2-NPs. NADPH-oxidase activation triggered by FPR1- and FPR2-specific ligands in both cell types was not altered by SiO2-NPs. Microbial and tissue danger signals sensed by FPRs selectively amplified the functional responses of monocytes and PMNS to SiO2-NPs, and should be carefully considered in the assessment of the risk associated with nanoparticle exposure

Clinical Features, Short-Term Mortality, and Prognostic Risk Factors of Septic Patients Admitted to Internal Medicine Units: Results of an Italian Multicenter Prospective Study

Only a few studies provided data on the clinical history of sepsis within internal Medicine units.The aim of the study was to assess the short-term mortality and to evaluate the prognostic risk factors in a large cohort of septic patients treated in internal medicine units.Thirty-one internal medicine units participated to the study. Within each participating unit, all admitted patients were screened for the presence of sepsis.A total of 533 patients were included; 78 patients (14.6%, 95%CI 11.9, 18.0%) died during hospitalization; mortality rate was 5.5% (95% CI 3.1, 9.6%) in patients with nonsevere sepsis and 20.1% (95%CI 16.2, 28.8%) in patients with severe sepsis or septic shock. Severe sepsis or septic shock (OR 4.41, 95%CI 1.93, 10.05), immune system weakening (OR 2.10, 95%CI 1.12, 3.94), active solid cancer (OR 2.14, 95% CI 1.16, 3.94), and age (OR 1.03 per year, 95% CI 1.01, 1.06) were significantly associated with an increased mortality risk, whereas blood culture positive for Escherichia coli was significantly associated with a reduced mortality risk (OR 0.46, 95%CI 0.24, 0.88).In-hospital mortality of septic patients treated in internal medicine units appeared similar to the mortality rate obtained in recent studies conducted in the ICU setting

Are multiple-choice questions a good tool for the assessment of clinical competence in Internal Medicine?

There are many feasible tools for the assessment of clinical practice, but there is a wide consensus on the fact that the simultaneous use of several different methods could be strategic for a comprehensive overall judgment of clinical competence. Multiple-choice questions (MCQs) are a well-established reliable method of assessing knowledge. Constructing effective MCQ tests and items requires scrupulous care in the design, review and validation stages. Creating high-quality multiple-choice questions requires a very deep experience, knowledge and large amount of time. Hereby, after reviewing their construction, strengths and limitations, we debate their completeness for the assessment of professional competence

Proinflammatory effects of bare and PEGylated ORMOSIL-, PLGA- and SUV-NPs on monocytes and PMNs and their modulation by f-MLP

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Lower respiratory tract infections among human immunodeficiency virus-exposed, uninfected infants

Objectives: To evaluate whether maternal HIV disease severity during pregnancy is associated with an increased likelihood of lower respiratory tract infections (LRTIs) in HIV-exposed, uninfected infants.Methods: HIV-exposed, uninfected, singleton, term infants enrolled in the NISDI Perinatal Study, with birth weight >2500 g were followed from birth until 6 months of age. LRTI diagnoses, hospitalizations, and associated factors were assessed.Results: of 547 infants, 103 (18.8%) experienced 116 episodes of LRTI (incidence = 0.84 LRTIs/100 child-weeks). Most (81%) episodes were bronchiolitis. Forty-nine (9.0%) infants were hospitalized at least once with an LRTI. There were 53 hospitalizations (45.7%) for 116 LRTI episodes. None of these infants were breastfed. the odds of LRTI in infants whose mothers had CD4% = 29 (p = 0.003). the odds of LRTI in infants with a CD4+ count (cells/ mm(3)) = 750 (p = 0.002). Maternal CD4+ decline and infant hemoglobin at the 6-12 week visit were associated with infant LRTIs after 6-12 weeks and before 6 months of age.Conclusions: Acute bronchiolitis is common and frequently severe among HIV-exposed, uninfected infants aged 6 months or less. Lower maternal and infant CD4+ values were associated with a higher risk of infant LRTIs. Further understanding of the immunological mechanisms of severe LRTIs is needed. (C) 2010 International Society for Infectious Diseases. Published by Elsevier B.V. All rights reserved.NICHDUniv São Paulo, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP, BrazilWESTAT Corp, Rockville, MD 20850 USAUniv Caxias Sul, Rio Grande Do Sul, BrazilHosp Diego Paroissien, Buenos Aires, DF, ArgentinaUniversidade Federal de São Paulo, São Paulo, BrazilUniv W Indies, Kingston 7, JamaicaHosp Juan Fernandez, Buenos Aires, DF, ArgentinaHosp Agudos Dra Cecilia Grierson, Buenos Aires, DF, ArgentinaNICHD, Pediat Adolescent & Maternal AIDS Branch, CRMC, NIH,DHHS, Bethesda, MD USAUniversidade Federal de São Paulo, São Paulo, BrazilNICHD: N01-HD-3-3345NICHD: HHSN267200800001CNICHD: N01-DK-8-0001Web of Scienc

Self-Assembled Biocompatible Fluorescent Nanoparticles for Bioimaging

Fluorescence is a powerful tool for mapping biological events in real-time with high spatial resolution. Ultra-bright probes are needed in order to achieve high sensitivity: these probes are typically obtained by gathering a huge number of fluorophores in a single nanoparticle (NP). Unfortunately this assembly produces quenching of the fluorescence because of short-range intermolecular interactions. Here we demonstrate that rational structural modification of a well-known molecular fluorophore N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) (NBD) produces fluorophores that self-assemble in nanoparticles in the biocompatible environment without any dramatic decrease of the fluorescence quantum yield. Most importantly, the resulting NP show, in an aqueous environment, a brightness which is more than six orders of magnitude higher than the molecular component in the organic solvent. Moreover, the NP are prepared by nanoprecipitation and they are stabilized only via non-covalent interaction, they are surprisingly stable and can be observed as individual bright spots freely diffusing in solution at a concentration as low as 1 nM. The suitability of the NP as biocompatible fluorescent probes was demonstrated in the case of HeLa cells by fluorescence confocal microscopy and MTS assays

Planeamiento estratégico para la región San Martín

El presente trabajo consiste en el Plan Estratégico para el desarrollo de las competencias agrícolas de café y cacao y el crecimiento del turismo para la región San Martín para el 2027. Se han planteado objetivos claros y alcanzables para conseguir el bienestar social en salud y educación de la región y el progreso económico a través de puestos de trabajo con salarios adecuados, así como una mejora en el nivel de capacidades técnicas de la región, lo que elevará la calidad de vida de sus habitantes y potenciará los negocios para que San Martín esté dentro de las diez regiones con ciudades turísticas más visitadas del Perú y sea la tercera región productora y, sobre todo, exportadora de cacao y café del país, manteniendo la sostenibilidad del ecosistema y respeto a sus habitantes. Para ello se ha elaborado una visión y una misión sólida, clara y alcanzable; resaltando la identidad de los ciudadanos, la responsabilidad social y ambiental, el compromiso de las instituciones públicas y privadas con transparencia en la gestión pública, y, como algo fundamental, el respeto por las personas, costumbres, cultura y religión. El plan estratégico que a continuación se presenta se trabajó en función del Modelo Secuencial del Proceso Estratégico de Fernando D’Alessio, siguiendo las pautas de formulación, implementación, evaluación y control que se llevaron a cabo durante todo el proceso. Las fortalezas de la región se ven claramente resaltadas en la agricultura; sin embargo, la región también es débil en la industrialización de la misma, pero presenta un gran potencial turístico que se puede explotar más. Es por eso que las estrategias formuladas generarán un crecimiento sostenible en la región San MartínThe present work consists of the proposal of the Strategic Plan for the development of the agricultural competences of coffee and cocoa and the growth of tourism for the San Martín Region for 2027, clear and achievable objectives have been established to achieve social welfare in health and education of the region and economic well-being through jobs with adequate salaries, as well as improving the level of technical capabilities of the region by raising the quality of life of its inhabitants, boosting business to position ourselves within the ten regions with cities tourist destinations most visited in Peru and be the third producer and above all exporter of cocoa and coffee in the country maintaining the sustainability of the ecosystem and respect for its inhabitants, for which a vision and mission has been developed solid, clear and achievable; highlighting the identity of citizens, social and environmental responsibility, commitment of public and private institutions with transparency in public management and very important respect for people, customs, culture and religion. The strategic plan that is presented below was worked on according to the Sequential Model of the Strategic Process of Fernando D'Alessio following the formulation, implementation and evaluation and control guidelines that were carried out throughout the process. The strengths of the region are clearly highlighted in the agronomy, however, the region is also weak in the industrialization of agriculture, but with much tourism potential. That is why the strategies formulated will generate sustainable growth in the San Martín regionTesi

Storia e caratteristiche del progetto multicentrico di ricerca "International Self - Report Delinquency Study": il contributo della Criminologia italiana

The present paper reviews the history, the principal characteristics, the recent evolutions and the objectives of the international multi-centric study on juvenile self-report delinquency and victimization called ISRD, and describes the contribution of Italian criminology to the project. The most important international results of the first two waves of the research (ISRD 1 and ISRD2), and the innovations introduced in the planning of the third wave (ISRD3) are also described: The collection of data has been concluded in Italy, but not in all the 35 countries participating to the study

C1q-Mediated Complement Activation and C3 Opsonization Trigger Recognition of Stealth Poly(2-methyl-2-oxazoline)-Coated Silica Nanoparticles by Human Phagocytes

Poly(2-methyl-2-oxazoline) (PMOXA) is an alternative promising polymer to poly(ethylene glycol) (PEG) for design and engineering of macrophage-evading nanoparticles (NPs). Although PMOXA-engineered NPs have shown comparable pharmacokinetics and in vivo performance to PEGylated stealth NPs in the murine model, its interaction with elements of the human innate immune system has not been studied. From a translational angle, we studied the interaction of fully characterized PMOXA-coated vinyltriethoxysilane-derived organically modified silica NPs (PMOXA-coated NPs) of approximately 100 nm in diameter with human complement system, blood leukocytes, and macrophages and compared their performance with PEGylated and uncoated NP counterparts. Through detailed immunological and proteomic profiling, we show that PMOXA-coated NPs extensively trigger complement activation in human sera exclusively through the classical pathway. Complement activation is initiated by the sensing molecule C1q, where C1q binds with high affinity (Kd = 11 \ub1 1 nM) to NP surfaces independent of immunoglobulin binding. C1q-mediated complement activation accelerates PMOXA opsonization with the third complement protein (C3) through the amplification loop of the alternative pathway. This promoted NP recognition by human blood leukocytes and monocyte-derived macrophages. The macrophage capture of PMOXA-coated NPs correlates with sera donor variability in complement activation and opsonization but not with other major corona proteins, including clusterin and a wide range of apolipoproteins. In contrast to these observations, PMOXA-coated NPs poorly activated the murine complement system and were marginally recognized by mouse macrophages. These studies provide important insights into compatibility of engineered NPs with elements of the human innate immune system for translational steps