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Determination of arterial compliance using blood pressure waveform analysis with the CR-2000 system: Reliability, repeatability, and establishment of normal values for healthy European population--the seven European sites study (SESS).

BACKGROUND: We determined the reliability and repeatability of measurements of arterial compliance (AC) and gender- and age-specific normal ranges for a healthy European population. METHODS: Three hundred eight healthy volunteers from seven sites were evaluated. Two measurements were taken during the first visit, repeated on a second visit 1 to 4 weeks later. We used the HDI/PulseWave CR-2000 for measurements of AC. RESULTS: Intravisit measurements, taken 5 min apart, differed by less than 3% (range, 0.36% to 2.97%). All intervisit measures differed by less than 4% (range, 0.24% to 3.67%); none of these differences was statistically significant. All correlation coefficients for pairs of AC parameters measured 5 min apart at the same visit were significant at P < .0001. Paired AC parameters at visit 1 and 2 were highly correlated (P < .0001). Repeated measures GLM (general linear model) failed to detect a significant association between either of the AC parameters and visit (first or second), time (first or second measure at the same visit), and visit-by-time (the interaction of the two preceding factors), suggesting that order of measure had no effect on the final value. Analysis of reliability was used to develop a strictly parallel model estimate of unbiased reliability. Both intravisit and intervisit estimates of reliability indicate good repeatability of measure and were significant (P < .0001). The AC values were found to differ significantly by age group, with an inverse association between each of the AC parameters and age group. CONCLUSIONS: Measurement of the arterial waveform with the CR-2000 system is highly reproducible in healthy subjects.

Adolescent↗

Increased levels of atherosclerosis markers in salt-sensitive hypertension.

BACKGROUND: Salt sensitivity in essential hypertension is associated with both endothelial dysfunction and increased cardiovascular risk. We evaluated several serum markers of atherosclerosis and endothelial function in a group of essential hypertensive patients classified on the basis of their salt sensitivity. METHODS: Forty-three patients were classified as having salt-sensitive (20 subjects) or salt-resistant (23 subjects) hypertension on the basis of their 24-h blood pressure (BP) response from low salt (50 mmol/d) to high salt (250 mmol/d) intake. Endothelium-dependent and independent responses were measured in the forearm previously to salt manipulation. High-sensitivity C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), e-selectin, p-selectin, interleukin-6 (IL-6), monocyte chemotactic protein type 1 (MCP-1), matrix metalloproteinases types 1, 2, and 9 (MMP-1, MMP-2, and MMP-9), and the tissue inhibitor of metalloproteinases type 1 (TIMP-1) were measured in serum on the last day of both low salt and high salt intakes. RESULTS: Compared to salt-resistant patients, salt-sensitive hypertensives showed age-adjusted increased levels of p-selectin (P = .006), e-selectin (P = .042), and MCP-1 (P = .036), although differences in e-selectin were not maintained after adjustment for BP values. Moreover, salt-sensitive subjects exhibited decreased serum levels of MMP-9 (P = .007) and increased levels of TIMP-1 (P = .045). No differences in serum CRP, sICAM-1, sVCAM-1, or IL-6 were observed between salt-sensitive and salt-resistant patients. Finally, maximal acetylcholine-induced vasodilation (319% +/- 153% v 414% +/- 178% increase in forearm blood flow; P = .022 age-adjusted) was significantly impaired in salt-sensitive hypertensives. CONCLUSIONS: Serum markers of inflammation, especially selectins and chemokines, as well as markers of vascular remodeling, and endothelium-dependent vasodilation are altered in salt-sensitive hypertension. These alterations could help to explain the greater target organ damage and cardiovascular risk observed in salt-sensitive subjects.

Adult↗

Interaction of myocilin with the C-terminal region of hevin.

Myocilin, a matricellular protein, is mutated in glaucoma. Here we report the identification and characterization, by the yeast two-hybrid system, of a putative interacting protein with myocilin. One of the positive clones exhibited 100% identity with the carboxyl-terminal (C-t) region of hevin, a member of the BM-40/SPARC/osteonectin family of extracellular matrix proteins. Protein interaction was assayed, in doubly transfected 293-T cells, by Western blot and fluorescent microscopy. Western blot analysis of the culture medium and lysates from cotransfected cells indicated that myocilin causes intracellular accumulation of hevin-C-t and impairs its secretion. This effect on hevin-C-t was augmented when coexpressed with the myocilin P370L mutant, known to cause a severe form of glaucoma. By fluorescent microscopy, myocilin localizes with hevin-C-t in the Golgi in cotransfected 293-T cells and with hevin-wt in the ocular ciliary epithelium. Overall, these results suggested that the C-t of hevin contains important determinants for interaction with myocilin.

Binding Sites↗

Variables affecting efficiency of molasses fermentation wastewater ozonation.

The main operating variables affecting ozonation efficiencies of wastewater from beet molasses alcoholic fermentation have been studied. Semibatch experiments have been performed in order to analyze the influence of pH, bicarbonate ion, temperature and stirring rate on color and organic matter removals. The efficiencies were similar regardless of the pH, which indicates that direct reactions of ozone with wastewater organics were predominant to radical reactions. Gel permeation chromatography confirmed the reduction in the concentration of organics absorbing light at 475 nm after ozonation. The elimination of bicarbonate ion, strong inhibitor of hydroxyl radical reactions, yielded an improvement in both color and COD reduction efficiencies. Acidification for removing bicarbonate ions produced a shift of colored compounds to smaller molecular weights. The highest efficiencies were achieved at 40 degrees C. Color and COD reductions at 40 degrees C were about 90% and 37%, respectively. In no case, the percentage of TOC removed was higher than 10-15%. Stirring rate had a slightly positive effect during the first stage of the ozonation showing that mass transfer played a role only during the initial reaction phase when direct attack of ozone molecules to aromatic/olefinic structures of colored substances was the predominant pathway.

Bicarbonates↗

Analysis of fatty acid epoxidation by high performance liquid chromatography coupled with evaporative light scattering detection and mass spectrometry.

Conventionally, epoxidation of unsaturated fatty acids has been studied either with titrimetric methods or in a lengthy procedure involving derivatization followed by gas chromatography (GC). We have developed a more rapid and descriptive analysis procedure for the substances using high performance liquid chromatography (HPLC) with evaporative light scattering detection (ELSD). Chemo-enzymatic epoxidation of unsaturated fatty acids (oleic, linoleic and linolenic acid, respectively) has been performed using hydrogen peroxide and immobilized lipase from Candida antarctica (Novozym 435). The fatty acids and their epoxidation products were separated by HPLC on a C-18 reversed-phase column using methanol-water containing 0.05% acetic acid as mobile phase. The method facilitated the simultaneous determination of fatty acids and epoxides differing from each other in the number of epoxide rings, the degree of unsaturation and the position of the epoxide rings and double bonds. An important aspect of the method development was the use of electrospray ionization and tandem mass spectrometry to confirm the structure of the epoxide products. It is suggested that the HPLC method, providing more information about the kind and concentration of fatty acids and their epoxides, represents a powerful complement to the existing methods for monitoring epoxidation processes on fatty acids.

Chromatography, High Pressure Liquid↗

Adsorption characterisation of different volatile organic compounds over alumina, zeolites and activated carbon using inverse gas chromatography.

Adsorption parameters (enthalpy of adsorption, free energy of adsorption) of several alkanes, cyclic hydrocarbons, aromatic hydrocarbons and chlorinated compounds on different adsorbents (alumina, zeolites 13X and 5 A, and activated carbon) were determined by inverse gas chromatography. Dispersive surface energy interaction and specific interaction parameters were determined for each solute-adsorbent system. It was found that mesoporous alumina presents lower enthalpy of adsorption than the microporous materials. Furthermore, zeolite 13X, which has wider pores than zeolite 5 A, exhibits a higher adsorption capacity.

Adsorption↗

Characterization of Co, Fe and Mn-exchanged zeolites by inverse gas chromatography.

The adsorption of several alkanes, cyclic hydrocarbons, aromatic hydrocarbons and chlorinated compounds on NaX, CaA, and exchanged Co, Mn and Fe zeolites as adsorbents was investigated. Zeolite composition and structure was determined by ICP-mass spectroscopy, XRD, and nitrogen adsorption. Adsorption parameters (enthalpy of adsorption and free energy of adsorption) as well as dispersive surface energy interaction and specific interaction parameters were determined for each solute-adsorbent system by inverse gas chromatography (IGC). The original zeolites NaX and CaA show the higher values of enthalpy of adsorption but specific interactions depend on the metal exchanged. Zeolites Mn-NaX and Co-NaX exhibit the strongest interactions with benzene, whereas zeolite Co-CaA shows the strongest interactions with chlorinated compounds. The trivalent cation (Fe3+) does not affect the either the adsorption efficiency or specific interaction.

Adsorption↗

Historical trends in the production and consumption of illicit drugs in Mexico: implications for the prevention of blood borne infections.

Mexico has cultivated opium poppy since before the 1900's and has been an important transit route for South American cocaine for decades. However, only recently has drug use, particularly injection drug use, been documented as an important problem. Heroin is the most common drug used by Mexican injection drug users (IDUs). Increased cultivation of opium poppy in some Mexican states, lower prices for black tar heroin and increased security at U.S.-Mexican border crossings may be contributing factors to heroin use, especially in border cities. Risky practices among IDUs, including needle sharing and shooting gallery attendance are common, whereas perceived risk for acquiring blood borne infections is low. Although reported AIDS cases attributed to IDU in Mexico have been low, data from sentinel populations, such as pregnant women in the Mexican-U.S. border city of Tijuana, suggest an increase in HIV prevalence associated with drug use. Given widespread risk behaviors and rising numbers of blood borne infections among IDUs in Mexican-U.S. border cities, there is an urgent need for increased disease surveillance and culturally appropriate interventions to prevent potential epidemics of blood borne infections. We review available literature on the history of opium production in Mexico, recent trends in drug use and its implications, and the Mexican response, with special emphasis on the border cities of Ciudad Juarez and Tijuana.

Coca↗

Liquid Biopsy-Multiomics Link Adhesion Pathway Dysregulation to Kidney Injury Severity.

INTRODUCTION: Severe acute kidney injury (AKI) is strongly associated with the risk of developing chronic kidney disease; however, little is known about the cell type-specific mechanisms driving kidney injury severity. METHODS: In this multicenter observational study, we used clinically obtained liquid biopsy proteomics and machine learning (ML) to predict severe outcomes in patients with COVID-associated and non-COVID AKI. Further, we orthogonally combined 169 urine proteomics with 437 plasma proteomics samples and 40 urine sediment single-cell transcriptomics samples to identify complementary dysregulated mechanisms. RESULTS: Using a 10-fold cross-validated random forest algorithm, we identified a set of urinary proteins that demonstrate predictive power for both discovery and validation set with AUC of 87% and 76%, respectively. These predictive proteomics features obtained demonstrate that cell adhesion and autophagy-associated pathways are uniquely impacted in severe AKI. Differentially abundant proteins (DAPSs) associated with these pathways are highly expressed in cells of the juxtamedullary nephron, endothelial cells (ECs), and podocytes, indicating that these kidney cell types could be potential targets. Single-cell transcriptomic analysis in the in vitro model of kidney organoids infected with SARS-CoV-2 reveal dysregulation of extracellular matrix (ECM) organization in multiple nephron segments, recapitulating the clinically observed fibrotic response across multiomics datasets. Ligand-receptor interaction analysis of the podocyte and tubule organoid clusters shows significant reduction and loss of interaction between integrins and basement membrane receptors in the infected kidney organoids. CONCLUSION: Collectively, these data suggest that ECM degradation and adhesion-associated mechanisms could be the main driver of severe kidney injury.

AKI↗

KIM-1 in Advanced Papillary and Clear Cell Renal Cell Carcinoma.

Kidney injury molecule 1 (KIM-1) is a promising biomarker in adjuvant clear cell renal cell carcinoma (ccRCC), but its relevance in advanced ccRCC or papillary RCC (pRCC) remains unclear. CALYPSO (NCT02819596) was a prospective, multi-arm trial that evaluated durvalumab alone or in combination with tremelimumab or savolitinib in metastatic ccRCC and pRCC. Circulating KIM-1 levels were measured at baseline and on-treatment. The primary endpoint was to explore if KIM-1 levels were raised in pRCC. Analyses were exploratory and p values were nominal. KIM-1 was measured in 123 patients with ccRCC and 31 patients with pRCC. Higher median concentrations occurred in pRCC compared to ccRCC (7835 vs 5470&#xa0;pg/ml, p =&#xa0;0.05). Reductions in KIM-1 levels occurred with systemic therapy in both ccRCC and pRCC (-59.2% and -32% respectively). In pRCC, radiological responders had significantly lower baseline KIM-1 levels (p =&#xa0;0.025). In ccRCC, high baseline KIM-1 levels were associated with significantly shorter overall survival (OS) (hazard ratio [HR] 1.77; 95% CI, 1.15-2.72; p =&#xa0;0.01). Also, an increase in KIM-1 during therapy was linked to worse progression-free survival (HR 1.7; 95% CI, 1.13-2.58; p =&#xa0;0.01) and OS (HR 1.95; 95% CI, 1.23-3.08; p =&#xa0;0.004) in ccRCC. This exploratory analysis supports the utility of KIM-1 in advanced ccRCC and pRCC.

Aged↗

Pathogenicity assessment of genetic variants identified in patients with severe hypertriglyceridemia: Novel cases of familial chylomicronemia syndrome from the Dyslipidemia Registry of the Spanish Atherosclerosis Society.

PURPOSE: Genetic testing is required to confirm a diagnosis of familial chylomicronemia syndrome (FCS). We assessed the pathogenicity of variants identified in the FCS canonical genes to diagnose FCS cases. METHODS: 245 patients with severe hypertriglyceridemia underwent next-generation sequencing. Preliminary variant pathogenicity criteria and classification, based on the American College of Medical Genetics and Genomics guidelines, were obtained online and verified. Phenotype evaluation was based on lipoprotein lipase activity deficiency, a clinical score, and/or type I hyperlipoproteinemia determined in 25 patients. RESULTS: Twenty-four biallelic variants were analyzed. Evidence-based criteria allowed the reclassification of 8 likely pathogenic (LP) variants in the LPL, APOA5, and LMF1 genes into pathogenic (P) and the change of 2 variants of uncertain significance (VUS) to LP. Conversely, 2 variations in LMF1 remained as VUS. Additionally, 1 variant in LPL and 2 in GPIHBP1 were likely benign. Twenty FCS cases had biallelic P/LP variants and 1 patient, with an FCS phenotype, harbored biallelic VUS. FCS was excluded from 4 patients with pathogenic/likely benign combinations. CONCLUSION: The analysis of the clinical and biochemical features of patients with variants in the FCS canonical genes allowed a confident variant classification that helped in the diagnosis of novel FCS cases.

Humans↗

Predictors of adverse outcome among patients with hypertension and coronary artery disease.

OBJECTIVES: We sought to determine predictors for adverse outcomes in hypertensive patients with coronary artery disease (CAD). BACKGROUND: Factors leading to adverse outcomes in hypertensive patients with CAD are poorly understood. The INternational VErapamil-trandolapril STudy (INVEST) compared outcomes in hypertensive patients with CAD that were assigned randomly to either a verapamil sustained-release (SR)- or an atenolol-based strategy for blood pressure (BP) control. Trandolapril and hydrochlorothiazide were used as added agents. During follow-up (61,835 patient-years), BP control and the primary outcome (death, nonfatal myocardial infarction, and nonfatal stroke) were not different between strategies. METHODS: We investigated risk for adverse outcome associated with baseline factors, follow-up BP, and drug treatments using Cox modeling. RESULTS: Previous heart failure (adjusted hazard ratio [HR] 1.96), as well as diabetes (HR 1.77), increased age (HR 1.63), U.S. residency (HR 1.61), renal impairment (HR 1.50), stroke/transient ischemic attack (HR 1.43), smoking (HR 1.41), myocardial infarction (HR 1.34), peripheral vascular disease (HR 1.27), and revascularization (HR 1.15) predicted increased risk. Follow-up systolic BP <140 mm Hg or diastolic BP <90 mm Hg (HRs 0.82 or 0.70, respectively) and trandolapril with verapamil SR (HRs 0.78 and 0.79) were associated with reduced risk. CONCLUSIONS: In hypertensive patients with CAD, increased risk for adverse outcomes was associated with conditions related to the severity of CAD and diminished left ventricular function. Lower follow-up BP and addition of trandolapril to verapamil SR each were associated with reduced risk.

Angiotensin-Converting Enzyme Inhibitors↗

Corneal-thickness spatial profile and corneal-volume distribution: tomographic indices to detect keratoconus.

PURPOSE: To evaluate whether the corneal-thickness spatial profile and corneal-volume distribution differentiate keratoconic corneas from normal corneas using new tomography parameters. SETTING: Subspecialty cornea and refractive practice, Fluminense Federal University, Rio de Janeiro, Brazil. METHODS: Forty-six eyes diagnosed with mild to moderate keratoconus and 364 normal eyes were studied by the Pentacam Comprehensive Eye Scanner. Corneal thickness at the thinnest point and the averages of the points on 22 imaginary circles centered on the thinnest point with increased diameters at 0.4 mm steps were calculated to create a corneal-thickness spatial profile. Corneal volume was calculated within diameters from 1.0 to 7.0 mm with 0.5 mm steps centered on the thinnest point to create the corneal-volume distribution. The percentage increase in thickness and the percentage increase in volume were calculated for each position of the corneal-thickness spatial profile and corneal-volume distribution from their first value. Statistical analysis was done using the Wilcoxon 2-independent-sample test to compare mean levels using S-Plus-4.0 software (MathSoft) and a normal linear model under a Bayesian frame for estimating the mean variation in thickness and volume using the BUGS 0.6 package. RESULTS: Statistically significant differences were observed between the groups (P<.05) in all positions of corneal-thickness spatial profile and corneal-volume distribution and in the percentage increase in thickness and percentage increase in volume between 3.5 mm and 7.0 mm diameters. CONCLUSIONS: Corneal-thickness spatial profile, corneal-volume distribution, percentage increase in thickness, and percentage increase in volume were different between keratoconic corneas and normal corneas and could serve as indices to diagnose keratoconus and screen refractive candidates. Further studies are necessary to evaluate whether these tomographic indices are more sensitive and specific than the classic Placido-based topography.

Cornea↗

Treatment of oil-in-water emulsions: performance of a sawdust bed filter.

The effect of operating conditions on the performance of a sawdust bed filter used for the treatment of an oil-in-water emulsion was investigated. A metalworking fluid (3 vol.% oil) was used as oil-in-water emulsion and sawdust as filter medium and sorbent. Because of the high stability of the emulsion, small amounts of inorganic salt (calcium sulphate) were mixed with the sorbent, acting as coagulant to achieve the emulsion breakdown. The influence of flow rate, bed height, temperature and the amount of coagulant salt added was studied. Experimental results show that several processes are involved in oil removal from oil-in-water emulsions, i.e. coagulation, coalescence, adsorption or straining. More than 99% of oil content in the influent stream was removed. Experimental results show that low-cost sorbents like sawdust are feasible to be used in the treatment of oil-in-water emulsions if small amounts of coagulant salts are added to the filter media.

Adsorption↗

Recovery of gallium and vanadium from gasification fly ash.

The Puertollano Integrated Coal Gasification Combined Cycle (IGCC) Power Plant (Spain) fly ash is characterized by a relatively high content of Ga and V, which occurs mainly as Ga2O3 and as Ga3+ and V3+ substituting for Al3+ in the Al-Si fly ash glass matrix. Investigations focused on evaluating the potential recovery of Ga and V from these fly ashes. Several NaOH based extraction tests were performed on the IGCC fly ash, at different temperatures, NaOH/fly ash (NaOH/FA) ratios, NaOH concentrations and extraction times. The optimal Ga extraction conditions was determined as 25 degrees C, NaOH 0.7-1 M, NaOH/FA ratio of 5 L/kg and 6 h, attaining Ga extraction yields of 60-86%, equivalent to 197-275 mg of Ga/kg of fly ash. Re-circulation of leachates increased initial Ga concentrations (25-38 mg/L) to 188-215 mg/L, while reducing both content of impurities and NaOH consumption. Carbonation of concentrated Ga leachate demonstrated that 99% of the bulk Ga content in the leachate precipitates at pH 7.4. At pH 10.5 significant proportions of impurities, mainly Al (91%), co-precipitate while >98% of the bulk Ga remains in solution. A second carbonation of the remaining solution (at pH 7.5) recovers the 98.8% of the bulk Ga. Re-dissolution (at pH 0) of the precipitate increases Ga purity from 7 to 30%, this being a suitable Ga end product for further purification by electrolysis. This method produces higher recovery efficiency than currently applied for Ga on an industrial scale. In contrast, low V extraction yields (<64%) were obtained even when using extreme alkaline extraction conditions, which given the current marked price of this element, limits considerably the feasibility of V recovery from IGCC fly ash.

Carbon↗

Photocatalytic degradation of pollutants from Elcogas IGCC power station effluents.

The aim of this work is to improve the quality of water effluents coming from Elcogas IGCC power station (Puertollano, Spain) with the purpose of fulfilling future more demanding normative, using heterogeneous photocatalytic oxidation processes (UV/H(2)O(2)/TiO(2) or ZnO). The efficiency of photocatalytic degradation for the different catalysts (TiO(2) and ZnO) was determined from the analysis of the following parameters: cyanides, formates and ammonia content. In a first stage, the influence of two parameters (initial concentration of H(2)O(2) and amount of catalyst) on the degradation kinetics of cyanides and formates was studied based on a factorial experimental design. pH was always kept in a value >9.5 to avoid gaseous HCN formation. The degradation of cyanides and formates was found to follow pseudo-first order kinetics. Experimental kinetic constants were fitted using neural networks (NNs). The mathematical model reproduces experimental data within 90% of confidence and allows the simulation of the process for any value of parameters in the experimental range studied. Moreover, a measure of the saliency of the input variables was made based upon the connection weights of the neural networks, allowing the analysis of the relative relevance of each variable with respect to the others. Results showed that the photocatalytic process was effective, being the degradation rate of cyanides about five times higher when compared to removal of formates. Finally, the effect of lowering pH on the degradation of formates was evaluated after complete cyanides destruction was reached (10 min of reaction). Under the optimum conditions (pH 5.2, [H(2)O(2)]=40 g/l; [TiO(2)]=2g/l), 100% of cyanides and 92% of initial NH(3) concentration are degraded after 10 min, whereas 35 min are needed to degrade 98% of formates.

Catalysis↗

Are there any common effects in preclinical models of micro- and nanoplastic (MNP) exposure? A systematic review.

Micro- and nanoplastics (MNPs) are emerging contaminants detected in food sources and the marine food chain, raising concerns about human health. Although no causal relationship has been established between MNP exposure and specific diseases, growing evidence suggests adverse developmental, behavioral, cognitive and biochemical effects. This systematic review synthesized evidence from common preclinical neurotoxicology models, including C. elegans, D. rerio, D. melanogaster, in vitro systems and rodents, to identify convergent developmental, behavioral and biochemical outcomes. The protocol was preregistered in OSF, followed PRISMA-P guidelines, applied PICOS criteria, and assessed methodological quality using the European Commission's ToxRTool. Overall, 185 studies were included. Consistent findings showed impaired survival and disrupted development across all models. Behavioral alterations affecting anxiety, memory, learning, sociability and locomotor activity were also consistently reported. In addition, numerous studies identified disruptions in the serotonergic (5-HT) system, including changes in neurotransmitter levels, transporters and metabolic enzymes. Despite methodological heterogeneity, these findings indicate that MNP exposure produces reproducible neurodevelopmental and neurochemical alterations across experimental models. Future studies should improve methodological harmonization, strengthen cross-model comparability and identify robust biomarkers and key mechanisms underlying MNP-induced neurotoxicity, facilitating translation to human health risk assessment frameworks.

Animals↗