A retrospective database analysis of burden of IPD and pneumonia in children <15y in Veneto region

Abstract Background IPD and pneumonia are associated with high mortality and healthcare resource utilization (HCRU). This analysis assessed incidence, HCRU and costs of IPD and pneumonia following PCV13 introduction in 2010 in Veneto. Methods IPD, unspecified invasive disease episodes, outpatient pneumococcal and unspecified pneumonia episodes were identified in Pedianet, a pediatric primary care database from 2010-2017. HCRU includes primary care and specialist visits, antibiotic prescriptions, diagnostics, ER visits and hospitalizations. Incidence rates (IRs) were numbers of episodes/1,000 person-years. Standardized regional incidence rates (SRIRs) were calculated by standardizing IRs with regional population data by age and year. Regional expenditures (€/1,000 person-years) were calculated by multiplying SRIRs with average costs per episode. Interrupted time series (ITS) analyses assessed trends in annual IRs in the early and late PCV13 (2010-2013, 2014-2017) periods. Results During 2010-2017, IPD and unspecified invasive disease incidence decreased from 0.40 to 0.31/1,000 person-years. While incidence was numerically lower in 2017 than in 2010, ITS analysis did not detect a significant trend in the early (coef=1.97; p = 0.63) or late PCV13 (coef=0.50; p = 0.90) periods. Average cost per episode was €4206 and average regional expenditure was €171/1,000 person-year. SRIR for outpatient pneumonia decreased from 13.35 to 5.48/1,000 person-year during 2010 to 2017. Pneumonia episodes were associated with 0.29 ER visits and 0.15 short stay and 0.06 long stay hospitalization. Average cost per episode was €345, majority of which was associated with ER visits (€50.8) and hospitalizations (€243.9). Regional expenditures decreased from €12852.31 to €5351.98/1,000 person-year. Conclusions IPD and unspecified invasive disease burden did not change significantly following PCV13 introduction, while disease burden declined for outpatient pneumococcal and unspecified pneumonia. Key messages IPD and unspecified invasive disease burden did not change significantly following PCV13 introduction. Disease burden declined for outpatient pneumococcal and unspecified pneumonia following PCV13

High-resolution imaging at the SOAR telescope

Bright single and binary stars were observed at the 4.1-m telescope with a fast electron-multiplication camera in the regime of partial turbulence correction by the visible-light adaptive optics system. We compare the angular resolution achieved by simple averaging of AO-corrected images (long-exposure), selection and re-centering (shift-and-add or "lucky" imaging) and speckle interferometry. The effect of partial AO correction, vibrations, and image post-processing on the attained resolution is shown. Potential usefulness of these techniques is evaluated for reaching the diffraction limit in ground-based optical imaging. Measurements of 75 binary stars obtained during these tests are given and objects of special interest are discussed. We report tentative resolution of the astrometric companion to Zeta Aqr B. A concept of advanced high-resolution camera is outlined.Comment: Accepted for publication in PASP. 14 pages, 9 figures, 2 tabl

Transporte de NO3 e NH4 em agregados de Latossolo Vermelho com e sem atividade biológica.

Objetivou-se, com este trabalho, avaliar a influência do tamanho dos agregados de um Latossolo Vermelho distrófico sobre as transformações e transporte do amônio e do nitrato em condições de presença e ausência de atividade biológica. Utilizou-se o fatorial 23 x 4, com fatores e níveis: vegetação de cobertura do solo (cerrado e milho ); atividade biológica (com e sem esterilização do solo); fontes de N da solução com 10 mmol L-1 de N, para saturação das colunas (Ca(NO3)2 e NH4CI) e classes de agregados (2,0 a 1,0; 1,0 a 0,5; 0,5 a 0,25 e 0,25 a 0,105 mm). Na primeira eluição, o efluente das colunas contendo microbiota ativa e saturação com Ca(NO3)2 apresentou teor de NO3 - menor no efluente dos agregados de 0,25 a 0,105 mm; já em condições de esterilização, ocorreu o inverso: maior concentração do NO3 -no efluente dos agregados de 0,25 a 0,105 mm. Para as colunas saturadas com NH4CI, na primeira eluição os teores do NH4+ foram maiores nos efluentes dos agregados de 0,25 a 0,105 mm para todas as combinações de cobertura de solo e esterilização, enquanto na presença da microbiota ativa o efluente dos agregados de 0,25 a 0,105 mm apresentou teor semelhante ao dos agregados de 0,5 a 0,25 mm

Carbon based substrates for interfacing neurons: Comparing pristine with functionalized carbon nanotubes effects on cultured neuronal networks

Pristine (as prepared) carbon nanotube (CNT) based substrates have been widely used to grow and interface neurons in culture. Nerve cells normally differentiate on CNTs and the synaptic networks, newly formed at the interface with this material, usually show an improved robustness in signal transfer. However manipulation of pristine CNTs is often prevented by their low dispersibility and tendency to aggregate in most solvents. This issue can be at least partially solved by adding solubilizing groups to the surface of CNT, which also helps improving their biocompatibility. It becomes therefore of crucial importance to determine whether chemically manipulated CNTs may maintain their performance in improving nerve signaling. Here we study and compare the impact in vitro on neuronal signaling of two classes of chemically modified multiwalled CNTs in reference to pristine CNTs, which are known to be a substrate able to boost neuronal growth and communication. We found that the extent of functionalization and the nature of the functional groups on MWNT sidewalls affect the conductivity and the biological effects of the final derivatives. This information is important for the future design of biointegrated devices

Calcium Binds to Transthyretin with Low Affinity

The plasma protein transthyretin (TTR), a transporter for thyroid hormones and retinol in plasma and cerebrospinal fluid, is responsible for the second most common type of systemic (ATTR) amyloidosis either in its wild type form or as a result of destabilizing genetic mutations that increase its aggregation propensity. The association between free calcium ions (Ca2+) and TTR is still debated, although recent work seems to suggest that calcium induces structural destabilization of TTR and promotes its aggregation at non-physiological low pH in vitro. We apply high-resolution NMR spectroscopy to investigate calcium binding to TTR showing the formation of labile interactions, which leave the native structure of TTR substantially unaltered. The effect of calcium binding on TTR-enhanced aggregation is also assessed at physiological pH through the mechano-enzymatic mechanism. Our results indicate that, even if the binding is weak, about 7% of TTR is likely to be Ca2+-bound in vivo and therefore more aggregation prone as we have shown that this interaction is able to increase the protein susceptibility to the proteolytic cleavage that leads to aggregation at physiological pH. These events, even if involving a minority of circulating TTR, may be relevant for ATTR, a pathology that takes several decades to develop

Conversion of the Native N-Terminal Domain of TDP-43 into a Monomeric Alternative Fold with Lower Aggregation Propensity

TAR DNA-binding protein 43 (TDP-43) forms intraneuronal cytoplasmic inclusions associated with amyotrophic lateral sclerosis and ubiquitin-positive frontotemporal lobar degeneration. Its N-terminal domain (NTD) can dimerise/oligomerise with the head-to-tail arrangement, which is essential for function but also favours liquid-liquid phase separation and inclusion formation of full-length TDP-43. Using various biophysical approaches, we identified an alternative conforma-tional state of NTD in the presence of Sulfobetaine 3-10 (SB3-10), with higher content of α-helical structure and tryptophan solvent exposure. NMR shows a highly mobile structure, with partially folded regions and β-sheet content decrease, with a concomitant increase of α-helical structure. It is monomeric and reverts to native oligomeric NTD upon SB3-10 dilution. The equilibrium GdnHCl-induced denaturation shows a cooperative folding and a somewhat lower conformational stability. When the aggregation processes were compared with and without pre-incubation with SB3-10, but at the identical final SB3-10 concentration, a slower aggregation was found in the former case, despite the reversible attainment of the native conformation in both cases. This was attributed to protein monomerization and oligomeric seeds disruption by the conditions promoting the alternative con-formation. Overall, the results show a high plasticity of TDP-43 NTD and identify strategies to monomerise TDP-43 NTD for methodological and biomedical applications