Bridge functions of classical one-component plasmas.

In a recent paper, Lucco Castello et al. [arXiv:2107.03537] performed systematic extractions of classical one-component plasma bridge functions from molecular dynamics simulations and provided an accurate parametrization that was incorporated in their isomorph-based empirically modified hypernetted chain approach for Yukawa one-component plasmas. Here the extraction technique and parametrization strategy are described in detail, while the deficiencies of earlier efforts are discussed. The structural and thermodynamic predictions of the updated version of the integral equation theory approach are compared with extensive available simulation results revealing a truly unprecedented level of accuracy in the entire dense liquid region of the Yukawa phase diagram.

Integral equation theory based dielectric scheme for strongly coupled electron liquids.

In a recent paper, Lucco Castello et al. (arXiv:2107.03537) provided an accurate parameterization of classical one-component plasma bridge functions that was embedded in a novel dielectric scheme for strongly coupled electron liquids. Here, this approach is rigorously formulated, its set of equations is formally derived, and its numerical algorithm is scrutinized. A systematic comparison with available and new path integral Monte Carlo simulations reveals a rather unprecedented agreement especially in terms of the interaction energy and the long wavelength limit of the static local field correction.

Structure and thermodynamics of two-dimensional Yukawa liquids.

The thermodynamic and structural properties of two-dimensional dense Yukawa liquids are studied with molecular dynamics simulations. The "exact" thermodynamic properties are simultaneously employed in an advanced scheme for the determination of an equation of state that shows an unprecedented level of accuracy for the internal energy, pressure, and isothermal compressibility. The "exact" structural properties are utilized to formulate a novel empirical correction to the hypernetted-chain approach that leads to a very high accuracy level in terms of static correlations and thermodynamics.

Testing the isomorph invariance of the bridge functions of Yukawa one-component plasmas.

It has been recently conjectured that bridge functions remain nearly invariant along phase diagram lines of constant excess entropy for the broad class of R-simple liquids. To test this hypothesis, the bridge functions of Yukawa systems are computed outside the correlation void with the Ornstein-Zernike inversion method employing structural input from ultra-accurate molecular dynamics simulations and inside the correlation void with the cavity distribution method employing structural input from ultra-long specially designed molecular dynamics simulations featuring a tagged particle pair. Yukawa bridge functions are revealed to be isomorph invariant to a very high degree. The observed invariance is not exact, however, since isomorphic deviations exceed the overall uncertainties.

Prognostic utility of electrocardiograms in patients with hypertension older than 65 years. The PAFRES study. / Utilidad pronóstica del electrocardiograma en pacientes hipertensos mayores de 65 años. Estudio FAPRES.

OBJECTIVE: Left ventricular hypertrophy is the most common marker of target organ damage in arterial hypertension. Electrocardiograms are typically performed to identify left ventricular hypertrophy. The aim of this study was to analyse the prognostic utility of other electrocardiographic abnormalities in patients with arterial hypertension, beyond ventricular hypertrophy. MATERIALS AND METHODS: The study included 1003 patients older than 65years with arterial hypertension. We recorded risk factors, previous cardiovascular history and medical treatment and analysed various electrocardiographic abnormalities including the Sokolow-Lyon index, the Cornell index, ventricular overload and branch blocks. The study conducted a 2-year follow-up, recording the major cardiovascular events (mortality, myocardial infarction, stroke and hospitalisation for heart failure). RESULTS: The study population's mean age was 72.9±5.8years, 47.5% of whom were men. During the follow-up, 13.9% of the patients experienced a major cardiovascular event. These patients were older, more often smokers and engaged in less physical exercise, without presenting differences in the antihypertensive therapy or blood pressure control. The ventricular overload pattern (HR: 1.93; 95%CI: 1.160-3.196; P=.011) and the complete left bundle branch block (HR: 2.27; 95%CI: 1.040-4.956; P=.040) behaved as independent electrocardiographic predictors of major cardiovascular events; however, left ventricular hypertrophy using the Sokolow and/or Cornell index did not behave as such. CONCLUSIONS: For patients with hypertension, the presence in the baseline electrocardiogram of complete left bundle branch block or a pattern of ventricular overload identifies a population at increased cardiovascular risk.

Grape pomace polyphenols improve insulin response to a standard meal in healthy individuals: A pilot study.

BACKGROUND & AIMS: Dietary polyphenols have beneficial effects on glucose/lipid metabolism in subjects at high risk to develop type 2 diabetes; however, the underlying mechanisms are not clear. We aimed to evaluate: 1) the acute effects of the consumption of a drink rich in polyphenols from red grape pomace (RGPD) on glucose/insulin and triglyceride responses to a standard meal in healthy individuals, and, 2) the relationship between plasma levels of phenolic metabolites and metabolic parameters. METHODS: Twelve healthy men, aged 20-40 years participated in a randomized, controlled study according to a cross-over design. After a 3-day low-polyphenol diet, all participants consumed, on two different days and separated by a one week interval, after an overnight fast, a drink rich in polyphenols (1.562 g gallic acid equivalents (GAE)) or a control drink (CD, no polyphenols), followed after 3 h by a standard meal (960 kcal, 18% protein, 30% fat, 52% CHO). Blood samples were taken at fasting, 3 h after the drink, over 5 h after the standard meal and at fasting on the next day to measure plasma concentrations of glucose, insulin, triglyceride and phenolic metabolites. RESULTS: Glycemic and triglyceride post-meal responses were similar after both the RGPD and the control drink. In contrast, postprandial insulin incremental area (iAUC0-5h) was 31% lower (p < 0.05), insulin secretion index was 18% lower (p < 0.016) and insulin sensitivity (SI) index was 36% higher (p = 0.037) after the RGPD compared to CD. Among phenolic metabolites, gallic acid correlated inversely with the insulin response (r = -0.604; p = 0.032) and positively with the SI index (r = 0.588, p = 0.037). CONCLUSIONS: RGPD consumption acutely reduced postprandial insulin levels and improved insulin sensitivity. This effect could be likely related to the increase in gallic acid levels. This drink, added to usual diet, could contribute to increase the daily intake of polyphenols, with potential health benefits. CLINICALTRIALS. GOV IDENTIFIER: NCT02865278.

Interaction of YOYO-3 with different DNA templates to form H-aggregates.

Homodimeric cyanine dyes are DNA intercalators that display a large enhancement of fluorescence emission when bound to double-stranded DNA. However, other different interaction modes are possible, such as H-type molecular aggregates of the dye, templated by the nucleic acid. In this paper, we study in depth the formation of nonfluorescent H-aggregates of the cyanine homodimer YOYO-3 with two different DNA templates using absorption and both steady-state and time-resolved fluorescence spectroscopy. First, a nonfluorescent YOYO-3 H-aggregate complex was found to form in single-stranded polycytidine chains, resulting in the appearance of a new absorption band at approximately 500 nm. The specific interaction of cytosine bases suggests the involvement of the C-rich i-motif in facilitating the formation of the H-aggregate complex. Second, the interaction of YOYO-3 with double-stranded poly(A·T) tracts also led to the appearance of a new absorption band at approximately 500 nm, and hence of a different type of H-aggregate. We found that the aggregate is formed mainly in double-stranded regions with consecutive adenine bases in the same strand (and thymine bases in the complementary strand). These poly(A·T) tracts provide narrow minor grooves and enhanced electrostatic negative potential to promote the aggregation of the negatively charged cyanine. As the YOYO-3 H-aggregates are nonfluorescent, our results provide an important basis to quantitatively understand the fluorescence emission of this cyanine dye in the presence of DNA strands.

Statins and osteoporosis: myth or reality?

Several beneficial effects produced by statins over and above the reduction in plasma cholesterol levels, the so-called ''pleiotropic effects'' of statins, have been described. Recent clinical and experimental data have suggested a potential new effect of these drugs, namely a reduction in the risk of osteoporotic fractures. In 1999 the role of statins in bone formation was shown and, after that, observations of large groups of patients have pointed to a reduction in the risk of osteoporotic fractures with the use of statins compared to those using other lipid-lowering drugs or to the control group. The first prospective studies have produced contrasting results as to the effects of therapy with several statins (atorvastatin, fluvastatin, simvastatin) at different doses on biochemical markers of bone remodelling. To date only one randomised trial has been published. This compares the effects of treatment with simvastatin and atorvastatin on the levels of biochemical markers of bone remodelling, but still with non-univocal results: only therapy with simvastatin (but not atorvastatin) reduced the levels of bone-specific alkaline phosphatase. To conclude, observational studies have shown a reduction in the risk of osteoporotic fractures with the use of statins, but it is not yet known whether using these drugs may have a beneficial effect on bone turnover. We must therefore await larger prospective randomised clinical trials before prescribing these drugs in osteoporotic patients.

Treatment of hydrops fetalis with hemofiltration.

The treatment of hydrops fetalis, a critical state of extravascular fluid overload in the newborn, poses a great medical challenge. The aim of this study was to investigate the use of continuous arteriovenous hemofiltration (CAVH) in the treatment of five critically ill newborns with hydrops fetalis of different etiology. All patients had anasarca, oliguria not responsive to diuretics, were on mechanical ventilation, and were treated with inotropic drugs and sedation. The duration of treatment ranged from 42 to 114 h and all patients, except one who died from congenital heart disease, achieved the clinical goals of weight loss and restoration of diuresis. Regular clinical and neurological follow-up to the age of 2 years was normal for the four surviving patients. In conclusion, CAVH appears to be a safe treatment of fluid overload in newborns with hydrops fetalis.

Heparin therapy and reversal of protein-losing enteropathy in a case with congenital heart disease.

We describe a patient with tricuspid hypoplasia who developed a protein-losing enteropathy. Having failed to respond to medical and surgical treatments, a heparin regimen was started with immediate decrease in enteric protein loss.

Therapeutic effects of docosahexaenoic acid ethyl ester in patients with generalized peroxisomal disorders.

Generalized peroxisomal disorders are severe congenital diseases that involve the central nervous system, leading to severe psychomotor retardation, retinopathy, liver disease, and early death. In these disorders, peroxisomes are not normally formed and their enzymes are deficient. Characteristically, plasmalogen synthesis and beta-oxidation of very-long-chain fatty acids (VLCFAs) are affected. We found that patients with generalized peroxisomal disorders have a profound brain deficiency of docosahexaenoic acid (DHA; 22:6n-3) and low DHA concentrations in all tissues and the blood. Given the fundamental role of DHA in neuronal and retinal membranes, a DHA deficiency of this magnitude might be pathogenic. Thus, we studied the possible therapeutic effect of normalizing DHA concentrations in patients with peroxisomal disorders. We chose the DHA ethyl ester (DHA-EE) because of its high degree of purity at daily oral doses of 100-500 mg. This article summarizes the results of treatment of 13 patients with DHA-EE, with some follow-up evidence of clinical improvement. Supplementation with DHA-EE normalized blood DHA values within a few weeks. Plasmalogen concentrations increased in erythrocytes in most patients and after DHA concentrations were normalized, amounts of VLCFAs decreased in plasma. Liver enzymes returned almost to normal in most cases. From a clinical viewpoint, most patients showed improvement in vision, liver function, muscle tone, and social contact. In 3 patients, normalization of brain myelin was detected by magnetic resonance imaging. In 3 others, myelination improved. In a seventh patient, myelination is progressing at a normal rate. These results suggest a fundamental role of DHA in the pathogenesis of Zellweger syndrome. DHA therapy is thus strongly recommended, not only to alleviate symptoms in patients with life-threatening diseases, but also to clarify remaining questions regarding the role of DHA in health and disease.

The Pediatric Risk of Mortality (PRISM) Score and Injury Severity Score (ISS) for predicting resource utilization and outcome of intensive care in pediatric trauma.

OBJECTIVE: Mortality prediction in trauma is assessed using the Injury Severity Score (ISS) and Revised Trauma Score using Trauma Injury Severity Score (TRISS) methodology. The Pediatric Risk of Mortality (PRISM) score assesses mortality risk in critically ill children. We compared the ability of PRISM and ISS (using TRISS methodology) to predict resource utilization and outcome in pediatric trauma. DESIGN: Retrospective chart and database review. SETTING: Pediatric intensive care unit (PICU). PATIENTS: Consecutive admissions to a PICU over a 2-yr period. MEASUREMENTS AND MAIN RESULTS: Demographic data including PICU resource utilization and outcome were recorded. Data were recorded on 1,052 admissions (31 deaths), including 125 pediatric trauma patients (11 deaths). Patients were stratified into low- and high-risk categories based on PRISM and ISS scores. Patients with PRISM scores <6 and ISS scores <10 were classified as low risk. While both low-risk PRISM and ISS scores readily identified survivors, PRISM was the more sensitive indicator of resource utilization. PRISM, however, performed less well in determining risk-adjusted mortality as compared with ISS. CONCLUSION: PRISM readily stratifies pediatric trauma patients for resource utilization. PRISM appears to underestimate mortality in pediatric trauma as compared with ISS using TRISS methodology.

[Treatment of generalized peroxisomal disorders with docosahexaenoic acid ethyl ether]. / Tratamiento de las enfermedades peroxisomales generalizadas con etil éster del ácido docosahexaenoico.

INTRODUCTION: We found that patients with the Zellweger syndrome and other generalized peroxisomal disorders have a dramatic decrease of docosahexaenoic acid (DHA, 22:6n-3) in the blood, brain, retina and other tissues. DHA is believed to play an important role in the brain and retina. DEVELOPMENT: Patients with the Zellweger syndrome and its variants have severe cerebral and retinal defects that could be related to their DHA deficiency. With this rationale, we have been treating peroxisomal-disorder patients with a DHA derivative of a high degree of purity (DHA ethyl ester, > 90% pure) since 1991. So far, we have treated 13 DHA-deficient peroxisomal patients, one with the classic Zellweger syndrome and 12 with milder variants of the disease. This paper presents the follow-up of these DHA-treated patients. In summary, we have found important improvements in liver function, in the plasmalogen levels and in the two ratios 26:0/22:0 y 26:1/22:0, diagnostic of the disease. We have also found clear clinical improvements in most cases. Most significantly, magnetic resonance imaging has shown advances in brain myelination, so far in 6 of the treated patients. CONCLUSION: We strongly recommend treatment with DHA ethyl ester in all DHA-deficient patients with generalized peroxisomal disorders. Logically, treatment should be started as soon as possible, in the hope of preventing cerebral and visual damage.

Monitoring of brain spiking activity and autoantibodies to N-terminus domain of GluR1 subunit of AMPA receptors in blood serum of rats with cobalt-induced epilepsy.

We have monitored EEG spontaneous spiking activity and analyzed serum from rats with cobalt-induced epilepsy for the presence of autoreactive antibodies to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and ELISA with synthetic peptide specific to the N-terminus domain of the GluR1 subunit of the AMPA receptor. Rats with cobalt-induced epilepsy exhibited strong GluR1 immunoreactivity at the end of the first week after surgery compared with vehicle-treated rats. We showed that GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy preceded the spiking activity maximum in the EEG. Levels of autoantibodies to GluR1 detected in blood of these rats remained elevated when EEG spiking activity was significantly reduced and seizures disappeared. The EEG monitoring of spiking activity showed a correlation with accumulation of GluR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy.

Recurrence of the D409H mutation in Spanish Gaucher disease patients: description of a new homozygous patient and haplotype analysis.

Gaucher disease results, in most patients, from mutations in the gene encoding glucocerebrosidase. Mutation D409H is the third most frequent in Spanish patients, accounting for 5.7% of all mutated alleles. This allele is associated mainly with the neurological forms of the disease. Recently, homozygosity for the D409H mutation has been associated with a particular phenotype, including specific cardiovascular symptoms. Here we report a second Spanish patient bearing the D409H/D409H genotype with a very early manifestation of the disease. The patient started enzyme replacement therapy at 3 months of age. A common origin for the Spanish D409H alleles was ruled out by haplotype analysis using an internal polymorphism of the glucocerebrosidase gene and two external microsatellite markers.

Lessons learned from autopsies at a pediatric teaching hospital.

Twenty-six percent of pediatric patients had discrepant major diagnoses revealed at autopsy. A printed form used to document permission for autopsies improved the autopsy rate. No variables were found to predict the success rate for obtaining autopsies.