Is autumn the key for dengue epidemics in non endemic regions? The case of Argentina

Background. Dengue is a major and rapidly increasing public health problem. In Argentina, the southern extreme of its distribution in the Americas, epidemic transmission takes place during the warm season. Since its re-emergence in 1998 two major outbreaks have occurred, the biggest during 2016. To identify the environmental factors that trigger epidemic events, we analyzed the occurrence and magnitude of dengue outbreaks in time and space at different scales in association with climatic, geographic and demographic variables and number of cases in endemic neighboring countries. Methods. Information on dengue cases was obtained from dengue notifications reported in the National Health Surveillance System. The resulting database was analyzed by Generalized Linear Mixed Models (GLMM) under three methodological approaches to: identify in which years the most important outbreaks occurred in association with environmental variables and propose a risk estimation for future epidemics (temporal approach); characterize which variables explain the occurrence of local outbreaks through time (spatio-temporal approach); and select the environmental drivers of the geographical distribution of dengue positive districts during 2016 (spatial approach). Results. Within the temporal approach, the number of dengue cases country-wide between 2009 and 2016 was positively associated with the number of dengue cases in bordering endemic countries and negatively with the days necessary for transmission (DNT) during the previous autumn in the central region of the country. Annual epidemic intensity in the period between 1999-2016 was associated with DNT during previous autumn and winter. Regarding the spatio-temporal approach, dengue cases within a district were also associated with mild conditions in the previous autumn along with the number of dengue cases in neighboring countries. As for the spatial approach, the best model for the occurrence of two or more dengue cases per district included autumn minimum temperature and human population as fixed factors, and the province as a grouping variable. Explanatory power of all models was high, in the range 57-95%. Discussion. Given the epidemic nature of dengue in Argentina, virus pressure from endemic neighboring countries along with climatic conditions are crucial to explain disease dynamics. In the three methodological approaches, temperature conditions during autumn were best associated with dengue patterns. We propose that mild autumns represent an advantage for mosquito vector populations and that, in temperate regions, this advantage manifests as a larger egg bank from which the adult population will re-emerge in spring. This may constitute a valuable anticipating tool for high transmission risk events.Fil: Carbajo, Anibal Eduardo. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cardo, María Victoria. Universidad Nacional de San Martín. Instituto de Investigación en Ingeniería Ambiental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guimarey, Pilar Consuelo. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Lizuain, Arturo Andrés. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Buyayisqui, María Pía. Ministerio de Salud de la Nación; ArgentinaFil: Varela, Teresa. Ministerio de Salud de la Nación; ArgentinaFil: Utgés, Maria E.. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; ArgentinaFil: Giovacchini, Carlos. Ministerio de Salud de la Nación; ArgentinaFil: Santini, Maria Soledad. Dirección Nacional de Instituto de Investigación.Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Adhesion of Immature and Mature T Cells Induces in Human Thymic Epithelial Cells (TEC) Activation of IL-6 Gene Trascription Factors (NF-κB And NF-IL6) and IL-6 Gene Expression : Role of αtβ1 and α6β4 Integrins

T cell precursors homed to thymus develop in close contact with stromal cells. Among them, thymic epithelial cells (TEC) are known to exert dominant roles in their survival and functional shaping. Key molecules mediating TEC/thymocytes interactions include cytokines and growth factors secreted by the two cell types and adhesion receptors mediating cell contact. Signaling events triggered in thymocytes by adhesion to epithelial cells have been extensively investigated, whereas little is known on the opposite phenomenon. We have previously investigated this issue in a co-culture system composed of TEC cultures derived from human normal thymus and heterologous thymocytes. We demonstrated that thymocytes adhere to TEC involving β1 and β4 integrins and induce the clustering of (α3β1 and α6β4 heterodimers at the TEC surface. In addition thymocyte adhesion was followed by activation of NF-κB and NF-IL6 gene transciption factors and enhanced IL-6 production. The two latter phenomena were reproduced by the cross-linking of the α3, α6, β1 and β4 integrins, thus implying that the α3β1 and α6β4 heterodimers can signal during thymocyte adhesion. We have extended our previous work investigating in the same experimental setting the inducing activity of non stimulated or activated policlonal or clonal mature T cells as representative of the more mature thymocyte subset. We found that adhesion of unstimulated T cell i) involved β1, but not β4 integrin functions at the surface ii) induced the clustering of α3β1 , but not α2β1 heterodimers at the TEC surface and iii) up-regulated the nuclear binding activity of NF-κB transcription factor and the IL-6 secretion. We propose that α3β1 and α6β4 heterodimers are induced to cluster at the TEC surface recognizing yet unknown cellular ligands differentially expressed during T cell development

Arsenite oxidase in complex with antimonite and arsenite oxyanions - insights into the catalytic mechanism

Arsenic contamination of groundwater is among one of the biggest health threats affecting millions of people in the world. There is an urgent need for efficient arsenic biosensors where the use of arsenic metabolizing enzymes can be explored. In this work we have solved the crystal structures of four complexes of arsenite oxidase (Aio) obtained in complex with arsenic and antimony oxyanions and the structures determined correspond to intermediate states of the enzymatic mechanism. These structural data were complemented with DFT calculations providing a unique view of the molybdenum active site at different time points that, together with mutagenesis data, enabled to clarify the enzymatic mechanism and the molecular determinants for the oxidation of As(III) to the less toxic As(V) species

Low elasticity of thyroid nodules at ultrasound elastography is correlated with malignancy, degree of fibrosis and high expression of galectin-3 and fibronectin-1

ackground: Thyroid ultrasound (US) elastography provides an estimation of tissue stiffness and is helpful to differentiate malignant from benign lesions. Tissue proprieties and molecules causing stiffness are not established. The aim of the study was to correlate US elastography findings with tissue properties in thyroid nodules. Methods: A total of 115 thyroid nodules from 112 patients who underwent surgery for the presence of Thy 3 (indeterminate) cytology (n = 67), Thy 4-5 (suspicious - indicative of carcinoma) cytology (n = 47), or large goiter in the presence of Thy 2 cytology (n = 1) and suspicious US features were examined by US elastography. Tissues obtained after surgery were characterized for cell number, microvessel density, fibrosis, and expression of galectin-3 (Gal-3) and fibronectin-1 (FN-1). Results: Low elasticity on qualitative US elastography (LoEl) was found in 66 nodules (one benign and 65 carcinomas); high elasticity (HiEl) was found in 49 nodules (46 benign and three carcinomas; p < 0.0001). Quantitative analysis, performed in 24 nodules and expressed as elastic ratio between the strain of the nodule and that of the surrounding thyroid parenchyma, showed a mean of 1.90 (interquartile range [IQR] 1.18-2.77) in 14 nodules with LoEl, and a mean of 1.01 (IQR 0.91-1.10) in 10 nodules with HiEl (p = 0.002). Stiffness did not correlate with cell number and was inversely correlated with microvessel density. Fibrosis was higher in nodules with LoEl than in those with HiEl (p = 0.009) and in carcinomas than in benign nodules (p = 0.02). Fibrosis was higher in nodules with high expression of Gal-3 (p < 0.001) and FN-1 (p = 0.004). Fibrosis and expression of Gal-3 and FN-1 were higher in the classic compared with the follicular variant of papillary thyroid carcinoma and lower in follicular adenomas. Conclusions: Low elasticity at US elastography is highly correlated with malignancy. Nodule stiffness is correlated with fibrosis and expression of Gal-3 and FN-1. These features are more evident in the classic than in the follicular variant of papillary thyroid carcinoma

Recommended vaccinations for asplenic and hyposplenic adult patients

Asplenic or hyposplenic (AH) individuals are particularly vulnerable to invasive infections caused by encapsulated bacteria. Such infections have often a sudden onset and a fulminant course. Infectious diseases (IDs) incidence in AH subjects can be reduced by preventive measures such as vaccination. The aim of our work is to provide updated recommendations on prevention of infectious diseases in AH adult patients, and to supply a useful and practical tool to healthcare workers for the management of these subjects, in hospital setting and in outpatients consultation. A systematic literature review on evidence based measures for the prevention of IDs in adult AH patients was performed in 2015. Updated recommendations on available vaccines were consequently provided. Vaccinations against S. pneumoniae, N. meningitidis, H. influenzae type b and influenza virus are strongly recommended and should be administered at least 2 weeks before surgery in elective cases or at least 2 weeks after the surgical intervention in emergency cases. In subjects without evidence of immunity, 2 doses of live attenuated vaccines against measles-mumps-rubella and varicella should be administered 4–8 weeks apart from each other; a booster dose of tetanus, diphtheria and pertussis vaccine should be administered also to subjects fully vaccinated, and a 3-dose primary vaccination series is recommended in AH subjects with unknown or incomplete vaccination series (as in healthy people). Evidence based prevention data support the above recommendations to reduce the risk of infection in AH individuals

The Role of Anti-Angiogenics in Pre-Treated Metastatic BRAF-Mutant Colorectal Cancer: A Pooled Analysis

: Background. FOLFOXIRI plus Bevacizumab is one of the most frequently used first-line treatments for patients with BRAF-mutant colorectal cancer (CRC), while second-line treatment requires extensive further research. In this pooled analysis, we evaluate the impact of anti-angiogenics in patients with pre-treated BRAF-mutant CRC. Methods. We monitored patients in randomized, controlled studies who had advanced CRC and were undergoing second-line chemotherapy in addition to utilizing Bevacizumab, Ramucirumab or Aflibercept treatments. These data were pooled together with the data and results of BRAF-mutant patients enrolled in two phase III trials (TRIBE and TRIBE-2 study), who had been treated with second-line treatment both with or without Bevacizumab. Overall survival (OS), in relation to BRAF mutational status, was the primary focus. Results. Pooled analysis included 129 patients. Anti-angiogenics were found to have a significant advantage over the placebo in terms of OS (HR 0.50, 95%CI 0.29-0.85) (p = 0.01). Conclusions. Our pooled analysis confirms the efficacy of anti-angiogenics in pre-treated BRAF-mutant CRC, establishing the combination of chemotherapy plus Bevacizumab or Ramucirumab or Aflibercept as a valid treatment option

Do Tuscan people adhere to meningococcal C vaccination during an emergency campaign?

Introduction: Tuscany region (Italy) recorded a rise in the number of meningococcal disease cases between January 2015 and February 2016,(52 cases) compared to 2014(16 cases). The aim of this study was to describe the emergency meningococcal C (MenC) vaccination programme in Tuscany and the population’s adherence to the activities performed in the Local Health Unit (LHU) of Florence.Methods:The MenC vaccination programme and the planning of the prevention and communication activities were analysed in the LHU of Florence. As an indicator of population’s adherence, the vaccination coverage (VC)during the emergency campaignwas investigated and adverse drug reactions (ADR) surveillance was reported.Results:The communication campaign included a dedicated toll-free telephone number, press releases (newspapers, radio, television, websites), and informative letters addressed to mayors, secondary schools, and sports associations. Citizens aged 11–20 years were the primary target of the campaign. Due to the high incidence of cases among older people, the vaccination was extended to subjectsover 45 years. The population’s adherence to the vaccination campaignwas satisfactory: VC reached 47.1%for the primary target. The ADR reporting rate (3.1/10,000) on meningococcal disease in our study confirmed the safety of the vaccination.Conclusions:In 2017, only 10 IMD cases were reported, suggesting the effectiveness of the immunization campaign. Similar VC during emergency MenC vaccination programmes have been reached in other Italian regions and other EU countries, too.The achievement of greater vaccination coverage is restricted by a sentiment of hesitancy towards vaccines among the general population