Plant Sample Collection and Shipment for Multi-omic Analyses and Phytosanitary Evaluation.

Plant sample preparation for analyses is a fundamental step in high-throughput omics strategies. Especially for plant metabolomics, quenching of hydrolytic enzymes able to affect metabolite concentrations is crucial for the accuracy of results. Given that DNA is usually less labile than metabolites, most sampling and shipment procedures able to preserve the metabolome are also suitable for preventing the degradation of plant DNA or of DNA of pathogens in the plant tissue. In this article, we describe all the steps of sample collection, shipment (including the phytosanitary issues of moving plant samples), and processing for combined genomics and metabolomics from a single sample, as well as the protocols used in our laboratories for downstream approaches for crop plants, allowing collection of multi-omic datasets in large experimental setups. The protocols have been adjusted to apply to both freeze-dried and fresh-frozen material to allow the processing of crop plant samples that will require long-distance transport. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Preparation of freeze-dried leaf disks for multiplexed PCR or DArT-Seq genotyping Basic Protocol 2: Medium-throughput preparation of pathogen-free nucleic acids for most genotyping-resequencing applications or pathogen detection Alternate Protocol: Low-throughput extraction of high-quality DNA for resequencing using commercial kits Support Protocol: DNA quality control Basic Protocol 3: Preparation of freeze-dried plant material for metabolomics Basic Protocol 4: Preparation of fresh-frozen plant material for metabolomics Basic Protocol 5: Preparation and shipment of metabolite extracts for metabolomic analyses Basic Protocol 6: Sample shipping and long-term storage.

Plant biochemical genetics in the multiomics era.

Our understanding of plant biology has been revolutionized by modern genetics and biochemistry. However, biochemical genetics can be traced back to the foundation of Mendelian genetics; indeed, one of Mendel's milestone discoveries of seven characteristics of pea plants later came to be ascribed to a mutation in a starch branching enzyme. Here, we review both current and historical strategies for the elucidation of plant metabolic pathways and the genes that encode their component enzymes and regulators. We use this historical review to discuss a range of classical genetic phenomena including epistasis, canalization, and heterosis as viewed through the lens of contemporary high-throughput data obtained via the array of approaches currently adopted in multiomics studies.

Cold stress and freezing tolerance negatively affect the fitness of Arabidopsis thaliana accessions under field and controlled conditions.

MAIN CONCLUSION: Higher acclimated freezing tolerance improved winter survival, but reduced reproductive fitness of Arabidopsis thaliana accessions under field and controlled conditions. Low temperature is one of the most important abiotic factors influencing plant fitness and geographical distribution. In addition, cold stress is known to influence crop yield and is therefore of great economic importance. Increased freezing tolerance can be acquired by the process of cold acclimation, but this may be associated with a fitness cost. To assess the influence of cold stress on the fitness of plants, long-term field trials over 5 years were performed with six natural accessions of Arabidopsis thaliana ranging from very tolerant to very sensitive to freezing. Fitness parameters, as seed yield and 1000 seed mass, were measured and correlation analyses with temperature and freezing tolerance data performed. The results were compared with fitness parameters from controlled chamber experiments over 3 years with application of cold priming and triggering conditions. Winter survival and seed yield per plant were positively correlated with temperature in field experiments. In addition, winter survival and 1000 seed mass were correlated with the cold-acclimated freezing tolerance of the selected Arabidopsis accessions. The results provide strong evidence for a trade-off between higher freezing tolerance and reproductive fitness in A. thaliana, which might have ecological impacts in the context of global warming.

Derivation of original RESP atomic partial charges for MD simulations of the LDAO surfactant with AMBER: applications to a model of micelle and a fragment of the lipid kinase PI4KA.

In this paper, we describe the derivation and the validation of original RESP atomic partial charges for the N, N-dimethyl-dodecylamine oxide (LDAO) surfactant. These charges, designed to be fully compatible with all the AMBER force fields, are at first tested against molecular dynamics simulations of pure LDAO micelles and with a fragment of the lipid kinase PIK4A (DI) modeled with the QUARK molecular modeling server. To model the micelle, we used two distinct AMBER force fields (i.e. Amber99SB and Lipid14) and a variety of starting conditions. We find that the micelle structural properties (such as the shape, size, the LDAO headgroup hydration, and alkyl chain conformation) slightly depend on the force field but not on the starting conditions and more importantly are in good agreement with experiments and previous simulations. We also show that the Lipid14 force field should be used instead of the Amber99SB one to better reproduce the C(sp3)C(sp3)C(sp3)C(sp3) conformation in the surfactant alkyl chain. Concerning the simulations with LDAO-DI protein, we carried out different runs at two NaCl concentrations (i.e. 0 and 300 mM) to mimic, in the latter case, the experimental conditions. We notice a small dependence of the simulation results with the LDAO parameters and the salt concentration. However, we find that in the simulations, three out of four tryptophans of the DI protein are not accessible to water in agreement with our fluorescence spectroscopy experiments reported in the paper.

On the Structural and Dynamical Properties of DOPC Reverse Micelles.

The structure and dynamics of phospholipid reverse micelles are studied by molecular dynamics. We report all-atom unconstrained simulations of 1,2-dioleoyl-sn-phosphatidylcholine (DOPC) reverse micelles in benzene of increasing sizes, with water-to-surfactant number ratios ranging from W0 = 1 to 16. The aggregation number, i.e., the number of DOPC molecules per reverse micelle, is determined to fit experimental light-scattering measurements of the reverse micelle diameter. The simulated reverse micelles are found to be approximately spherical. Larger reverse micelles (W0 > 4) exhibit a layered structure with a water core and the hydration structure of DOPC phosphate head groups is similar to that found in phospholipid membranes. In contrast, the structure of smaller reverse micelles (W0 ≤ 4) cannot be described as a series of concentric layers successively containing water, surfactant head groups, and surfactant tails, and the head groups are only partly hydrated and frequently present in the core. The dynamics of water molecules within the phospholipid reverse micelles slow down as the reverse micelle size decreases, in agreement with prior studies on AOT and Igepal reverse micelles. However, the average water reorientation dynamics in DOPC reverse micelles is found to be much slower than in AOT and Igepal reverse micelles with the same W0 ratio. This is explained by the smaller water pool and by the stronger interactions between water and the charged head groups, as confirmed by the red-shift of the computed infrared line shape with decreasing W0.

Relation of red cell distribution width with dipper and non-dipper hypertension.

Aim Red cell distribution width (RDW), an index of erythrocyte size, is associated with high risk for cardiovascular disease. Nondipping hypertension (HT) is lack of nocturnal fall in blood pressure(BP). The association between RDW and non-dipping BP in normotensive and hypertensive patients was investigated. Methods A total of 170 patients were categorized into 4 groups: Normotensive-Dipper (NT-D), Normotensive-Non-dipper (NTND), Hypertensive-Dipper (HT-D) and Hypertensive-Non-dipper(HT-ND). RDW and hs-CRP levels were measured. Results Hypertensive patients had higher RDW and hs-CRP levels(14.5 ± 0.87 vs.12.7 ± 0.66, p<0.001 for RDW; 0.99 ± 0.52 vs.0.63 ± 0.43, p<0.001 for hs-CRP). Besides, the RDW levels were higher in non-dippers (13.0 ± 0.63 vs.12.4 ± 0.55, p<0.001 for NT-ND and NT-D; 14.9 ± 0.78 vs.14.2 ± 0.82, p<0.001 for HT-ND and HT-D) Conclusion RDW is elevated in non-dipping BP both in normotensive and hypertensive subjects, which may be related with increased inflammatory state.

Evaluation of the effects of red blood cell distribution width on survival in lung cancer patients.

AIM OF THE STUDY: Data are available indicating that red blood cell distribution width (RDW) is higher in cancer patients compared to healthy individuals or benign events. In our study, we aimed to investigate the influence of different RDW levels on survival in lung cancer patients. MATERIAL AND METHODS: Clinical and laboratory data from 146 patients with lung cancer and 40 healthy subjects were retrospectively studied. RDW was recorded before the application of any treatment. Patients were categorised according to four different RDW cut-off values (median RDW, RDW determined by ROC curve analysis, the upper limit at the automatic blood count device, and RDW cut of value which used in previous studies). Kaplan-Meier survival analysis was used to examine the effect of RDW on survival for each cut-off level. RESULTS: The median age of patients was 56.5 years (range: 26-83 years). The difference in median RDW between patients and the control group was statistically significant (14.0 and 13.8, respectively, p = 0.04). There was no difference with regard to overall survival when patients with RDW ≥ 14.0 were compared to those with RDW < 14.0 (p = 0.70); however, overall survival was 3.0 months shorter in low values of its own group in each of the following cut-off values: ≥ 14.2 (p = 0.34), ≥ 14.5 (p = 0.25), ≥ 15 (p = 0.59), although no results were statistically significant. DISCUSSION: We consider that the difference between low and high RDW values according to certain cut-off values may reflect the statistics of larger studies although there is a statistically negative correlation between RDW level and survival.

Prognostic role of pretreatment platelet/lymphocyte ratio in patients with non-small cell lung cancer.

BACKGROUND: It was reported that hematological markers of systemic inflammatory response might be prognostic in various cancer types. We aimed to evaluate the platelet/lymphocyte ratio (PLR) as a prognostic factor and its effect on overall survival in non-small cell lung cancer (NSCLC). METHODS: Clinicopathological characteristics and basal (pretreatment) PLR of 145 patients with NSCLC were evaluated retrospectively. The preoperative or pretreatment blood count data were obtained from the recorded computerized database. PLR was defined as the absolute platelet count divided by the absolute lymphocyte count. RESULTS: A total of 145 patients were enrolled. Median age was 57 years(range 26-83). Receiver operating characteristic curves for overall survival prediction were plotted to verify the optimum cut-off point for PLR. The recommended cut-off values for PLR was 198.2 with a sensitivity of 65.0 % and a specificity of 71.4 %. Median overall survival was 34.0 (95 % confidence interval (CI) 14.7-53.3) months in the group with low PLR (< 198.2), while it was 11.0 (95 % CI 5.6-16.3) months in the group with high PLR (≥ 198.2). The difference between the groups was statistically significant (p < 0.0001). CONCLUSIONS: Our study supports the view that a high basal PLR is a poor prognostic factor in NSCLC. However, the validity of the cut-off values for PLR identified in our study needs further prospective trials.

Structure of Bolaamphiphile Sophorolipid Micelles Characterized with SAXS, SANS, and MD Simulations.

The micellar structure of sophorolipids, a glycolipid bolaamphiphile, is analyzed using a combination of small-angle X-ray scattering (SAXS), small-angle neutron scattering (SANS), and molecular dynamics (MD) simulations. Numerical modeling of SAXS curves shows that micellar morphology in the noncharged system (pH< 5) is made of prolate ellipsoids of revolution with core-shell morphology. Opposed to most surfactant systems, the hydrophilic shell has a nonhomogeneous distribution of matter: the shell thickness in the axial direction of the ellipsoid is found to be practically zero, while it measures about 12 Å at its cross-section, thus forming a "coffee bean"-like shape. The use of a contrast-matching SANS experiment shows that the hydrophobic component of sophorolipids is actually distributed in a narrow spheroidal region in the micellar core. These data seem to indicate a complex distribution of sophorolipids within the micelle, divided into at least three domains: a pure hydrophobic core, a hydrophilic shell, and a region of less defined composition in the axial direction of the ellipsoid. To account for these results, we make the hypothesis that sophorolipid molecules acquire various configurations within the micelle including bent and linear, crossing the micellar core. These results are confirmed by MD simulations which do show the presence of multiple sophorolipid configurations when passing from spherical to ellipsoidal aggregates. Finally, we also used Rb(+) and Sr(2+) counterions in combination with anomalous SAXS experiments to probe the distribution of the COO(-) group of sophorolipids upon small pH increase (5 < pH < 7), where repulsive intermicellar interactions become important. The poor ASAXS signal shows that the COO(-) groups are rather diffused in the broad hydrophilic shell rather than at the outer micellar/water interface.

Assessment of Prognostic Value of "Neutrophil to Lymphocyte Ratio" and "Prognostic Nutritional Index" as a Sytemic Inflammatory Marker in Non-small Cell Lung Cancer.

BACKGROUND: Systemic inflammatory response was shown to play an important role in development and progression of many cancer types and different inflammation-based indices were used for determining prognosis. We aimed to investigate the prognostic effects of neutrophil to lymphocyte ratio (NLR) and prognostic nutritional index (PNI) in patients with non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: NSCLC patients diagnosed in our institution were retrospectively reviewed. Demographic and clinicopathologic characteristics were recorded. NLR and PNI was calculated before the application of any treatment. RESULTS: A total of 138 patients were included in the study. Patients were divided into two groups according to NLR (<3.24 or ≥3.24) and PNI (<49.5 or ≥49.5). While median overall survival was 37.0 (95% CI 17.5-56.5) months in the group with low NLR, it was calculated as 10.0 (95%CI 5.0-15.0) months in the group with high NLR (p<0.0001). While median overall survival was 7.0 (95%CI 3.5-10.5) months in the group with low PNI, it was calculated as 33.0 (95% CI 15.5-50.4) months in the group with high PNI (p<0.0001). Stage, NLR and PNI levels were evaluated as independent risk factors for overall survival for all patients in multivariate analysis (p<0.0001, p=0.04 and p<0.001, respectively). CONCLUSIONS: NLR (≥3.24) and PNI (<49.5) at diagnosis is an independent marker of poor outcome in patients with NSCLC. NLR and PNI is an easily measured, reproducible prognostic tests that could be considered in NSCLC patients.

Correlation of neutrophil to lymphocyte ratio with the presence and severity of metabolic syndrome.

PURPOSE: The aim of this study is to investigate the relationship between the criteria comprising metabolic syndrome (MS) and neutrophil-lymphocyte ratio (NLR), a simple and reliable indicator of inflammation. METHOD: Seventy patients with MS and 71 age- and sex-matched control participants were included. Patients were classified into 3 groups based on the number of MS criteria: group 1 (with 3 criteria), group 2 (with 4 criteria), and group 3 (with 5 criteria). The NLR was calculated from complete blood count. RESULTS: Patients with MS had significantly higher NLR compared to the control group. Moreover, the group 3 patients had higher NLR than those in groups 2 and 1 (P = .008 and P = .078, respectively), whereas there was no difference between the patients meeting 3 and 4 MS criteria (P = .320). Besides, NLR increased as the severity of MS increased (r = .586, P < .001). The cutoff level for NLR with optimal sensitivity and specificity was calculated as 1.84. Serum glucose and high-sensitive C-reactive protein level were found to be independent predictors of an NLR value greater than 1.84. CONCLUSION: The present study indicated a significant correlation between the criteria of MS and inflammation on the basis of NLR. Furthermore, there an increase in NLR as the severity of MS increases.

Conformational restriction of G-proteins Coupled Receptors (GPCRs) upon complexation to G-proteins: a putative activation mode of GPCRs?

GPCRs undergo large conformational changes during their activation. Starting from existing X-ray structures, we used Normal Modes Analyses to study the collective motions of the agonist-bound ß2-adrenergic receptor both in its isolated "uncoupled" and G-protein "coupled" conformations. We interestingly observed that the receptor was able to adopt only one major motion in the protein:protein complex. This motion corresponded to an anti-symmetric rotation of both its extra- and intra-cellular parts, with a key role of previously identified highly conserved proline residues. Because this motion was also retrieved when performing NMA on 7 other GPCRs which structures were available, it is strongly suspected to possess a significant biological role, possibly being the "activation mode" of a GPCR when coupled to G-proteins.

The serum pentraxin-3 is elevated in patients with cardiac syndrome X.

OBJECTIVES: Cardiac syndrome X (CSX) is a clinical entity that is defined as normal coronary arteries with angina pectoris and objective sins of ischemia. The correlation between CSX and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) is well established, however an association with pentraxin-3 (PTX-3) has not been examined. The aim of this study was to investigate the association between PTX-3 and CSX. STUDY DESIGN: A total of 122 patients (58 female, 64 male, mean age 49.6±5.8 years) with suspected of coronary artery disease (CAD) were included in the study. Those with evidence of ischemia (50 patients with positive treadmill tests, 32 patients with positive myocardial perfusion scintography) underwent coronary angiography (82 patients). Patients with a normal angiogram were considered the CSX group (n=41) and patients with coronary lesions were referred to as the CAD group (n=41). Patients without signs of ischemia served as the control group. Serum PTX-3 and hs-CRP levels were measured in all patients. RESULTS: The CSX group had significantly increased PTX-3 levels relative to the control group (0.46±0.16 vs. 0.23±0.09 ng/ml, p<0.001). However there were no differences in levels of PTX-3 and hs-CRP between the CSX and the CAD groups (PTX-3: 0.46±0.16 vs. 0.51±0.13 ng/ml, p=0.21; hs-CRP: 1.04±0.45 vs. 1.16±0.64 mg/dl, p=0.62). The control group had significantly lower hs-CRP levels (0.73±0.51 mg/dl) when compared to the both CSX and CAD groups (p=0.03 and p=0.002, respectively). Serum PTX-3 levels were weakly correlated with hs-CRP levels (r=0.30, p=0.001). CONCLUSION: PTX-3, a novel inflammatory marker, is elevated in patients with CSX, similar to the well known inflammatory marker hs-CRP, and may be a promising biomarker reflecting inflammatory status in these patients.

Assessment of left ventricular dyssynchrony in dipper and non-dipper hypertension.

BACKGROUND: Ventricular dyssynchrony is an co-determinant of progression and exacerbation of heart failure (HF). The co-existence of ventricular dyssynchrony with hypertension (HT) and HF were shown, however there is no data regarding the effect of circadian rhythm of blood pressure (BP) on ventricular synchrony. Therefore, we aimed to study the left ventricular synchrony in dipper and non-dipper normotensive and hypertensive participants. METHODS: Participants (n = 142) were categorized into four groups as "Normotensive-Dipper" (NT-D) (n = 40), "Normotensive-Non-dipper" (NT-ND) (n = 30), "Hypertensive-Dipper" (HT-D) (n = 38) and "Hypertensive-Non-dipper" (HT-ND) (n = 34). Left ventricular dyssynchrony was investigated by color-coded tissue Doppler imaging. RESULTS: Non-dippers had higher 24-h and night-time BP both in normotensives and hypertensives. The incidence of ventricular dyssynchrony (a Ts-SD-12 > 34.4 ms) was higher in the hypertensive group (47.2% vs 24.3%, p = 0.005). The frequency of ventricular dyssynchrony was higher in the HT-ND group than the HT-D group (58.8% vs 36.8%, p = 0.05); however, the frequency of ventricular dyssynchrony was similar among the normotensives (26.7% vs 22.5%, p = 0.45). Ts-SD-12 and Ts-12 were higher in NT-ND group than the NT-D group. CONCLUSIONS: Non-dipping BP pattern was associated with impaired left ventricular contraction synchrony in both normotensive and hypertensive participants, which may be related with short- and long-term effects of HT on myocardium.

Left ventricular dyssynchrony is an early manifestation of heart involvement in sickle cell anemia.

BACKGROUND: Sickle cell anemia (SCA) is the most common inherited anemia. Although heart involvement in SCA is well-established, there is no data about changes of contraction synchrony in SCA. Therefore, we aimed to study the left ventricular contraction synchrony in SCA patients with narrow QRS and normal ejection fraction (EF). METHODS: Thirty-six patients with SCA and 37 age- and gender-matched control subjects were included in the study. Left ventricular dyssynchrony was investigated by color-coded tissue Doppler imaging. RESULTS: The SCA patients had lower hemoglobin (Hb) and higher ferritin, left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular mass index (LVMI), and pulmonary artery pressure. Peak A velocity, Dt, and E/E' values were higher in the SCA group however, E/A ratio and average Em were higher in the control group. LV systolic dyssynchrony parameters including Ts-SD-12, Ts-12, Ts-SD-6, and Ts-6 were found to be higher in SCA group when compared with controls. In addition to that, the patients with ventricular dyssynchrony (a Ts-SD-12 > 34.4 msec) were higher in the SCA group than the control group (55.6% vs. 8.1%, P < 0.001). In the correlation analysis, systolic dyssynchrony parameters were found to be correlated with Hb, ferritin, LVMI, E/A, Dt, Em. CONCLUSION: Our results revealed that in SCA patients with normal EF and narrow QRS, left ventricular systolic dyssynchrony was an early manifestation of heart involvement and might be coexisted with or preceding diastolic dysfunction.

Serum pentraxin 3 levels are associated with the complexity and severity of coronary artery disease in patients with stable angina pectoris.

BACKGROUND: Atherosclerosis is a complex inflammatory process in which inflammatory markers are involved. Although pentraxin 3 (PTX-3), a newly identified inflammatory marker, was associated with adverse outcomes in stable angina pectoris, no association between PTX-3 and the complexity of coronary artery disease (CAD) has been reported. Thus, the aim of the present study was to assess the association between the level of PTX-3 and the complexity and severity of CAD assessed with SYNTAX and Gensini scores in patients with stable angina pectoris. METHODS: The study population consisted of 2 groups: 161 patients with anginal symptoms and evidence of ischemia who underwent coronary angiography and 50 age- and sex- matched control subjects without evidence of ischemia were included. Patients were grouped into 3 groups according to the complexity and severity of coronary lesions assessed by the SYNTAX score (30 patients with a SYNTAX score of 0 were excluded). Serum PTX-3 and high-sensitivity C-reactive protein (hs-CRP) levels were measured. RESULTS: The PTX-3 levels demonstrated an increase from low to high SYNTAX groups (r = 0.72, P < 0.001). Whereas the low SYNTAX group had statistically significantly higher PTX-3 levels when compared with the control group (0.50 ± 0.01 vs 0.24 ± 0.01 ng/mL, P < 0.001), the hs-CRP levels were not different (0.81 ± 0.42 vs 0.86 ± 0.53 mg/dL, P = 0.96). However, the intermediate SYNTAX group had higher hs-CRP levels compared with the low SYNTAX group (1.3 ± 0.66 vs 0.86 ± 0.53 mg/dL, P = 0.002). Serum PTX-3 levels and hs-CRP levels were correlated with the SYNTAX scores and Gensini scores (for SYNTAX: r = 0.87 [P < 0.001] and r = 0.36 [P = 0.01]; for Gensini: r = 0.75 [P < 0.001] and r = 0.27 [P = 0.002], respectively), and according to the results of univariate and multivariate analyses, for "intermediate and high" SYNTAX scores, age, diabetes mellitus, low-density lipoprotein cholesterol, hs-CRP, and PTX-3 were found to be independent predictors, whereas for the presence of "high" SYNTAX score only PTX-3 was found to be an independent predictor. The receiver operating characteristic curve analysis further revealed that the PTX-3 level was a strong indicator of high SYNTAX score with an area under the curve of 0.91 (95% confidence interval, 0.86-0.96). CONCLUSIONS: Pentraxin 3, a novel inflammatory marker, was more tightly associated with the complexity and severity of CAD than hs-CRP and was found to be an independent predictor for high SYNTAX score.

Serum pentraxin-3 levels are associated with the severity of metabolic syndrome.

OBJECTIVES: The aim of the present study was to assess the association between the level of pentraxin-3 (PTX-3) and the severity of metabolic syndrome (MS). SUBJECTS AND METHOD: One hundred and two patients with MS and 101 consecutive age- and sex-matched control subjects were included in the study. The MS patients were classified into three groups based on the number of MS criteria, i.e. group 1: patients with 3 MS criteria, group 2: patients with 4 MS criteria, and group 3: patients with 5 MS criteria. Serum PTX-3 and high-sensitivity C-reactive protein (hs-CRP) levels were measured. RESULTS: Group 1 had higher PTX-3 levels compared to the control group (0.58 ± 0.11 ng/ml vs. 0.36 ± 0.15 ng/ml, p < 0.001). PTX-3 levels were higher in group 3 than in both group 1 (0.90 ± 0.06 ng/ml vs. 0.58 ± 0.11 ng/ml, p < 0.001) and group 2 (0.90 ± 0.06 ng/ml vs. 0.63 ± 0.12 ng/ml, p < 0.001). Group 3, however, had higher hs-CRP levels than both group 1 (1.89 ± 0.45 mg/dl vs. 1.40 ± 0.44 mg/dl, p = 0.007) and group 2 (1.89 ± 0.45 mg/dl vs. 1.47 ± 0.58 mg/dl, p = 0.01). The control group had lower hs-CRP levels than group 1 (0.81 ± 0.47 mg/dl vs. 1.40 ± 0.44 mg/dl, p < 0.001) and group 2 (0.81 ± 0.47 mg/dl vs. 1.47 ± 0.58 mg/dl, p < 0.001). Serum PTX-3 levels correlated with serum hs-CRP levels (r = 0.49, p < 0.001). CONCLUSIONS: PTX-3, a novel inflammatory marker, was found to be associated with the severity of MS.

Molecular dynamics simulation of PEGylated bilayer interacting with salt ions: a model of the liposome surface in the bloodstream.

PEGylation is an effective mechanism to prolong the bloodstream lifetime, and thus efficacy, of drug delivery liposomes. The mechanism through which poly(ethylene glycol) (PEG) increases bloodstream lifetime is, however, not completely understood. The interaction with salt ions found in the bloodstream is known to play a role in this. We have used all-atom molecular dynamics simulation to study the effect of PEGylated lipid density, salt concentration, and the interaction with KCl and CaCl(2) salts in addition to NaCl. Increasing the PEGylated lipid concentration in the formulation from 1:18 to 1:9 molar density decreased the extent to which the Cl(-) ions penetrated the PEG layer, thus causing the PEG layer to become effectively positively charged. The interaction of the PEG with the K(+) ions was weaker than for the Na(+) ions, and nonexistent for the Ca(2+) ions. This work expands on our previous work where we studied the gel and liquid crystalline membranes in physiological salt concentration. Our results provide both an explanation for the experimental observation that PEGylation inhibits calcium-induced liposome fusion and further insight into the mechanisms through which PEG may inhibit uptake of the liposome by the reticuloendothilial system (RES).

The Correlation between Infarct Size and the QRS Axis Change after Thrombolytic Therapy in ST Elevation Acute Myocardial Infarction.

OBJECTIVE: Electrocardiography (ECG) may be a practical guiding tool for prognostic infarct sizing in ST elevation acute myocardial infarction (STEAMI). In this study, we sought to find a relation between the infarct size and the change in the QRS axis after thrombolytic therapy. MATERIALS AND METHODS: Patients with STEAMI who received thrombolytic therapy were selected retrospectively. The mean QRS axes of two ECGs (before and 90 minutes after thrombolytic therapy) were calculated. Creatinine kinase MB (CKMB) was used as the marker of infarct size. RESULTS: We did not detect any correlation between infarct size and change in the QRS axis with respect to any myocardial infarction MI localizations (p=0.80). However, in the isolated inferior MI group, there was a good correlation between CKMB and change in the QRS axis (r=-0.52 p=0.049). CONCLUSION: The change in the QRS axis is rarely emphasized, providing a practical and promising tool for evaluating both the efficiency of the thrombolytic therapy and prognostic infarct sizing.