Markers of Increased Cardiovascular Risk in Postmenopausal Women: Focus on Oxidized-LDL and HDL Subpopulations

Objective. To evaluate the effect of gender and menopause in cardiovascular risk (CVR) in a healthy population based on both classical and nontraditional markers. Methods. 56 men and 68 women (48 pre- and 20 postmenopause) were enrolled in the study. The following markers were analyzed: blood pressure (BP), body mass index (BMI), waist circumference (WC), glucose, total cholesterol (total-c), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-c), oxidized-LDL (Ox-LDL), HDL-c and subpopulations, paraoxonase-1 activity, hsCRP, uric acid, tumor necrosis factor alpha (TNF-α), adiponectin, vascular endothelial growth factor (VEGF), and intercellular adhesion molecular 1 (ICAM1). Results. Relative to the women, men present significantly increased BMI, WC, BP, glucose, total-c, TGs, LDL-c, Ox-LDL, uric acid, and TNF-α and reduced adiponectin and total and large HDL-c. The protective profile of women is lost after menopause with a significantly increased BMI, WC, BP, glucose, LDL-c, Ox-LDL, hsCRP, and VEGF and decreased total and large HDL-c. Significant correlations were found in women population and in postmenopausal women between Ox-LDL and total, large, and small HDL-c and between TNF-α and total, large, and small HDL-c, LDL-c, and Ox-LDL. Conclusions. Men present higher CVR than women who lost protection after menopause, evidenced by nontraditional markers, including Ox-LDL and HDL subpopulations.     

Can tobacco use promote HCV-induced miR-122 hijacking and hepatocarcinogenesis?

Chronic hepatitis C virus (HCV) infection is a well-recognized risk factor for hepatocellular carcinoma (HCC). As a co-risk factor, the role of tobacco use in HCV-driven carcinogenesis and relevant underlying mechanisms remain largely unclear. The latest discoveries about HCV replication have shown that HCV RNA hijacks cellular miRNA-122 by forming an Ago2-HCV-miR-122 complex that stabilizes the HCV genome and enhances HCV replication. Our previous work has demonstrated that aqueous tobacco smoke extract (TSE) is a potent activator of HIV replication via TSE-mediated viral protection from oxidative stress and activation of a set of genes that can promote viral replication. Since HCV is, like HIV, an enveloped virus that should be equally susceptible to lipid peroxidation, and since one of the TSE-upregulated genes, the DDX3 helicase, is known to facilitate HCV replication, we hypothesize that (1) tobacco use can similarly enhance HCV viability and replication, and promote HCC progression by up-regulation of DDX3, and (2) by competing for binding with miR-122 as a competing endogenous RNA (ceRNA), HCV replication can liberate miR-122’s direct target, oncogenic gene cyclin G1 (CCNG1); furthermore, simultaneous tobacco use can synergistically enhance this competing effect via HCV upregulation. Our hypotheses may lay a foundation for better understanding of carcinogenesis in HCV-driven HCC and the potential role of tobacco as a cofactor. Disrupting the HCV ceRNA effect may provide a new strategy for designing anti HCV/HCC drugs.     

The association of health literacy with illness and medication beliefs among older adults with asthma

Objective

Suboptimal health literacy (HL) and asthma beliefs are associated with poor asthma self-management and outcomes. We tested the hypothesis that low HL is associated with inaccurate beliefs.

Methods

Asthmatics ≥60 were recruited from hospital and community practices in New York, NY and Chicago, IL (n = 420). HL was measured with the Short Test of Functional Health Literacy in Adults; validated instruments derived from the self regulation model were used to assess beliefs. The association of beliefs with HL was evaluated with multivariate models.

Results

Thirty-six percent of patients had low HL; 54% believed they only have asthma when symptoms are present, 29% believed they will not always have asthma and 20% believed that their doctor can cure asthma. HL was associated with beliefs of not having asthma all the time and that asthma can be cured (OR: 1.84, 95% CI: 1.2–2.82; OR: 2.22, 95% CI: 1.29–3.82, respectively). Patients with low HL were also more likely to be concerned about medication use (β = 0.92, p = .05), despite recognizing their necessity (β = −1.36, p = .01).

Conclusions

Older asthmatics with low HL endorse erroneous asthma beliefs.

Practice implications

Health communications for improving self-management behaviors in asthma should employ both health literacy-appropriate strategies and messages to counter illness-related misconceptions.     

Will diminishing cochlear delay affect speech perception in noise?

Objective: Normal auditory systems appear well habituated to time/phase delays inherent to sound encoding along the hearing organ, sending frequency information non-simultaneously to the central auditory system. Eliminating, or simply perturbing, the cochlear delay might be expected to decrease speech recognition ability, especially under demanding listening conditions. Resources of a larger-scale investigation permitted a preliminary examination of this issue, particularly on a relevant timescale of empirically demonstrated cochlear delays. Design: In a randomized controlled trial study, word recognition was tested for mono-syllabic tokens treated digitally to exacerbate, if not diminish/nullify, such delays. Speech-weighted noise was used to interfere with listening to time-frequency reversed (nominally no delay) versus non-reversed (natural timing) transforms under three treatments of speech tokens: (1) original-digitally recorded; digitally processed to emphasize (2) transient versus (3) quasi-steady-state components. Study sample: Ten normal-hearing young-adult females. Results: The findings failed to demonstrate statistically significant differences between delay conditions for any of the three speech-token treatments. Conclusions: An algorithm putatively diminishing frequency-dependent cochlear delays failed to systematically deteriorate performance in all subjects for the fixed time-frequency transform, stimulus parameters, and test materials employed. Yet, trends were evident such that some effect of perturbing cochlear delays could not be ruled out completely.     

Clinical Profile of Nonresponders to Surgical Myectomy with Obstructive Hypertrophic Cardiomyopathy

Background

Surgical myectomy reverses heart failure symptoms in the vast majority of obstructive hypertrophic cardiomyopathy patients. However, a small subgroup fails to experience sustained postoperative improvement despite relief of obstruction. Clinical profile of such patients has not been well defined.

Blood–spinal cord barrier disruption contributes to early motor-neuron degeneration in ALS-model mice

Humans with ALS and transgenic rodents expressing ALS-associated superoxide dismutase (SOD1) mutations develop spontaneous blood–spinal cord barrier (BSCB) breakdown, causing microvascular spinal-cord lesions. The role of BSCB breakdown in ALS disease pathogenesis in humans and mice remains, however, unclear, although chronic blood–brain barrier opening has been shown to facilitate accumulation of toxic blood-derived products in the central nervous system, resulting in secondary neurodegenerative changes. By repairing the BSCB and/or removing the BSCB-derived injurious stimuli, we now identify that accumulation of blood-derived neurotoxic hemoglobin and iron in the spinal cord leads to early motor-neuron degeneration in SOD1^G93A mice at least in part through iron-dependent oxidant stress. Using spontaneous or warfarin-accelerated microvascular lesions, motor-neuron dysfunction and injury were found to be proportional to the degree of BSCB disruption at early disease stages in SOD1^G93A mice. Early treatment with an activated protein C analog restored BSCB integrity that developed from spontaneous or warfarin-accelerated microvascular lesions in SOD1^G93A mice and eliminated neurotoxic hemoglobin and iron deposits. Restoration of BSCB integrity delayed onset of motor-neuron impairment and degeneration. Early chelation of blood-derived iron and antioxidant treatment mitigated early motor-neuronal injury. Our data suggest that BSCB breakdown contributes to early motor-neuron degeneration in ALS mice and that restoring BSCB integrity during an early disease phase retards the disease process.The blood–brain barrier (BBB) and blood–spinal cord barrier (BSCB) prevent entry of toxic circulating molecules and cells into the central nervous system (CNS) (1). Amyotrophic lateral sclerosis (ALS) is the most prominent adult motor-neuron disorder resulting in progressive motor-neuron loss in the spinal cord, brainstem, and motor cortex (2). Most ALS cases are sporadic (90%) whereas 10% are familial ALS. Over twenty independent studies in postmortem human tissue and cerebrospinal fluid (CSF) sampling from living ALS patients have established that the BBB and BSCB are damaged in familial and sporadic ALS, as reviewed elsewhere (1, 3). This BBB and BSCB disruption has been shown by spinal-cord and/or motor-cortex accumulation of different plasma proteins (e.g., IgG, fibrin, thrombin), erythrocytes, erythrocyte-derived hemoglobin and iron-containing hemosiderin, elevated CSF/serum albumin ratios, and diminished expression or degradation of the BSCB tight-junction proteins (1, 3–5). Deposition of hemoglobin-derived iron within the CNS has also been shown in ALS patients (3, 6, 7). Because human postmortem studies reflect, however, end-stage disease, it has remained unclear as to which stage of disease is enhanced by BSCB disruption. Longitudinal CSF or BSCB imaging studies have yet to be performed in living ALS patients (3) to clarify whether spinal-cord vascular dysfunction contributes to early- or late-stage disease.Transgenic rodents expressing human ALS-associated Cu/Zn superoxide dismutase (SOD1) mutations that represent 20% of all familial cases also develop a spontaneous BBB/BSCB disruption (8–12) similar to vascular pathology reported in humans (1, 3–7). Mice with a chronic BBB disruption due to aberrant signal transduction between the central nervous system endothelial cells and pericytes or astrocytes and pericytes develop a chronic BBB opening accompanied by accumulation of toxic blood-derived products in the central nervous system and secondary functional and structural neuronal changes (13–15).To determine whether BSCB disruption contributes to fatal paralytic disease caused by expression of an ALS-causing mutant, we now report how perturbing the BSCB, repairing the BSCB, and/or removing the BSCB-derived injurious stimuli influence development of disease in SOD1^G93A mice that develop a spontaneous BSCB breakdown (8, 9, 12).     

Liquid crystal self-assembly of random-sequence DNA oligomers

In biological systems and nanoscale assemblies, the self-association of DNA is typically studied and applied in the context of the evolved or directed design of base sequences that give complementary pairing, duplex formation, and specific structural motifs. Here we consider the collective behavior of DNA solutions in the distinctly different regime where DNA base sequences are chosen at random or with varying degrees of randomness. We show that in solutions of completely random sequences, corresponding to a remarkably large number of different molecules, e.g., approximately 10(12) for random 20-mers, complementary still emerges and, for a narrow range of oligomer lengths, produces a subtle hierarchical sequence of structured self-assembly and organization into liquid crystal (LC) phases. This ordering follows from the kinetic arrest of oligomer association into long-lived partially paired double helices, followed by reversible association of these pairs into linear aggregates that in turn condense into LC domains.