Functional outcome and self-perceived overall health status following surgery to remove primary brain tumor

The entire thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file; a non-technical public abstract appears in the public.pdf file.Title from PDF of title page (University of Missouri--Columbia, viewed on September 25, 2009).Thesis advisors: Dr. N. Scott Litofsky & Dr. Anand Chandrasekhar.M.S. University of Missouri--Columbia 2008.Impaired functional abilities, especially those associated with ambulation and standing balance, are common sequelae of brain tumors. A majority of research regarding the effectiveness of surgery in treating individuals with brain tumor (BT) has measured length of survival, recurrence rate, and amount of tumor removed. Objective measurements of functional abilities and self-perceived overall health status (OHS) prior to and after surgery are important aspects of treatment, yet these areas have been inadequately studied. 9 adults with diagnosis of primary brain tumor were assessed prior to, immediately following, and at 3 months after surgery using the Timed Up-and-Go (TUG) and Tinetti Performance-Oriented Mobility Assessment (Tinetti) and Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Repeated measures ANOVA demonstrated significant differences in all outcome measures from pre- to immediately post-surgery with OHS (SF-36: df=1, F=6.3, p=0.04) and physical functioning (TUG: df=1, F=6.4, p=0.05; Tinetti: df=1, F=7.2, p=0.03) and from immediately post-surgery to 3 months post-surgery, ( SF-36: df=1, F=14.8, p=0.006; TUG: df=1, F=24.3, p=0.003; Tinetti: df=1, F=39.0, p<0.001). From pre-surgery to 3 months post-surgery, no significant difference was noted for any outcome measure (SF-36: df=1, F=2.3, p=0.18; TUG: df=1, F=0.03, p=0.86); Tinetti: df=1, F=3.4, p=0.11). All measures' post-surgery scores significantly correlated post-surgery. This included the two physical functioning measures (TUG and Tinetti) immediately post-surgery (r=-0.833, p=0.01) and 3 months post-surgery (r=-0.966, p=0.0). It also included the OHS and physical functioning measures: SF-36 and TUG (r=-0.762, p=0.028) and SF-36 and Tinetti immediately post-surgery (r=0.883, p=0.002); SF-36 and TUG (r=-0.845, p=0.004), and SF-36 and Tinetti 3 months post-surgery (r=0.849, p=0.004). Physical functioning and self-perceived OHS are closely linked. It is recommended that future studies of surgery for brain tumor use measures of physical functioning and OHS. The TUG, Tinetti, and SF-36 are appropriate for these purposes.Includes bibliographical references

U94, the Human Herpesvirus 6 Homolog of the Parvovirus Nonstructural Gene, Is Highly Conserved among Isolates and Is Expressed at Low mRNA Levels as a Spliced Transcript

AbstractHuman herpesvirus 6 variants A and B (HHV-6A and HHV-6B, respectively) encode homologs (U94) of the parvovirus nonstructural gene, ns1 or rep. Here we describe the HHV-6B homolog and analyze its genetic heterogeneity and transcription. U94 nucleotide and amino acid sequences differ by approximately 3.5% and 2.5%, respectively, between HHV-6A and HHV-6B. Among a collection of 17 clinically and geographically disparate HHV-6 isolates, intravariant nucleotide and amino acid sequence divergence was less than 0.6% and 0.2%, respectively; all 13 HHV-6B isolates had identical amino acid sequences. The U94 transcript is spliced to remove a 2.6-kb intron and is expressed at very low levels relative to other HHV-6B genes, reaching approximately 10 copies per cell 3 days after infection. The mRNA has several small AUG-initiated open reading frames upstream of the U94 open reading frame, a hallmark of proteins expressed at low levels. Consistent with this, the U94-encoded protein was immunologically undetectable in HHV-6B-infected cells. The high degree of sequence conservation suggests that the gene function is nearly intolerant of sequence variation. The low abundance of U94 transcripts and the presence of encoded inefficient translation initiation suggest that the U94 protein may be required only in small amounts during infection

Detection of postoperative granulation tissue with an ICG-enhanced integrated OI-/X-ray System

<p>Abstract</p> <p>Background</p> <p>The development of postoperative granulation tissue is one of the main postoperative risks after lumbar spine surgery. This granulation tissue may lead to persistent or new clinical symptoms or complicate a follow up surgery. A sensitive non-invasive imaging technique, that could diagnose this granulation tissue at the bedside, would help to develop appropriate treatments. Thus, the purpose of this study was to establish a fast and economic imaging tool for the diagnosis of granulation tissue after lumbar spine surgery, using a new integrated Optical Imaging (OI)/X-ray imaging system and the FDA-approved fluorescent contrast agent Indocyanine Green (ICG).</p> <p>Methods</p> <p>12 male Sprague Dawley rats underwent intervertebral disk surgery. Imaging of the operated lumbar spine was done with the integrated OI/X-ray system at 7 and 14 days after surgery. 6 rats served as non-operated controls. OI/X-ray scans of all rats were acquired before and after intravenous injection of the FDA-approved fluorescent dye Indocyanine Green (ICG) at a dose of 1 mg/kg or 10 mg/kg. The fluorescence signal of the paravertebral soft tissues was compared between different groups of rats using Wilcoxon-tests. Lumbar spines and paravertebral soft tissues were further processed with histopathology.</p> <p>Results</p> <p>In both dose groups, ICG provided a significant enhancement of soft tissue in the area of surgery, which corresponded with granulation tissue on histopathology. The peak and time interval of fluorescence enhancement was significantly higher using 10 mg/kg dose of ICG compared to the 1 mg/kg ICG dose. The levels of significance were p < 0.05. Fusion of OI data with X-rays allowed an accurate anatomical localization of the enhancing granulation tissue.</p> <p>Conclusion</p> <p>ICG-enhanced OI is a suitable technique to diagnose granulation tissue after lumbar spine surgery. This new imaging technique may be clinically applicable for postoperative treatment monitoring. It could be also used to evaluate the effect of anti-inflammatory drugs and may even allow evaluations at the bedside with new hand-held OI scanners.</p

The impact of a ten-week physical exercise program on health-related quality of life in patients with inflammatory bowel disease: A prospective randomized controlled trial

BACKGROUND Improving health-related quality of life is a primary target of therapy for patients with inflammatory bowel disease. Physical activity has been demonstrated to improve health-related quality of life in several patient populations with chronic disease. There are very few studies investigating the effects of physical activity on health-related quality of life in inflammatory bowel disease. The primary purpose of this study is to investigate the effects of 10 weeks of moderate physical activity on health-related quality of life in patients with inflammatory bowel disease. METHODS Thirty patients with mild to moderate IBD (Crohn's Disease Activity Index (CDAI) \textless220 or Rachmilewitz Index (RI) \textless11) were randomized 1:1 to either supervised moderate-intensity running thrice a week for 10 weeks or a control group who were not prescribed any exercise. Health-related quality of life, symptoms, and inflammation were assessed at baseline and after 10 weeks. RESULTS Participants were 41 ± 14 years (73% female), had a body mass index of 22.8 ± 4.1 kg/m(2), and an average CDAI or RI of 66.8 ± 42.4 and 3.6 ± 3.1. No adverse events occurred during the 10-week training period. Health-related quality of life, reported as IBDQ total score, improved 19% in the intervention group and 8% in the control group. Scores for the IBDQ social sub-scale were significantly improved in the intervention group compared with controls (\textgreekDIBDQsocial = 6.27 ± 5.46 vs. 1.87 ± 4.76, p = 0.023). CONCLUSION Patients suffering from moderately active IBD are capable of performing symptom-free regular endurance exercise. Our data support the assumption that PA is feasible in IBD patients. PA may furthermore improve quality of life through improvements in social well-being, and may, therefore, be a useful adjunct to IBD therapy

Deformation Mechanisms, Microstructures, and Seismic Anisotropy of Wadsleyite in the Earth's Transition Zone

Wadsleyite is the dominant mineral of the upper portion of the Earth's mantle transition zone (MTZ). As such, understanding plastic deformation of wadsleyite is relevant for the interpretation of observations of seismic signals from this region in terms of mantle flow. Despite its relevance, however, the deformation mechanisms of wadsleyite and their effects on microstructures and anisotropy are still poorly understood. Here, we present the results of new deformation experiments on polycrystalline wadsleyite at temperatures of 1400–1770 K and pressures between 12.3 and 20.3 GPa in the laser-heated diamond anvil cell. We rely on multigrain X-ray crystallography to follow the evolution of individual grain orientations and extract lattice preferred orientations at the sample scale at different steps of the experiments. A comparison of experimental results of our work and the literature with polycrystal plasticity simulations, indicates that ⟨111⟩{101} is the most active slip system of dislocations in wadsleyite at all investigated conditions. Secondary slip systems such as [001](010), [100](001), and [100]{0kl}, however, play a critical role in the resulting microstructures and their activity depends on both temperature and water content, from which we extract an updated deformation map of wadsleyite at MTZ conditions. Lastly, we propose several seismic anisotropy models of the upper part of the MTZ, depending on temperature, geophysical context, and levels of hydration that will be useful for the interpretation of seismic signals from the MTZ in terms of mantle flow and water conten

Training practices of Filipino athletes during the early COVID-19 lockdown

The imposition of COVID-19 lockdown restricted the daily activities of many people, including athletes. This study investigated the training practices of athletes in the Philippines during the early COVID-19 lockdown. A total of 442 athletes answered an online survey (May-July 2020), with questions pertaining to training practices, such as training frequency and duration. Data were analyzed according to: athlete classification (world-class, international, national, state, or recreational), sport category (individual or team), and sex (male or female). During lockdown, significant reductions in training frequency (except recreational, i.e., lower pre-lockdown training) and duration were observed for all athletic classifications. Similarly, training frequency and duration decreased significantly irrespective of sport category and sex. World class athletes appeared to be less affected by lockdown (types of exercise and specific training) as compared to lower classification athletes. Athletes grouped in accordance with sex and sport category demonstrated little to no difference in training practices during the COVID-19 lockdown. The findings of the current study highlight the challenges experienced by athletes during lockdown, which may aid policy makers in the development of guidelines related to lockdown or lockdown-like situations to establish appropriate support for affected athletes

Immunotoxins and Anticancer Drug Conjugate Assemblies: The Role of the Linkage between Components

Immunotoxins and antibody-drug conjugates are protein-based drugs combining a target-specific binding domain with a cytotoxic domain. Such compounds are potentially therapeutic against diseases including cancer, and several clinical trials have shown encouraging results. Although the targeted elimination of malignant cells is an elegant concept, there are numerous practical challenges that limit conjugates’ therapeutic use, including inefficient cellular uptake, low cytotoxicity, and off-target effects. During the preparation of immunoconjugates by chemical synthesis, the choice of the hinge component joining the two building blocks is of paramount importance: the conjugate must remain stable in vivo but must afford efficient release of the toxic moiety when the target is reached. Vast efforts have been made, and the present article reviews strategies employed in developing immunoconjugates, focusing on the evolution of chemical linkers

Plasmacytoid Dendritic Cells Sequester High Prion Titres at Early Stages of Prion Infection

In most transmissible spongiform encephalopathies prions accumulate in the lymphoreticular system (LRS) long before they are detectable in the central nervous system. While a considerable body of evidence showed that B lymphocytes and follicular dendritic cells play a major role in prion colonization of lymphoid organs, the contribution of various other cell types, including antigen-presenting cells, to the accumulation and the spread of prions in the LRS are not well understood. A comprehensive study to compare prion titers of candidate cell types has not been performed to date, mainly due to limitations in the scope of animal bioassays where prohibitively large numbers of mice would be required to obtain sufficiently accurate data. By taking advantage of quantitative in vitro prion determination and magnetic-activated cell sorting, we studied the kinetics of prion accumulation in various splenic cell types at early stages of prion infection. Robust estimates for infectious titers were obtained by statistical modelling using a generalized linear model. Whilst prions were detectable in B and T lymphocytes and in antigen-presenting cells like dendritic cells and macrophages, highest infectious titers were determined in two cell types that have previously not been associated with prion pathogenesis, plasmacytoid dendritic (pDC) and natural killer (NK) cells. At 30 days after infection, NK cells were more than twice, and pDCs about seven-fold, as infectious as lymphocytes respectively. This result was unexpected since, in accordance to previous reports prion protein, an obligate requirement for prion replication, was undetectable in pDCs. This underscores the importance of prion sequestration and dissemination by antigen-presenting cells which are among the first cells of the immune system to encounter pathogens. We furthermore report the first evidence for a release of prions from lymphocytes and DCs of scrapie-infected mice ex vivo, a process that is associated with a release of exosome-like membrane vesicles