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Background Resistance to osimertinib in advanced EGFR- mutated non-small cell lung cancer (NSCLC) constitutes a significant challenge for clinicians either in terms of molecular diagnosis and subsequent therapeutic implications. Methods This is a prospective single-centre study with the primary objective of characterising resistance mechanisms to osimertinib in advanced EGFR- mutated NSCLC patients treated both in first- and in second-line. Next-Generation Sequencing analysis was conducted on paired tissue biopsies and plasma samples. A concordance analysis between tissue and plasma was performed. Results Sixty-five advanced EGFR -mutated NSCLC patients treated with osimertinib in first- ( n  = 56) or in second-line ( n  = 9) were included. We managed to perform tissue and liquid biopsies in 65.5% and 89.7% of patients who experienced osimertinib progression, respectively. Acquired resistance mechanisms were identified in 80% of 25 patients with post-progression samples, with MET amplification ( n  = 8), EGFR C797S ( n  = 3), and SCLC transformation ( n  = 2) the most frequently identified. The mean concordance rates between tissue and plasma for the EGFR activating mutation and for the molecular resistance mechanisms were 87.5% and 22.7%, respectively. Conclusions Resistance to osimertinib demonstrated to be highly heterogeneous, with MET amplification the main mechanism. Plasma genotyping is a relevant complementary tool which might integrate tissue analysis for the study of resistance mechanisms.

We conducted four rounds of cognitive testing of self-report items that included 66 sociodemographically diverse participants, then field tested the three best items from the cognitive testing in a clinic waiting room ( N  = 351) and in an online social networking site for men who have sex with men ( N  = 6,485). As part of the online survey we conducted a randomized assessment of two versions of the adherence questionnaire—one which asked about adherence to a specific antiretroviral medication, and a second which asked about adherence to their “HIV medicines” as a group. Participants were better able to respond using adjectival and adverbial scales than visual analogue or percent items. The internal consistency reliability of the three item adherence scale was 0.89. Mean scores for the two different versions of the online survey were similar (91.0 vs. 90.2, p  < 0.05), suggesting that it is not necessary, in general, to ask about individual medications in an antiretroviral therapy regimen when attempting to describe overall adherence.

Atlantification of Arctic ocean is causing a sharp increase in temperature and salinity around Svalbard Islands and in Kongsfjorden. Such phenomenon and the input of sediment-rich glacial meltwater influence salinity, water column turbidity, and light penetration with ecological implications on the microbial features. With the aim to address the temporal variability of the microbial assemblage in relation to environmental variables, a 7-day study was carried out in Kongsfjorden, in late summer 2013. Abiotic (temperature, salinity, nutrients, total suspended matter, particulate inorganic, and organic carbon) and biotic (phyto -, picophyto-, bacterio-, and virioplankton abundance and microbial respiration) parameters were investigated at a station in the inner fjord area, ca. 8.5 km away from the glacier front. Phyto-, picophyto-, and virioplankton showed low abundance. Dinoflagellates and coccolithophorids dominated the phytoplankton community while Synechococcus sp. the picophytoplankton alone, in relation with Atlantic water. Low virus to bacteria ratios were detected, presumably linked to the high sedimentation rates. Interesting variability for picophytoplankton with depth, virioplankton with both time and depth, and respiratory rates with time were found. Moreover, the organic matter turnover was slower on the first sampling day compared to that of the following days. Planktonic abundance depended on the variability of both hydrology (seawater mass inflow) and freshwater runoff from the glacier (relative turbidity degree). Differently, the metabolic rates of respiration appeared to be linked with the particulate carbon pool. Over 1-week study, the diverse microbial dynamics appeared to be conditioned on complex forcing, emphasizing the importance of high-resolution experiment.

Estimation of microbial biomass depends on cell shape and size determinations, and thus, there is a wide biovolume variability among morphotypes. Nevertheless, data on morphology and morphometry of prokaryotic cells under different trophic status are seldom published, due to the methodological difficulties of cell measurements. The main question addressed in this paper concerns the suitability of prokaryotic size and shape for environmental characterization. Microbial biovolumes were compared among different ecosystems, located in temperate and tropical regions. Samples were taken from fresh, brackish, mixohaline, and estuarine waters that were classified as oligo-, meso-, eu-, and hypertrophic by comparing synoptically different trophic indices. Prokaryotic cell abundance and volume were quantified by Image Analysis, used to calculate biomass, and correlated to environmental variables. Some samples were analyzed by flow cytometry also, and data from sub-populations with a different apparent DNA content were available. Prokaryotic abundances generally increased from oligo- to hypertrophic waters while cell volumes increased from oligotrophic to eutrophic waters. Although significant correlations between cell volumes and environmental variables were detected (positive with salinity and negative with Chlorophyll- a ), different morphotypes dominated each studied regions. Our results sustain the hypothesis that prokaryotic cell size and shape could be useful to ecosystem characterization.

Carrageenans are sulfated galactans found in certain red seaweeds with proven biological activities. In this work, we have prepared purified native and degraded κ-, ι-; and λ-carrageenans, including the disaccharides (carrabioses) and disaccharide-alditols (carrabiitols) from seaweed extracts as potential antitumor compounds and identified the active principle of the cytotoxic and potential antitumor properties of these compounds. Both κ and ι-carrageenan, as well as carrageenan oligosaccharides showed cytotoxic effect over LM2 tumor cells. Characterized disaccharides (carrabioses) and the reduced product carrabiitols, were also tested. Only carrabioses were cytotoxic, and among them, κ-carrabiose was the most effective, showing high cytotoxic properties, killing the cells through an apoptotic pathway. In addition, the cells surviving treatment with κ-carrabiose, showed a decreased metastatic ability in vitro , together with a decreased cell-cell and cell-matrix interactions, thus suggesting possible antitumor potential. Overall, our results indicate that most cytotoxic compounds derived from carrageenans have lower molecular weights and sulfate content. Potential applications of the results emerging from the present work include the use of disaccharide units such as carrabioses coupled to antineoplasics in order to improve its cytotoxicity and antimetastatic properties, and the use of ι-carrageenan as adjuvant or carrier in anticancer treatments.

Infectious diseases are one of the major drivers of coral reef decline worldwide. White plague-like disease (WPL) is a widespread disease with a complex etiology that infects several coral species, including the Brazilian endemic species Mussismilia braziliensis. Gene expression profiles of healthy and WPL-affected M. braziliensis were analyzed in winter and summer seasons. The de novo assembly of the M. braziliensis transcriptome from healthy and white plague samples produced a reference transcriptome containing 119,088 transcripts. WPL-diseased samples were characterized by repression of immune system and cellular defense processes. Autophagy and cellular adhesion transcripts were also repressed in WPL samples, suggesting exhaustion of the coral host defenses. Seasonal variation leads to plasticity in transcription with upregulation of intracellular signal transduction, apoptosis regulation, and oocyte development in the summer. Analysis of the active bacterial rRNA indicated that Pantoea bacteria were more abundant in WPL corals, while Tistlia, Fulvivirga, and Gammaproteobacteria Ga0077536 were more abundant in healthy samples. Cyanobacteria proliferation was also observed in WPL, mostly in the winter. These results indicate a scenario of dysbiosis in WPL-affected M. braziliensis, with the loss of potentially symbiotic bacteria and proliferation of opportunistic microbes after the start of the infection process.

Human immunodeficiency virus type 1 (HIV-1) infection of the brain produces a characteristic disease called acquired immunodeficiency syndrome (AIDS) dementia in which productive infection and inflammatory activation of microglia and macrophages play a central role. In this report, the authors demonstrate that minocycline (MC), a second-generation tetracycline with proven safety and penetration to the central nervous system, potently inhibited viral production from microglia. Inhibition of viral release was sustained through the entire course of infection and even when the drug exposure was limited to the first day of infection. Minocycline was effective even at low viral doses, and against R5- and X4R5-HIV, as well as in single-cycle reporter virus assays. Electrophoretic mobility shift analysis showed that minocycline inhibited nuclear factor (NF)-κ B activation in microglia. HIV-1 long terminal repeat (LTR)-promoter activity in U38 cells was also inhibited. These results, combined with recently demonstrated in vivo anti-inflammatory effects of MC on microglia, suggest a potential utility for MC as an effective adjunct therapy for AIDS dementia.

Background: Biliopancreatic gallstone disorders (BPD) manifesting during pregnancy are relatively rare. The management of these conditions remains controversial. Although perioperative problems and fetal loss have been reported, recent publications have advocated an early surgical approach. Patients and methods: Thirty-two pregnant women underwent operation for BPD between January 1993 and December 1997. The mean age was 29 years and ranged from 18 to 41 years. Results: Twelve patients underwent a laparoscopic cholecystectomy (LC), and 20 open cholecystectomies (OC), including two conversions from laparoscopic. Seven of the OC patients required additional open CBD exploration and intraoperative choledochoscopy for CBD stones. No maternal mortality was observed. A single fetal demise (3%) occurred for a patient with gallstone pancreatitis who underwent open cholecystectomy during her 14th week of gestation. Conclusions: Early involvement of the obstetric team, with preoperative and postoperative fetal monitoring, and adequate management of anesthetic and tocolytic agents make cholecystectomy a safe procedure at any stage of pregnancy.

Because of its exceptional salinity tolerance, inland saltgrass [Distichlis spicata var. stricta (L.) Greene] has great potential for use as a turfgrass and revegetation species of saline sites. However, saltgrass seeds have a low germination rate due to seed dormancy. Three experiments were conducted to evaluate different seed treatments to enhance germination and establishment of inland saltgrass. In Experiment I, seven different seed treatments were tested for their ability to enhance germination percentage in the growth chamber and compared with a control of no treatment. These treatments included treatments with hot water, hydrogen peroxide (H₂O₂), sulfuric acid (H₂SO₄), potassium nitrate (KNO₃), bleach, machine scarification, stratification, and hand nicking. Results indicated that germination percentage was increased only by stratification, hand nicking, and machine scarification treatments as compared with the control. In Experiment II, machine scarification, stratification, hand nicking, and the control were tested in the growth chamber. Hand nicking, scarification, and stratification increased percentage germination from 13.0% to 54.0 to 61.7%. Stratification resulted in the fastest germination, followed by hand nicking and scarification. Experiment III was conducted in the field, and seed treatments included machine scarification, stratification, and the control. Two months after seeding, plots seeded with stratified and scarified saltgrass seeds established adequate plot coverage as a turf, whereas the coverage for the control was inadequate, exhibiting inferior turf quality. In summary, stratification and machine scarification improve germination and establishment of seeded saltgrass.

Background Enteral immunodiet has been gaining increasing attention, but experimental data of its clinical effects in patients with gastric cancer are inconsistent, contradictory, and poorly investigated. The aim of this study was to assess the impact of early postoperative enteral immunonutrition on clinical and immunological outcomes in a homogeneous group of gastric cancer patients submitted to total gastrectomy. Methods A total of 109 patients with gastric cancer were randomized to receive early postoperative enteral immunonutrition (formula supplemented with arginine, omega-3 fatty acids and ribonucleic acid [RNA]), or an isocaloric–isonitrogenous control. The postoperative outcome was evaluated based on clinical variables, including postoperative infectious complications, anastomotic leak rate, and length of hospitalization. In addition, state of cellular immunity was evaluated and compared between the 2 groups. Results The incidence of postoperative infectious complications in the immunodiet group (7.4 %) was significantly ( p  < .05) lower than that of the control group (20 %), as well as the anastomotic leak rate (3.7 % in immunodiet group vs 7.3 % in standard nutrition group, p  < .05). Mortality rate did not show any significant differences; patients of the immunodiet group were found to have a significantly reduced length of hospitalization (12.7 ± 2.3 days) when compared with standard diet group (15.9 ± 3.4 days, p  = .029). The data on cellular immunity showed that the postoperative CD4 + T-cell counts decreased in both groups, but the reduction in the IED group was significantly higher ( p  = .032) compared with the SND group. Conclusions Early postoperative enteral immunonutrition significantly improves clinical and immunological outcomes in patients undergoing gastrectomy for gastric cancer.