306 research outputs found
The association between back pain and trunk posture of workers in a special school for the severe handicaps
<p>Abstract</p> <p>Background</p> <p>The present study aims to determine the time spent in different static trunk postures during a typical working day of workers in a special school for the severe handicaps.</p> <p>Methods</p> <p>Eighteen workers with low back pain (LBP) and fifteen asymptomatic workers were recruited. A cross-sectional design was employed to study the time spent in different static trunk postures which was recorded by a biaxial accelerometer attached to the T<sub>12 </sub>level of the back of the subjects.</p> <p>Results</p> <p>The results of ANCOVA revealed that subjects with LBP spent significantly longer percentage of time in static trunk posture when compared to normal (p < 0.05). It was also shown that they spent significantly longer time in trunk flexion for more than 10° (p < 0.0125).</p> <p>Conclusion</p> <p>An innovative method has been developed for continuous tracking of spinal posture, and this has potential for widespread applications in the workplace. The findings of the present investigation suggest that teachers in special schools are at increased risk of getting LBP. In order to minimise such risk, frequent postural change and awareness of work posture are recommended.</p
Genomic Structure and Chromosomal Location of the Rat Gene Encoding the Zinc Finger Transcription Factor Kid-1
We have previously cloned and sequenced a novel zinc finger cDNA, Kid-1 , from the rat. Because of its developmentally regulated expression pattern and its suppression after renal injury, as well as its kindey-predominant expression, we propose that Kid-1 is likely to play an important role in renal gene regulation. Kid-1 encodes a predicted protein with 13 zinc fingers at the carboxy end and Krüppel-associated box (KRAB) A and B regions at the amino terminus. Expression of a Kid-1-GAL4 chimeric protein results in strong transcriptional repression of cotransfected constructs containing GAL4 binding sites and a chloramphenicol acetyl transferase gene driven by either a minimal promoter or a SV40 enhancer. We now report the cloning, structural organization, and chromosomal localization of the Kid-1 gene. The Kid-1 gene is composed of four exons and three introns, closely reflecting the organization of the Kid-1 protein. The KRAB A and B regions are encoded by the second and third exons, respectively. The entire zinc finger region is encoded by the fourth exon. Using a combination of linkage analysis and somatic cell hybrid analysis, Kid-1was mapped to rat chromosome (RNO) 10. Kid-1, Il3, and Sparc form a tight linkage group on RNO10. Regional sublocalization to RNO10q21.3-q22 was established by fluorescence in situ hybridization.
Coercive Nuclear Campaigns in the 21st Century: Understanding Adversary Incentives and Options for Nuclear Escalation
FY 2012-2013. Project Leads: Lieber, Keir A. and Press, Daryl G.The project leads will examine why and how regional powers armed with nuclear weapons may employ them coercively during a conventional war. More specifically, a set of research questions will provide insight on the paths of nuclear escalation, weak state strategies of coercive escalation, and the type of targets regional powers may strike to pursue escalatory strategies.NAApproved for public release; distribution is unlimited
Sweet Syndrome due to Myelodysplastic Syndrome: Possible Therapeutic Role of Intravenous Immunoglobulin in Addition to Standard Treatment
We report an 82-year-old lady who developed sudden onset nodular and erythematous lesions and neutrophilia following an episode of urinary tract infection. Skin biopsy confirmed the diagnosis of Sweet syndrome. Response to the use of prednisolone alone was not satisfactory. The skin lesions however showed a sustained response to the regular use of intravenous immunoglobulin (IVIG) and prednisolone was slowly weaned off. Our case highlights the possible therapeutic role of IVIG in managing this condition
New Classes of Alanine Racemase Inhibitors Identified by High-Throughput Screening Show Antimicrobial Activity against Mycobacterium tuberculosis
In an effort to discover new drugs to treat tuberculosis (TB) we chose alanine racemase as the target of our drug discovery efforts. In Mycobacterium tuberculosis, the causative agent of TB, alanine racemase plays an essential role in cell wall synthesis as it racemizes L-alanine into D-alanine, a key building block in the biosynthesis of peptidoglycan. Good antimicrobial effects have been achieved by inhibition of this enzyme with suicide substrates, but the clinical utility of this class of inhibitors is limited due to their lack of target specificity and toxicity. Therefore, inhibitors that are not substrate analogs and that act through different mechanisms of enzyme inhibition are necessary for therapeutic development for this drug target.To obtain non-substrate alanine racemase inhibitors, we developed a high-throughput screening platform and screened 53,000 small molecule compounds for enzyme-specific inhibitors. We examined the 'hits' for structural novelty, antimicrobial activity against M. tuberculosis, general cellular cytotoxicity, and mechanism of enzyme inhibition. We identified seventeen novel non-substrate alanine racemase inhibitors that are structurally different than any currently known enzyme inhibitors. Seven of these are active against M. tuberculosis and minimally cytotoxic against mammalian cells.This study highlights the feasibility of obtaining novel alanine racemase inhibitor lead compounds by high-throughput screening for development of new anti-TB agents
Incidence of Deep Vein Thrombosis in Hospitalized Chinese Medical Patients and the Impact of DVT Prophylaxis
Objective. To evaluate the incidence of deep vein thrombosis in hospitalized Chinese medical patients and the impact of DVT prophylaxis. Methods. All cases of confirmed proximal DVT from 1 January 2005 to 31 December 2008 were reviewed retrospectively to determine the presence of risk factors and whether DVT developed: during hospitalization in medical wards or in case of readmission with a diagnosis of DVT within 14 days of discharge from a recent admission to medical wards. The impact of prophylaxis will be estimated by comparing the annual incidence of proximal DVT among medical patients hospitalized from 2005 to 2007 with that of 2008 (DVT prophylaxis commonly used). Results. From 1 January 2005 to 31 December 2008, 3938 Doppler ultrasound studies were performed for suspected DVT. Proximal DVT was diagnosed in 687 patients. The calculated incidence of proximal DVT among medical patients hospitalized for at least two days was 1.8%, 2%, and 1.7% for the year 2005, 2006, and 2007, respectively. The incidence was 1.1% for 2008 (P < .001). Conclusion. Proximal DVT was substantial in Chinese medical patients, and DVT prophylaxis might reduce such risk
Modulation of Immune Checkpoints by Chemotherapy in Human Colorectal Liver Metastases.
Metastatic colorectal cancer (CRC) is a major cause of cancer-related death, and incidence is rising in younger populations (younger than 50 years). Current chemotherapies can achieve response rates above 50%, but immunotherapies have limited value for patients with microsatellite-stable (MSS) cancers. The present study investigates the impact of chemotherapy on the tumor immune microenvironment. We treat human liver metastases slices with 5-fluorouracil (5-FU) plus either irinotecan or oxaliplatin, then perform single-cell transcriptome analyses. Results from eight cases reveal two cellular subtypes with divergent responses to chemotherapy. Susceptible tumors are characterized by a stemness signature, an activated interferon pathway, and suppression of PD-1 ligands in response to 5-FU+irinotecan. Conversely, immune checkpoint TIM-3 ligands are maintained or upregulated by chemotherapy in CRC with an enterocyte-like signature, and combining chemotherapy with TIM-3 blockade leads to synergistic tumor killing. Our analyses highlight chemomodulation of the immune microenvironment and provide a framework for combined chemo-immunotherapies
Prognostic Value of Sarcopenia and Metabolic Parameters of F-FDG-PET/CT in Patients with Advanced Gastroesophageal Cancer
We investigated the prognostic value of sarcopenia measurements and metabolic parameters of primary tumors derived from F-FDG-PET/CT among patients with primary, metastatic esophageal and gastroesophageal cancer. A total of 128 patients (26 females; 102 males; mean age 63.5 ± 11.7 years; age range: 29-91 years) with advanced metastatic gastroesophageal cancer who underwent F-FDG-PET/CT as part of their initial staging between November 2008 and December 2019 were included. Mean and maximum standardized uptake value (SUV) and SUV normalized by lean body mass (SUL) were measured. Skeletal muscle index (SMI) was measured at the level of L3 on the CT component of the F-FDG-PET/CT. Sarcopenia was defined as SMI < 34.4 cm/m in women and <45.4 cm/m in men. A total of 60/128 patients (47%) had sarcopenia on baseline F-FDG-PET/CT. Mean SMI in patients with sarcopenia was 29.7 cm/m in females and 37.5 cm/m in males. In a univariable analysis, ECOG (<0.001), bone metastases (p = 0.028), SMI (p = 0.0075) and dichotomized sarcopenia score (p = 0.033) were significant prognostic factors for overall survival (OS) and progression-free survival (PFS). Age was a poor prognostic factor for OS (p = 0.017). Standard metabolic parameters were not statistically significant in the univariable analysis and thus were not evaluated further. In a multivariable analysis, ECOG (p < 0.001) and bone metastases (p = 0.019) remained significant poor prognostic factors for OS and PFS. The final model demonstrated improved OS and PFS prognostication when combining clinical parameters with imaging-derived sarcopenia measurements but not metabolic tumor parameters. In summary, the combination of clinical parameters and sarcopenia status, but not standard metabolic values from F-FDG-PET/CT, may improve survival prognostication in patients with advanced, metastatic gastroesophageal cancer
Networking - A Statistical Physics Perspective
Efficient networking has a substantial economic and societal impact in a
broad range of areas including transportation systems, wired and wireless
communications and a range of Internet applications. As transportation and
communication networks become increasingly more complex, the ever increasing
demand for congestion control, higher traffic capacity, quality of service,
robustness and reduced energy consumption require new tools and methods to meet
these conflicting requirements. The new methodology should serve for gaining
better understanding of the properties of networking systems at the macroscopic
level, as well as for the development of new principled optimization and
management algorithms at the microscopic level. Methods of statistical physics
seem best placed to provide new approaches as they have been developed
specifically to deal with non-linear large scale systems. This paper aims at
presenting an overview of tools and methods that have been developed within the
statistical physics community and that can be readily applied to address the
emerging problems in networking. These include diffusion processes, methods
from disordered systems and polymer physics, probabilistic inference, which
have direct relevance to network routing, file and frequency distribution, the
exploration of network structures and vulnerability, and various other
practical networking applications.Comment: (Review article) 71 pages, 14 figure
Tumor slice culture as a biologic surrogate of human cancer.
Background: The tumor microenvironment (TME) is critical to every aspect of cancer biology. Organotypic tumor slice cultures (TSCs) preserve the original TME and have demonstrated utility in predicting drug sensitivity, but the association between clinicopathologic parameters and
Methods: One hundred and eight fresh tumor specimens from liver resections at a tertiary academic center were procured and precisely cut with a Vibratome to create 250 μm × 6 mm slices. These fixed-dimension TSCs were grown on polytetrafluoroethylene inserts, and their metabolic activities were determined by a colorimetric assay. Correlation between baseline activities and clinicopathologic parameters was assessed. Tissue CEA mRNA expression was determined by RNAseq.
Results: By standardizing the dimensions of a slice, we found that adjacent tumor slices have equivalent metabolic activities, while those derived from different tumors exhibit \u3e30-fold range in baseline MTS absorbances, which correlated significantly with the percentage of tumor necrosis based on histologic assessment. Extending this to individual cancers, we were able to detect intra-tumoral heterogeneity over a span of a few millimeters, which reflects differences in tumor cell density and Ki-67 positivity. For colorectal cancers, tissue CEA expression based on RNAseq of tumor slices was found to correlate with clinical response to chemotherapies.
Conclusions: We report a standardized method to assess and compare human cancer growth ex vivo across a wide spectrum of tumor samples. TSC reflects the state of tumor behavior and heterogeneity, thus providing a simple approach to study of human cancers with an intact TME
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