The association between aortic arterial stiffness, carotid intima-media thickness and carotid plaques in community-dwelling older adults: A population-based study.

OBJECTIVE: Information on the associations among arterial stiffness, carotid intima-media thickness (cIMT) and carotid plaques as biomarkers of atherosclerosis is limited in diverse populations. We aimed to assess whether aortic pulse wave velocity (aPWV) - as a surrogate of arterial stiffness - is associated with increased cIMT and the presence of carotid plaques in a cohort of older adults of Amerindian ancestry. METHODS: Atahualpa residents aged ≥60 years (n = 320) underwent aPWV determinations, and carotid ultrasounds for cIMT and plaque assessment. Multivariate models were fitted to assess the independent association between the aPWV, and cIMT and carotid plaques, after adjusting for relevant confounders. Differences in risk factors across these biomarkers were investigated. RESULTS: Mean values of aPWV were 10.3 ± 1.8 m/s, and those of cIMT were 0.91 ± 0.21 mm (24% had a cIMT >1 mm). Carotid plaques were observed in 118 (37%) subjects. In univariate analyses, risk factors associated with an increased aPWV included age, female gender, poor physical activity and high blood pressure. An increased cIMT was associated with age, male gender, a poor diet, high blood pressure and severe tooth loss. The presence of carotid plaques was associated with increasing age, poor physical activity and high blood pressure. Multivariate models showed a significant association between aPWV and cIMT (ß: 0.028; 95% C.I.: 0.001-0.056; p = 0.047) but not between aPWV and carotid plaques (OR: 1.14; 95% C.I.: 0.83-1.56; p = 0.423). CONCLUSIONS: This study shows an independent association between aPWV and cIMT but not with carotid plaques. These biomarkers may indicate distinct phenotypes for atherosclerosis.

A Stimuli-Responsive, Binary Reagent System for Rapid Isolation of Protein Biomarkers.

Magnetic microbeads exhibit rapid separation characteristics and are widely employed for biomolecule and cell isolations in research laboratories, clinical diagnostics assays, and cell therapy manufacturing. However, micrometer particle diameters compromise biomarker recognition, which leads to long incubation times and significant reagent demands. Here, a stimuli-responsive binary reagent system is presented that combines the nanoscale benefits of efficient biomarker recognition and the microscale benefits of rapid magnetic separation. This system comprises magnetic nanoparticles and polymer-antibody (Ab) conjugates that transition from hydrophilic nanoscale reagents to microscale aggregates in response to temperature stimuli. The binary reagent system was benchmarked against Ab-labeled Dynabeads in terms of biomarker isolation kinetics, assay speed, and reagent needs. Surface plasmon resonance (SPR) measurements showed that polymer conjugation did not significantly alter the Ab's binding affinity or kinetics. ELISA analysis showed that the unconjugated Ab, polymer-Ab conjugates, and Ab-labeled Dynabeads exhibited similar equilibrium dissociation constants (Kd), ∼2 nM. However, the binary reagent system isolated HIV p24 antigen from spiked serum specimens (150 pg/mL) much more quickly than Dynabeads, which resulted in shorter binding times by tens of minutes, or about 30-50% shorter overall assay times. The binary reagent system showed improved performance because the Ab molecules were not conjugated to large, solid microparticle surfaces. This stimuli-responsive binary reagent system illustrates the potential advantages of nanoscale reagents in molecule and cell isolations for both research and clinical applications.

Nanostructured glycopolymer augmented liposomes to elucidate carbohydrate-mediated targeting.

Carbohydrate receptors on alveolar macrophages are attractive targets for receptor-mediated delivery of nanostructured therapeutics. In this study, we employed reversible addition fragmentation chain transfer polymerization to synthesize neoglycopolymers, consisting of mannose- and galactose methacrylate-based monomers copolymerized with cholesterol methacrylate for use in functional liposome studies. Glycopolymer-functional liposomes were employed to elucidate macrophage mannose receptor (CD206) and macrophage galactose-type lectin (CD301) targeting in both primary macrophage and immortal macrophage cell lines. Expression of CD206 and CD301 was observed to vary significantly between cell lines (murine alveolar macrophage, murine bone marrow-derived macrophage, RAW264.7, and MH-S), which has significant implications in in vitro targeting and uptake studies. Synthetic glycopolymers and glycopolymer augmented liposomes demonstrated specific receptor-mediated uptake in a manner dependent on carbohydrate receptor expression. These results establish a platform capable of probing endogenous carbohydrate receptor-mediated targeting via glycofunctional nanomaterials.

Review and role of plyometrics and core rehabilitation in competitive sport.

Core stability and plyometric training have become common elements of training programs in competitive athletes. Core stability allows stabilization of the spine and trunk of the body in order to allow maximal translation of force to the extremities. Plyometric training is more dynamic and involves explosive-strength training. Integration of these exercises theoretically begins with core stabilization using more static exercises, allowing safe and effective transition to plyometric exercises. Both core strengthening and plyometric training have demonstrated mixed but generally positive results on injury prevention rehabilitation of certain types of injuries. Improvement in performance compared to other types of exercise is unclear at this time. This article discusses the theory and strategy behind core stability and plyometric training; reviews the literature on injury prevention, rehabilitation of injury, and performance enhancement with these modalities; and discusses the evaluation and rehabilitation of core stability.

Association Between Pulsatile Components of Blood Pressure and Severe Tooth Loss in Rural Ecuador: The Three Villages Study.

Background: Arterial hypertension has been associated with severe tooth loss, but differential associations with individual components of blood pressure (BP) have scarcely been investigated. We assessed the independent associations between pulsatile/steady components of BP and severe tooth loss in community-dwelling adults residing in 3 rural Ecuadorian villages. Methods: Individuals aged ≥40 years living in Atahualpa, El Tambo, and Prosperidad were identified during door-to-door surveys. Data collection focused on the number of remaining teeth and measurements of pulsatile/steady components of BP. Multivariate models were fitted to assess independent associations between pulsatile/steady BP components and severe tooth loss, after adjusting for relevant covariates. Results: A total of 1543 individuals were included. Oral exams identified 426 (28%) individuals with severe tooth loss. BP levels ≥140/90 mm Hg were determined in 481 (31%) individuals. The mean pulse pressure (PP) level was 55.3 ± 19 mm Hg. For systolic BP (SBP), the mean level was 133.1 ± 23.5 mm Hg, and for diastolic BP (DBP) it was 77.8 ± 11.5 mm Hg. Univariate models showed significant associations between severe tooth loss and SBP and PP, but not with DBP. However, the significance was taken away in fully adjusted generalized linear models. Age remained as an independent significant covariate in models using SBP and PP. Causal mediation analyses disclosed that percentages of the effect of severe tooth loss mediated by age were 99.5% for SBP and 98.9% for PP. Conclusion: This study shows that age captures most of the effect of the association between pulsatile components of BP and severe tooth loss.

Sports Ultrasound: Applications Beyond the Musculoskeletal System.

BACKGROUND: Traditionally, ultrasound has been used to evaluate musculoskeletal injuries in athletes; however, ultrasound applications extend well beyond musculoskeletal conditions, many of which are pertinent to athletes. EVIDENCE ACQUISITION: Articles were identified in PubMed using the search terms ultrasound, echocardiogram, preparticipation physical examination, glycogen, focused assessment with sonography of trauma, optic nerve, and vocal cord dysfunction. No date restrictions were placed on the literature search. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: Several potential applications of nonmusculoskeletal ultrasound in sports medicine are presented, including extended Focused Assessment with Sonography for Trauma (eFAST), limited echocardiographic screening during preparticipation physical examinations, assessment of muscle glycogen stores, optic nerve sheath diameter measurements in athletes with increased intracranial pressure, and assessment of vocal cord dysfunction in athletes. CONCLUSION: Ultrasound can potentially be used to assist athletes with monitoring their muscle glycogen stores and the diagnosis of multiple nonmusculoskeletal conditions within sports medicine.

Thermodynamic and dynamic factors involved in the stability of native protein structure in amorphous solids in relation to levels of hydration.

The internal, dynamical fluctuations of protein molecules exhibit many of the features typical of polymeric and bulk small molecule glass forming systems. The response of a protein's internal molecular mobility to temperature changes is similar to that of other amorphous systems, in that different types of motions freeze out at different temperatures, suggesting they exhibit the alpha-beta-modes of motion typical of polymeric glass formers. These modes of motion are attributed to the dynamic regimes that afford proteins the flexibility for function but that also develop into the large-scale collective motions that lead to unfolding. The protein dynamical transition, T(d), which has the same meaning as the T(g) value of other amorphous systems, is attributed to the temperature where protein activity is lost and the unfolding process is inhibited. This review describes how modulation of T(d) by hydration and lyoprotectants can determine the stability of protein molecules that have been processed as bulk, amorphous materials. It also examines the thermodynamic, dynamic, and molecular factors involved in stabilizing folded proteins, and the effects typical pharmaceutical processes can have on native protein structure in going from the solution state to the solid state.

Inhibition of endothelial lipase activity by sphingomyelin in the lipoproteins.

Endothelial lipase (EL) is a major determinant of plasma HDL concentration, its activity being inversely proportional to HDL levels. Although it is known that it preferentially acts on HDL compared to LDL and VLDL, the basis for this specificity is not known. Here we tested the hypothesis that sphingomyelin, a major phospholipid in lipoproteins is a physiological inhibitor of EL, and that the preference of the enzyme for HDL may be due to low sphingomyelin/phosphatidylcholine (PtdCho) ratio in HDL, compared to other lipoproteins. Using recombinant human EL, we showed that sphingomyelin inhibits the hydrolysis of PtdCho in the liposomes in a concentration-dependent manner. While the enzyme showed lower hydrolysis of LDL PtdCho, compared to HDL PtdCho, this difference disappeared after the degradation of lipoprotein sphingomyelin by bacterial sphingomyelinase. Analysis of molecular species of PtdCho hydrolyzed by EL in the lipoproteins showed that the enzyme preferentially hydrolyzed PtdCho containing polyunsaturated fatty acids (PUFA) such as 22:6, 20:5, 20:4 at the sn-2 position, generating the corresponding PUFA-lyso PtdCho. This specificity for PUFA-PtdCho species was not observed after depletion of sphingomyelin by sphingomyelinase. These results show that sphingomyelin not only plays a role in regulating EL activity, but also influences its specificity towards PtdCho species.