Effects of footwear variations on three-dimensional kinematics and tibial accelerations of specific movements in American football

American football is associated with a high rate of non-contact chronic injuries. Players are able to select from both high and low cut footwear. The aim of the current investigation was to examine the influence of high and low cut American football specific footwear on tibial accelerations and three-dimensional (3D) kinematics during three sport specific movements. Twelve male American football players performed three movements, run, cut and vertical jump whilst wearing both low and high cut footwear. 3D kinematics of the lower extremities were measured using an eight-camera motion analysis system alongside tibial acceleration parameters which were obtained using a shank mounted accelerometer. Tibial acceleration and 3D kinematic differences between the different footwear were examined using either repeated measures or Friedman’s ANOVA. Tibial accelerations were significantly greater in the low cut footwear in comparison to the high cut footwear for the run and cut movements. In addition, peak ankle eversion and tibial internal rotation parameters were shown to be significantly greater in the low cut footwear in the running and cutting movement conditions. The current study indicates that the utilization of low cut American football footwear for training/performance may place American footballers at increased risk from chronic injuries

Cauda equina syndrome following a lumbar puncture.

Lumbar puncture (LP), a common diagnostic procedure, is usually associated with low morbidity. We describe the case of a 29-year-old woman who underwent a non-traumatic LP in the setting of normal coagulation. Cauda equina syndrome subsequently developed secondary to an extradural spinal haematoma. Avoidance, identification and management of this uncommon complication are discussed. Iatrogenic cauda equina syndrome following LP is rare, but can cause significant morbidity. Our patient's experience and our review of the literature highlight that: (i) normal coagulation and a non-traumatic LP do not exclude this diagnostic possibility; (ii) early recognition determines the management and prognosis, as 50% of patients remain paraplegic if the condition is identified more than 12 hours after symptom onset; and (iii) neurosurgical intervention can be avoided, despite bladder dysfunction, if there are early signs of recovery

A glutamine 'tug-of-war': targets to manipulate glutamine metabolism for cancer immunotherapy

Within the tumour microenvironment (TME), there is a cellular ‘tug-of-war’ for glutamine, the most abundant amino acid in the body. This competition is most evident when considering the balance between a successful anti-tumour immune response and the uncontrolled growth of tumour cells that are addicted to glutamine. The differential effects of manipulating glutamine abundance in individual cell types is an area of intense research and debate. Here, we discuss some of the current strategies in development altering local glutamine availability focusing on inhibition of enzymes involved in the utilisation of glutamine and its uptake by cells in the TME. Further studies are urgently needed to complete our understanding of glutamine metabolism, to provide critical insights into the pathways that represent promising targets and for the development of novel therapeutic strategies for the treatment of advanced or drug resistant cancers

Plasmalogens and Alzheimer's disease: a review

Abstract Growing evidence suggests that ethanolamine plasmalogens (PlsEtns), a subtype of phospholipids, have a close association with Alzheimer’s disease (AD). Decreased levels of PlsEtns have been commonly found in AD patients, and were correlated with cognition deficit and severity of disease. Limited studies showed positive therapeutic outcomes with plasmalogens interventions in AD subjects and in rodents. The potential mechanisms underlying the beneficial effects of PlsEtns on AD may be related to the reduction of γ–secretase activity, an enzyme that catalyzes the synthesis of β-amyloid (Aβ), a hallmark of AD. Emerging in vitro evidence also showed that PlsEtns prevented neuronal cell death by enhancing phosphorylation of AKT and ERK signaling through the activation of orphan G-protein coupled receptor (GPCR) proteins. In addition, PlsEtns have been found to suppress the death of primary mouse hippocampal neuronal cells through the inhibition of caspase-9 and caspase-3 cleavages. Further in-depth investigations are required to determine the signature molecular species of PlsEtns associated with AD, hence their potential role as biomarkers. Clinical intervention with plasmalogens is still in its infancy but may have the potential to be explored for a novel therapeutic approach to correct AD pathology and neural function

外耳道モデル内での超音波の音圧分布検討

電気通信大学201

Methylated DNA recognition during the reversal of epigenetic silencing is regulated by cysteine and cerine residues in the Epstein-Barr Virus lytic switch protein

Epstein-Barr virus (EBV) causes infectious mononucleosis and is associated with various malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma. Like all herpesviruses, the EBV life cycle alternates between latency and lytic replication. During latency, the viral genome is largely silenced by host-driven methylation of CpG motifs and, in the switch to the lytic cycle, this epigenetic silencing is overturned. A key event is the activation of the viral BRLF1 gene by the immediate-early protein Zta. Zta is a bZIP transcription factor that preferentially binds to specific response elements (ZREs) in the BRLF1 promoter (Rp) when these elements are methylated. Zta's ability to trigger lytic cycle activation is severely compromised when a cysteine residue in its bZIP domain is mutated to serine (C189S), but the molecular basis for this effect is unknown. Here we show that the C189S mutant is defective for activating Rp in a Burkitt's lymphoma cell line. The mutant is compromised both in vitro and in vivo for binding two methylated ZREs in Rp (ZRE2 and ZRE3), although the effect is striking only for ZRE3. Molecular modeling of Zta bound to methylated ZRE3, together with biochemical data, indicate that C189 directly contacts one of the two methyl cytosines within a specific CpG motif. The motif's second methyl cytosine (on the complementary DNA strand) is predicted to contact S186, a residue known to regulate methyl-ZRE recognition. Our results suggest that C189 regulates the enhanced interaction of Zta with methylated DNA in overturning the epigenetic control of viral latency. As C189 is conserved in many bZIP proteins, the selectivity of Zta for methylated DNA may be a paradigm for a more general phenomenon

A multi-exon deletion within WWOX is associated with a 46,XY disorder of sex development

Disorders of sex development (DSD) are congenital conditions where chromosomal, gonad or genital development is atypical. In a significant proportion of 46,XY DSD cases it is not possible to identify a causative mutation, making genetic counseling difficult and potentially hindering optimal treatment. Here, we describe the analysis of a 46,XY DSD patient that presented at birth with ambiguous genitalia. Histological analysis of the surgically removed gonads showed bilateral undifferentiated gonadal tissue and immature testis, both containing malignant germ cells. We screened genomic DNA from this patient for deletions and duplications using an Illumina whole-genome SNP microarray. This analysis revealed a heterozygous deletion within the WWOX gene on chromosome 16, removing exons 6-8. Analysis of parental DNA showed that the deletion was inherited from the mother. cDNA analysis confirmed that the deletion maintained the reading frame, with exon 5 being spliced directly onto exon 9. This deletion is the first description of a germline rearrangement affecting the coding sequence of WWOX in humans. Previously described Wwox knockout mouse models showed gonadal abnormalities, supporting a role for WWOX in human gonad development