A Pre-transplant Blood-based Lipid Signature for Prediction of Antibody-mediated Rejection in Kidney Transplant Patients

Purpose. The aim of this study is to demonstrate the potential of the pre-transplant lipidome to predict post-transplant antibody-mediated rejection (AMR) in kidney transplant patients. Methods. Patients were selected from a prospective observational cohort of a single-center adult kidney transplant center in the United States. The study included 16 kidney transplant patients who develop AMR within 2 years post-transplant and 29 stable control (SC) kidney transplant patients who did not develop AMR at any time within the post-transplant follow up. Selection of group differences on the day of transplant was determined by t-test analysis. Stepwise forward method was used to create Linear Discrimination Analysis with regularized correction (RLDA). Changes over time were estimated using sparse partial least square method which is validated by permutation testing. T-test was performed to compare two time points for the same group and groups at matched time points. JMP Pro 13 and MetaboAnalyst were used in the analysis of the Data. Results. A comparison of lipids classes on the day of transplant revealed PLs relative concentration differences between SC and AMR. Concentration of phosphatidylcholine (PC) was significantly diminished in AMR, while there was a trend for increased concentration of lysophosphatidylcholine (LPC). AMR group also showed significantly lower concentration of phosphatidylethanolamine (PE), lysophosphatidylethanolamine (LPE), plasmanylethanolamine (PE-O), and plasmenylethanolamine (PE-P). Our data demonstrated that there are significant differences in the lipidome between SC and AMR on the day of transplant. The analysis identified 7 distinct lipids that discriminated between AMR and SC (AUC) =0.95 (95%CI=0.84- 0.98), R2=0.63 (95%CI=0.4-0.8). A sPLSDA analysis of the data revealed a statistically significant alteration in the lipid profile at 6 months post-transplant compared to the day of transplant. The analysis revealed a panel of 13 lipids that were found to differentiate the two groups at 6 month post-transplant . Further data analysis confirms the presence of a sustained lipid metabolic difference between SC and AMR over time that distinguish between the patients with favorable and non-favorable transplant outcomes. Conclusion. This study demonstrates the potential of the pre-transplant lipidome towards determining AMR in kidney transplant patients, raising the possibility of using this information in risk stratification of patients about to undergo transplant.https://scholarscompass.vcu.edu/gradposters/1086/thumbnail.jp

All Terrain Vehicle (ATV) crashes in an unregulated environment: A prospective study of 56 cases

All terrain vehicle (ATV) use is increasing at a rapid pace in settings without proper safety regulations. Aim: To define injury patterns, impairments, and outcomes among patients injured in ATV crashes; to determine prevalence of protective equipment use; and to define the potential role of injury prevention in addressing the problem. Methods: During a recent 10 month period, 56 patients were reported as injured in ATV crashes seriously enough to require admission and were prospectively entered into a study-specific database. Patient demographics, site of crash, prior ATV experience, and use of safety equipment were recorded. Injuries were characterized by body system and tabulated. Outcomes, including deaths and impairments, were defined. Results: There were 47 males (84%) and 9 females (16%). Most injuries occurred in patients older than 18 years, but 20% occurred in children less than 14 years of age. Helmet use was confirmed in 12%. Three patients died (5% mortality). Significant disability occurred in 19 patients (34%) and was permanent in 4 (7%). Head, face and musculoskeletal injuries were most common. Conclusions: ATV crashes can cause serious injuries including death and permanent disability. The lack of awareness of the injury potential for this popular recreational activity has escalated the risk of injury, and the absence of safety programs and regulations has further aggravated the problem. Based on these data, a public education program, compulsory use of helmets and other protective clothing, and penalties for non-compliance should be implemented. Interventions at recreation sites and the point of ATV sale may be most beneficial

Analysis of the backward bending modes in damped rotating beams

[EN] This article presents a study of the backward bending mode of a simply supported rotating Rayleigh beam with internal damping. The study analyses the natural frequency behaviour of the backward mode according to the internal viscous damping ratio, the slenderness of the beam and its spin speed. To date, the behaviour of the natural frequency of the backward mode is known to be a monotonically decreasing function with spin speed due to gyroscopic effects. In this article, however, it is shown that this behaviour of the natural frequency may not hold for certain damping and slenderness conditions, and reaches a minimum value (concave function) from which it begins to increase. Accordingly, the analytical expression of the spin speed for which the natural frequency of the backward mode attains the minimum value has been obtained. In addition, the internal damping ratio and slenderness intervals associated with such behaviour have been also provided.The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The authors gratefully acknowledge the financial support of Ministerio de Ciencia, Innovacion y Universidades Agencia Estatal de Investigacion and the European Regional Development Fund (project TRA2017-84701-R), as well as Generalitat Valenciana (project Prometeo/2016/007) and European Commission through the project 'RUN2Rail - Innovative RUNning gear soluTiOns for new dependable, sustainable, intelligent and comfortable RAIL vehicles' (Horizon 2020 Shift2Rail JU call 2017, grant number 777564)Martínez Casas, J.; Denia Guzmán, FD.; Fayos Sancho, J.; Nadal, E.; Giner Navarro, J. (2019). Analysis of the backward bending modes in damped rotating beams. Advances in Mechanical Engineering. 11(4):1-13. https://doi.org/10.1177/1687814019840474S113114Zorzi, E. S., & Nelson, H. D. (1977). Finite Element Simulation of Rotor-Bearing Systems With Internal Damping. Journal of Engineering for Power, 99(1), 71-76. doi:10.1115/1.3446254Ku, D.-M. (1998). FINITE ELEMENT ANALYSIS OF WHIRL SPEEDS FOR ROTOR-BEARING SYSTEMS WITH INTERNAL DAMPING. Mechanical Systems and Signal Processing, 12(5), 599-610. doi:10.1006/mssp.1998.0159Dimentberg, M. F. (2005). Vibration of a rotating shaft with randomly varying internal damping. Journal of Sound and Vibration, 285(3), 759-765. doi:10.1016/j.jsv.2004.11.025Vatta, F., & Vigliani, A. (2008). Internal damping in rotating shafts. Mechanism and Machine Theory, 43(11), 1376-1384. doi:10.1016/j.mechmachtheory.2007.12.009Rosales, M. B., & Filipich, C. P. (1993). Dynamic Stability of a Spinning Beam Carrying an Axial Dead Load. Journal of Sound and Vibration, 163(2), 283-294. doi:10.1006/jsvi.1993.1165Mazzei, A. J., & Scott, R. A. (2003). Effects of internal viscous damping on the stability of a rotating shaft driven through a universal joint. Journal of Sound and Vibration, 265(4), 863-885. doi:10.1016/s0022-460x(02)01256-7Ehrich, F. F. (1964). Shaft Whirl Induced by Rotor Internal Damping. Journal of Applied Mechanics, 31(2), 279-282. doi:10.1115/1.3629598Vance, J. M., & Lee, J. (1974). Stability of High Speed Rotors With Internal Friction. Journal of Engineering for Industry, 96(3), 960-968. doi:10.1115/1.3438468Vila, P., Baeza, L., Martínez-Casas, J., & Carballeira, J. (2014). Rail corrugation growth accounting for the flexibility and rotation of the wheel set and the non-Hertzian and non-steady-state effects at contact patch. Vehicle System Dynamics, 52(sup1), 92-108. doi:10.1080/00423114.2014.881513Glocker, C., Cataldi-Spinola, E., & Leine, R. I. (2009). Curve squealing of trains: Measurement, modelling and simulation. Journal of Sound and Vibration, 324(1-2), 365-386. doi:10.1016/j.jsv.2009.01.048Bauer, H. F. (1980). Vibration of a rotating uniform beam, part I: Orientation in the axis of rotation. Journal of Sound and Vibration, 72(2), 177-189. doi:10.1016/0022-460x(80)90651-3Shiau, T. N., & Hwang, J. L. (1993). Generalized Polynomial Expansion Method for the Dynamic Analysis of Rotor-Bearing Systems. Journal of Engineering for Gas Turbines and Power, 115(2), 209-217. doi:10.1115/1.2906696Hili, M. A., Fakhfakh, T., & Haddar, M. (2006). Vibration analysis of a rotating flexible shaft–disk system. Journal of Engineering Mathematics, 57(4), 351-363. doi:10.1007/s10665-006-9060-3Young, T. H., Shiau, T. N., & Kuo, Z. H. (2007). Dynamic stability of rotor-bearing systems subjected to random axial forces. Journal of Sound and Vibration, 305(3), 467-480. doi:10.1016/j.jsv.2007.04.016Wang, J., Hurskainen, V.-V., Matikainen, M. K., Sopanen, J., & Mikkola, A. (2017). On the dynamic analysis of rotating shafts using nonlinear superelement and absolute nodal coordinate formulations. Advances in Mechanical Engineering, 9(11), 168781401773267. doi:10.1177/1687814017732672Lee, C.-W. (1993). Vibration Analysis of Rotors. Solid Mechanics and Its Applications. doi:10.1007/978-94-015-8173-8Genta, G. (1999). Vibration of Structures and Machines. doi:10.1007/978-1-4612-1450-2Cheng, C. C., & Lin, J. K. (2003). Modelling a rotating shaft subjected to a high-speed moving force. Journal of Sound and Vibration, 261(5), 955-965. doi:10.1016/s0022-460x(02)01374-

Presence of functionally active protease-activated receptors 1 and 2 in myenteric glia

Protease-activated receptors (PARs) belong to the family of membrane receptors coupled to G-proteins; their presence is reported in a wide variety of cells. The object of this study was to demonstrate the presence of PAR-1 and PAR-2 in myenteric glia of the guinea pig, and to elucidate the cellular mechanisms that are triggered upon receptor activation. Thrombin and PAR-1 agonist peptide (PARP-1) activate PAR-1 with a maximum mean ± SEM change in intracellular calcium concentration with respect to basal level (δ[Ca 2+ ] i ) of 183 ± 18 nm and 169 ± 6 nm, respectively. Trypsin and PAR-2 agonist peptide (PARP-2) activate PAR-2 with a maximum δ[Ca 2+ ] i of 364 ± 28 nm and 239 ± 19 nm, respectively. Inhibition of phospholipase C by U73312 (1 µm) decreased the δ[Ca 2+ ] i due to PAR-1 activation from 167 ± 10 nm to 87 ± 6 nm. The PAR-2-mediated δ[Ca 2+ ] i decreased from 193 ± 10 nm to 124 ± 8 nm when phospholipase C activity was inhibited. Blockade of sphingosine kinase with dimethylsphingosine (1 µm) decreased the δ[Ca 2+ ] i due to PAR-2 activation from 149 ± 19 nm to 67 ± 1 nm, but did not influence the PAR-1-mediated δ[Ca 2+ ] i . PAR-1 and PAR-2 were localized in myenteric glia by immunolabeling. Our results indicate that PAR-1 and PAR-2 are present in myenteric glia of the guinea pig, and their activation leads to increases in intracellular calcium via different signal transduction mechanisms that involve activation of phospholipase C and sphingosine kinase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66037/1/j.1471-4159.2002.01119.x.pd

Pin1 and neurodegeneration: a new player for prion disorders?

Pin1 is a peptidyl-prolyl isomerase that catalyzes the cis/trans conversion of phosphorylated proteins at serine or threonine residues which precede a proline. The peptidyl-prolyl isomerization induces a conformational change of the proteins involved in cell signaling process. Pin1 dysregulation has been associated with some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Proline-directed phosphorylation is a common regulator of these pathologies and a recent work showed that it is also involved in prion disorders. In fact, prion protein phosphorylation at the Ser-43-Pro motif induces prion protein conversion into a disease-associated form. Furthermore, phosphorylation at Ser-43-Pro has been observed to increase in the cerebral spinal fluid of sporadic Creutzfeldt-Jakob Disease patients. These findings provide new insights into the pathogenesis of prion disorders, suggesting Pin1 as a potential new player in the disease. In this paper, we review the mechanisms underlying Pin1 involvement in the aforementioned neurodegenerative pathologies focusing on the potential role of Pin1 in prion disorders

Science Teachers’ Views of Science and Religion vs. the Islamic Perspective: Conflicting or Compatible?

publication-status: Publishedtypes: ArticleThis paper reports a study that explores Egyptian science teachers' views on religion and science within the context of Islam. It also highlights an ontological and epistemological consideration of these views, particularly the ways through which Egyptian Muslim teachers understand such a relationship with reference to the Qur'anic/Islamic attitude toward science and knowledge. The study built upon Barbour's categorization scheme to guide the data collection and analysis and to guide the interpretation of the teachers' responses in the interviews. Informed by a multigrounded theory of the teachers' views of science and religion, and using Roth and Alexander's analytical framework to interpret how teachers accommodate the relationship between science and religion within their belief system, the findings suggest that participants' views of the relationship between science and a specific religion (Islam) confirmed the centrality of teachers' personal religious beliefs to their own thoughts and views concerning issues of both science and Islam. This centralization, in some cases, appeared to lead teachers to hold a conflicting relationship, hence to a creation of a false contradiction between science and Islam. Therefore, it could be concluded that teachers' personal Islamic-religious beliefs inform their beliefs about the nature of science and its purpose

Psoriasis and Hypertension Severity: Results from a Case-Control Study

BACKGROUND: Epidemiologic studies have provided new insights into the association between psoriasis and cardiovascular diseases. Previous population studies have examined hypertension frequency in psoriasis patients. However, the relationship between severity of hypertension and psoriasis has not been characterized. OBJECTIVE: We sought to investigate whether patients with psoriasis have more difficult-to-manage hypertension compared to non-psoriatic hypertensive patients. APPROACH: We performed a case-control study using the University of California Davis electronic medical records. The cases were defined as patients diagnosed with both psoriasis and hypertension, and controls were defined as patients with hypertension and without psoriasis. In this identified population, 835 cases were matched on age, sex, and body mass index (BMI) to 2418 control patients. KEY RESULTS: Treatment with multiple anti-hypertensives was significantly associated with the presence of psoriasis using univariate (p < 0.0001) and multivariable analysis, after adjusting for diabetes, hyperlipidemia, and race (p < 0.0001). Compared to hypertensive patients without psoriasis, psoriasis patients with hypertension were 5 times more likely to be on a monotherapy antihypertensive regimen (95% CI 3.607.05), 9.5 times more likely to be on dual antihypertensive therapy (95% CI 6.68-13.65), 16.5 times more likely to be on triple antihypertensive regimen (95% CI 11.01-24.84), and 19.9 times more likely to be on quadruple therapy or centrally-acting agent (95% CI 10.58-37.33) in multivariable analysis after adjusting for traditional cardiac risk factors. CONCLUSIONS: Psoriasis patients appear to have more difficult-to-control hypertension compared to non-psoriatic, hypertensive patients

Effects of elevated soil CO2 concentration on growth and competition in a grass-clover mix

To investigate potential environmental affects in the context of carbon dioxide (CO2) leakage from Carbon Capture and Storage (CCS) schemes. The ASGARD (Artificial Soil Gassing and Response Detection) facility was established, where CO2 can be injected into the soil in replicated open-air field plots. Eight plots were sown with a grass-clover mix, with four selected for CO2 treatment while four were left as controls. Observations of sward productivity throughout the study allowed three effects to be distinguished: a direct stress response to soil gassing, limiting productivity in both species but with a greater effect on the clover; competition between the grass and clover affected by their differential stress responses; and an overall temporal trend from dominance by clover to dominance by grass in CO2 treatments. The direct effect of soil CO2 (or associated oxygen (O2) deprivation due to the high levels of CO2 in the soil) gave estimated reductions in productivity of 42% and 41% in grass, compared to 66% and 32% for clover in the high and low CO2 gassed zones respectively. Canopy CO2 increased by 70 parts per million (ppm) for every 1% increase in soil CO2 and a significant positive response of stomatal conductance in clover was observed; although carbon acquisition by the plants should not therefore be impeded, the reduction in productivity of the gassed plants is indicative of carbon-based metabolic costs probably related to soil CO2 affecting root physiology. Biomass measurements made after gassing has ceased indicated that recovery of vegetation was close to complete after 12 months

Randomized comparison of the effects of the vitamin D(3 )adequate intake versus 100 mcg (4000 IU) per day on biochemical responses and the wellbeing of patients

BACKGROUND: For adults, vitamin D intake of 100 mcg (4000 IU)/day is physiologic and safe. The adequate intake (AI) for older adults is 15 mcg (600 IU)/day, but there has been no report focusing on use of this dose. METHODS: We compared effects of these doses on biochemical responses and sense of wellbeing in a blinded, randomized trial. In Study 1, 64 outpatients (recruited if summer 2001 25(OH)D <61 nmol/L) were given 15 or 100 mcg/day vitamin D in December 2001. Biochemical responses were followed at subsequent visits that were part of clinical care; 37 patients completed a wellbeing questionnaire in December 2001 and February 2002. Subjects for Study 2 were recruited if their 25(OH)D was <51 nmol/L in summer 2001. 66 outpatients were given vitamin D; 51 completed a wellbeing questionnaire in both December 2002 and February 2003. RESULTS: In Study 1, basal summer 25-hydroxyvitamin D [25(OH)D] averaged 48 ± 9 (SD) nmol/L. Supplementation for more than 6 months produced mean 25(OH)D levels of 79 ± 30 nmol/L for the 15 mcg/day group, and 112 ± 41 nmol/L for the 100 mcg/day group. Both doses lowered plasma parathyroid hormone with no effect on plasma calcium. Between December and February, wellbeing score improved more for the 100-mcg/day group than for the lower-dosed group (1-tail Mann-Whitney p = 0.036). In Study 2, 25(OH)D averaged 39 ± 9 nmol/L, and winter wellbeing scores improved with both doses of vitamin D (two-tail p < 0.001). CONCLUSION: The highest AI for vitamin D brought summertime 25(OH)D to >40 nmol/L, lowered PTH, and its use was associated with improved wellbeing. The 100 mcg/day dose produced greater responses. Since it was ethically necessary to provide a meaningful dose of vitamin D to these insufficient patients, we cannot rule out a placebo wellbeing response, particularly for those on the lower dose. This work confirms the safety and efficacy of both 15 and 100 mcg/day vitamin D(3 )in patients who needed additional vitamin D

Soil Microbial Responses to Elevated CO2 and O3 in a Nitrogen-Aggrading Agroecosystem

Climate change factors such as elevated atmospheric carbon dioxide (CO2) and ozone (O3) can exert significant impacts on soil microbes and the ecosystem level processes they mediate. However, the underlying mechanisms by which soil microbes respond to these environmental changes remain poorly understood. The prevailing hypothesis, which states that CO2- or O3-induced changes in carbon (C) availability dominate microbial responses, is primarily based on results from nitrogen (N)-limiting forests and grasslands. It remains largely unexplored how soil microbes respond to elevated CO2 and O3 in N-rich or N-aggrading systems, which severely hinders our ability to predict the long-term soil C dynamics in agroecosystems. Using a long-term field study conducted in a no-till wheat-soybean rotation system with open-top chambers, we showed that elevated CO2 but not O3 had a potent influence on soil microbes. Elevated CO2 (1.5×ambient) significantly increased, while O3 (1.4×ambient) reduced, aboveground (and presumably belowground) plant residue C and N inputs to soil. However, only elevated CO2 significantly affected soil microbial biomass, activities (namely heterotrophic respiration) and community composition. The enhancement of microbial biomass and activities by elevated CO2 largely occurred in the third and fourth years of the experiment and coincided with increased soil N availability, likely due to CO2-stimulation of symbiotic N2 fixation in soybean. Fungal biomass and the fungi∶bacteria ratio decreased under both ambient and elevated CO2 by the third year and also coincided with increased soil N availability; but they were significantly higher under elevated than ambient CO2. These results suggest that more attention should be directed towards assessing the impact of N availability on microbial activities and decomposition in projections of soil organic C balance in N-rich systems under future CO2 scenarios