The kinematics of motor imagery: comparing the dynamics of real and virtual movements

Motor imagery (MI) is a key tool for studying the cognitive functions of movement. These studies assume that movements and their MI (virtual movements) involve the same cognitive functions. The real-virtual isochrony and isometry of movements of different complexity and accuracy, and the kinematics of real and virtual movements (real-virtual spatial homology and partial isometry) were studied to test this hypothesis. Isochrony was high in complex attention-demanding tasks but not in simple or inaccurate tasks, with isometry and spatial homology also being different for different motor patterns. These data suggest that movements and their MI do not always involve the same cognitive functions, and are particularly different in simple motor tasks requiring low attention levels.     

Accuracy and clinical usefulness of the CoaguChek S and XS Point of Care devices when starting warfarin in a hospital outreach setting

Objective

To assess clinical usefulness of CoaguChek S and XS monitors to measure International Normalised Ratio (INR) when starting warfarin in community patients.

Methods

INR in consecutive patients starting warfarin plus enoxaparin was measured in the laboratory and on capillary blood at home using CoaguChek S or XS point of care (POC) devices. INR was measured daily until > 2.0 for 2 consecutive readings. Linear regression and Bland Altman plots were derived to compare POC with laboratory INR. Percentages of POC measurements within 0.5 and 0.8 units of laboratory INR <2.0, 2.0-3.5 and > 3.5 were calculated. Clinical utility was assessed using previously reported criteria.

Results

200 CoaguChek S and 337 CoaguChek XS results were obtained from 57 and 98 patients respectively and paired with laboratory values. Correlation was acceptable between CoaguChek S and laboratory INRs (r² = 0.7732), and excellent between CoaguChek XS and laboratory INRs (r² = 0.9514). Bland-Altman plots showed an increasing difference between laboratory INR above 3.0 for CoaguChek S INRs but no systematic bias with increasing CoaguChek XS INRs. 83.5% of CoaguChek S and 93.5% of CoaguChek XS INRs were within 0.5 units of laboratory INR. 90% of CoaguChek S and 99.4% of the CoaguChek XS INRs were within 0.8 units of laboratory INR. Clinical agreement occurred in 89% and 99.7% of cases by expanded criteria and 82% and 99.4% of cases by narrow criteria when using CoaguChek S and CoaguChek XS respectively.

Conclusions

The CoaguChek XS is suitable for outpatient INR monitoring when starting warfarin.     

Poor-risk high-grade gliomas in three survivors of childhood acute lymphoblastic leukaemia—an overview of causative factors and possible therapeutic options

Purpose  Malignant high-grade gliomas are the most common secondary neoplasms in children cured of acute lymphoblastic leukaemia (ALL). Although many predisposing factors exist (including systemic or intrathecal chemotherapy, young age, brain infiltration and genetic predispositions), cranial irradiation appears to be the strongest one. Methods  Three cases of secondary high-grade gliomas (two multiform glioblastomas, grade IV; one anaplastic astrocytoma, grade III) developed in ALL survivors (F–M, 1:2) 3 to 6.3 years after stopping ALL therapy according to BFM-90 trial. Results  All tumours were supratentorial, contrast-enhancing, space-occupying, highly advanced and aggressive. Possible risk factors and current therapeutic options for paediatric ALL and malignant gliomas are reviewed and discussed. Conclusions  Prognosis in secondary malignant gliomas in children is poor (overall survival of 5, 10 and 19 months) despite intense therapy. Thus, protocols for paediatric ALL reduce prophylactic cranial irradiation in favour of intrathecal and intravenous high-dose MTX. Nevertheless, ALL survivors must undergo systematic, long-term surveillance for early detection of intracranial neoplasms.     

Basal and learning task-related brain oxidative metabolism in cirrhotic rats

Hepatic encephalopathy is a neurological complication observed in patients with liver disease. Subjects with hepatic encephalopathy can develop memory alterations. In order to investigate brain oxidative metabolism in an animal model of chronic cirrhosis and its modification after spatial working memory task, we determined the neural metabolic activity of several brain limbic system regions by cytochrome oxidase (COx) histochemistry and assessed the spatial working memory in the Morris water maze of rats with cirrhosis by administration of thioacetamide. This COx histochemistry was done in cirrhotic and control rats under basal conditions and after the spatial working memory task. The histochemical results showed differences in basal COx activity between control and cirrhotic rats in hippocampal and thalamic regions. In cirrhotic rats basal COx activity was increased in the CA1 and CA3 areas of the hippocampus and reduced in the anterodorsal and anteroventral thalamic nuclei. We found impaired spatial working memory in animals with cirrhosis. These animals showed absence of metabolic activation of the CA3 hippocampal subfield and the lateral mammillary nucleus and disturbance of COx activity in the medial mammillary nucleus and the anteroventral thalamus. These findings suggest that cirrhotic rats show spatial working memory deficits that could be related to the alteration of metabolic activity of neural regions thought to be involved in the processing of spatial memories.     

Molecular profiling of the “plexinome” in melanoma and pancreatic cancer

Plexins are transmembrane high‐affinity receptors for semaphorins, regulating cell guidance, motility, and invasion. Functional evidences implicate semaphorin signals in cancer progression and metastasis. Yet, it is largely unknown whether plexin genes are genetically altered in human tumors. We performed a comprehensive gene copy analysis and mutational profiling of all nine members of the plexin gene family (plexinome), in melanomas and pancreatic ductal adenocarcinomas (PDACs), which are characterized by high metastatic potential and poor prognosis. Gene copy analysis detected amplification of PLXNA4 in melanomas, whereas copy number losses of multiple plexin genes were seen in PDACs. Somatic mutations were detected in PLXNA4, PLXNB3, and PLXNC1; providing the first evidence that these plexins are mutated in human cancer. Functional assays in cellular models revealed that some of these missense mutations result in loss of plexin function. For instance, c.1613G>A, p.R538H mutation in the extracellular domain of PLXNB3 prevented binding of the ligand Sema5A. Moreover, although PLXNA4 signaling can inhibit tumor cell migration, the mutated c.5206C>T, p.H1736Y allele had lost this activity. Our study is the first systematic analysis of the “plexinome” in human tumors, and indicates that multiple mutated plexins may be involved in cancer progression. Hum Mutat 30,1–8, 2009. © 2009 Wiley‐Liss, Inc.     

High frequency of large genomic deletions in the PCCA gene causing propionic acidemia

Mutations in either the PCCA or PCCB genes are responsible for propionic acidemia (PA), one of the most frequent organic acidemias inherited in autosomal recessive fashion. Most of the mutations detected to date in both genes are missense. In the case of PCCA deficient patients, a high number of alleles remain uncharacterized, some of them suspected to carry an exonic deletion. We have now employed multiplex ligation probe amplification (MLPA) and long-PCR in some cases to screen for genomic rearrangements in the PCCA gene in 20 patients in whom standard mutation detection techniques had failed to complete genotype analysis. Eight different deletions were found, corresponding to a frequency of 21.3% of the total PCCA alleles genotyped at our center. Two of the exonic deletions were frequent, one involving exons 3–4 and another exon 23 although in the first case two different chromosomal breakpoints were identified. Absence of exons 3 and 4 which is also the consequence of the novel splicing mutation c.231 + 1g > c present in two patients, presumably results in an in-frame deletion covering 39 aminoacids, which was expressed in a eukaryotic system confirming its pathogenicity. This work describes for the first time the high frequency of large genomic deletions in the PCCA gene, which could be due to the characteristics of the PCCA gene structure and its abundance in intronic repetitive elements. Our data underscore the need of using gene dosage analysis to complement routine genetic analysis in PCCA patients.     

Changes in the proteome and infectivity of Leishmania infantum induced by in vitro exposure to a nitric oxide donor

Leishmania species are protozoan parasites that exhibit an intracellular amastigote form within mammalian macrophages and an extracellular promastigote form inside the sandfly vector. The generation of nitric oxide (NO) upon activation of macrophages is surely the principal killing effector of intracellular amastigotes but little is known about the potential action of NO against the promastigote phase during its multiplication inside the digestive tract of the sandfly vector. Therefore, we have approached this issue by using an in vitro model to study the effect of an NO donor, 3-morpholinosydnonimine (SIN-1), on the proteome and infectivity of promastigotes of Leishmania infantum. Exposure of promastigotes to SIN-1 during its logarithmic growth phase caused a dramatic effect on parasite protein expression and viability, consequently killing about 60-70% of the promastigotes. The significant changes in the proteome included the over-expression of enolase, peroxidoxin precursors, and heat-shock protein 70 (HSP70), under-expression of 20S proteasome alpha 5 unit, and phosphomannomutase and induced expression of 3-hydroxy-3-methyglutaryl-CoA (HMG-CoA) synthase and prostaglandine f2-alpha (PGD2) synthase. Interestingly, promastigotes that resisted treatment showed enhanced infectivity to J774 macrophages in comparison to the controls. This finding together with the appearance of the PGD2S and an over-expression of HSP70 isoforms in treated promastigotes led us to speculate the existence of NO-mediated programmed cell death (PCD) events as a potential mechanism of population regulation and selection of properly infecting forms that predominantly operate on the promastigote stage.     

Cystatin C Associates with Arterial Stiffness in Older Adults

Large arteries commonly become stiff in kidney failure, but few studies have investigated arterial stiffness in earlier stages of kidney disease. We evaluated the association between kidney function and aortic pulse wave velocity (aPWV) and its potential modification by race, diabetes, or coronary heart disease in older adults. We measured aPWV in 2468 participants in the Health Aging and Body Composition (Health ABC) study; mean age was 73.7 yr, 40% were black, and 24% had diabetes. After categorizing kidney function into three groups on the basis of cystatin C level, multivariable analysis revealed that the medium and high cystatin C groups associated with a 5.3% (95% confidence interval 0.8 to 10.0%) and 8.0% (95% confidence interval 2.2 to 14.1%) higher aPWV than the low cystatin C group; however, chronic kidney disease, as defined by estimated GFR <60 ml/min per 1.73 m², did not significantly associate with aPWV. We did not identify interactions between cystatin C and race, diabetes, or coronary heart disease. In conclusion, stiffness of large arteries, a major risk factor for cardiovascular disease, may partially mediate the association between cystatin C and cardiovascular risk in older adults.Cardiovascular disease (CVD) is the primary cause of mortality in patients with kidney failure, accounting for >50% of deaths. Large vessel arterial stiffness is believed to be one of the mechanisms underlying this elevated risk. Recent studies have demonstrated that dialysis patients have less compliant arteries compared with control subjects matched for age and blood pressure (BP).¹ Furthermore, both pulse pressure and increased aortic pulse wave velocity (aPWV),^2,3 manifestations of large vessel stiffness, are independent risk factors for adverse outcomes in this population.Recent studies have demonstrated that even mildly decreased kidney function is a powerful and independent risk factor for CVD outcomes.^4–6 One candidate explanation for this association is that individuals with early stages of kidney disease may have abnormalities in large arterial compliance. This mechanism could be important in older adults, who have increased risk for both kidney disease and CVD.The Health Aging and Body Composition (Health ABC) study is an ideal cohort to study the association of kidney function with vascular stiffness in older adults, because the participants encompass a broad range of kidney function and have large representation of black individuals and patients with diabetes and coronary heart disease (CHD). In addition, Health ABC measured both creatinine and cystatin C at baseline. As a measure of kidney function, cystatin C offers the advantage of not being influenced to the same extent as serum creatinine by gender, race, and muscle mass and particularly in older adults may be a better marker of kidney function.⁷ Furthermore, cystatin C has been shown to have a more linear relationship with CVD outcomes in older adults, compared with creatinine, which had a J- or U-shaped relationship.^4,6 The purpose of this study was to evaluate the association between kidney function, using both cystatin C and creatinine-based estimated GFR (eGFR), and arterial stiffness measured by aPWV in Health ABC. We also evaluated whether any associations would be modified by race, diabetes, or CHD.     

Changes in lipid profile and insulin resistance in obese patients after Scopinaro biliopancreatic diversion

Background  Obesity is associated with many cardiovascular risk factors. The aim of this study is to evaluate the effect of bariatric surgery (BS) in lipid profile and insulin resistance in obese patients. Material and Methods  We studied changes in lipid parameters glucose, insulin, and insulin resistance (IR) before biliopancreatic diversion and 3, 6, 12, 18, and 24 months after surgery, in 115 obese patients divided in two groups: diabetics (DM) and nondiabetics (non-DM). Results  In both groups, all parameters significantly decreased at 3 months; however, high-density lipoprotein cholesterol levels (HDL-c) and total cholesterol (TC) to HDL-c ratio decreased up to 6 months. At baseline, in DM, we found a negative correlation between body mass index (BMI) and TC to HDL-c ratio and glucose with HDL-c and homeostasis model assessment (HOMA) with BMI and a direct correlation between glucose with TC to HDL-c ratio and glucose with triglycerides. In non-DM, no correlations were found. Comparing both groups for each parameter, we found significant differences at basal levels for glucose, HOMA, triglycerides (TG), and TG to HDL-c ratio. Changes between basal levels and 1 year after surgery were significantly different in glucose and HOMA. Conclusion  BS offers excellent results in weight reduction and significantly improves IR, diabetes, and the lipid profile, decreasing global cardiovascular risk.