836 research outputs found
Signal transduction and activator of transcription-3 (STAT3) in patients with colorectal cancer: associations with the phenotypic features of the tumour and host
Purpose: In patients with colorectal cancer (CRC), a high-density local inflammatory infiltrate response is associated with improved survival, whereas elevated systemic inflammatory responses are associated with poor survival. One potential unifying mechanism is the IL-6/JAK/STAT3 pathway. The present study examines the relationship between tumour total STAT3 and phosphorylated STAT3Tyr705 (pSTAT3) expression, host inflammatory responses and survival in patients undergoing resection of stage I-III CRC. Experimental Design: Immunohistochemical assessment of STAT3/pSTAT3 expression was performed using a tissue microarray and tumour cell expression divided into tertiles using the weighted histoscore. The relationship between STAT3/pSTAT3 expression and local inflammatory (CD3+, CD8+, CD45R0+, FOXP3+ T-cell density and Klintrup-MĂ€kinen grade) and systemic inflammatory responses and cancer-specific survival were examined. Results: 196 patients were included in the analysis. Cytoplasmic and nuclear STAT3 expression strongly correlated (r=0.363, P<0.001); nuclear STAT3 and pSTAT3 expression weakly correlated (r=0.130, P=0.068). Cytoplasmic STAT3 was inversely associated with the density of CD3+ (P=0.012), CD8+ (P=0.003) and FOXP3+ T-lymphocytes (P=0.002) within the cancer cell nests and was associated with an elevated systemic inflammatory response as measured by modified Glasgow Prognostic Score (mGPS2: 19% vs. 4%, P=0.004). The combination of nuclear STAT3/pSTAT3 stratified five-year survival from 81% to 62% (P=0.012), however was not associated with survival independent of venous invasion, tumour perforation or tumour budding. Conclusion In patients undergoing CRC resection, STAT3 expression was associated with adverse host inflammatory responses and reduced survival. Up-regulation of tumour STAT3 may be an important mechanism whereby the tumour deregulates local and systemic inflammatory responses
Ensuring climate-smart agriculture is gender-smart: a participatory method for local adaptation planning with a gender focus
Interstitial chemotherapy with biodegradable BCNU (GliadelÂź) wafers in the treatment of malignant gliomas
Malignant gliomas represent the majority of primary brain tumors, and the prognosis of the patients afflicted with these tumors has been historically dismal, with almost uniform progressive neurologic impairment and rapid death. Even with multimodal treatment using surgery, focal radiation, and chemotherapy, no major strides were made until recently. The development of interstitial BCNU wafers (carmustine wafers, GliadelÂź) has led to promising results in the treatment of a selected patients with malignant gliomas, as well as with other intracranial malignancies.BCNU is one of the first systemic chemotherapies which had obtained United States Food and Drug Administration (FDA) approval for the treatment of brain tumors. However, systemic use has been hampered by the modest prolongation of survival and by the prolonged myelosuppression and potentially fatal pulmonary toxicity. The development of interstitial therapies with BCNU represented a great step forward, allowing direct delivery to the tumor bed, with virtually no systemic toxicities. Clinical studies of BCNU wafers have showed good efficacy in both newly diagnosed and recurrent gliomas, as well as a possible therapeutic role in other primary or secondary intracranial malignancies. New studies are currently underway trying to improve the efficacy of the BCNU wafers (GliadelÂź) by combining them with different systemic chemotherapies. An overview of the current knowledge ranging from the preclinical developments, to the efficacy and safety seen in the clinical trials and in clinical practice following the drug approval to the future avenues of research is therefore timely
Friends-Based Protective Strategies and Unwanted Sexual Experiences: A Daily Diary Examination of First Year College Women
Risk for unwanted sexual experiences can emerge in social contextsâthe same contexts that early college women navigate with their friends. Though friends naturally engage in prevention strategies, less is known about how capable guardianship influences risk. Using multilevel structural equation modeling, the present study examined guardianship at the person and situation levels. First-year college women (N = 132) completed eight weekends of daily surveys. We examined whether guardianship (e.g., more friends present, greater proportion of female friends, no intoxicated friends) would reduce unwanted sexual experience risk and if this relation was mediated by friends-based strategy use. An alternative model was also tested with the same predictors, but with unwanted sexual experiences as the mediator and friends-based strategy use as the outcome. Over half (58%) of extended weekend nights with friends involved drinking or using drugs. Friends-based strategies were used on 29% of nights. Across models, being with one or more intoxicated friends was associated with friends-based strategy use and an unwanted sexual experience, but only at the situation level. Parents, educators, and policy makers can encourage college women to draw on their social networks to enhance safety. Interventions could incorporate more universal strategies for responding to risk in social contexts
The Solar Neighborhood. XXXIV. A Search for Planets Orbiting Nearby M Dwarfs using Astrometry
Astrometric measurements are presented for seven nearby stars with previously
detected planets: six M dwarfs (GJ 317, GJ 667C, GJ 581, GJ 849, GJ 876, and GJ
1214) and one K dwarf (BD 10 3166). Measurements are also presented for six
additional nearby M dwarfs without known planets, but which are more favorable
to astrometric detections of low mass companions, as well as three binary
systems for which we provide astrometric orbit solutions. Observations have
baselines of three to thirteen years, and were made as part of the RECONS
long-term astrometry and photometry program at the CTIO/SMARTS 0.9m telescope.
We provide trigonometric parallaxes and proper motions for all 16 systems, and
perform an extensive analysis of the astrometric residuals to determine the
minimum detectable companion mass for the 12 M dwarfs not having close stellar
secondaries. For the six M dwarfs with known planets, we are not sensitive to
planets, but can rule out the presence of all but the least massive brown
dwarfs at periods of 2 - 12 years. For the six more astrometrically favorable M
dwarfs, we conclude that none have brown dwarf companions, and are sensitive to
companions with masses as low as 1 for periods longer than two years.
In particular, we conclude that Proxima Centauri has no Jovian companions at
orbital periods of 2 - 12 years. These results complement previously published
M dwarf planet occurrence rates by providing astrometrically determined upper
mass limits on potential super-Jupiter companions at orbits of two years and
longer. As part of a continuing survey, these results are consistent with the
paucity of super-Jupiter and brown dwarf companions we find among the over 250
red dwarfs within 25 pc observed longer than five years in our astrometric
program.Comment: 18 pages, 5 figures, 4 tables, accepted for publication in A
Selenium hyperaccumulation offers protection from cell disruptor herbivores
<p>Abstract</p> <p>Background</p> <p>Hyperaccumulation, the rare capacity of certain plant species to accumulate toxic trace elements to levels several orders of magnitude higher than other species growing on the same site, is thought to be an elemental defense mechanism against herbivores and pathogens. Previous research has shown that selenium (Se) hyperaccumulation protects plants from a variety of herbivores and pathogens. Selenium hyperaccumulating plants sequester Se in discrete locations in the leaf periphery, making them potentially more susceptible to some herbivore feeding modes than others. In this study we investigate the protective function of Se in the Se hyperaccumulators <it>Stanleya pinnata </it>and <it>Astragalus bisulcatus </it>against two cell disrupting herbivores, the western flower thrips (<it>Frankliniella occidentalis</it>) and the two-spotted spider mite (<it>Tetranychus urticae</it>).</p> <p>Results</p> <p><it>Astragalus bisulcatus </it>and <it>S. pinnata </it>with high Se concentrations (greater than 650 mg Se kg<sup>-1</sup>) were less subject to thrips herbivory than plants with low Se levels (less than 150 mg Se kg<sup>-1</sup>). Furthermore, in plants containing elevated Se levels, leaves with higher concentrations of Se suffered less herbivory than leaves with less Se. Spider mites also preferred to feed on low-Se <it>A. bisulcatus </it>and <it>S. pinnata </it>plants rather than high-Se plants. Spider mite populations on <it>A. bisulcatus </it>decreased after plants were given a higher concentration of Se. Interestingly, spider mites could colonize <it>A. bisulcatus </it>plants containing up to 200 mg Se kg<sup>-1 </sup>dry weight, concentrations which are toxic to many other herbivores. Selenium distribution and speciation studies using micro-focused X-ray fluorescence (ÎŒXRF) mapping and Se K-edge X-ray absorption spectroscopy revealed that the spider mites accumulated primarily methylselenocysteine, the relatively non-toxic form of Se that is also the predominant form of Se in hyperaccumulators.</p> <p>Conclusions</p> <p>This is the first reported study investigating the protective effect of hyperaccumulated Se against cell-disrupting herbivores. The finding that Se protected the two hyperaccumulator species from both cell disruptors lends further support to the elemental defense hypothesis and increases the number of herbivores and feeding modes against which Se has shown a protective effect. Because western flower thrips and two-spotted spider mites are widespread and economically important herbivores, the results from this study also have potential applications in agriculture or horticulture, and implications for the management of Se-rich crops.</p
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Urinary Retention Evaluation and Catheterization Algorithm for Adult Inpatients
Importance: Acute urinary retention (UR) is common, yet variations in diagnosis and management can lead to inappropriate catheterization and harm. Objective: To develop an algorithm for screening and management of UR among adult inpatients. Design, Setting, and Participants: In this mixed-methods study using the RAND/UCLA Appropriateness Method and qualitative interviews, an 11-member multidisciplinary expert panel of nurses and physicians from across the US used a formal multi-round process from March to May 2015 to rate 107 clinical scenarios involving diagnosis and management of adult UR in postoperative and medical inpatients. The panel ratings informed the first algorithm draft. Semistructured interviews were conducted from October 2020 to May 2021 with 33 frontline cliniciansânurses and surgeons from 5 Michigan hospitalsâto gather feedback and inform algorithm refinements. Main Outcomes and Measures: Panelists categorized scenarios assessing when to use bladder scanners, catheterization at various scanned bladder volumes, and choice of catheterization modalities as appropriate, inappropriate, or uncertain. Next, qualitative methods were used to understand the perceived need, usability, and potential algorithm uses. Results: The 11-member expert panel (10 men and 1 woman) used the RAND/UCLA Appropriateness Method to develop a UR algorithm including the following: (1) bladder scanners were preferred over catheterization for UR diagnosis in symptomatic patients or starting as soon as 3 hours since last void if asymptomatic, (2) bladder scanner volumes appropriate to prompt catheterization were 300 mL or greater in symptomatic patients and 500 mL or greater in asymptomatic patients, and (3) intermittent was preferred to indwelling catheterization for managing lower bladder volumes. Interview findings were organized into 3 domains (perceived need, feedback on algorithm, and implementation suggestions). The 33 frontline clinicians (9 men and 24 women) who reviewed the algorithm reported that an evidence-based protocol (1) was needed and could be helpful to clinicians, (2) should be simple and graphically appealing to improve rapid clinician review, and (3) should be integrated within the electronic medical record and prominently displayed in hospital units to increase awareness. The draft algorithm was iteratively refined based on stakeholder feedback. Conclusions and Relevance: In this study using a systematic, multidisciplinary, evidence- and expert opinionâbased approach, a UR evaluation and catheterization algorithm was developed to improve patient safety by increasing appropriate use of bladder scanners and catheterization. This algorithm addresses the need for practical guidance to manage UR among adult inpatients.</p
The association between markers of tumour cell metabolism, the tumour microenvironment and outcomes in patients with colorectal cancer
Tumour cell anaerobic metabolism has been reported to be a prognostic factor in colorectal cancer. The present study investigated the association between monocarboxylate transporter (MCT) 1, MCT 2, lactate dehydrogenase (LDH) 1 and LDH 5, the tumour microenvironment, and outcome in patients with colorectal cancer. A cohort of 150 patients with stage IâIII CRC were utilised to assess tumour cell expression of MCTâ1, MCTâ2, LDHâ1 and LDHâ5 by immunohistochemistry. Expression levels were dichotomised and associations with tumour factors, the tumour microenvironment and survival analysed. Nuclear LDHâ5 associates with poor prognosis (HR 1.68 95% CI 0.99â2.84, p = 0.050) and trends toward increased tumour stroma percentage (TSP, p = 0.125). Cytoplasmic MCTâ2 also trends toward increased TSP (p = 0.081). When combined into a single score; nuclear LDHâ5 + TSP significantly associated with decreased survival independent of stage (HR 2.61 95% CI 1.27â5.35, p = 0.009), increased tumour budding (p = 0.002) and decreased stromal Tâlymphocytes (p = 0.014). Similarly, cytoplasmic MCTâ2 + TSP significantly associated with decreased survival (HR 2.32 95% CI 1.31â4.11, p = 0.003), decreased necrosis (p = 0.039), and increased tumour budding (p = 0.004). The present study reports that the combination of TSP and nuclear LDHâ5 was significantly associated with survival, increased tumour budding, and decreased stromal Tâlymphocytes. This supports the hypothesis that increased stromal invasion promotes tumour progression via modulation of tumour metabolism. Moreover, MCTâ2 and LDHâ5 may provide promising therapeutic targets for patients with stromalârich CRC
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