Tinnitus and Qigong

Subjective tinnitus is the perception of sound despite the absence of an external stimulus. This challenging sensory event affects millions of people per year. There currently is no cure for tinnitus, but there have been many different options researched to help patients manage its effects, albeit with varying efficacy. In a viral internet video, the Beating the Heavenly Drum maneuver, found in the Eastern practice of Qigong, was said to eliminate the perception of tinnitus for the participants. In this current study, the Beating the Heavenly Drum maneuver was compared to a sham maneuver and evaluated for effectiveness in relieving tinnitus. To be included in this study, participants had experienced tinnitus for at least 6 months and were not currently receiving other tinnitus care. Exclusionary criteria included a diagnosis of Post-Traumatic Stress Disorder, Traumatic Brain Injury, any neurological condition, whiplash, neck injury, or severe anxiety or depression, as determined by the Hospital Anxiety and Depression Scale. Participants completed a tinnitus case history form, Tinnitus Functional Index (TFI), Tinnitus Handicap Index (THI), and Visual Analog Scale (VAS) ranking the annoyance of their tinnitus. Participants were assigned to groups in an alternating fashion, with odd identifiers in Group 1 and even identifiers in Group 2. In Group 2, participants received the experimental maneuver (Beating the Heavenly Drum) during the first session and the sham maneuver (circles rubbed at the base of the skull) during the second. In Group 1, participants received a sham maneuver during the first session and the experimental maneuver during the second session. Within 48 hours after each session, participants completed the TFI, THI, and rated the annoyance of their tinnitus on a scale of 0 to 10 (keeping the same parameters from the VAS) via phone call. Of the twelve participants, two reported that the experimental maneuver, Qigong, was effective for tinnitus relief; while five reported the sham condition relieved their tinnitus. The remaining five participants stated that neither maneuver altered their tinnitus sensation. Across all participants, there were no significant difference scores on the THI, and only one significant difference score on the TFI. While participants reported some change in their tinnitus with either maneuver, none of the questionnaire measures corroborated their subjective report. Additionally, the sham maneuver was perceived as more effective than the experimental maneuver. The Qigong maneuver was not effective for tinnitus relief in this study. It should be noted that a limitation to this study is the small sample size. While this Qigong maneuver did not relieve tinnitus, there are other Internet tinnitus “cures” that should be investigated for their effectiveness in tinnitus relief. With the rise of the Internet and more patients searching for “quick fixes” to tinnitus, it is vital that clinicians provide appropriate education and research to best help patients manage their tinnitus

Quantitative Imaging of Protein-Protein Interactions by Multiphoton Fluorescence Lifetime Imaging Microscopy using a Streak camera

Fluorescence Lifetime Imaging Microscopy (FLIM) using multiphoton excitation techniques is now finding an important place in quantitative imaging of protein-protein interactions and intracellular physiology. We review here the recent developments in multiphoton FLIM methods and also present a description of a novel multiphoton FLIM system using a streak camera that was developed in our laboratory. We provide an example of a typical application of the system in which we measure the fluorescence resonance energy transfer between a donor/acceptor pair of fluorescent proteins within a cellular specimen.Comment: Overview of FLIM techniques, StreakFLIM instrument, FRET application

Hierarchically Porous ZSM-5 Synthesized by Nonionic- and Cationic-Templating Routes and Their Catalytic Activity in Liquid-Phase Esterification

Hierarchically porous MFI zeolites (ZSM-5) have been synthesized by hydrothermal treatment in the presence of trialkoxysilylated-derivatives of nonionic poly(oxyethylene) alkyl ether or alkyl quaternary ammonium cation as mesopore-generating agent, along with tetrapropylammonium cation as zeolite structure-directing agent. Powder X-ray diffraction revealed that zeolites have been crystallized, and scanning electron microscopy showed rugged surface morphology that was quite different from conventional ZSM-5. The mesoporosity was confirmed by nitrogen adsorption-desorption measurement showing type IV isotherms with narrow distribution of mesopore diameters. The catalytic activity of these mesoporous ZSM-5 was tested in liquid-phase esterification of benzyl alcohol with hexanoic acid. The conversion of benzyl alcohol on mesoporous ZSM-5 prepared via cationic-templating route was almost 100%, being much higher than on mesoporous ZSM-5 prepared with silylated nonionic surfactant as well as on conventional ZSM-5 with no mesopores. The presence of Brønsted acid sites, together with the mesopores, was responsible for this catalytic conversion, as confirmed by pyridine adsorption monitored by in situ infrared and 27Al magic angle spinning nuclear magnetic resonance spectroscopy

Sub-clinical diabetic cardiomyopathy - assessment by systolic time intervals

Left ventricular performance in diabetics wit he at hypertension, ischemic Tie art disease, or clinical evidence of other heart diseases was assessed by systolic time intervals and echo-cardiography. The PEP/ LVET ratio was 3.48% higher in diabetics than in controls. There was good correlation of abnormality of PEP/LVET ratio with duration of diabetes. There was no correlation with age of patient or severity of diabetes. There was good correlation between abnormal PEP/LVET and incidence of retinopathy and nephropathy. This suggests the possibility of the presence of subclinical diabetic cardiomyopathy in these individuals

Defects in Friction Stir Welding of Steel

Defects associated with friction stir welding of two steel grades including DH36 and EH46 were investigated. Different welding parameters including tool rotational and tool traverse (linear) speeds were applied to understand their effect on weld seam defects including microcracks and voids formation. SEM images and infinite focus microscopy were employed to identify the defects types. Two new defects associated with the friction stir welding process are introduced in this work. The first defect identified in this work is a microcrack found between the plunge and the steady state region and attributed to the traverse moving of the tool with unsuitable speed from the plunge-dwell to the steady state stage. The tool traverse speed has recommended to travel 20 mm more with accelerated velocity range of 0.1 from the maximum traverse speed until reaching the steady state. The maximum recommended traverse speed in the steady state was also suggested to be less than 400 mm/min in order to avoid the lack in material flow. The second type of defect observed in this work was microcracks inside the stirred zone caused by elemental precipitations of TiN. The precipitates of TiN were attributed to the high tool rotational speed which caused the peak temperature to exceed 1200 °C at the top of the stirred zone and based on previous work. The limit of tool rotational speed was recommended to be maintained in the range of 200-500 RPM based on the mechanical experiments on the FSW samples

The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

Development of a Multiphoton Fluorescence Lifetime Imaging Microscopy (FLIM) system using a Streak Camera

We report the development and detailed calibration of a multiphoton fluorescence lifetime imaging system (FLIM) using a streak camera. The present system is versatile with high spatial (0.2 micron) and temporal (50 psec) resolution and allows rapid data acquisition and reliable and reproducible lifetime determinations. The system was calibrated with standard fluorescent dyes and the lifetime values obtained were in very good agreement with values reported in literature for these dyes. We also demonstrate the applicability of the system to FLIM studies in cellular specimens including stained pollen grains and fibroblast cells expressing green fluorescent protein. The lifetime values obtained matched well with those reported earlier by other groups for these same specimens. Potential applications of the present system include the measurement of intracellular physiology and Fluorescence Resonance Energy Transfer (FRET) imaging which are discussed in the context of live cell imaging

Evaluating the effectiveness of abbreviated breast MRI (abMRI) interpretation training for mammogram readers: a multi-centre study assessing diagnostic performance, using an enriched dataset

This is the final version. Available on open access from BMC via the DOI in this recordAvailability of data and materials: The dataset generated and analysed during the current study is not yet publicly available because it is currently being developed into a publicly shareable format. Instead, it is available from the corresponding author on reasonable request.BACKGROUND: Abbreviated breast MRI (abMRI) is being introduced in breast screening trials and clinical practice, particularly for women with dense breasts. Upscaling abMRI provision requires the workforce of mammogram readers to learn to effectively interpret abMRI. The purpose of this study was to examine the diagnostic accuracy of mammogram readers to interpret abMRI after a single day of standardised small-group training and to compare diagnostic performance of mammogram readers experienced in full-protocol breast MRI (fpMRI) interpretation (Group 1) with that of those without fpMRI interpretation experience (Group 2). METHODS: Mammogram readers were recruited from six NHS Breast Screening Programme sites. Small-group hands-on workstation training was provided, with subsequent prospective, independent, blinded interpretation of an enriched dataset with known outcome. A simplified form of abMRI (first post-contrast subtracted images (FAST MRI), displayed as maximum-intensity projection (MIP) and subtracted slice stack) was used. Per-breast and per-lesion diagnostic accuracy analysis was undertaken, with comparison across groups, and double-reading simulation of a consecutive screening subset. RESULTS: 37 readers (Group 1: 17, Group 2: 20) completed the reading task of 125 scans (250 breasts) (total = 9250 reads). Overall sensitivity was 86% (95% confidence interval (CI) 84-87%; 1776/2072) and specificity 86% (95%CI 85-86%; 6140/7178). Group 1 showed significantly higher sensitivity (843/952; 89%; 95%CI 86-91%) and higher specificity (2957/3298; 90%; 95%CI 89-91%) than Group 2 (sensitivity = 83%; 95%CI 81-85% (933/1120) p < 0.0001; specificity = 82%; 95%CI 81-83% (3183/3880) p < 0.0001). Inter-reader agreement was higher for Group 1 (kappa = 0.73; 95%CI 0.68-0.79) than for Group 2 (kappa = 0.51; 95%CI 0.45-0.56). Specificity improved for Group 2, from the first 55 cases (81%) to the remaining 70 (83%) (p = 0.02) but not for Group 1 (90-89% p = 0.44), whereas sensitivity remained consistent for both Group 1 (88-89%) and Group 2 (83-84%). CONCLUSIONS: Single-day abMRI interpretation training for mammogram readers achieved an overall diagnostic performance within benchmarks published for fpMRI but was insufficient for diagnostic accuracy of mammogram readers new to breast MRI to match that of experienced fpMRI readers. Novice MRI reader performance improved during the reading task, suggesting that additional training could further narrow this performance gap.National Institute for Health Research (NIHR

Heme Oxygenase Isoforms Differ in Their Subcellular Trafficking during Hypoxia and Are Differentially Modulated by Cytochrome P450 Reductase

Heme oxygenase (HO) degrades heme in concert with NADPH cytochrome P450 reductase (CPR) which donates electrons to the reaction. Earlier studies reveal the importance of the hydrophobic carboxy-terminus of HO-1 for anchorage to the endoplasmic reticulum (ER) which facilitates the interaction with CPR. In addition, HO-1 has been shown to undergo regulated intramembrane proteolysis of the carboxy-terminus during hypoxia and subsequent translocation to the nucleus. Translocated nuclear HO-1 was demonstrated to alter binding of transcription factors and to alter gene expression. Little is known about the homologous membrane anchor of the HO-2 isoform. The current work is the first systematic analysis in a eukaryotic system that demonstrates the crucial role of the membrane anchor of HO-2 for localization at the endoplasmic reticulum, oligomerization and interaction with CPR. We show that although the carboxy-terminal deletion mutant of HO-2 is found in the nucleus, translocation of HO-2 to the nucleus does not occur under conditions of hypoxia. Thus, we demonstrate that proteolytic regulation and nuclear translocation under hypoxic conditions is specific for HO-1. In addition we show for the first time that CPR prevents this translocation and promotes oligomerization of HO-1. Based on these findings, CPR may modulate gene expression via the amount of nuclear HO-1. This is of particular relevance as CPR is a highly polymorphic gene and deficiency syndromes of CPR have been described in humans

Apoptosis-Related Gene Expression Profiling in Hematopoietic Cell Fractions of MDS Patients

Contains fulltext : 168172.pdf (publisher's version ) (Open Access)Although the vast majority of patients with a myelodysplastic syndrome (MDS) suffer from cytopenias, the bone marrow is usually normocellular or hypercellular. Apoptosis of hematopoietic cells in the bone marrow has been implicated in this phenomenon. However, in MDS it remains only partially elucidated which genes are involved in this process and which hematopoietic cells are mainly affected. We employed sensitive real-time PCR technology to study 93 apoptosis-related genes and gene families in sorted immature CD34+ and the differentiating erythroid (CD71+) and monomyeloid (CD13/33+) bone marrow cells. Unsupervised cluster analysis of the expression signature readily distinguished the different cellular bone marrow fractions (CD34+, CD71+ and CD13/33+) from each other, but did not discriminate patients from healthy controls. When individual genes were regarded, several were found to be differentially expressed between patients and controls. Particularly, strong over-expression of BIK (BCL2-interacting killer) was observed in erythroid progenitor cells of low- and high-risk MDS patients (both p = 0.001) and TNFRSF4 (tumor necrosis factor receptor superfamily 4) was down-regulated in immature hematopoietic cells (p = 0.0023) of low-risk MDS patients compared to healthy bone marrow