Different gait tasks distinguish immediate vs. long-term effects of concussion on balance control

The purpose of this study was to longitudinally compare the sensitivity of previously documented paradigms for measuring balance control during gait following a concussion. We hypothesized that gait with a concurrent cognitive task would be most sensitive to the effects of concussion on dynamic balance control. Individuals with concussion (n = 30) and matched controls (n = 30) performed a single task of level walking, attention divided walking, and an obstacle-crossing task at two heights. Testing occurred four times post-injury. Balance control during gait was assessed with whole-body center of mass and center of pressure motion. The single-task level walking task did not result in any significant differences in balance control between individuals with concussion and control subjects. Within 48 hours post-injury, individuals with concussion walked slower and allowed less motion of their center of mass in the sagittal plane when attention was divided during walking, but there were no group differences by day 6 for this task. Group differences in balance control during obstacle crossing was unremarkable during the first two testing sessions, but by day 14 individuals with concussion displayed less mediolateral motion of their center of mass. Attention divided gait is able to better distinguish gait adaptations immediately following a concussion, but obstacle crossing can be used further along in the recovery process to detect new gait adaptations.     

Tid1 functions as a tumour suppressor in head and neck squamous cell carcinoma

Human tumourous imaginal disc (Tid1), a human homologue of the Drosophila tumour suppressor protein Tid56, is involved in multiple intracellular signalling pathways such as apoptosis, cell proliferation, and cell survival. Here, we investigated the anti‐tumourigenic activity of Tid1 in head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo. Firstly, the clinical association between Tid1 expression and progression of HNSCC was explored. It was found that expression of Tid1 was negatively associated with tumour status, recurrence, and survival prognosis using immunohistochemical analysis of primary HNSCC patient tumour tissue. Secondly, ectopic expression of Tid1 in HNSCC cells was shown to significantly inhibit cell proliferation, migration, invasion, anchorage‐independent growth, and xenotransplantation tumourigenicity. Thirdly, we showed that overexpression of Tid1 attenuated EGFR activity and blocked the activation of AKT in HNSCC cells, which are known to be involved in the regulation of survival in HNSCC cells. On the other hand, ectopic expression of constitutively active AKT greatly reduced apoptosis induced by Tid1 overexpression. Together, these findings suggest that Tid1 functions as a tumour suppressor in HNSCC tumourigenesis. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Lack of association of genetic polymorphisms in the interleukin-1beta,interleukin-1 receptor antagonist,interleukin-4 and interleukin-10 genes with mitral valve prolapse in Taiwan Chinese

BACKGROUND AND AIMS OF THE STUDY: Inflammation and genetics may play a role in the pathogenesis of mitral valve prolapse (MVP). The study aim was to test whether interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4 or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in MVP among the Chinese population in Taiwan. METHODS: A group of 100 patients with MVP diagnosed echocardiographically, and 103 age- and sex-matched normal control subjects was studied. IL-1beta promoter, IL-1beta exon 5, IL-1Ra, IL-4 promoter, IL-4 intron 3 and IL-10 gene polymorphisms were identified by polymerase chain reaction-based restriction analysis. RESULTS: There was no significant difference in the distribution of genotypes and allelic frequencies between MVP cases and controls for IL-1beta promoter, IL-1beta exon 5, IL-1Ra, IL-4 promoter, IL-4 intron 3 and IL-10 gene polymorphisms. Further categorization of MVP patients into mild and severe subgroups also revealed no statistical difference in these gene polymorphisms when compared with controls. CONCLUSION: These findings suggest that the IL-1beta, IL-1Ra, IL-4 or IL-10 gene polymorphisms are not suitable genetic markers of MVP in Taiwan Chinese.     

Activation of the small GTPases, rac and cdc42, after ligation of the platelet PAR-1 receptor

Stimulation of platelet PAR-1 receptors results in the rapid (10 to 30 seconds) and extensive (30% to 40% of total) guanosine triphosphate (GTP) charging of endogenous platelet rac, previously identified as a possible key intermediate in the signal pathway between PAR-1 and actin filament barbed-end uncapping, leading to actin assembly. During PAR-1-mediated platelet activation, rac distributes from the cell interior to the cell periphery, and this reorganization is resistant to the inhibition of PI-3-kinase activity. Rac, in resting or activated platelets, is Triton X-100 soluble, suggesting that it does not form tight complexes with actin cytoskeletal proteins, though its retention in octyl-glucoside-treated platelets and ultrastructural observations of activated platelets implies that rac binds to plasma membranes, where it can interact with phosphoinositide kinases implicated in actin assembly reactions. PAR-1 stimulation also rapidly and extensively activates cdc42, though, in contrast to rac, some cdc42 associates with the actin cytoskeleton in resting platelets, and the bound fraction increases during stimulation. The differences in subcellular distribution and previous evidence showing quantitatively divergent effects of rac and cdc42 on actin nucleation in permeabilized platelets indicate different signaling roles for these GTPases.     

The association between white matter changes and development of malignant middle cerebral artery infarction: A case–control study

Disrupted blood–brain barrier (BBB) in patients with ischemic stroke plays a critical role in malignant middle cerebral artery infarction (MMI) development.Cerebral white matter changes (WMC), particularly in the deep subcortical area or in severe one, may be also underlain by disrupted BBB. It is unclear whether the presence of WMC with potential premorbid disruption of BBB makes patients susceptible to MMI. Therefore, this study aimed to clarify any putative relationship between the MMI and WMC in terms of their severity and locations.In this case–control study, patients with infarction in the middle cerebral artery territory were retrospectively reviewed. Brain magnetic resonance images were analyzed according to Fazekas scale, and identified WMC were divided into periventricular WMC (PV-WMC) and deep subcortical WMC (deep-WMC). Patients were scored as having WMC, PV-WMC, deep-WMC, severe PV-WMC, and severe deep-WMC according to the severity and locations. Patients were defined as having MMI if either a progressive conscious disturbance or signs of uncal herniation was recorded in combination with a midline shift >5 mm identified on the follow-up computed tomography.Among 297 patients admitted between July 2009 and February 2015, 92 patients were eligible for final analysis. Compared to patients without MMI, patients with MMI had a higher score of National Institutes of Health Stroke Scale, a larger infarct volume, and an increasingly greater proportion of severe PV-WMC, deep-WMC, and severe deep-WMC, respectively. After adjustment for sex, age, infarct volume, and history of hypertension, severe deep-WMC (odds ratio [OR] = 6.362, 95% confidence interval [CI] = 1.444–28.023, P = .0144) and severe PV-WMC (odds ratio = 5.608, 95% confidence interval = 1.107–28.399, P = .0372) were significantly associated with MMI development.MMI and WMC are significantly associated such that MMI development is more likely when PV-WMC or deep-WMC is more severe. We hypothesize that Fazekas scale-defined severe deep-WMC and PV-WMC may be considered as clinically approachable predictors of MMI development. These findings support that the WMC with potential premorbid disrupted BBB may make patients susceptible to MMI, and further prospective study should be conducted to clarify this hypothesis.     

Angiotensin II type 1 receptor gene adenine/cytosine1166 polymorphism is not associated with mitral valve prolapse syndrome in Taiwan Chinese.

The adenine/cytosine1166 (A/C1166) polymorphism of the angiotensin-II type 1 receptor (AGTR1) gene is presumed to be associated with mitral valve prolapse syndrome (MVPS) in Caucasians. To investigate whether a similar association exists among the Chinese population in Taiwan, 100 patients with MVP diagnosed by echocardiography and 100 normal subjects were studied by polymerase chain reaction-based restriction analysis. The difference in genotype (chi2=0.24; p=0.89) and allelic (Yates' chi2=0.06; p=0.81) frequencies between the groups were not significant. Further categorization of the MVP patients into mild and severe subgroups also revealed no statistical difference from the controls. It was concluded that A/C1166 polymorphism of the AGTR1 gene is not a suitable genetic marker of MVPS in Taiwan Chinese.