Transient Lamb Wave Velocity Determination Using Holographic Mapping of Spatial Feautres of Propagating Waves

Measurement of surface displacements resulting from acoustic wave propagation in solids has been used extensively in determining elastic properties of materials [1],[2]. Additionally, examination of acoustic wave propagation in materials has been used as a nondestructive tool in testing the integrity of structures, evaluating the size and position of bulk material defects, determining material dimensions, and in general, characterizing a number of material or structural parameters [3]</p

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva

BackgroundCorticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.MethodsWe investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.ResultsMaternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate &lt;0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P &lt; 0.05, β = 0.64, SE = 0.30).ConclusionIn our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood

Rotavirus NSP1 Inhibits NFκB Activation by Inducing Proteasome-Dependent Degradation of β-TrCP: A Novel Mechanism of IFN Antagonism

Mechanisms by which viruses counter innate host defense responses generally involve inhibition of one or more components of the interferon (IFN) system. Multiple steps in the induction and amplification of IFN signaling are targeted for inhibition by viral proteins, and many of the IFN antagonists have direct or indirect effects on activation of latent cytoplasmic transcription factors. Rotavirus nonstructural protein NSP1 blocks transcription of type I IFNα/β by inducing proteasome-dependent degradation of IFN-regulatory factors 3 (IRF3), IRF5, and IRF7. In this study, we show that rotavirus NSP1 also inhibits activation of NFκB and does so by a novel mechanism. Proteasome-mediated degradation of inhibitor of κB (IκBα) is required for NFκB activation. Phosphorylated IκBα is a substrate for polyubiquitination by a multisubunit E3 ubiquitin ligase complex, Skp1/Cul1/F-box, in which the F-box substrate recognition protein is β-transducin repeat containing protein (β-TrCP). The data presented show that phosphorylated IκBα is stable in rotavirus-infected cells because infection induces proteasome-dependent degradation of β-TrCP. NSP1 expressed in isolation in transiently transfected cells is sufficient to induce this effect. Targeted degradation of an F-box protein of an E3 ligase complex with a prominent role in modulation of innate immune signaling and cell proliferation pathways is a unique mechanism of IFN antagonism and defines a second strategy of immune evasion used by rotaviruses

Participants’ perspectives on mindfulnessbased cognitive therapy for inflammatory bowel disease: a qualitative study nested within a pilot randomised controlled trial

Background: Mindfulness-based interventions have shown to improve depression and anxiety symptoms as well as quality of life in patients with inflammatory bowel disease (IBD). However, little is known about the experiences of this group of patients participating in mindfulness interventions. This paper sets out to explore the perspectives of patients with IBD recruited to a pilot randomised controlled trial (RCT) of mindfulness-based cognitive therapy (MBCT) about the intervention. Methods: In a qualitative study nested within a parallel two-arm pilot RCT of mindfulness-based cognitive therapy for patients with IBD, two focus group interviews (using the same schedule) and a free text postal survey were conducted. Data from both were analysed using thematic analysis. Data and investigator triangulation was performed to enhance confidence in the ensuing findings. Forty-four patients with IBD were recruited to the pilot RCT from gastroenterology outpatient clinics from two Scottish NHS boards. Eighteen of these patients (ten from mindfulness intervention and eight from control group) also completed a postal survey and participated in two focus groups after completing post intervention assessments. Results: The major themes that emerged from the data were the following: perceived benefits of MBCT for IBD, barriers to attending MBCT and expectations about MBCT. Participants identified MBCT as a therapeutic, educational and an inclusive process as key benefits of the intervention. Key barriers included time and travel constraints. Conclusions: This qualitative study has demonstrated the acceptability of MBCT in a group of patients with IBD. Participants saw MBCT as a therapeutic and educational initiative that transformed their relationship with the illness. The inclusive process and shared experience of MBCT alleviated the sense of social isolation commonly associated with IBD. However, time commitment and travel were recognised as a barrier to MBCT which could potentially influence the degree of therapeutic gain from MBCT for some participants. Keywords: Inflammatory bowel disease, Mindfulness, MBCT, Focus groups, Qualitative stud

Primary brain T-cell lymphoma of the lymphoblastic type presenting as altered mental status

The authors present a case of a 56-year-old man with altered mental status. Magnetic resonance imaging (MRI) of the brain revealed non-enhancing abnormalities on T2 and FLAIR imaging in the brainstem, cerebellum, and cerebrum. Immunohistochemisty demonstrated precursor T-cell lymphoblastic lymphoma. After treatment with methotrexate, he improved clinically without focal sensorimotor deficits and with improving orientation. MRI showed almost complete resolution of brainstem and cerebral lesions. To the authors’ knowledge, there are only five previous reports of primary central nervous system T-cell lymphoblastic lymphoma. Since treatable, it deserves consideration in patients with altered mental status and imaging abnormalities that include diffuse, non-enhancing changes with increased signal on T2-weighted images

Assessment of Chronic Illness-Related Cognitive Fusion: Preliminary Development and Validation of a New Scale with an IBD Sample

Although research recognizes the advantages of creating specific content measures, no specific measure of chronic illness-related cognitive fusion had been developed to date. The current study presents the development and validation of the Cognitive Fusion Questionnaire-Chronic Illness (CFQ-CI) in a sample of inflammatory bowel disease (IBD) patients and the analysis of the role of this construct in the psychological health of those patients. Results indicated that the 7-item CFQ-CI was a unidimensional measure of cognitive fusion in patients with chronic illnesses, and that scores had adequate/good internal consistency and construct, convergent, and discriminant validity. This study also showed that chronic illness-related cognitive fusion as assessed by the CFQ-CI acted as a mediator in the association between both IBD-related symptoms and shame with quality of life. The development of the CFQ-CI may thus contribute to a better understanding of the mechanisms influencing functional outcomes in chronic illness

Individual and combined soy isoflavones exert differential effects on metastatic cancer progression

To investigate the effects soy isoflavones in established cancers, the role of genistein, daidzein, and combined soy isoflavones was studied on progression of subcutaneous tumors in nude mice created from green fluorescent protein (GFP) tagged-MDA-MB-435 cells. Following tumor establishment, mice were gavaged with vehicle or genistein or daidzein at 10 mg/kg body weight (BW) or a combination of genistein (10 mg/kg BW), daidzein (9 mg/kg BW), and glycitein (1 mg/kg BW) three times per week. Tumor progression was quantified by whole body fluorescence image analysis followed by microscopic image analysis of excised organs for metastases. Results show that daidzein increased while genistein decreased mammary tumor growth by 38 and 33% respectively, compared to vehicle. Daidzein increased lung and heart metastases while genistein decreased bone and liver metastases. Combined soy isoflavones did not affect primary tumor growth but increased metastasis to all organs tested, which include lung, liver, heart, kidney, and bones. Phosphoinositide-3-kinase (PI3-K) pathway real time PCR array analysis and western blotting of excised tumors demonstrate that genistein significantly downregulated 10/84 genes, including the Rho GTPases RHOA, RAC1, and CDC42 and their effector PAK1. Daidzein significantly upregulated 9/84 genes that regulate proliferation and protein synthesis including EIF4G1, eIF4E, and survivin protein levels. Combined soy treatment significantly increased gene and protein levels of EIF4E and decreased TIRAP gene expression. Differential regulation of Rho GTPases, initiation factors, and survivin may account for the disparate responses of breast cancers to genistein and daidzein diets. This study indicates that consumption of soy foods may increase metastasis

Integrin-Linked Kinase Overexpression and Its Oncogenic Role in Promoting Tumorigenicity of Hepatocellular Carcinoma

Background: Integrin-linked kinase (ILK) was first discovered as an integrin β1-subunit binding protein. It localizes at the focal adhesions and is involved in cytoskeleton remodeling. ILK overexpression and its dysregulated signaling cascades have been reported in many human cancers. Aberrant expression of ILK influenced a wide range of signaling pathways and cellular functions. Although ILK has been well characterized in many malignancies, its role in hepatocellular carcinoma (HCC) is still largely unknown. Methodology/Principal Findings: Quantitative PCR analysis was used to examine ILK mRNA expression in HCC clinical samples. It was shown that ILK was overexpressed in 36.9% (21/57) of HCC tissues when compared to the corresponding non-tumorous livers. The overall ILK expression level was significantly higher in tumorous tissues (P = 0.004), with a significant stepwise increase in expression level along tumor progression from tumor stage I to IV (P = 0.045). ILK knockdown stable clones were established in two HCC cell lines, BEL7402 and HLE, and were subjected to different functional assays. Knockdown of ILK significantly suppressed HCC cell growth, motility and invasion in vitro and inhibited tumorigenicity in vivo. Western blot analysis revealed a reduced phosphorylated-Akt (pAkt) at Serine-473 expression in ILK knockdown stable clones when compared to control clones. Conclusion/Significance: This study provides evidence about the clinical relevance of ILK in hepatocarcinogenesis. ILK was found to be progressively elevated along HCC progression. Here our findings also provide the first validation about the oncogenic capacity of ILK in vivo by suppressing its expression in HCC cells. The oncogenic role of ILK is implicated to be mediated by Akt pathway. © 2011 Chan et al.published_or_final_versio

Nasal Acai Polysaccharides Potentiate Innate Immunity to Protect against Pulmonary Francisella tularensis and Burkholderia pseudomallei Infections

Pulmonary Francisella tularensis and Burkholderia pseudomallei infections are highly lethal in untreated patients, and current antibiotic regimens are not always effective. Activating the innate immune system provides an alternative means of treating infection and can also complement antibiotic therapies. Several natural agonists were screened for their ability to enhance host resistance to infection, and polysaccharides derived from the Acai berry (Acai PS) were found to have potent abilities as an immunotherapeutic to treat F. tularensis and B. pseudomallei infections. In vitro, Acai PS impaired replication of Francisella in primary human macrophages co-cultured with autologous NK cells via augmentation of NK cell IFN-γ. Furthermore, Acai PS administered nasally before or after infection protected mice against type A F. tularensis aerosol challenge with survival rates up to 80%, and protection was still observed, albeit reduced, when mice were treated two days post-infection. Nasal Acai PS administration augmented intracellular expression of IFN-γ by NK cells in the lungs of F. tularensis-infected mice, and neutralization of IFN-γ ablated the protective effect of Acai PS. Likewise, nasal Acai PS treatment conferred protection against pulmonary infection with B. pseudomallei strain 1026b. Acai PS dramatically reduced the replication of B. pseudomallei in the lung and blocked bacterial dissemination to the spleen and liver. Nasal administration of Acai PS enhanced IFN-γ responses by NK and γδ T cells in the lungs, while neutralization of IFN-γ totally abrogated the protective effect of Acai PS against pulmonary B. pseudomallei infection. Collectively, these results demonstrate Acai PS is a potent innate immune agonist that can resolve F. tularensis and B. pseudomallei infections, suggesting this innate immune agonist has broad-spectrum activity against virulent intracellular pathogens