Quantification of lipoproteins by proton nuclear magnetic resonance spectroscopy (1H-NMRS) improves the prediction of cardiac autonomic dysfunction in patients with type 1 diabetes.

AIMS: To assess if advanced characterization of serum glycoprotein and lipoprotein profile, measured by proton nuclear magnetic resonance spectroscopy (1H-NMRS) improves a predictive clinical model of cardioautonomic neuropathy (CAN) in subjects with type 1 diabetes (T1D). METHODS: Cross-sectional study (ClinicalTrials.gov Identifier: NCT04950634). CAN was diagnosed using Ewing's score. Advanced characterization of macromolecular complexes including glycoprotein and lipoprotein profiles in serum samples were measured by 1H-NMRS. We addressed the relationships between these biomarkers and CAN using correlation and regression analyses. Diagnostic performance was assessed by analyzing their areas under the receiver operating characteristic curves (AUCROC). RESULTS: Three hundred and twenty-three patients were included (46% female, mean age and duration of diabetes of 41 ± 13 years and 19 ± 11 years, respectively). The overall prevalence of CAN was 28% [95% confidence interval (95%CI): 23; 33]. Glycoproteins such as N-acetylglucosamine/galactosamine and sialic acid showed strong correlations with inflammatory markers such as high-sensitive C-reactive protein, fibrinogen, IL-10, IL-6, and TNF-α. On the contrary, we did not find any association between the former and CAN. A stepwise binary logistic regression model (R2 = 0.078; P = 0.003) retained intermediate-density lipoprotein-triglycerides (IDL-TG) [ß:0.082 (95%CI: 0.005; 0.160); P = 0.039], high-density lipoprotein-triglycerides (HDL-TGL)/HDL-Cholesterol [ß:3.633 (95%CI: 0.873; 6.394); P = 0.010], and large-HDL particle number [ß: 3.710 (95%CI: 0.677; 6.744); P = 0.001] as statistically significant determinants of CAN. Adding these lipoprotein particles to a clinical prediction model of CAN that included age, duration of diabetes, and A1c enhanced its diagnostic performance, improving AUCROC from 0.546 (95%CI: 0.404; 0.688) to 0.728 (95%CI: 0.616; 0.840). CONCLUSIONS: When added to clinical variables, 1H-NMRS-lipoprotein particle profiles may be helpful to identify those patients with T1D at risk of CAN.

A molecular dynamics study on the mechanical response of thermal-pressure rejuvenated CuxZr100-x metallic glasses.

A molecular dynamics study was performed on the mechanical response of thermal-pressure rejuvenated CuxZr100-x metallic glasses. The effect of temperature (50, 300, 600 K) and pressure (0-50 GPa) on the rejuvenation process and the mechanical properties of CuxZr100-x including stress-strain response, shear localization formation and elastic modulus were investigated. The thermal-pressure rejuvenation process involves transitioning the system to a higher potential energy state and a lower atomic volume, demonstrating the significant influence of pressure on rejuvenation. Our findings reveal that increasing pressure at specific temperatures and material compositions results in reduced yield stress and stress drop. They also indicate that with increasing pressure, the system undergoes a transition towards homogeneity, resulting in enhanced ductility compared to its initial amorphous state. Additionally, high temperatures contribute to lower values of Young's, shear, and bulk moduli, as well as decreased yield stress and stress drop. Consequently, the system becomes more homogeneous, promoting rejuvenation. Furthermore, we observed that the final yield strength of the system increases with higher Cu content for all structures at specific pressures and temperatures. The level of rejuvenation is additionally impacted by the amount of Cu, and structures containing varying content of Cu demonstrate varying degrees of rejuvenation. To validate our findings, we utilized Voronoi analysis, which revealed a higher fraction of densely-packed clusters in the samples. Finally, a total of 10 materials properties were calculated and explored using statistical analysis which shows there are different correlations between pressure, temperature and atomic composition with mechanical properties.

Particle size and cholesterol content of circulating HDL correlate with cardiovascular death in chronic heart failure.

Evidence regarding any association of HDL-particle (HDL-P) derangements and HDL-cholesterol content with cardiovascular (CV) death in chronic heart failure (HF) is lacking. To investigate the prognostic value of HDL-P size (HDL-Sz) and the number of cholesterol molecules per HDL-P for CV death in HF patients. Outpatient chronic HF patients were enrolled. Baseline HDL-P number, subfractions and HDL-Sz were measured using 1H-NMR spectroscopy. The HDL-C/P ratio was calculated as HDL-cholesterol over HDL-P. Endpoint was CV death, with non-CV death as the competing event. 422 patients were included and followed-up during a median of 4.1 (0-8) years. CV death occurred in 120 (30.5%) patients. Mean HDL-Sz was higher in CV dead as compared with survivors (8.39 nm vs. 8.31 nm, p < 0.001). This change in size was due to a reduction in the percentage of small HDL-P (54.6% vs. 60% for CV-death vs. alive; p < 0.001). HDL-C/P ratio was higher in the CV-death group (51.0 vs. 48.3, p < 0.001). HDL-Sz and HDL-C/P ratio were significantly associated with CV death after multivariable regression analysis (HR 1.22 [95% CI 1.01-1.47], p = 0.041 and HR 1.04 [95% CI 1.01-1.07], p = 0.008 respectively). HDL-Sz and HDL-C/P ratio are independent predictors of CV death in chronic HF patients.

A one-year longitudinal study of enterohemorrhagic Escherichia coli O157 fecal shedding in a beef cattle herd.

Bovines are the primary reservoir of enterohemorrhagic Escherichia coli (EHEC) O157:H7 and the main source of its transmission to humans. Here, we present a one-year longitudinal study of fecal shedding of E. coli O157. E. coli O157 obtained from recto-anal mucosal samples were characterized by multiplex PCR. The E. coli O157 prevalence ranged from 0.84% in July to 15.25% in November. The confinement within pens resulted in prevalence of 11%. Most animals (61.86%; 75/118) shed E. coli O157 at least in one sampling occasion. Of the positive animals, 82.19%, 16.44%, and 1.37% were stx positive on one, two and three sampling occasions, respectively. All the E. coli O157 isolated strains carried the genes eae and rfbO157, whereas 11%, 33% and 56% contained stx1, stx2 and stx1/stx2, respectively. The stx1/stx2 and stx2 types were significantly higher during the grazing and finishing periods, respectively, in comparison with the rearing and grazing periods. The presence of stx2a subtype was evident in four isolates, whereas stx2c was present in at least seven. However, both subtypes were present simultaneously in two isolates. The stx1/stx2c, stx1/stx2d and stx1/stx2NT genotypes occurred in 24, 2 and 15 isolates, respectively. The simultaneous occurrence of stx1 and stx2c significantly increased during grazing. Some cases of within-pen and between-pen transmission occurred throughout the study. Contagion levels during in-field grazing were higher than during permanent confinement in the pens. Thus, the individual patterns of shedding varied depending on the proportion of animals shedding the bacteria within pens and the time of shedding.

LDL particle size and composition and incident cardiovascular disease in a South-European population: The Hortega-Liposcale Follow-up Study.

BACKGROUND: The association of low-density lipoprotein (LDL) particle composition with cardiovascular risk has not been explored before. The aim was to evaluate the relationship between baseline LDL particle size and composition (proportions of large, medium and small LDL particles over their sum expressed as small-LDL %, medium-LDL % and large-LDL %) and incident cardiovascular disease in a population-based study. METHODS: Direct measurement of LDL particles was performed using a two-dimensional NMR-technique (Liposcale®). LDL cholesterol was assessed using both standard photometrical methods and the Liposcale® technique in a representative sample of 1162 adult men and women from Spain. RESULTS: The geometric mean of total LDL particle concentration in the study sample was 827.2 mg/dL (95% CI 814.7, 839.8). During a mean follow-up of 12.4 ±â€¯3.3 years, a total of 159 events occurred. Medium LDL particles were positively associated with all cardiovascular disease, coronary heart disease (CHD) and stroke after adjustment for traditional risk factors and treatment. Regarding LDL particle composition, the multivariable adjusted hazard ratios for CHD for a 5% increase in medium and small LDL % by a corresponding decrease of large LDL % were 1.93 (1.55, 2.39) and 1.41 (1.14, 1.74), respectively. CONCLUSIONS: Medium LDL particles were associated with incident cardiovascular disease. LDL particles showed the strongest association with cardiovascular events when the particle composition, rather than the total concentration, was investigated. A change in baseline composition of LDL particles from large to medium and small LDL particles was associated with an increased cardiovascular risk, especially for CHD.

Effect of diets rich in either saturated fat or n-6 polyunsaturated fatty acids and supplemented with long-chain n-3 polyunsaturated fatty acids on plasma lipoprotein profiles.

BACKGROUND/OBJECTIVES: Abnormalities in lipoprotein profiles (size, distribution and concentration) play an important role in the pathobiology of atherosclerosis and coronary artery disease. Dietary fat, among other factors, has been demonstrated to modulate lipoprotein profiles. We aimed to investigate if background dietary fat (saturated, SFA versus omega-6 polyunsaturated fatty acids, n-6PUFA) was a determinant of the effects of LCn-3PUFA supplementation on lipoprotein profiles. SUBJECTS/METHODS: A randomized controlled clinical intervention trial in a parallel design was conducted. Healthy subjects (n=26) were supplemented with 400 mg eicosapentaenoic acid plus 2000 mg docosahexaenoic acid daily and randomized to consume diets rich in either SFA or n-6PUFA for a period of 6 weeks. Blood samples, collected at baseline and after 6 weeks of intervention, were assessed for plasma lipoprotein profiles (lipoprotein size, concentration and distribution in subclasses) determined using nuclear magnetic resonance spectroscopy. RESULTS: Study participants receiving the SFA or the n-6PUFA enriched diets consumed similar percentage energy from fat (41 and 42% respectively, P=0.681). However, subjects on the SFA diet consumed 50% more energy as saturated fat and 77% less as linoleic acid than those consuming the n-6PUFA diet (P<0.001). The diets rich in SFA and n-6PUFA reduced the concentration of total very-low-density lipoprotein (VLDL) particles (P<0.001, both), and their subclasses and increased VLDL (P=0.042 and P=0.007, respectively) and LDL (P=0.030 and 0.027, respectively) particle size. In addition, plasma triglyceride concentration was significantly reduced by LCn-3PUFA supplementation irrespective of the dietary fat. CONCLUSIONS: LCn-3PUFA modulated lipoprotein profiles in a similar fashion when supplemented in diets rich in either SFA or n-6PUFA.

Effect of summer intermission on skeletal muscle of adolescent soccer players.

BACKGROUND: To study the effect of some weeks of rest on three groups of adolescent soccer players, who had undergone systematic training for eleven months. EXPERIMENTAL DESIGN: Retrospective and comparative investigation; duration 4-8 weeks. SETTING: young amateur players from a Spanish football club were examined at the beginning and at the end of the summer rest period. PARTICIPANTS: 37 young soccer players aged 14, 15 and 16 years old. They were members of three football teams. INTERVENTIONS: during the rest period they were free from any training program. MEASURES: biopsies of M. vastus lateralis were taken immediately after training and after the summer holidays. The type, percentage and diameter of the fibers, as well as the enzymes of glycogen metabolism (glycogen synthase and glycogen phosphorylase), glycolysis (phosphofructokinase and lactate dehydrogenase), oxidative metabolism (succinate dehydrogenase and citrate synthase) and creatine kinase and transaminase (aspartate and alanine aminotransferase) were studied. RESULTS: Detraining had an adaptation effect, decreasing the cross-sectional area of type I and type II fibers, and decreasing the activities of creatine kinase, citrate synthase, phosphofructokinase, lactate dehydrogenase and aspartate aminotransferase. CONCLUSIONS: The results can help trainers to plan the length of the rest period between training.

[Lazarus phenomenon: spontaneous resuscitation]. / El fenómeno de lázaro: reanimación espontánea.

A 94-year-old woman undergoing surgery for simple repair of a duodenal perforation experienced a sudden massive hemorrhage (1500 mL) when the duodenum was separated from adjacent structures. Hemodynamic stability was re-established when fluids were replaced. After the abdominal wall was closed, increased amplitude of the QRS wave was observed and heart rate slowed until there was no pulse. Electromechanical dissociation (EMD) was diagnosed and cardiopulmonary resuscitation was started. When EMD persisted after 40 minutes, resuscitative measures were stopped and the ventilator was disconnected, though orotracheal intubation and arterial and electrocardiographic monitoring were maintained. After 2 or 3 minutes, heart rhythm restarted spontaneously and arterial pressure waves reappeared on the monitor. The patient progressed well for 72 hours, after which she developed septic shock and multiorgan failure, dying 18 days later. The Lazarus phenomenon may be more common than the medical literature would indicate, possibly because a large gap in our understanding of the pathophysiology of the phenomenon underlies anecdotes about "miracles". As we wait for adequate international consensus on a protocol for monitoring the withdrawal of resuscitative measures, we should act prudently before definitively certifying death. The case we report occurred during a surgical intervention in which the patient had received general anesthesia. We believe that the causes that might explain the Lazarus phenomenon are quite different in that context than they would be in a nonsurgical setting, such that it would be useful to create a national database to keep a record of such intraoperative events.

The distribution of rest periods affects performance and adaptations of energy metabolism induced by high-intensity training in human muscle.

The effect of the distribution of rest periods on the efficacy of interval sprint training is analysed. Ten male subjects, divided at random into two groups, performed distinct incremental sprint training protocols, in which the muscle load was the same (14 sessions), but the distribution of rest periods was varied. The 'short programme' group (SP) trained every day for 2 weeks, while the 'long programme' group (LP) trained over a 6-week period with a 2-day rest period following each training session. The volunteers performed a 30-s supramaximal cycling test on a cycle ergometer before and after training. Muscle biopsies were obtained from the vastus lateralis before and after each test to examine metabolites and enzyme activities. Both training programmes led to a marked increase (all significant, P < 0.05) in enzymatic activities related to glycolysis (phosphofructokinase - SP 107%, LP 68% and aldolase - SP 46%, LP 28%) and aerobic metabolism (citrate synthase - SP 38%, LP 28.4% and 3-hydroxyacyl-CoA dehydrogenase - SP 60%, LP 38.7%). However, the activity of creatine kinase (44%), pyruvate kinase (35%) and lactate dehydrogenase (45%) rose significantly (P < 0.05) only in SP. At the end of the training programme, SP had suffered a significant decrease in anaerobic ATP consumption per gram muscle (P < 0.05) and glycogen degradation (P < 0.05) during the post-training test, and failed to improve performance. In contrast, LP showed a marked improvement in performance (P < 0.05) although without a significant increase in anaerobic ATP consumption, glycolysis or glycogenolysis rate. These results indicate that high-intensity cycling training in 14 sessions improves enzyme activities of anaerobic and aerobic metabolism. These changes are affected by the distribution of rest periods, hence shorter rest periods produce larger increase in pyruvate kinase, creatine kinase and lactate dehydrogenase. However, performance did not improve in a short training programme that did not include days for recovery, which suggests that muscle fibres suffer fatigue or injury.

Failure of cesarean section to prevent intracranial hemorrhage in siblings with isoimmune neonatal thrombocytopenia.

Two siblings with isoimmune neonatal thrombocytopenia developed severe neurological sequelae secondary to intracranial hemorrhage despite delivery by cesarean section. These cases demonstrate that cesarean section alone will not prevent intracranial hemorrhage, in utero or postnatally, in isoimmune neonatal thrombocytopenia.