The effect of incorporating the midge resistance (Sm1) gene in wheat

Non-Peer ReviewedOrange wheat blossom midge, Sitodiplosis mosellana (Géhin), was first detected in Manitoba in 1901, but now is present in all three prairie provinces of western Canada. In severe infestations, this insect may cause significant yield losses to spring wheat. To mitigate losses, midge-resistant wheat varietal blends, consisting of cultivars carrying the Sm1 midge resistance gene and 10% interspersed midge susceptible refuge, are now available to farmers. The refuge prevents this resistance to be overcome by the insect. To test the field performance of these varietal blends, relative to conventional midge-susceptible cultivars, four varietal blends were grown during four consecutive years, at eight locations in the provinces of Manitoba Saskatchewan and Alberta, in comparison to four conventional, midge-susceptible cultivars. Midge damage was higher in 2007 and 2010, than in 2008 and 2009. In general, the varietal blends, as a group, yielded more grain than the susceptible cultivars, especially when grown in environments with high midge pressure (5.5 - 35% seed damage). In environments with low midge pressure (0 – 2.6% seed damage), the varietal blend average yield advantage was smaller but still significant, indicating that some of the varietal blends had additional superior attributes, in addition to midge resistance. Significant differences in midge damage were observed within the resistant and the susceptible groups of the cultivars tested. Midge resistance did not protect wheat against loss of market grade

Feasibility of the electrolarynx for enabling communication in the chronically critically ill:The EECCHO study

PurposeTo assess feasibility of producing intelligible and comprehensible speech with an electrolarynx; measure anxiety, communication ease, and satisfaction before/after electrolarynx training; and identify barriers/facilitators.MethodsWe included tracheostomized adults from 3 units following commands, reading English, and mouthing words. On enrolment, we measured anxiety, ease, and satisfaction with communication. We gave electrolarynx instruction for ≤5 days then 2 independent raters assessed intelligibility, sentence comprehensibility (9-point difficulty scale), and Electrolarynx Effectiveness Score (EES), and re-evaluated anxiety, communication ease, and satisfaction. Interviews explored barriers/facilitators.Measurements and main resultsWe recruited 24 participants (Jan2015-Dec2016). Mean (SD) intelligibility was 45%(18%) words correct: 57%(21%) when facing. Mean comprehension difficulty was 6.4(2.0) overall, indicating moderate difficulty (5.5(2.5) scored visualizing). Mean EES was 2.9(1.0) (3 = improved lip-reading through recognizable sounds). Anxiety decreased from median 3.8 to 2.0 (P = .007). Communication was rated easier (median 15 vs 12, P = .04) whereas satisfaction remained similar (P = .06). Facilitators included device friendliness, patient independence, and word intelligibility. Barriers were patient weakness, difficulty positioning the device, and limited sentence as opposed to word intelligibility.ConclusionThe electrolarynx may aid intelligible speech for some tracheostomized patients if the communication partner can visualize the users face, and reduce anxiety and make patient perceived communication easier

Calidad de Vida: a systematic review of quality of life in Latino cancer survivors in the USA

Background: Cancer is the leading cause of death among Hispanics/Latinos. Thus, understanding health-related quality of life (HRQOL) needs among this diverse racial/ethnic group is critical. Using Ferrell’s multidimensional framework for measuring QOL, we synthesized evidence on HRQOL needs among Hispanic/Latino cancer survivors. Methods: We searched MEDLINE/PubMed, EMBASE, CINAHL, and PsycINFO, for English language articles published between 1995 and January 2020, reporting HRQOL among Hispanic/Latino cancer survivors in the USA. Results: Of the 648 articles reviewed, 176 met inclusion criteria, with 100 of these studies focusing exclusively on breast cancer patients and no studies examining end-of-life HRQOL issues. Compared with other racial/ethnic groups, Hispanics/Latinos reported lower HRQOL and a higher symptom burden across multiple HRQOL domains. Over 80% of studies examining racial/ethnic differences in psychological well-being (n = 45) reported worse outcomes among Hispanics/Latinos compared with other racial/ethnic groups. Hispanic/Latino cancer survivors were also more likely to report suboptimal physical well-being in 60% of studies assessing racial/ethnic differences (n = 27), and Hispanics/Latinos also reported lower social well-being relative to non-Hispanics/Latinos in 78% of studies reporting these outcomes (n = 32). In contrast, reports of spiritual well-being and spirituality-based coping were higher among Hispanics/Latinos cancer survivors in 50% of studies examining racial/ethnic differences (n = 15). Discussion: Findings from this review point to the need for more systematic and tailored interventions to address HRQOL needs among this growing cancer survivor population. Future HRQOL research on Hispanics/Latinos should evaluate variations in HRQOL needs across cancer types and Hispanic/Latino subgroups and assess HRQOL needs during metastatic and end-of-life disease phases

Characterization of a c-Rel inhibitor that mediates anticancer properties in hematologic malignancies by blocking NF-κB-controlled oxidative stress responses

NF-\u3baB plays a variety of roles in oncogenesis and immunity that may be beneficial for therapeutic targeting, but strategies to selectively inhibit NF-\u3baB to exert antitumor activity have been elusive. Here, we describe IT-901, a bioactive naphthalenethiobarbiturate derivative that potently inhibits the NF-\u3baB subunit c-Rel. IT-901 suppressed graft-versus-host disease while preserving graft-versus-lymphoma activity during allogeneic transplantation. Further preclinical assessment of IT-901 for the treatment of human B-cell lymphoma revealed antitumor properties in vitro and in vivo without restriction to NF-\u3baB-dependent lymphoma. This nondiscriminatory, antilymphoma effect was attributed to modulation of the redox homeostasis in lymphoma cells resulting in oxidative stress. Moreover, NF-\u3baB inhibition by IT-901 resulted in reduced stimulation of the oxidative stress response gene heme oxygenase-1, and we demonstrated that NF-\u3baB inhibition exacerbated oxidative stress induction to inhibit growth of lymphoma cells. Notably, IT-901 did not elicit increased levels of reactive oxygen species in normal leukocytes, illustrating its cancer selective properties. Taken together, our results provide mechanistic insight and preclinical proof of concept for IT-901 as a novel therapeutic agent to treat human lymphoid tumors and ameliorate graft-versus-host disease

Computer-Aided Imaging Analysis of Probe-Based Confocal Laser Endomicroscopy With Molecular Labeling and Gene Expression Identifies Markers of Response to Biological Therapy in IBD Patients: The Endo-Omics Study

Abstract Background We aimed to predict response to biologics in inflammatory bowel disease (IBD) using computerized image analysis of probe confocal laser endomicroscopy (pCLE) in vivo and assess the binding of fluorescent-labeled biologics ex vivo. Additionally, we investigated genes predictive of anti-tumor necrosis factor (TNF) response. Methods Twenty-nine patients (15 with Crohn’s disease [CD], 14 with ulcerative colitis [UC]) underwent colonoscopy with pCLE before and 12 to 14 weeks after starting anti-TNF or anti-integrin α4β7 therapy. Biopsies were taken for fluorescein isothiocyanate–labeled infliximab and vedolizumab staining and gene expression analysis. Computer-aided quantitative image analysis of pCLE was performed. Differentially expressed genes predictive of response were determined and validated in a public cohort. Results In vivo, vessel tortuosity, crypt morphology, and fluorescein leakage predicted response in UC (area under the receiver-operating characteristic curve [AUROC], 0.93; accuracy 85%, positive predictive value [PPV] 89%; negative predictive value [NPV] 75%) and CD (AUROC, 0.79; accuracy 80%; PPV 75%; NPV 83%) patients. Ex vivo, increased binding of labeled biologic at baseline predicted response in UC (UC) (AUROC, 83%; accuracy 77%; PPV 89%; NPV 50%) but not in Crohn’s disease (AUROC 58%). A total of 325 differentially expressed genes distinguished responders from nonresponders, 86 of which fell within the most enriched pathways. A panel including ACTN1, CXCL6, LAMA4, EMILIN1, CRIP2, CXCL13, and MAPKAPK2 showed good prediction of anti-TNF response (AUROC >0.7). Conclusions Higher mucosal binding of the drug target is associated with response to therapy in UC. In vivo, mucosal and microvascular changes detected by pCLE are associated with response to biologics in inflammatory bowel disease. Anti-TNF–responsive UC patients have a less inflamed and fibrotic state pretreatment. Chemotactic pathways involving CXCL6 or CXCL13 may be novel targets for therapy in nonresponders

Recruitment strategies and HPV self-collection return rates for under-screened women for cervical cancer prevention

In the United States, medically underserved women carry a heavier burden of cancer incidence and mortality, yet are largely underrepresented in cancer prevention studies. My Body, My Test is a n observational cohort, multi-phase cervical cancer prevention study in North Carolina that recruited low-income women, aged 30–65 years and who had not undergone Pap testing in ≥ 4 years. Participants were offered home-based self-collection of cervico-vaginal samples for primary HPV testing. Here, we aimed to describe the recruitment strategies utilized by study staff, and the resulting recruitment and self-collection kit return rates for each specific recruitment strategy. Participants were recruited through different approaches: either direct (active, staff-effort intensive) or indirect (passive on the part of study staff). Of a total of 1,475 individuals screened for eligibility, 695 were eligible (47.1%) and 487 (70% of eligible) participants returned their self-collection kit. Small media recruitment resulted in the highest number of individuals found to be study eligible, with a relatively high self-collection kit return of 70%. In-clinic in-reach resulted in a lower number of study-eligible women, yet had the highest kit return rate (90%) among those sent kits. In contrast, 211 recruitment which resulted in the lowest kit return of 54%. Small media, word of mouth, and face-to-face outreach resulted in self-collection kit return rates ranging from 72 to 79%. The recruitment strategies undertaken by study staff support the continued study of reaching under-screened populations into cervical cancer prevention studies