Visit-to-visit lipid variability: Clinical significance,effects of lipid-lowering treatment,and (pharmaco) genetics

In recent years, visit-to-visit variability of serum lipids has been linked to both clinical outcomes and surrogate markers for vascular disease. In this article, we present an overview of the current evidence connecting this intraindividual variability to these outcome measures, discuss its interplay with lipid-lowering treatment, and describe the literature regarding genetic factors of possible interest. In addition, we undertook an explorative genome-wide association analysis on visit-to-visit variability of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, examining additive effects in 2530 participants from the placebo arm of the PROspective Study of Pravastatin in the Elderly at Risk trial. While we identified suggestive associations (P < 1 × 10^?6) at 3 different loci (KIAA0391, amiloride-sensitive cation channel 1 neuronal [ACCN1], and Dickkopf WNT signaling pathway inhibitor 3 [DKK3]), previously published data from the genome-wide association study literature did not suggest plausible mechanistic pathways. Given the large degree of both clinical and methodological heterogeneity in the literature, additional research is needed to harmonize visit-to-visit variability parameters across studies and to definitively assess the possible role of (pharmaco)genetic factors.     

Flavivirus cell entry and membrane fusion

Flaviviruses, such as dengue virus and West Nile virus, are enveloped viruses that infect cells through receptor-mediated endocytosis and fusion from within acidic endosomes. The cell entry process of flaviviruses is mediated by the viral E glycoprotein. This short review will address recent advances in the understanding of flavivirus cell entry with specific emphasis on the recent study of Zaitseva and coworkers, indicating that anionic lipids might play a crucial role in the fusion process of dengue virus [1].     

The histopathologic features which follow repeated applications of tobacco tar to rat lip mucosa

The response of rat lip mucosa to two tobacco tar preparations combined with heat was examined histopathologically. It was shown that the magnitude of irritational hyperplasia produced was related to the level of irritation. This was greatest in those rats subjected to the longest period of application of the tobacco extract with the greatest concentration of tar combined with heating the site of application. Neoplastic changes were not produced.     

Trunk sway in patients with spinocerebellar ataxia.

We investigated whether quantified measurements of trunk sway during stance and gait tests in patients with autosomal dominant spinocerebellar ataxia (SCA) could be a useful approach to assess ataxia, which is highly relevant for adequate follow-up and future intervention studies. Examined were 11 SCA patients and 11 age-matched, healthy controls. Postural and balance control were quantified using peak-to-peak measurements of trunk angle and angular velocity, in the roll (lateral) and pitch (anterior-posterior) directions, during a battery of stance and gait tasks. In all stance tasks, trunk angle displacement and angular velocity in both the pitch and roll planes were significantly larger in the SCA group compared with the control group. Among the ataxia patients instability was more increased in the pitch than in the roll direction for two-legged stance tasks, especially when standing on foam, with pronounced oscillations in the pitch plane at 1.4 and 2.5 Hz. A similar dominance of pitch over roll instability was also observed in most gait tasks, especially for tandem gait and while walking with simultaneous head rotations. Trunk sway measurements were effective in detecting and quantifying the gait and balance abnormalities in SCA patients, suggesting that this method might be used for follow-up studies of SCA patients. Furthermore, the method might help to identify early symptomatic individuals and those patients at risk of falling. The postural instability in SCA was found to be multidirectional, although there is generally more pitch than roll instability corresponding with predominant involvement of the spinocerebellum.     

Postoperative gait deterioration after bilateral subthalamic nucleus stimulation in Parkinson's disease

Deep brain stimulation of the subthalamic nuclei (STN) is a good therapeutic option to reduce dyskinesias and improve appendicular motor signs in well‐selected patients with advanced Parkinson's disease (PD). Concerns about long‐term adverse effects play an increasingly role in the decision whether or not to refer patients for this treatment. Worsening of gait as a consequence of STN stimulation for PD has been described, but may be under‐recognized in clinical practice. The aim of this study was to evaluate the effects of STN stimulation on gait relative to global outcome in a group of consecutively operated patients. For this purpose, we used a standardized patient questionnaire that asked about global outcome and specific effects on gait, as experienced both 6 months postoperatively and currently (at the time of completing the questionnaire; mean: 2.7 +/? 1.1 years). A delayed worsening of gait after bilateral STN stimulation was experienced by a considerable proportion of patients (42% of subjects, for gait in the OFF phase), and this was apparently relatively “selective” because their global outcome scores continued to be improved. These findings highlight the presence of a hitherto poorly recognized long‐term complication of bilateral STN stimulation. Further systematic studies are required to pinpoint the clinical and surgical determinants of this late gait deterioration. © 2008 Movement Disorder Society     

Dynamics of magnetization in hyperpolarized gas MRI of the lung

The magnetization in hyperpolarized gas (HP) MRI is generated by laser polarization that is independent of the magnet and imaging process. As a consequence, there is no equilibrium magnetization during the image acquisition. The competing processes of gas inflow and depolarization of the spins lead to large changes in signal as one samples k-space. A model is developed of dynamic changes in polarization of hyperpolarized ³He during infusion and in vivo imaging of the lung and verified experimentally in a live guinea pig. Projection encoding is used to measure the view-to-view variation with temporal resolution <4 ms. Large excitation angles effectively sample the magnetization in the early stages of inflow, highlighting larger airways, while smaller excitation angles produce images of the more distal spaces. The work provides a basis for pulse sequences designed to effectively exploit HP MRI in the lung.