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  • Roman Gustavsen posted an update 3 weeks, 5 days ago

    PURPOSE Despite compelling support for the benefits of low-dose CT (LDCT) screening for lung cancer among high-risk individuals, awareness of LDCT screening and uptake remain low. The aim of this project was to explore the perspectives of ACR mammography screening program directors (MPDs) regarding efforts to raise LDCT screening awareness and appropriate referrals by identifying high-risk individuals participating in routine mammography. METHODS MPDs were recruited from ACR-accredited mammography facilities to participate in semistructured interviews after the completion of an online survey. Interviews were conducted over the telephone, recorded, transcribed, and subsequently reviewed for accuracy. Twenty MPDs were interviewed, and 18 interviews were transcribed and included in the thematic analysis. A theme codebook was developed, and all interviews were coded using NVivo by two trained reviewers. NSC 2382 research buy RESULTS Key themes were organized into four broad domains (1) general attitudes toward the integration of LDCT screening, (2) identifying mammography patients at high risk for lung cancer, (3) counseling about LDCT screening, and (4) strategies to identify high-risk women and increase awareness and knowledge of LDCT screening. Overall, MPDs recognized the benefits of integrating mammography and LDCT screening and were receptive to educating and referring women for LDCT screening. However, training and workflow changes are needed to ensure successful implementation. CONCLUSIONS Qualitative data suggest that MPDs are amenable to leveraging the mammography setting to engage women about LDCT screening; however, additional tools, training, and/or staffing may be necessary to leverage the full potential of reaching women at high risk for lung cancer within the context of mammographic screening. Quantification of therapeutic antibodies is commonly based on physico-chemical assays such as enzyme-linked immunoabsorption assays (ELISA) and lately on mass spectrometry. However, the functional integrity of evaluated immunoglobulins is yet not assessed. Consequently, a commercially available reporter cell line was used to quantify the functional concentration of the anti-tumor necrosis factor alpha (TNF-α) antibody adalimumab present in serum of a healthy beagle dog treated with 3 mg intravenous adalimumab (Humira®). HEK-Blue™-hTLR3 cells express a secreted alkaline phosphatase under the control of a nuclear factor kappa B (NF-κB) response element. Its enzymatic activity can be recorded using colorimetry, which reports activity of extracellular NF-κB stimuli such as TNF-α. Using an adalimumab concentration-response calibration curve, the functional concentration of serum adalimumab was estimated to be 4.9 ± 1.4 μg/ml, which was in excellent agreement with ELISA results (4.8 μg/ml). The obtained data suggest that this simple, easy-to-handle reporter cell assay can be used for the functional quantification of adalimumab present in samples from in vitro or pre-clinical in vivo experiments. Moreover, this assay could be used in vitro to compare the pharmacodynamics of adalimumab biosimilars or different anti-TNF-α compounds, respectively. The development of new drugs targeting neglected animal diseases is imperative. In Asia and South America, Trypanosoma evansi is a pathogen that affects horses and other species, causing economic losses associated with reduced animal productivity and death. In order to accelerate the identification of drugs with activity against neglected diseases, Medicines for Malaria Venture has developed Pathogen Box®, a library of 400 different molecules. The present work aimed to identify compounds present in the Pathogen Box® library, measuring in vitro activity against T. evansi. Among the 400 compounds, 5 showed anti-T.evansi activity pentamidine, MMV688410, MMV687273, MMV022478 and auranofin. Suramin, a trypanocidal activity molecule present on the Pathogen Box® reference compound list, demonstrated no anti-T. evansi activity in the in vitro assays. MMV688410 is the most promising candidate because it induces death and reduces the number of parasites in cell culture, and mainly because its mechanism of action is probably associated with inhibition of trypanosomal reductase enzyme, an exclusive target of trypanosomatides. Further in vitro and in vivo assays are needed to determine the efficacy of the compounds identified in this work, especially by associating tissue distribution and the ability of drugs to cross the blood brain barrier, as T. evansi is able to invade the central nervous system. The reptile-associated Borrelia represent a monophyletic group of bacteria transmitted by several species of hard ticks, which has been reported to only infect amphibians and reptiles in Eurasia and Middle East, however, this bacterial group has not been studied in North America. The aim of this study was to assess the presence of Borrelia spirochetes in blood samples of native reptiles of Mexico. Blood samples were directly obtained from individuals, DNA extractions were performed using Chelex-100. The Borrelia detection was performed by conventional PCR. From 102 reptiles tested, only five individuals of Boa constrictor were positive for the presence of DNA of the reptile-associated Borrelia group. Supported by phylogenetic analysis, this study presents the first record of these spirochetes group in Mexico, and initial evidence of B. constrictor as a host of this group. To survive, cancers cells must resist numerous internal and environmental insults associated with neoplasia that jeopardize proteostasis within the endoplasmic reticulum (ER). Solid and hematopoietic tumors often experience genomic instability, oncogene activation, increased protein secretion demands, and somatic mutations in proteins handled by the secretory pathway that impede their folding. Invasion or metastasis into foreign environments can expose tumor cells to hypoxia, oxidative stress, lack of growth signals, inadequate amino acid supplies, glucose deprivation, and lactic acidosis, all of which pose challenges for protein processing in the ER. Together, these conditions can promote the buildup of misfolded proteins in the ER to cause “ER stress,” which then activates the unfolded protein response (UPR). An intracellular signaling network largely initiated by three ER transmembrane proteins, the UPR constantly surveils protein folding conditions within the ER lumen and when necessary initiates counteractive measures to maintain ER homeostasis.