Assessment of Oxidative, Inflammatory, and Fibrinolytic Biomarkers and DNA Strand Breakage in Hypercholesterolemia

The aim of this study was to assess the levels of oxidative, inflammatory, and fibrinolytic biomarkers as well as DNA strand breakage in hypercholesterolemic subjects. Fasting glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, uric acid, total protein, albumin, apolipoprotein (Apo) A, Apo B, advanced oxidation protein products (AOPP), increased ischemia-modified albumin (IMA), ―SH, NOx, IL-6, and D-dimer levels were assessed, and DNA strand breakage was evaluated using comet assay in 38 patients with hypercholesterolemia and 20 healthy controls. Total cholesterol, triglycerides, LDL cholesterol, Apo A, Apo B, AOPP, IMA, IL-6, and D-dimer concentrations were significantly higher in subjects with hypercholesterolemia. However, NOx and plasma ―SH group concentrations were lower in hypercholesterolemic subjects, while no significant differences were observed with respect to DNA strand breakage between the two groups. Hypercholesterolemia is related to oxidative stress and inflammation. Accordingly, AOPP concentration was higher in subjects with hypercholesterolemia, and we speculate that AOPP can reflect the enhancement of protein oxidation and inflammation.     

Highly accelerated,real‐time phase‐contrast MRI using radial k‐space sampling and GROG‐GRASP reconstruction: a feasibility study in pediatric patients with congenital heart disease

Retrospective electrocardiogram‐gated, 2D phase‐contrast (PC) flow MRI is routinely used in clinical evaluation of valvular/vascular disease in pediatric patients with congenital heart disease (CHD). In patients not requiring general anesthesia, clinical standard PC is conducted with free breathing for several minutes per slice with averaging. In younger patients under general anesthesia, clinical standard PC is conducted with breath‐holding. One approach to overcome this limitation is using either navigator gating or self‐navigation of respiratory motion, at the expense of lengthening scan times. An alternative approach is using highly accelerated, free‐breathing, real‐time PC (rt‐PC) MRI, which to date has not been evaluated in CHD patients. The purpose of this study was to develop a 38.4‐fold accelerated 2D rt‐PC pulse sequence using radial k‐space sampling and compressed sensing with 1.5 × 1.5 × 6.0 mm³ nominal spatial resolution and 40 ms nominal temporal resolution, and evaluate whether it is capable of accurately measuring flow in 17 pediatric patients (aortic valve, pulmonary valve, right and left pulmonary arteries) compared with clinical standard 2D PC (either breath‐hold or free breathing). For clinical translation, we implemented an integrated reconstruction pipeline capable of producing DICOMs of the order of 2 min per time series (46 frames). In terms of association, forward volume, backward volume, regurgitant fraction, and peak velocity at peak systole measured with standard PC and rt‐PC were strongly correlated (R² > 0.76; P < 0.001). Compared with clinical standard PC, in terms of agreement, forward volume (mean difference = 1.4% (3.0% of mean)) and regurgitant fraction (mean difference = ?2.5%) were in good agreement, whereas backward volume (mean difference = ?1.1 mL (28.2% of mean)) and peak‐velocity at peak systole (mean difference = ?21.3 cm/s (17.2% of mean)) were underestimated by rt‐PC. This study demonstrates that the proposed rt‐PC with the said spatial resolution and temporal resolution produces relatively accurate forward volumes and regurgitant fractions but underestimates backward volumes and peak velocities at peak systole in pediatric patients with CHD.     

Migraine and the Risk for Stroke and Cardiovascular Disease

Numerous data have pointed to an association between migraine and cardiovascular diseases. The majority of the available data have indicated that migraine with aura can be considered a risk factor for ischemic stroke, whereas migraine without aura cannot be reliably considered as such. High frequency of attacks and a recent onset of migraine have been related to an increased ischemic stroke risk. In addition, in young subjects with ischemic stroke migraine with aura represents an independent risk factor of overall recurrent vascular events and of recurrent ischemic stroke. Also the risk of transient ischemic attack seems to be increased in migraineurs, although this issue has not been extensively investigated. Several studies have also addressed the possible association between migraine and hemorrhagic stroke. Although the results of these individual studies were conflicting, their meta-analysis showed that migraine is associated with a 1.5-fold increase in the risk of hemorrhagic stroke (including intracerebral and subarachnoid hemorrhage). Some studies have identified migraine also as a possible risk factor for cardiac vascular events while others have yielded negative results. A meta-analysis did not show an increased risk of myocardial infarction in subjects with any migraine vs no migraine but subsequently, data has pointed to an association between any migraine with cardiac ischemic disease. Migraine has also been associated by some studies with vascular mortality and with vascular diseases in regions other than the brain and the heart. Several studies have also indicated that compared with nonmigraineurs, migraineurs have a higher burden of asymptomatic white matter brain lesions and, according to some studies, also infarct-like lesions at brain magnetic resonance. The mechanisms underlying the relationship between migraine and cardiovascular disease are still unclear. The possible explanation may rely on a peculiar vascular vulnerability of migraineurs that may contribute to the pathogenesis of migraine and, in the presence of some other unknown factors may also contribute, over time, to the development of cardiovascular disease. At the moment, there are no reliable features that may indicate which subjects, across the overall migraine population, will develop vascular events and so far, no drugs are recommended for the vascular prevention in migraineurs unless other clear indications are present. In general, the acute treatment and the secondary prevention measures of a patient with stroke who has a history of migraine do not differ from that of other stroke patients. There is currently no direct evidence to support that a migraine prophylactic treatment will reduce future stroke risk in secondary prevention.     

Neuroarchitecture of the central complex of the desert locust: Tangential neurons

The central complex (CX) comprises a group of midline neuropils in the insect brain, consisting of the protocerebral bridge (PB), the upper (CBU) and lower division (CBL) of the central body and a pair of globular noduli. It receives prominent input from the visual system and plays a major role in spatial orientation of the animals. Vertical slices and horizontal layers of the CX are formed by columnar, tangential, and pontine neurons. While pontine and columnar neurons have been analyzed in detail, especially in the fruit fly and desert locust, understanding of the organization of tangential cells is still rudimentary. As a basis for future functional studies, we have studied the morphologies of tangential neurons of the CX of the desert locust Schistocerca gregaria. Intracellular dye injections revealed 43 different types of tangential neuron, 8 of the PB, 5 of the CBL, 24 of the CBU, 2 of the noduli, and 4 innervating multiple substructures. Cell bodies of these neurons were located in 11 different clusters in the cell body rind. Judging from the presence of fine versus beaded terminals, the vast majority of these neurons provide input into the CX, especially from the lateral complex (LX), the superior protocerebrum, the posterior slope, and other surrounding brain areas, but not directly from the mushroom bodies. Connections are largely subunit- and partly layer-specific. No direct connections were found between the CBU and the CBL. Instead, both subdivisions are connected in parallel with the PB and distinct layers of the noduli.     

Update on treatment in multiple sclerosis

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. In recent years, many disease-modifying therapies (DMT) have been approved for MS treatment. For this reason, a profound knowledge of the characteristics and indications of the available compounds is required to tailor the therapeutic strategy to the individual patient characteristics. This should include the mechanism of action and pharmacokinetic of the drug, the safety and efficacy profile provided by clinical trials, as well as the understanding of possible side effects. Moreover, the evolving knowledge of the disease is paving the way to new and innovative therapeutic approaches, as well as the development of new biomarkers to monitor the therapeutic response and to guide the clinician's therapeutic choices. In this review we provide a comprehensive overview on currently approved therapies in MS and the emerging evidence-based strategies to adopt for initiating, monitoring, and eventually adapting a therapeutic regimen with DMT.