Effect of Malondialdehyde-Acetaldehyde-Protein Adducts on the Protein Kinase C-Dependent Secretion of Urokinase-Type Plasminogen Activator in Hepatic Stellate Cells

Previous studies from our laboratory have shown that malondialdehyde-acetaldehyde-protein adducts (MAA adducts) are formed in hepatocytes of ethanol-fed rats and directly influence the hepatic stellate cells (HSCs) to induce their secretion of chemokines and to up-regulate their expression of adhesion molecules. Since protein kinase C (PKC) is known to play a major role in many diverse intracellular signal transduction processes, we investigated whether MAA adducts influence the function of HSCs via a PKC-dependent pathway. HSCs in culture were exposed to MAA adducts, and PKC activity was determined. We observed a time- and concentration-dependent activation of PKC when cultures were exposed to BSA-MAA as compared with unmodified BSA. Using PKC isoform-specific inhibitors, we also showed that BSA-MAA induces the activation of a specific isoform of PKC, PKC-a, in HSCs. No activation of PKC was observed when HSCs were exposed to other aldehyde adducts such as BSA-acetaldehyde or BSA-malondialdehyde, indicating that the effects of MAA adducts on HSCs were somewhat specific. We further examined whether the observed increase in PKC activation induced by MAA adducts in HSCs, in turn, causes a functional effect. We observed that BSA-MAA induces the increased secretion of urokinase-type plasminogen activator, a key component of the plasmin-generating system, and that PKC activation is necessary for this enhanced urokinase-type plasminogen activator secretion. These results indicate that MAA adducts via a PKC-mediated pathway may regulate plasmin-mediated matrix degradation in the liver, thereby contributing to the progression of hepatic fibrosis

To What Extent Does Text Simplification Entail a More Optimized Comprehension in Human-Oriented CNLs?

International audienceThe main goal of the current study is to develop a new cockpit controlled language for future Airbus aircraft by using psycholinguistic testing to optimize pilot comprehension. Pilots are aided by cockpit messages in order to deal with different situations during aircraft operations. The current controlled languages used on the Airbus aircraft have been carefully constructed to avoid ambiguity, inaccuracy, inconsistency, and inadequacy (Spaggiari, Beaujard, Cannesson (2003)) in order to ensure the safety of the navigation, operational needs, and the adaptability of the human-computer interaction to different situations in the cockpit. However, this controlled language has several limitations, mostly due to small screen sizes (limited number of words and sentences) and is highly codified (non-conforming to natural language syntax, color-coded and so on) so that it requires prior pilot training in order to achieve fluency. As future cockpit design is under construction, we might be looking at a different flexibility margin. Our experimentation plan is to go against the tide of common CNL (Controlled Natural Language) construction, in the sense that we will not be taking natural language and simplifying it, but rather taking a highly controlled codified language (therefore theoretically most simple) and " complexifying " it (bring it closer to natural language: theoretically most complex) in order to make it more accessible, and limit prior training needs

The Effect of an Exercise-Based Balance Intervention on Physical and Cognitive Performance for Older Adults: A Pilot Study

Background: Several exercise-based falls prevention interventions produced significant long-term reductions in fall rate, but few demonstrate long-term improvements in falls risk factors. A strong body of evidence supports a protective effect of aerobic or strength-training exercise on cognition. Individuals participating in an exercise-based balance improvement program may also experience this protective effect. This may contribute to the decreased rate of falls reported in the literature. Purpose: To determine if individuals participating in an evidence-based exercise program to reduce falls would demonstrate improvements in both physical and cognitive performance

Blood Cell Salvage and Autotransfusion Does Not Worsen Oncologic Outcomes Following Liver Transplantation with Incidental Hepatocellular Carcinoma: A Propensity Score-Matched Analysis

BACKGROUND: Intraoperative blood cell salvage and autotransfusion (IBSA) during liver transplantation (LT) for hepatocellular carcinoma (HCC) is controversial for concern regarding adversely impacting oncologic outcomes. OBJECTIVE: We aimed to evaluate the long-term oncologic outcomes of patients who underwent LT with incidentally discovered HCC who received IBSA compared with those who did not receive IBSA. METHODS: Patients undergoing LT (January 2001-October 2018) with incidental HCC on explant pathology were retrospectively identified. A 1:1 propensity score matching (PSM) was performed. HCC recurrence and patient survival were compared. Kaplan-Meier survival analyses were performed, and univariable Cox proportional hazard analyses were performed for risks of recurrence and death. RESULTS: Overall, 110 patients were identified (IBSA, n = 76 [69.1%]; non-IBSA, n = 34 [30.9%]). Before matching, the groups were similar in terms of demographics, transplant, and tumor characteristics. Overall survival was similar for IBSA and non-IBSA at 1, 3, and 5 years (96.0%, 88.4%, 83.0% vs. 97.1%, 91.1%, 87.8%, respectively; p = 0.79). Similarly, the recurrence rate at 1, 3, and 5 years was not statistically different (IBSA 0%, 1.8%, 1.8% vs. non-IBSA 0%, 3.2%, 3.2%, respectively; p = 0.55). After 1:1 matching (26 IBSA, 26 non-IBSA), Cox proportional hazard analysis demonstrated similar risk of death and recurrence between the groups (IBSA hazard ratio [HR] of death 1.26, 95% confidence interval [CI] 0.52-3.05, p = 0.61; and HR of recurrence 2.64, 95% CI 0.28-25.30, p = 0.40). CONCLUSIONS: IBSA does not appear to adversely impact oncologic outcomes in patients undergoing LT with incidental HCC. This evidence further supports the need for randomized trials evaluating the impact of IBSA use in LT for HCC

An Effective Community–Academic Partnership to Extend the Reach of Screenings for Fall Risk

Older adults should be screened for fall risk annually. Community providers (people without formal medical training who work with older adults in senior centers or aging services) may be a viable group to expand the reach of screenings. Our community–academic partnership developed a program to increase and assess fall risk screenings by community providers. Community sites hosted training workshops and screening events. Community screenings were well attended and received by providers and older adults. With administrative support from the regional fall prevention coalition and technical support from academia, community providers screened 161 older adults from a broad geographic area. Twenty-one community providers completed the training. Knowledge and confidence surveys demonstrated improvements before and after training (P < .001). Skills assessments demonstrated mastery of most skills, but some providers required additional training. Provider feedback indicated screening procedures were complex. Future projects will examine this model using simplified screening procedures

Facet-Enhanced Dielectric Sensitivity in Plasmonic Metal Oxide Nanocubes

The resonant frequency of plasmonic nanoparticles depends on the refractive index of the local environment, a property which is directly useful for sensing applications and is indicative of potential utility for other applications based on near-field enhancement of light intensity. While the morphology dependence of dielectric sensitivity has been well studied in noble metal nanoparticles, less investigated is the sensitivity of degenerately doped metal oxide nanocrystals, whose plasmon resonances lie in the near- to mid- infrared. Here, we report the dielectric sensitivity of fluorine and tin co-doped indium oxide nanocubes, its dependence on their sharp faceting that gives rise to multiple plasmonic modes, and on their tin-dopant concentration. We find that the plasmon mode associated with the nanocube corners is the most sensitive and that raising dopant concentration increases dielectric sensitivity. Comparing to finite element simulations that assume a spatially uniform free electron distribution in the nanocubes, we show that the plasmon modes associated with the edges and the faces of the nanocubes are less sensitive than expected, and that their reduced dielectric sensitivity can be rationalized by the presence of band bending and a resulting surface depletion layer. Interestingly, simulations suggest that Fermi level pinning occurs predominantly on the cube faces, reshaping the free electron volume so that the depletion layer effectively insulates the faces and edges from the surrounding environment, while the corner mode remains sensitive.This work was primarily supported by the National Science Foundation (CHE-1905263), with additional support from the Welch Foundation (F-1848), an NSF graduate research program fellowship to S. S.-Z. (DGE-2137420), and with partial support through the Center for Dynamics and Control of Materials: an NSF Materials Research Science and Engineering Center (NSF MRSEC) under Cooperative Agreement DMR-1720595.Center for Dynamics and Control of Material

Perception versus reality: A National Cohort Analysis of the surgery-first approach for resectable pancreatic cancer

INTRODUCTION: Although surgical resection is necessary, it is not sufficient for long-term survival in pancreatic ductal adenocarcinoma (PDAC). We sought to evaluate survival after up-front surgery (UFS) in anatomically resectable PDAC in the context of three critical factors: (A) margin status; (B) CA19-9; and (C) receipt of adjuvant chemotherapy. METHODS: The National Cancer Data Base (2010-2015) was reviewed for clinically resectable (stage 0/I/II) PDAC patients. Surgical margins, pre-operative CA19-9, and receipt of adjuvant chemotherapy were evaluated. Patient overall survival was stratified based on these factors and their respective combinations. Outcomes after UFS were compared to equivalently staged patients after neoadjuvant chemotherapy on an intention-to-treat (ITT) basis. RESULTS: Twelve thousand and eighty-nine patients were included (n = 9197 UFS, n = 2892 ITT neoadjuvant). In the UFS cohort, only 20.4% had all three factors (median OS = 31.2 months). Nearly 1/3rd (32.7%) of UFS patients had none or only one factor with concomitant worst survival (median OS = 14.7 months). Survival after UFS decreased with each failing factor (two factors: 23 months, one factor: 15.5 months, no factors: 7.9 months) and this persisted after adjustment. Overall survival was superior in the ITT-neoadjuvant cohort (27.9 vs. 22 months) to UFS. CONCLUSION: Despite the perceived benefit of UFS, only 1-in-5 UFS patients actually realize maximal survival when known factors highly associated with outcomes are assessed. Patients are proportionally more likely to do worst, rather than best after UFS treatment. Similarly staged patients undergoing ITT-neoadjuvant therapy achieve survival superior to the majority of UFS patients. Patients and providers should be aware of the false perception of \u27optimal\u27 survival benefit with UFS in anatomically resectable PDAC

Developing an evidence-based fall prevention curriculum for community health workers

This perspective paper describes processes in the development of an evidence-based fall prevention curriculum for community health workers/promotores (CHW/P) that highlights the development of the curriculum and addresses: (1) the need and rationale for involving CHW/P in fall prevention; (2) involvement of CHW/P and content experts in the curriculum development; (3) best practices utilized in the curriculum development and training implementation; and (4) next steps for dissemination and utilization of the CHW/P fall prevention curriculum. The project team of CHW/P and content experts developed, pilot tested, and revised bilingual in-person training modules about fall prevention among older adults. The curriculum incorporated the following major themes: (1) fall risk factors and strategies to reduce/prevent falls; (2) communication strategies to reduce risk of falling and strategies for developing fall prevention plans; and (3) health behavior change theories utilized to prevent and reduce falls. Three separate fall prevention modules were developed for CHW/P and CHW/P Instructors to be used during in-person trainings. Module development incorporated a five-step process: (1) conduct informal focus groups with CHW/P to inform content development; (2) develop three in-person modules in English and Spanish with input from content experts; (3) pilot-test the modules with CHW/P; (4) refine and finalize modules based on pilot-test feedback; and (5) submit modules for approval of continuing education units. This project contributes to the existing evidence-based literature by examining the role of CHW/P in fall prevention among older adults. By including evidence-based communication strategies such as message tailoring, the curriculum design allows CHW/P to personalize the information for individuals, which can result in an effective dissemination of a curriculum that is evidence-based and culturally appropriate.U48 DP001924 - NCCDPHP CDC HHS; U48 DP001944 - NCCDPHP CDC HHSPublished versio

Comparison of balance assessment modalities in emergency department elders: a pilot cross-sectional observational study

<p>Abstract</p> <p>Background</p> <p>More than one-third of US adults 65 and over fall every year. These falls may cause serious injury including substantial long-term morbidity (due declines in activities of daily living) and death. The emergency department (ED) visit represents an opportunity for identifying high risk elders and potentially instituting falls-related interventions. The unique characteristic of the ED environment and patient population necessitate that risk-assessment modalities be validated in this specific setting. In order to better identify elders at risk of falls, we examined the relationship between patient-provided history of falling and two testing modalities (a balance plate system and the timed up-and-go [TUG] test) in elder emergency department (ED) patients.</p> <p>Methods</p> <p>We conducted a cross-sectional observational study of patients ≥ 60 years old being discharged from the ED. Patient history of falls in the past week, month, 6 months, and year was obtained. Balance plate center of pressure excursion (COP) measurements and TUG testing times were recorded. COP was recorded under four conditions: normal stability eyes open (NSEO) and closed (NSEC), and perturbed stability eyes open and closed. Correlation between TUG and COP scores was measured. Univariate logistic regression was used to identify the relationship between patient-provided falls history and the two testing modalities. Proportions, likelihood ratios, and receiver-operating-characteristic (ROC) curves for prediction of previous falls were reported.</p> <p>Results</p> <p>Fifty-three subjects were enrolled, 11% had fallen in the previous week and 42% in the previous year. There was no correlation between TUG and any balance plate measurements. In logistic regression, neither testing modality was associated with prior history of falls (<it>p </it>> 0.05 for all time periods). Balance plate NSEO and NSEC testing cutoffs could be identified which were 83% sensitive and had a negative likelihood ratio (LR-) of 0.3 for falls in the past week. TUG testing was not useful for falls in the past week, but performed best for more distant falls in the past month, 6 months, or year. TUG cutoffs with sensitivity over 80% and LR(-) of 0.17-0.32 could be identified for these time periods.</p> <p>Conclusion</p> <p>Over 40% of community-dwelling elder ED patients report a fall within the past year. Balance plate and TUG testing were feasibly conducted in an ED setting. There is no relationship between scores on balance plate and TUG testing in these patients. In regression analysis, neither modality was significantly associated with patient provided history of falls. These modalities should not be adopted for screening purposes in elders in the ED setting without validation in future studies or as part of multi-factorial risk assessment.</p