REM sleep behavior disorder and narcoleptic features in anti-Ma2-associated encephalitis

A 69-year-old man with anti-Ma2 paraneoplastic encephalitis presented with subacute onset of severe hypersomnia, memory loss, parkinsonism, and gaze palsy. A brain magnetic resonance imaging study showed bilateral damage in the dorsolateral midbrain, amygdala, and paramedian thalami. Videopolysomnography disclosed rapid eye movement (REM) sleep behavior disorder, and a Multiple Sleep Latency Test showed a mean sleep latency of 7 minutes and 4 sleep-onset REM periods. The level of hypocretin-1 in the cerebrospinal fluid was low (49 pg/mL). This observation illustrates that REM sleep behavior disorder and narcoleptic features are 2 REM-sleep abnormalities that (1) may share the same autoimmune-mediated origin affecting the brainstem, limbic, and diencephalic structures and (2) may occur in the setting of the paraneoplastic anti-Ma2-associated encephalitis.     

Therapeutic agents in perioperative third molar surgical procedures

Surgical extraction of third molars is one of the most common of all surgical procedures. The outcome of third molar surgery includes pain, trismus, edema, nausea, infection, and alveolar osteitis. The intent of this article is to provide a literature review and analysis of the various chemotherapeutic agents used to control, minimize, or eliminate these outcomes. Unfortunately, comparison of the published studies represents a tremendous challenge because of the variability in parameters and methods used for each study. A trend does exist among many of the current researchers, who realize that randomized, controlled, evidence-based research rather than personal experience is necessary to develop appropriate guidelines for using chemotherapeutic agents.     

Genetic characterization of Carnivore Parvoviruses in Spanish wildlife reveals domestic dog and cat‐related sequences

The impact of carnivore parvovirus infection on wild populations is not yet understood; disease signs are mainly developed in pups and assessing the health of litters in wild carnivores has big limitations. This study aims to shed light on the virus dynamics among wild carnivores thanks to the analysis of 213 samples collected between 1994 and 2013 in wild ecosystems from Spain. We determined the presence of carnivore parvovirus DNA by real‐time PCR and sequenced the vp2 gen from 22 positive samples to characterize the strains and to perform phylogenetic analysis. The presence of carnivore parvovirus DNA was confirmed in 18% of the samples, with a higher prevalence detected in wolves (Canis lupus signatus, 70%). Fourteen sequences belonging to nine wolves, three Eurasian badgers (Meles meles), a common genet (Genetta genetta) and a European wildcat (Felis silvestris) were classified as canine parvovirus 2c (CPV‐2c); five sequences from three wolves, a red fox (Vulpes vulpes) and a stone marten (Martes foina) as CPV‐2b; and three sequences from a badger, a genet and a stone marten as feline parvovirus (FPV). This was the first report of a wildcat infected with a canine strain. Sequences described in this study were identical or very close related to others previously found in domestic carnivores from distant countries, suggesting that cross‐species transmission takes place and that the parvovirus epidemiology in Spain, as elsewhere, could be influenced by global factors.     

Plasmin activity is required for myogenesis in vitro and skeletal muscle regeneration in vivo

Plasmin, the primary fibrinolytic enzyme, has a broad substrate spectrum and is implicated in biologic processes dependent upon proteolytic activity, such as tissue remodeling and cell migration. Active plasmin is generated from proteolytic cleavage of the zymogen plasminogen (Plg) by urokinase-type plasminogen activator (uPA) and tissue-type plasminogen activator (tPA). Here, we have investigated the role of plasmin in C2C12 myoblast fusion and differentiation in vitro, as well as in skeletal muscle regeneration in vivo, in wild-type and Plg-deficient mice. Wild-type mice completely repaired experimentally damaged skeletal muscle. In contrast, Plg(-/-) mice presented a severe regeneration defect with decreased recruitment of blood-derived monocytes and lymphocytes to the site of injury and persistent myotube degeneration. In addition, Plg-deficient mice accumulated fibrin in the degenerating muscle fibers; however, fibrinogen depletion of Plg-deficient mice resulted in a correction of the muscular regeneration defect. Because we found that uPA, but not tPA, was induced in skeletal muscle regeneration, and persistent fibrin deposition was also reproducible in uPA-deficient mice following injury, we propose that fibrinolysis by uPA-dependent plasmin activity plays a fundamental role in skeletal muscle regeneration. In summary, we identify plasmin as a critical component of the mammalian skeletal muscle regeneration process, possibly by preventing intramuscular fibrin accumulation and by contributing to the adequate inflammatory response after injury. Finally, we found that inhibition of plasmin activity with alpha2-antiplasmin resulted in decreased myoblast fusion and differentiation in vitro. Altogether, these studies demonstrate the requirement of plasmin during myogenesis in vitro and muscle regeneration in vivo.     

Bariatric surgery in morbidly obese patients improves the atherogenic qualitative properties of the plasma lipoproteins

Objective

The purpose of this study was to evaluate the effect of weight loss induced in morbidly obese subjects by Roux-en-Y gastric bypass bariatric surgery on the atherogenic features of their plasma lipoproteins.

Methods

Twenty-one morbidly obese subjects undergoing bariatric surgery were followed up for up to 1 year after surgery. Plasma and lipoproteins were assayed for chemical composition and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Lipoprotein size was assessed by non-denaturing polyacrylamide gradient gel electrophoresis, and oxidised LDL by ELISA. Liver samples were assayed for mRNA abundance of oxidative markers.

Results

Lipid profile analysis revealed a reduction in the plasma concentrations of cholesterol and triglycerides, which were mainly associated with a significant reduction in the plasma concentration of circulating apoB-containing lipoproteins rather than with changes in their relative chemical composition. All patients displayed a pattern A phenotype of LDL subfractions and a relative increase in the antiatherogenic plasma HDL-2 subfraction (>2-fold; P < 0.001). The switch towards predominantly larger HDL particles was due to an increase in their relative cholesteryl ester content. Excess weight loss also led to a significant decrease in the plasma concentration of oxidised LDL (∼−25%; P < 0.01) and in the total Lp-PLA2 activity. Interestingly, the decrease in plasma Lp-PLA2 was mainly attributed to a decrease in the apoB-containing lipoprotein-bound Lp-PLA2.

Conclusion

Our data indicate that the weight loss induced by bariatric surgery ameliorates the atherogenicity of plasma lipoproteins by reducing the apoB-containing Lp-PLA2 activity and oxidised LDL, as well as increasing the HDL-2 subfraction.     

Functional brain networks and cognitive deficits in Parkinson's disease

Graph‐theoretical analyses of functional networks obtained with resting‐state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are associated with changes in global and local network measures. Thirty‐six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting‐state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long‐range connections as well as increased local interconnectedness manifested as higher measures of clustering, small‐worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker. Hum Brain Mapp 35:4620–4634, 2014. © 2014 Wiley Periodicals, Inc .     

Changes in whole-brain functional networks and memory performance in aging

We used resting-functional magnetic resonance imaging data from 98 healthy older adults to analyze how local and global measures of functional brain connectivity are affected by age, and whether they are related to differences in memory performance. Whole-brain networks were created individually by parcellating the brain into 90 cerebral regions and obtaining pairwise connectivity. First, we studied age-associations in interregional connectivity and their relationship with the length of the connections. Aging was associated with less connectivity in the long-range connections of fronto-parietal and fronto-occipital systems and with higher connectivity of the short-range connections within frontal, parietal, and occipital lobes. We also used the graph theory to measure functional integration and segregation. The pattern of the overall age-related correlations presented positive correlations of average minimum path length (r = 0.380, p = 0.008) and of global clustering coefficients (r = 0.454, p < 0.001), leading to less integrated and more segregated global networks. Main correlations in clustering coefficients were located in the frontal and parietal lobes. Higher clustering coefficients of some areas were related to lower performance in verbal and visual memory functions. In conclusion, we found that older participants showed lower connectivity of long-range connections together with higher functional segregation of these same connections, which appeared to indicate a more local clustering of information processing. Higher local clustering in older participants was negatively related to memory performance.