Intensive follow-up strategies significantly improve outcomes in patients with nonmetastatic colorectal cancer after curative surgery.
A wide variety of follow-up strategies are used for patients ...with colorectal cancer (CRC) after curative surgery. The aim of this study is to review the evidence of the impact of different follow-up strategies in patients with nonmetastatic CRC after curative surgery, in relation to overall survival and other outcomes.
A systematic search of PubMed, EMBASE, SCOPUS and ISI Web of Knowledge up to June 2014 was carried out. Eligible studies were all randomized clinical trials comparing the effectiveness of different follow-up strategies after curative resection in nonmetastatic CRC.
Eleven studies withn = 4055 participants were included in a meta-analysis. A significant improvement in overall survival was observed in patients with more intensive follow-up strategies hazard ratio = 0.75; 95% confidence interval (CI) 0.66–0.86. A higher probability of detection of asymptomatic recurrences relative risk (RR) = 2.59; 95% CI 1.66–4.06, curative surgery attempted at recurrences (RR = 1.98; 95% CI 1.51–2.60), survival after recurrences (RR = 2.13; 95% CI 1.24–3.69), and a shorter time in detecting recurrences (mean difference = -5.23 months; 95% CI -9.58 to -0.88) was observed in the intervention group. There were no significant differences in the total tumor recurrences, nor in the mortality related to disease.
Intensive follow-up strategies improve overall survival, increase the detection of asymptomatic recurrences and curative surgery attempted at recurrence, and are associated with a shorter time in detecting recurrences. This more intensive follow-up could not be associated with an improvement in cancer-specific survival nor with an increased detection of total tumor recurrences. Follow-up with serum carcinoembryonic antigen and colonoscopies are related to an increase in overall survival.
Context.
Blazars are the most numerous class of high-energy (HE;
E
∼ 50 MeV−100 GeV) and very high-energy (VHE;
E
∼ 100 GeV−10 TeV) gamma-ray emitters. Currently, a measured spectroscopic redshift is ...available for only about 50% of gamma-ray BL Lacertae objects (BL Lacs), mainly due to the difficulty in measuring reliable redshifts from their nearly featureless continuum-dominated optical spectra. The knowledge of the redshift is fundamental for understanding the emission from blazars, for population studies and also for indirect studies of the extragalactic background light and searches for Lorentz invariance violation and axion-like particles using blazars.
Aims.
This paper is the first in a series of papers that aim to measure the redshift of a sample of blazars likely to be detected with the upcoming Cherenkov Telescope Array (CTA), a ground-based gamma-ray observatory.
Methods.
Monte Carlo simulations were performed to select those hard spectrum gamma-ray blazars detected with the
Fermi
-LAT telescope still lacking redshift measurements, but likely to be detected by CTA in 30 hours of observing time or less. Optical observing campaigns involving deep imaging and spectroscopic observations were organised to efficiently constrain their redshifts. We performed deep medium- to high-resolution spectroscopy of 19 blazar optical counterparts with the Keck II, SALT, and ESO NTT telescopes. We searched systematically for spectral features and, when possible, we estimated the contribution of the host galaxy to the total flux.
Results.
We measured eleven firm spectroscopic redshifts with values ranging from 0.1116 to 0.482, one tentative redshift, three redshift lower limits including one at
z
≥ 0.449 and another at
z
≥ 0.868. Four BL Lacs show featureless spectra.
•Anti-Leishmania IgG is a marker of disseminated leishmaniasis.•Anti-Leishmania IgG correlates with Th1 immune response in disseminated leishmaniasis.•Anti-Leishmania IgG2 correlates with the number ...of lesions in disseminated leishmaniasis.
In this study, we determined the accuracy of anti-Leishmania IgG and IgG subclasses to distinguish clinical forms of American tegumentary leishmaniasis (ATL) and and determined the relationship between antibodies levels with cytokine production and severity of ATL.
Participants were 40 patients with cutaneous leishmaniasis (CL), 20 patients with mucosal leishmaniasis (ML), 20 patients with disseminated leishmaniasis (DL), and 20 individuals with subclinical Leishmania braziliensis infection (SC). Diagnosis was performed by DNA of L. braziliensis or IFN-γ production in SC. IgG and subclasses of IgG to soluble Leishmania antigen and cytokine levels in supernatants of mononuclear cells were detected by ELISA.
IgG was detected in 95%, 95%, and 100% of patients with CL, ML, and DL, respectively. Higher levels of anti-Leishmania IgG and IgG2 were seen in DL compared to CL, ML, and SC. ROC analysis confirmed the ability of IgG to distinguish DL from the other clinical forms. A direct correlation was observed between IgG titers and levels of IFN-γ and CXCL10 in CL and DL, and IgG2 antibodies were correlated with the number of lesions in DL.
High anti-Leishmania IgG and IgG2 levels are characteristic of DL, and while IgG was correlated with pro-inflammatory cytokines, IgG2 was direct correlated with the number of lesions.
Cassava production in Africa is constrained by cassava mosaic disease (CMD) that is caused by the Cassava mosaic virus (CMV). The aim of this study was to evaluate the responses of a range of ...commonly cultivated West African cassava cultivars to varying inoculum doses of African cassava mosaic virus (ACMV). We grafted 10 cultivars of cassava plants with different inoculum doses of CMV (namely two, four, or six CMD-infected buds) when the experimental plants were 8, 10, or 12 weeks old, using non-inoculated plants as controls. Three cultivars showed disease symptoms when grafted with two buds, and four cultivars showed disease symptoms when grafted with four or six buds. Most cultivars became symptomatic six weeks after inoculation, but one ('TMS92/0326') was symptomatic two weeks after inoculation, and two ('Ntollo' and 'Excel') were symptomatic after four weeks. Root weight tended to be lower in the six-bud than in the two-bud dose, and disease severity varied with plant age at inoculation. These results indicate that the level of CMD resistance in cassava cultivars varies with inoculum dose and timing of infection. This will allow appropriate cultivars to be deployed in each production zone of Africa in accordance with the prevalence of CMD.
This study investigated the potential of selected compounds as inhibitors of SARS-CoV-2 Mpro through pharmacokinetic and toxicological analyses, molecular docking, and molecular dynamics simulations. ...In silico molecular docking simulations revealed promising ligands with favorable binding affinities for Mpro, ranging from −6.2 to −9.5 kcal/mol. Moreover, molecular dynamics simulations demonstrated the stability of protein–ligand complexes over 200 ns, maintaining protein secondary structures. MM-PBSA analysis revealed favorable interactions between ligands and Mpro, with negative binding energy values. Hydrogen bond formation capacity during molecular dynamics was confirmed, indicating consistent interactions with Mpro catalytic residues. Based on these findings, selected ligands show promise for future studies in developing COVID-19 treatments.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has received global attention due to the serious threat it poses to public health. Since ...the outbreak in December 2019, millions of people have been affected and its rapid global spread has led to an upsurge in the search for treatment. To discover hit compounds that can be used alone or in combination with repositioned drugs, we first analyzed the pharmacokinetic and toxicological properties of natural products from Brazil’s semiarid region. After, we analyzed the site prediction and druggability of the SARS-CoV-2 main protease (Mpro), followed by docking and molecular dynamics simulation. The best SARS-CoV-2 Mpro complexes revealed that other sites were accessed, confirming that our approach could be employed as a suitable starting protocol for ligand prioritization, reinforcing the importance of catalytic cysteine-histidine residues and providing new structural data that could increase the antiviral development mainly against SARS-CoV-2. Here, we selected 10 molecules that could be in vitro assayed in response to COVID-19. Two compounds (b01 and b02) suggest a better potential for interaction with SARS-CoV-2 Mpro and could be further studied.
Aedes aegypti mosquitoes transmit several human pathogens that cause millions of deaths worldwide, mainly in Latin America. The indiscriminate use of insecticides has resulted in the development of ...species resistance to some such compounds. Piperidine, a natural alkaloid isolated from Piper nigrum, has been used as a hit compound due to its larvicidal activity against Aedes aegypti. In the present study, piperidine derivatives were studied through in silico methods: pharmacophoric evaluation (PharmaGist), pharmacophoric virtual screening (Pharmit), ADME/Tox prediction (Preadmet/Derek 10.0®), docking calculations (AutoDock 4.2) and molecular dynamics (MD) simulation on GROMACS-5.1.4. MP-416 and MP-073 molecules exhibiting ΔG binding (MMPBSA −265.95 ± 1.32 kJ/mol and −124.412 ± 1.08 kJ/mol, respectively) and comparable to holo (ΔG binding = −216.21 ± 0.97) and pyriproxyfen (a well-known larvicidal, ΔG binding= −435.95 ± 2.06 kJ/mol). Considering future in vivo assays, we elaborated the theoretical synthetic route and made predictions of the synthetic accessibility (SA) (SwissADME), lipophilicity and water solubility (SwissADME) of the promising compounds identified in the present study. Our in silico results show that MP-416 and MP-073 molecules could be potent insecticides against the Aedes aegypti mosquitoes.
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