EGFR-mutated advanced lung cancer. Data from a single institution, the Hospital of Leon, in Spain.

INTRODUCTION: 10-16% of non-small cell lung cancer (NSCLC) cases have the epidermal growth factor receptor (EGFR) amplified and/or mutated. Studies show that EGFR tyrosine kinase inhibitors (TKIs) significantly prolong progression-free survival (PFS) in patients with advanced NSCLC compared to those treated with platinum-based chemotherapy (CT) doublets. Our aim is to perform a real-world survival analysis of patients treated with TKI as first-line therapy at the Hospital of Leon (CAULE) in Spain. The impact on global survival rates and responses to clinical and histopathological factors were also analyzed. MATERIAL AND METHODS: We retrospectively reviewed patients diagnosed with EGFR-mutated NSCLC who received treatment with EGFR-TKI in the Department of Oncology at the University of Leon Health Center complex between March 2011 and June 2018. Data was analyzed with Kaplan-Meier and Cox regression models to show overall survival (OS), progression-free survival (PFS), and the associated variables. RESULTS: 53 patients were included in the study, 50% (n = 27) were treated with gefitinib, 32% (n = 18) with erlotinib and 10% (n = 6) with afatinib. The median OS and PFS were 27.7 months (95% CI: 21-33.8 months) and 18 months (95% CI 14.25-21.89 months), respectively. The variables associated with OS and with PFS were exon19 deletion as a protective factor and presence of extrathoracic metastasis as a risk factor. The most frequent adverse effects were rash, diarrhea, asthenia, and conjunctivitis. CONCLUSIONS: Real-world analysis of this data confirms that treatment with TKI is beneficial for patients diagnosed with EGFR-mutated NSCLC. Our OS outcomes were similar to those reported in clinical trials.

Understanding structure/function relationships in nitrifying microbial communities after cross-transfer between freshwater and seawater.

In this study, nitrification before and after abrupt cross-transfer in salinity was investigated in two moving bed biofilm reactors inoculated with nitrifying cultures that had adaptation to freshwater (FR) and seawater salinities (SR). FR and SR MBRRs were exposed to short and long term cross-transfer in salinity, and the functional capacity of nitrifying microbial communities was quantified by the estimation of ammonia and nitrite oxidation rates. Salinity induced successions were evaluated before and after salinity change by deep sequencing of 16S rRNA gene amplicons and statistical analysis. The bacterial community structure was characterized and Venn diagrams were included. The results indicated that after salinity cross-transfer, the FR was not significantly recovered at seawater salinity whereas SR showed high resistance to stress caused by low-salt. Succession and physiological plasticity were the main mechanisms of the long-term adaption of the nitrifying communities exposed to abrupt salinity changes. Independently of salinity, some nitrifiers presented high physiological plasticity towards salinity and were very successful at both zero and full seawater salinity. SR culture is robust and suitable inoculum for ammonium removal from recirculating aquaculture systems and industrial wastewaters with variable and fast salinity changes. Our findings contradict the current perspective of the significance of salinity on the structure of nitrifying communities.

First observation of the quantized exciton-polariton field and effect of interactions on a single polariton.

Polaritons are quasi-particles that originate from the coupling of light with matter and that demonstrate quantum phenomena at the many-particle mesoscopic level, such as Bose-Einstein condensation and superfluidity. A highly sought and long-time missing feature of polaritons is a genuine quantum manifestation of their dynamics at the single-particle level. Although they are conceptually perceived as entangled states and theoretical proposals abound for an explicit manifestation of their single-particle properties, so far their behavior has remained fully accounted for by classical and mean-field theories. We report the first experimental demonstration of a genuinely quantum state of the microcavity polariton field, by swapping a photon for a polariton in a two-photon entangled state generated by parametric downconversion. When bringing this single-polariton quantum state in contact with a polariton condensate, we observe a disentangling with the external photon. This manifestation of a polariton quantum state involving a single quantum unlocks new possibilities for quantum information processing with interacting bosons.

Changes in the microbial community of an anammox consortium during adaptation to marine conditions revealed by 454 pyrosequencing.

The anammox activity of a freshwater anammox consortium was strongly inhibited at low-salinity level. Stepwise adaptation from 0 to 3 g NaCl L-1 took 153 days. Further adaptation to high-salinity concentration (from 3 to 30 g L-1) took only 40 days, and no inhibition was observed. A comprehensive insight into the salinity-induced successions of the total and the anammox communities was obtained by 454 pyrosequencing of 16S rRNA gene amplicons and statistical analysis. A major succession in the anammox community was observed at 3 g L-1 where the dominating population shifted from Candidatus Brocadia fulgida to Ca. Kuenenia stuttgartiensis. The latter dominated at high salinity and seemed to be essential for the high (˃96%) ammonium and nitrite removal efficiencies achieved. SIMPER analysis indicated that these two dominating anammox species explained most to the differences in community structure among samples and helped in identifying other important members at different salinities.

Nitrification at different salinities: Biofilm community composition and physiological plasticity.

This paper describes an experimental study of microbial communities of three moving bed biofilm reactors (MBBR) inoculated with nitrifying cultures originated from environments with different salinity; freshwater, brackish (20‰) and seawater. All reactors were run until they operated at a conversion efficiency of >96%. The microbial communities were profiled using 454-pyrosequencing of 16S rRNA gene amplicons. Statistical analysis was used to investigate the differences in microbial community structure and distribution of the nitrifying populations with different salinity environments. Nonmetric multidimensional scaling analysis (NMDS) and the PERMANOVA test based on Bray-Curtis similarities revealed significantly different community structure in the three reactors. The brackish reactor showed lower diversity index than fresh and seawater reactors. Venn diagram showed that 60 and 78% of the total operational taxonomic units (OTUs) in the ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB) guild, respectively, were unique OTUs for a given reactor. Similarity Percentages (SIMPER) analysis showed that two-thirds of the total difference in community structure between the reactors was explained by 10 OTUs, indicating that only a small number of OTUs play a numerically dominant role in the nitrification process. Acute toxicity of salt stress on ammonium and nitrite oxidizing activities showed distinctly different patterns, reaching 97% inhibition of the freshwater reactor for ammonium oxidation rate. In the brackish culture, inhibition was only observed at maximal level of salinity, 32‰. In the fully adapted seawater culture, higher activities were observed at 32‰ than at any of the lower salinities.

Agrochemicals, α-synuclein, and Parkinson's disease.

Epidemiological, population-based case-control, and experimental studies at the molecular, cellular, and organism levels revealed that exposure to various environmental agents, including a number of structurally different agrochemicals, may contribute to the pathogenesis of Parkinson's disease (PD) and several other neurodegenerative disorders. The role of genetic predisposition in PD has also been increasingly acknowledged, driven by the identification of a number of disease-related genes [e.g., α-synuclein, parkin, DJ-1, ubiquitin C-terminal hydrolase isozyme L1 (UCH-L1), and nuclear receptor-related factor 1]. Therefore, the etiology of this multifactorial disease is likely to involve both genetic and environmental factors. Various neurotoxicants, including agrochemicals, have been shown to elevate the levels of α-synuclein expression in neurons and to promote aggregation of this protein in vivo. Many agrochemicals physically interact with α-synuclein and accelerate the fibrillation and aggregation rates of this protein in vitro. This review analyzes some of the aspects linking α-synuclein to PD, provides brief structural and functional descriptions of this important protein, and represents some data connecting exposure to agrochemicals with α-synuclein aggregation and PD pathogenesis.

Biophysical Characterization of α-Synuclein and Rotenone Interaction.

Previous studies revealed that pesticides interact with α-synuclein and accelerate the rate of fibrillation. These results are consistent with the prevailing hypothesis that the direct interaction of α-synuclein with pesticides is one of many suspected factors leading to α-synuclein fibrillation and ultimately to Parkinson's disease. In this study, the biophysical properties and fibrillation kinetics of α-synuclein in the presence of rotenone were investigated and, more specifically, the effects of rotenone on the early-stage misfolded forms of α-synuclein were considered. The thioflavine T (ThT) fluorescence assay studies provide evidence that early-phase misfolded α-synuclein forms are affected by rotenone and that the fibrillation process is accelerated. Further characterization by attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) shows that rotenone increases the amount of ordered secondary structure in this intrinsically disordered protein. Morphological characterization by transmission electron microscopy (TEM) and atomic force microscopy (AFM) provide visualization of the differences in the aggregated α-synuclein species developing during the early kinetics of the fibrillation process in the absence and presence of rotenone. We believe that these data provide useful information for a better understanding of the molecular basis of rotenone-induced misfolding and aggregation of α-synuclein.

Inhibition of sulfate reduction by iron, cadmium and sulfide in granular sludge.

This study investigated the inhibition effect of iron, cadmium and sulfide on the substrate utilization rate of sulfate reducing granular sludge. A series of batch experiments in a UASB reactor were conducted with different concentrations of iron (Fe2+, 4.0-8.5 mM), cadmium (Cd2+, 0.53-3.0 mM) and sulfide (4.2-10.6 mM), the reactor was fed with ethanol at 1g chemical oxygen demand (COD)/L and sulfate to yield a COD/SO4(2-) (g/g) ratio of 0.5. The addition of iron, up to a concentration of 8.1mM, had a positive effect on the substrate utilization rate which increased 40% compared to the rate obtained without metal addition (0.25 g COD/gVSS-d). Nonetheless, iron concentration of 8.5 mM inhibited the specific substrate utilization rate by 57% compared to the substrate utilization rate obtained in the batch amended with 4.0 mM Fe2+ (0.44 g COD/gVSS-d). Cadmium had a negative effect on the specific substrate utilization rate at the concentrations tested; at 3.0 mM Cd2+ the substrate utilization rate was inhibited by 44% compared with the substrate utilization rate without metal addition. Cadmium precipitation with sulfide did not decrease the inhibition of cadmium on sulfate reduction. These results could have important practical implications mainly when considering the application of the sulfate reducing process to treat effluents with high concentrations of sulfate and dissolved metals such as iron and cadmium.

Valores normales de la hormona estimulante de la tiroides en el recién nacido sano / The levels normals of the stimulate thyroid hormone in newborns

Se estudió la concentración de la hormona estimulante de la glándula tiroides (TSH) en muestras de sangre del condón umbilical y de la sangre capilar obtenida de neonatos entre las 18 y 24 horas de vida. En 90 por ciento de 121 muestras de sangre del condón umbilical, la TSH fue menor de 30 uUI/ml. De las 49 muestras de sangre capilar, la TSH estuvo por debajo de 24 uUI/ml. Un niño tuvo 47.13 uUI/ml en muestra de sangre capilar, cifra arriba de dos desviaciones estándar de la media; al mes de nacido se le determinó la T3, la T4 y la TSH, y los resultados fueron normales. No se encontraron diferencias estadísticamente significativas entre las concentraciones de la TSH de las muestras tomadas del condón umbilical y de la sangre capilar. Se comenta la importancia de los programas de investigación masiva de hipotiroidismo congénito, así como la necesidad de implantarlos en nuestro país.