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Find video protocols related to scientific articles indexed in Pubmed.
Efficient iPS Cell Generation from Blood Using Episomes and HDAC Inhibitors.
J Vis Exp
PUBLISHED: 11-20-2014
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This manuscript illustrates a protocol for efficiently creating integration-free human induced pluripotent stem cells (iPSCs) from peripheral blood using episomal plasmids and histone deacetylase (HDAC) inhibitors. The advantages of this approach include: (1) the use of a minimal amount of peripheral blood as a source material; (2) nonintegrating reprogramming vectors; (3) a cost effective method for generating vector free iPSCs; (4) a single transfection; and (5) the use of small molecules to facilitate epigenetic reprogramming. Briefly, peripheral blood mononuclear cells (PBMCs) are isolated from routine phlebotomy samples and then cultured in defined growth factors to yield a highly proliferative erythrocyte progenitor cell population that is remarkably amenable to reprogramming. Nonintegrating, nontransmissible episomal plasmids expressing OCT4, SOX2, KLF4, MYCL, LIN28A, and a p53 short hairpin (sh)RNA are introduced into the derived erythroblasts via a single nucleofection. Cotransfection of an episome that expresses enhanced green fluorescent protein (eGFP) allows for easy identification of transfected cells. A separate replication-deficient plasmid expressing Epstein-Barr nuclear antigen 1 (EBNA1) is also added to the reaction mixture for increased expression of episomal proteins. Transfected cells are then plated onto a layer of irradiated mouse embryonic fibroblasts (iMEFs) for continued reprogramming. As soon as iPSC-like colonies appear at about twelve days after nucleofection, HDAC inhibitors are added to the medium to facilitate epigenetic remodeling. We have found that the inclusion of HDAC inhibitors routinely increases the generation of fully reprogrammed iPSC colonies by 2 fold. Once iPSC colonies exhibit typical human embryonic stem cell (hESC) morphology, they are gently transferred to individual iMEF-coated tissue culture plates for continued growth and expansion.
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FILTERING OF HIGH NOISE BREAST THERMAL IMAGES USING FAST NON-LOCAL MEANS.
Biomed Sci Instrum
PUBLISHED: 11-19-2014
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Analyses of breast thermograms are still a challenging task primarily due to the limitations such as low contrast, low signal to noise ratio and absence of clear edges. Therefore, always there is a requirement for preprocessing techniques before performing any quantitative analysis. In this work, a noise removal framework using fast non-local means algorithm, method noise and median filter was used to denoise breast thermograms. The images considered were subjected to Anscombe transformation to convert the distribution from Poisson to Gaussian. The pre-denoised image was obtained by subjecting the transformed image to fast non-local means filtering. The method noise which is the difference between the original and pre-denoised image was observed with the noise component merged in few structures and fine detail of the image. The image details presented in the method noise was extracted by smoothing the noise part using the median filter. The retrieved image part was added to the pre-denoised image to obtain the final denoised image. The performance of this technique was compared with that of Wiener and SUSAN filters. The results show that all the filters considered are able to remove the noise component. The performance of the proposed denoising framework is found to be good in preserving detail and removing noise. Further, the method noise is observed with negligible image details. Similarly, denoised image with no noise and smoothed edges are observed using Wiener filter and its method noise is contained with few structures and image details. The performance results of SUSAN filter is found to be blurred denoised image with little noise and also method noise with extensive structure and image details. Hence, it appears that the proposed denoising framework is able to preserve the edge information and generate clear image that could help in enhancing the diagnostic relevance of breast thermograms. In this paper, the introduction, objectives, materials and methods, results and discussion and conclusions are presented in detail.
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PROPOSAL OF A NEW TRACTOGRAPHIC FEATURE FOR ANALYSIS OF WHITE MATTER IN ALZHEIMER DIFFUSION MR IMAGES.
Biomed Sci Instrum
PUBLISHED: 11-19-2014
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Alzheimer's disease (AD) is a leading cause of dementia in elderly adults. In this, the white matter (WM) tracts in brain are disintegrated leading to loss of important cognitive functionality. Recent analysis have shown that early diagnosis of AD is still a challenging task. Although several reports are available, tractography remains the most promising and clinically relevant method for in-vivo study of WM tracts. In tractography, continuous WM pathways are reconstructed from voxel based models of discrete fiber orientation generated using diffusion tensor images. In this work an attempt has been made to classify AD using average length of tracts, a significant feature extracted from tractographic brain maps. The diffusion weighted images for AD and matched controls were obtained from ADNI, an international open access repository for Alzheimer's study. Data from equal number of AD and controls were used for this study. Fiber tracking was performed for the whole brain using tract based spatial statistics algorithm. ICBM Mori Labels 1 atlas provided in the Network Analysis option of ExploreDTI was used to divide the WM into 48 anatomical regions. Classification was performed using random forest, random tree and decision stumps, and their performance indices were compared. The results show that all the classifiers are able to classify AD and controls using the extracted feature. An accuracy of 78.4% is obtained using decision stumps. Random forest and random tree provide an increased accuracy of 96% and 97% respectively. The precision and recall is also found to be higher for random forest and random tree as compared to decision stumps. These results suggest that random forest and random tree are suitable for classification of AD and controls using average tract length as a feature. In this paper, the introduction, objectives, materials and methods, results and discussions and conclusions are presented in detail.
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DIFFERENTIATING sEMG SIGNALS UNDER MUSCLE FATIGUE AND NON-FATIGUE CONDITIONS USING LOGISTIC REGRESSION CLASSIFIERS.
Biomed Sci Instrum
PUBLISHED: 11-19-2014
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In this work, an attempt has been made to differentiate surface electromyography signals under fatigue and non-fatigue conditions. Signals are recorded from the biceps brachii muscles of 50 healthy volunteers. A well-established experimental protocol is followed for this purpose. Signals are subjected to further processing and features namely amplitude of first burst, myopulse percentage rate, Willison amplitude, power spectrum ratio and variance of central frequency are extracted. Three types of logistic regression classifiers, linear logistic, polykernel logistic regression and multinomial regression with ridge estimator are used for automated analysis. Classifier parameters are tuned to enhance the accuracy and performance indices of algorithms, and are compared. The results show distinct values for extracted features in fatigue conditions which are statistically significant (0.0027 = P = 0.03). All classifiers are found to be effective in demarcating the signals. The linear logistic regression algorithm provides 79% accuracy with 40 iterations. However, in the case of multinomial regression with ridge estimator, only 7 iterations are required to achieve 80% accuracy. The polykernel logistic regression algorithm (0.06 = ? = 0.1) also provides 80% accuracy but with a marginal increment (1 % to 4 %) for precision, recall and specificity compared to other two classifiers.
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SEGMENTATION OF VENTRICLES IN ALZHEIMER MR IMAGES USING ANISOTROPIC DIFFUSION FILTERING AND LEVEL SET METHOD.
Biomed Sci Instrum
PUBLISHED: 11-19-2014
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Ventricle enlargement is a useful structural biomarker for the diagnosis of Alzheimer?s Disease (AD). This devastating neurodegenerative disorder results in progression of dementia. Although AD results in the passive increment of ventricle volume, there exists a large overlap in the volume measurements of AD and normal subjects. Hence, shape based analysis of ventricle dilation is appropriate to detect the subtle morphological changes among these two groups. In this work, segmentation of ventricle in Alzheimer MR images is employed using level set method and anisotropic based diffusion filtering. Images considered for this study are preprocessed using filters. Anisotropic based diffusion filtering is employed to extract the edge map. This filtering performs region specific smoothing process using the diffusion coefficient as a function of image gradient. Filtered images are subjected to level set method which employs an improved diffusion rate equation for the level set evolution. Geometric features are extracted from the segmented ventricles. Results show that the diffusion filter could extract edge map with sharp region boundaries. The modified level set method is able to extract the morphological changes in ventricles. The observed morphological changes are distinct for normal and AD subjects (p < 0.0001). It is also observed that the sizes of ventricle in the AD subjects are noticeably enlarged when compared to normal subjects. Features obtained from the segmented ventricles are also clearly distinct and demonstrate the differences in the AD subjects. As ventricle volume and its morphometry are significant biomarkers, this study seems to be clinically relevant.
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ESTIMATION OF INSTANTANEOUS MEDIAN FREQUENCY IN SURFACE ELECTROMYOGRAPHY SIGNALS USING QUADRATIC TIME FREQUENCY DISTRIBUTION.
Biomed Sci Instrum
PUBLISHED: 11-19-2014
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Surface electromyography (sEMG) technique gives a non-stationary and multi component signal which can be used for neuromuscular analysis, ergonomics, rehabilitation and sports biomechanics. It records the electrical activity of skeletal muscles. The sEMG signals are often analyzed in the time domain, frequency domain and time-frequency domain. Although several methods of signal analyses are reported in the literature, the extraction of useful information still remains a challenging task. In this work, an attempt has been made to analyze sEMG signals in fatigue and non-fatigue conditions by using the quadratic time frequency distribution (QTFD). Signals are recorded for 25 normal control adult subjects during dynamic contractions in biceps brachii muscle. The acquired signals are subjected to QTFD by using a modified B distribution. The median frequency is extracted from the processed signal. The result shows that median frequency is distinct for fatigue and non fatigue conditions. Further it shows variation with flexion and extension. Thus the study seems to be clinically useful for the dynamic analysis of neuromuscular conditions.
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FPGA BASED HARDWARE SYNTHESIS FOR AUTOMATIC SEGMENTATION OF RETINAL BLOOD VESSELS IN DIABETIC RETINOPATHY IMAGES.
Biomed Sci Instrum
PUBLISHED: 11-19-2014
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Diabetic Retinopathy (DR) is a disorder that affects the structure of retinal blood vessels due to long-standing diabetes mellitus. Real-Time mass screening system for DR is vital for timely diagnosis and periodic screening to prevent the patient from severe visual loss. Human retinal fundus images are widely used for an automated segmentation of blood vessel and diagnosis of various blood vessel disorders. In this work, an attempt has been made to perform hardware synthesis of Kirsch template based edge detection for segmentation of blood vessels. This method is implemented using LabVIEW software and is synthesized in field programmable gate array board to yield results in real-time application. The segmentation of blood vessels using Kirsch based edge detection is compared with other edge detection methods such as Sobel, Prewitt and Canny. The texture features such as energy, entropy, contrast, mean, homogeneity and structural feature namely ratio of vessel to vessel free area are obtained from the segmented images. The performance of segmentation is analysed in terms of sensitivity, specificity and accuracy. It is observed from the results that the Kirsch based edge detection technique segmented the edges of blood vessels better than other edge detection techniques. The ratio of vessel to vessel free area classified the normal and DR affected retinal images more significantly than other texture based features. FPGA based hardware synthesis of Kirsch edge detection method is able to differentiate normal and diseased images with high specificity (93%). This automated segmentation of retinal blood vessels system could be used in computer-assisted diagnosis for diabetic retinopathy screening in real-time application.
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ANALYSIS OF CORTICAL AND SUB-CORTICAL REGIONS IN AUTISTIC MR IMAGES USING LEVEL SET METHOD AND STRUCTURE TENSORS.
Biomed Sci Instrum
PUBLISHED: 11-19-2014
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Autism is a complex disease that causes micro structural changes in brain due to delayed growth. In this work, the cortical regions of brain are extracted from T1 -weighted magnetic resonance mid-sagittal view slices. The images are skull stripped using edge based Level Set (LS) which is regularized by a signed distance function. This skull stripping technique is validated with the Brain extraction tool (BET). The extracted cortical regions are then analyzed by calculating the structure tensor matrix from the gradient of the skull stripped images. The anisotropy index derived from the tensor matrix is correlated with the clinical features such as verbal, full scale and performance Intelligent Quotients (IQ). The results show that the level set method is able to extract the cortical brain boundaries correctly with distinct edges. The structure tensor features extracted from the skull stripped images discriminates the control and autistic images. Also, the anisotropy index is negatively correlated with the performance IQ values of autistic subjects.
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Combination strategy targeting VEGF and HGF/c-met in human renal cell carcinoma models.
Mol. Cancer Ther.
PUBLISHED: 11-09-2014
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Alternative pathways to the vascular endothelial grow factor (VEGF), such as hepatocyte growth factor or HGF/c-met, are emerging as key players in tumor angiogenesis and resistance to anti-VEGF therapies. The aim of this study was to assess the effects of a combination strategy targeting VEGF and c-met pathway in clear cell renal cell carcinoma (ccRCC) models. Male SCID mice (8/group) were implanted with 786-O tumor pieces and treated with either a selective VEGF receptor tyrosine kinase inhibitor, axitinib (36 mg/kg, 2x/day), a c-met inhibitor, crizotinib (25 mg/kg, 1x/day), or combination. We further tested this drug combination in a human ccRCC patient derived xenograft, RP-R-01, in both VEGF-targeted therapy sensitive and resistant models. To evaluate the resistance phenotype, we established RP-R-01 sunitinib resistant model by continuous sunitinib treatment (60 mg/kg, 1x/day) of RP-R-01 bearing-mice. Treatment with single agent crizotinib reduced tumor vascularization but failed to inhibit tumor growth in either model, despite also a significant increase of c-met expression and phosphorylation in the sunitinib resistant tumors. In contrast, axitinib treatment was effective in inhibiting angiogenesis and tumor growth in both models, with its anti-tumor effect significantly increased by the combined treatment with crizotinib, independently from c-met expression. Combination treatment also induced prolonged survival and significant tumor growth inhibition in the 786-O human RCC model. Overall, our results support the rationale for the clinical testing of combined VEGF and HGF/c-met pathway blockade in the treatment of ccRCC, both in first and second line setting.
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Long term refractive and structural outcome following laser treatment for zone 1 aggressive posterior retinopathy of prematurity.
Oman J Ophthalmol
PUBLISHED: 11-08-2014
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To report the long term refractive, visual and structural outcome post-laser for zone 1 aggressive posterior retinopathy of prematurity (AP-ROP).
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Immunity and Immunopathology in the Tuberculous Granuloma.
Cold Spring Harb Perspect Med
PUBLISHED: 11-08-2014
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Granulomas, organized aggregates of immune cells, are a defining feature of tuberculosis (TB). Granuloma formation is implicated in the pathogenesis of a variety of inflammatory disorders. However, the tuberculous granuloma has been assigned the role of a host protective structure which "walls-off" mycobacteria. Work conducted over the past decade has provided a more nuanced view of its role in pathogenesis. On the one hand, pathogenic mycobacteria accelerate and exploit granuloma formation for their expansion and dissemination by manipulating host immune responses to turn leukocyte recruitment and cell death pathways in their favor. On the other hand, granuloma macrophages can preserve granuloma integrity by exerting a microbicidal immune response, thus preventing an even more rampant expansion of infection in the extracellular milieu. Even this host-beneficial immune response required to maintain the bacteria intracellular must be tempered, as an overly vigorous immune response can also cause granuloma breakdown, thereby directly supporting bacterial growth extracellularly. This review will discuss how mycobacteria manipulate inflammatory responses to drive granuloma formation and will consider the roles of the granuloma in pathogenesis and protective immunity, drawing from clinical studies of TB in humans and from animal models-rodents, zebrafish, and nonhuman primates. A deeper understanding of TB pathogenesis and immunity in the granuloma could suggest therapeutic approaches to abrogate the host-detrimental aspects of granuloma formation to convert it into the host-beneficial structure that it has been thought to be for nearly a century.
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Intradialytic Hypotension and Risk of Cardiovascular Disease.
Clin J Am Soc Nephrol
PUBLISHED: 11-08-2014
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Patients undergoing hemodialysis have an elevated risk of cardiovascular disease-related morbidity and mortality compared with the general population. Intradialytic hypotension (IDH) is estimated to occur during 20%-30% of hemodialysis sessions. To date, no large studies have examined whether IDH is associated with cardiovascular outcomes. This study determined the prevalence of IDH according to interdialytic weight gain (IDWG) and studied the association between IDH and outcomes for cardiovascular events and mortality to better understand its role.
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Tasquinimod modulates suppressive myeloid cells and enhances cancer immunotherapies in murine models.
Cancer Immunol Res
PUBLISHED: 11-06-2014
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A major barrier for cancer immunotherapy is the presence of suppressive cell populations in cancer patients, such as myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM), which contribute to the immunosuppressive microenvironment that promotes tumor growth and metastasis. Tasquinimod is a novel antitumor agent that is currently at an advanced stage of clinical development for treatment of castration-resistant prostate cancer. A target of tasquinimod is the inflammatory protein S100A9, which has been demonstrated to affect the accumulation and function of tumor-suppressive myeloid cells. Here, we report that tasquinimod provided a significant enhancement to the antitumor effects of two different immunotherapeutics in mouse models of cancer: a tumor vaccine (SurVaxM) for prostate cancer and a tumor-targeted superantigen (TTS) for melanoma. In the combination strategies, tasquinimod inhibited distinct MDSC populations and TAMs of the M2-polarized phenotype (CD206+). CD11b+ myeloid cells isolated from tumors of treated mice expressed lower levels of arginase-1 and higher levels of inducible nitric oxide synthase (iNOS), and were less immunosuppressive ex vivo, which translated into a significantly reduced tumor-promoting capacity in vivo when these cells were co-injected with tumor cells. Tumor-specific CD8+ T cells were increased markedly in the circulation and in tumors. Furthermore, T-cell effector functions, including cell-mediated cytotoxicity and IFN? production, were potentiated. Taken together, these data suggest that pharmacologic targeting of suppressive myeloid cells by tasquinimod induces therapeutic benefit and provide the rationale for clinical testing of tasquinimod in combination with cancer immunotherapies.
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Potential Mechanisms for Thrombocytopenia Development with Trastuzumab Emtansine (T-DM1).
Clin. Cancer Res.
PUBLISHED: 11-06-2014
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Purpose:Trastuzumab-emtansine (T-DM1) is an antibody-drug conjugate (ADC) comprising the cytotoxic agent DM1 conjugated to trastuzumab with a stable linker. Thrombocytopenia was the dose-limiting toxicity in the phase I study, and grade ?3 thrombocytopenia occurred in up to 13% of patients receiving T-DM1 in phase III studies. We investigated the mechanism of T-DM1-induced thrombocytopenia. Experimental Design:The effect of T-DM1 on platelet function was measured by aggregometry, and by flow cytometry to detect markers of activation. The effect of T-DM1 on differentiation and maturation of megakaryocytes (MKs) from human hematopoietic stem cells was assessed by flow cytometry and microscopy. Binding, uptake, and catabolism of T-DM1 in MKs, were assessed by various techniques including fluorescence microscopy, scintigraphy to detect T-[H(3)]-DM1 and (125)I-T-DM1, and mass spectrometry. The role of Fc?RIIa was assessed using blocking antibodies and mutant constructs of trastuzumab that do not bind Fc?R. Results:T-DM1 had no direct effect on platelet activation and aggregation, but it did markedly inhibit MK differentiation via a cytotoxic effect. Inhibition occurred with DM1-containing ADCs but not with trastuzumab demonstrating a role for DM1. MKs internalized these ADCs in a HER2-independent, Fc?RIIa-dependent manner, resulting in intracellular release of DM1. Binding and internalization of T-DM1 diminished as MKs matured; however, prolonged exposure of mature MKs to T-DM1 resulted in a disrupted cytoskeletal structure. Conclusions:These data support the hypothesis that T-DM1-induced thrombocytopenia is mediated in large part by DM1-induced impairment of MK differentiation, with a less pronounced effect on mature MKs.
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U2AF1 mutations alter splice site recognition in hematological malignancies.
Genome Res.
PUBLISHED: 10-01-2014
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Whole-exome sequencing studies have identified common mutations affecting genes encoding components of the RNA splicing machinery in hematological malignancies. Here, we sought to determine how mutations affecting the 3' splice site recognition factor U2AF1 alter its normal role in RNA splicing. We find that U2AF1 mutations influence the similarity of splicing programs in leukemias, but do not give rise to widespread splicing failure. U2AF1 mutations cause differential splicing of hundreds of genes, affecting biological pathways such as DNA methylation (DNMT3B), X chromosome inactivation (H2AFY), the DNA damage response (ATR, FANCA), and apoptosis (CASP8). We show that U2AF1 mutations alter the preferred 3' splice site motif in patients, in cell culture, and in vitro. Mutations affecting the first and second zinc fingers give rise to different alterations in splice site preference and largely distinct downstream splicing programs. These allele-specific effects are consistent with a computationally predicted model of U2AF1 in complex with RNA. Our findings suggest that U2AF1 mutations contribute to pathogenesis by causing quantitative changes in splicing that affect diverse cellular pathways, and give insight into the normal function of U2AF1's zinc finger domains.
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Identifying premature infants at high and low risk for motor delays using motor performance testing and MRS.
J Pediatr Rehabil Med
PUBLISHED: 09-28-2014
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To determine specific motor skills in premature infants, match those that correlate with standards tests of motor performance, and MRS measures of abnormal brain biochemistry.
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Phase I Trial of Bortezomib (PS-341; NSC 681239) and "Nonhybrid" (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms.
Clin. Cancer Res.
PUBLISHED: 09-23-2014
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This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma).
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Discrete wavelet transform and singular value decomposition based ECG steganography for secured patient information transmission.
J Med Syst
PUBLISHED: 09-04-2014
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ECG Steganography provides secured transmission of secret information such as patient personal information through ECG signals. This paper proposes an approach that uses discrete wavelet transform to decompose signals and singular value decomposition (SVD) to embed the secret information into the decomposed ECG signal. The novelty of the proposed method is to embed the watermark using SVD into the two dimensional (2D) ECG image. The embedding of secret information in a selected sub band of the decomposed ECG is achieved by replacing the singular values of the decomposed cover image by the singular values of the secret data. The performance assessment of the proposed approach allows understanding the suitable sub-band to hide secret data and the signal degradation that will affect diagnosability. Performance is measured using metrics like Kullback-Leibler divergence (KL), percentage residual difference (PRD), peak signal to noise ratio (PSNR) and bit error rate (BER). A dynamic location selection approach for embedding the singular values is also discussed. The proposed approach is demonstrated on a MIT-BIH database and the observations validate that HH is the ideal sub-band to hide data. It is also observed that the signal degradation (less than 0.6%) is very less in the proposed approach even with the secret data being as large as the sub band size. So, it does not affect the diagnosability and is reliable to transmit patient information.
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Quaternary climate change and social behavior shaped the genetic differentiation of an endangered montane primate from the southern edge of the Tibetan Plateau.
Am. J. Primatol.
PUBLISHED: 08-26-2014
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Multiple factors, including climate change, dispersal barriers, and social behavior influence the genetic structure of natural populations. While the effects of extrinsic factors such as historical climatic change and habitat topography have been well studied, mostly in temperate habitats, the simultaneous effects of intrinsic factors such as social behavior on genetic structure have rarely been explored. Such simultaneous effect, however, may particularly be common in social mammals such as many primates. Consequently, we studied the population structure of a rare and endangered social primate, the Arunachal macaque Macaca munzala, endemic to the northeastern Indian state of Arunachal Pradesh, located on the subtropical southern edge of the Tibetan Plateau and forming part of the Eastern Himalayan biodiversity hotspot. We studied a 534?bp-long mitochondrial DNA sequence and 22 autosomal microsatellite loci in individuals from three populations, Tawang, Upper Subansiri, and West Siang. The mtDNA data revealed three major divergence events: that between the Arunachal and bonnet macaques (ca. 1.61?mya), the founding of the West Siang population and the ancestral population of the present-day bonnet macaques (ca. 1.32?mya), and the divergence between the Tawang and Upper Subansiri populations (ca. 0.80?mya) that coincided with the major glacial events in the region. Comparing mitochondrial DNA with autosomal microsatellites, we also found evidence for female philopatry and male-driven long-distance gene flow. Arunachal macaques thus appear to be characterized by groups of philopatric females separated by geographical barriers and harsh climate but with dispersing males exerting a homogenizing effect on the nuclear gene pool. Given that severe population differentiation is of major concern in species conservation, we suggest that our study populations represent significant conservation units of this rare, endangered primate but, more importantly, emphasize the complex interplay of extrinsic and intrinsic factors in shaping the population structure of a social mammalian species. Am. J. Primatol. © 2014 Wiley Periodicals, Inc.
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Impact of acute guanfacine administration on stress and cue reactivity in cocaine-dependent individuals.
Am J Drug Alcohol Abuse
PUBLISHED: 08-20-2014
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Abstract Background: Stress and drug-paired cues increase drug craving and noradrenergic activity in cocaine-dependent individuals. Thus, medications that attenuate noradrenergic activity may be effective therapeutic treatment options for cocaine-dependent individuals. Objectives: To examine the impact of acute administration of the ?2 adrenergic receptor agonist guanfacine on responses to multiple risk factors for relapse in cocaine-dependent individuals. Methods: In a double-blind, placebo-controlled study, cocaine-dependent individuals (n?=?84), were randomized to receive either 2?mg guanfacine (n?=?50) or placebo (n?=?34). Within each treatment arm, subjects were randomized to either a stress (guanfacine n?=?26; placebo n?=?15) or a no-stress (guanfacine n?=?24; placebo n?=?19) group. Participants in the stress group performed the Trier Social Stress Test. Subjects in each group were exposed to a neutral cue and then to cocaine-related cues. Plasma cortisol and subjective responses were compared between the four groups. Results: The no-stress guanfacine group reported greater craving in response to cocaine cues as compared to the neutral cue (p??0.70). Conclusion: This study found no effects of a single 2?mg dose of guanfacine on reactivity to stress and cues alone or on the interaction of stress and drug cues. In cocaine-dependent individuals an acute 2?mg dose of guanfacine may not be an effective therapeutic treatment strategy.
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Autosomal Dominant Hearing Loss resulting from p.R75Q Mutation in the GJB2 Gene: Nonsyndromic presentation in a South Indian Family.
Ann. Hum. Genet.
PUBLISHED: 08-13-2014
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Mutations in the GJB2 gene encoding the gap junction protein Connexin 26 have been associated with autosomal recessive as well as dominant nonsyndromic hearing loss. Owing to the involvement of connexins in skin homeostasis, GJB2 mutations have also been associated with syndromic forms of hearing loss showing various skin manifestations. We report an assortatively mating hearing impaired family of south Indian origin with three affected members spread over two generations, having p.R75Q mutation in the GJB2 gene in the heterozygous condition. The inheritance pattern was autosomal dominant with mother and son being affected. Dermatological and histopathologic examinations showed absence of palmoplantar keratoderma. To the best of our knowledge, this is the first report from India on p.R75Q mutation in the GJB2 gene with nonsyndromic hearing loss.
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A study of impact of cost-effective nutritional supplement in patients on maintenance hemodialysis.
Indian J Nephrol
PUBLISHED: 08-07-2014
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Nutritional status in patients on hemodialysis is always of concern as malnutrition predisposes to excess morbidity and mortality. Most of the nutritional supplements available in the market are expensive. We explored the possibility of improving nutrition of the patients on maintenance hemodialysis by supplementation of calories and proteins that can be given in the form of a palatable and economical gruel in this prospectively designed, open labeled study. Patients who were on maintenance hemodialysis (twice a week) for a period of at least 6 months were divided into two groups. The study group was given the gruel supplement and the control group was not given the gruel supplement. Nutritional status was assessed in the study group and controls at 0 and 3 months by the following parameters: percentage body fat, mid arm muscle circumference and serum albumin. Analysis of results revealed that there was a significant decline in the protein intake at the end of the 3(rd) month in the control group (P = 0.01). Other parameters did not show significant change at the end of the study period in both groups. The nutritional supplement can be assumed to have helped at least in the maintenance of protein intake over this short period and could possibly in the long run contribute to improvement of nutritional parameters.
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Survival analysis of patients on maintenance hemodialysis.
Indian J Nephrol
PUBLISHED: 08-07-2014
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Despite the continuous improvement of dialysis technology and pharmacological treatment, mortality rates for dialysis patients are still high. A 2-year prospective study was conducted at a tertiary care hospital to determine the factors influencing survival among patients on maintenance hemodialysis. 96 patients with end-stage renal disease surviving more than 3 months on hemodialysis (8-12 h/week) were studied. Follow-up was censored at the time of death or at the end of 2-year study period, whichever occurred first. Of the 96 patients studied (mean age 49.74 ± 14.55 years, 75% male and 44.7% diabetics), 19 died with an estimated mortality rate of 19.8%. On an age-adjusted multivariate analysis, female gender and hypokalemia independently predicted mortality. In Cox analyses, patient survival was associated with delivered dialysis dose (single pool Kt/V, hazard ratio [HR] =0.01, P = 0.016), frequency of hemodialysis (HR = 3.81, P = 0.05) and serum albumin (HR = 0.24, P = 0.005). There was no significant difference between diabetes and non-diabetes in relation to death (Relative Risk = 1.109; 95% CI = 0.49-2.48, P = 0.803). This study revealed that mortality among hemodialysis patients remained high, mostly due to sepsis and ischemic heart disease. Patient survival was better with higher dialysis dose, increased frequency of dialysis and adequate serum albumin level. Efforts at minimizing infectious complications, preventing cardiovascular events and improving nutrition should increase survival among hemodialysis patients.
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High tracheal bifurcation: an unusual cause of left bronchial obstruction.
Ann. Thorac. Surg.
PUBLISHED: 08-05-2014
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Congenitally short trachea is an uncommon abnormality. It is characterized by a reduced number of tracheal cartilage rings. As a result, the carina is situated at a higher level than usual. That causes the left main bronchus to course abnormally behind the arch of the aorta, rendering it prone to compression. We report the case of an infant who underwent successful aortopexy of the aortic arch for this condition.
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Response Surface Methodology: Optimisation of Antifungal Bioemulsifier from Novel Bacillus thuringiensis.
ScientificWorldJournal
PUBLISHED: 07-03-2014
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An antifungal bioemulsifier compound was produced from a novel strain of Bacillus thuringiensis pak2310. To accentuate the production and as the first step to improve the yield, a central composite design (CCD) was used to study the effect of various factors like minimal salts (1X and 3X), glycerol concentration (2% and 4%), beef extract concentration (1% and 3%), and sunflower oil concentration (2% and 4%) on the production of bioemulsifier molecule and to optimize the conditions to increase the production. The E 24 emulsification index was used as the response variable as the increase in surfactant production was seen to be proportional to increased emulsification. A quadratic equation was employed to express the response variable in terms of the independent variables. Statistical tools like student's t-test, F-test, and ANOVA were employed to identify the important factors and to test the adequacy of the model. Under optimum conditions (1X concentration of minimal salts (MS), 2.6% glycerol (v/v), 1% beef extract (w/v), and 2% sunflower oil (v/v)) a 65% increase in yield was produced.
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Spotlight on zebrafish: translational impact.
Dis Model Mech
PUBLISHED: 06-29-2014
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In recent years, the zebrafish has emerged as an increasingly prominent model in biomedical research. To showcase the translational impact of the model across multiple disease areas, Disease Models & Mechanisms has compiled a Special Issue that includes thought-provoking reviews, original research reporting new and important insights into disease mechanisms, and novel resources that expand the zebrafish toolkit. This Editorial provides a summary of the issue's contents, highlighting the diversity of zebrafish disease models and their clinical applications.
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In-situ preparation and characterization of acid functionalized single walled carbon nanotubes with polyimide nanofibers.
J Nanosci Nanotechnol
PUBLISHED: 04-25-2014
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Nanofiber composites (Polyimide/f-SWCNT) of Pyromellitic dianhydride, 4,4'-Oxydianiline, and 4,4'-(4,4'-isopropylidene diphenyl-1,1'-diyl dioxy) dianiline (PMDA-ODA/IDDA) and surface-functionalized single walled carbon nanotubes (f-SWCNT) were made by electrospinning a solution of poly(amic acid) (PAA) containing 0-2 wt% f-SWCNT followed by thermal imidization. X-ray photoelectron spectroscopy spectra verified the oxidation of SWCNT surface after acid treatment, and indicated possible hydrogen bonding interactions between the f-SWCNTs and polyamic acid. High-resolution scanning electron microscopy images showed the average diameter of nanofibers to be below 150 nm, and transmission electron microscopy images showed that SWCNTs were aligned inside the polymer nanofiber. In thermogravimetric analysis, all composites showed increased thermal stability with increasing f-SWCNT content compared to neat PI. Storage modulus also increased from 124 MPa to 229 MPa from neat PI to 2% f-SWCNT composite.
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Tracing the Geographic Origin of Traded Leopard Body Parts in the Indian Subcontinent with DNA-Based Assignment Tests.
Conserv. Biol.
PUBLISHED: 03-30-2014
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Illicit trade in wildlife products is rapidly decimating many species across the globe. Such trade is often underestimated for wide-ranging species until it is too late for the survival of their remaining populations. Policing this trade could be vastly improved if one could reliably determine geographic origins of illegal wildlife products and identify areas where greater enforcement is needed. Using DNA-based assignment tests (i.e., samples are assigned to geographic locations), we addressed these factors for leopards (Panthera pardus) on the Indian subcontinent. We created geography-specific allele frequencies from a genetic reference database of 173 leopards across India to infer geographic origins of DNA samples from 40 seized leopard skins. Sensitivity analyses of samples of known geographic origins and assignments of seized skins demonstrated robust assignments for Indian leopards. We found that confiscated pelts seized in small numbers were not necessarily from local leopards. The geographic footprint of large seizures appeared to be bigger than the cumulative footprint of several smaller seizures, indicating widespread leopard poaching across the subcontinent. Our seized samples had male-biased sex ratios, especially the large seizures. From multiple seized sample assignments, we identified central India as a poaching hotspot for leopards. The techniques we applied can be used to identify origins of seized illegal wildlife products and trade routes at the subcontinent scale and beyond.
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Yohimbine administration and cue-reactivity in cocaine-dependent individuals.
Psychopharmacology (Berl.)
PUBLISHED: 03-23-2014
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Preclinical studies suggest that stress potentiates cue-induced cocaine seeking and that this effect is more pronounced in females. These findings have not been characterized in clinical populations.
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The zebrafish guide to tuberculosis immunity and treatment.
Cold Spring Harb. Symp. Quant. Biol.
PUBLISHED: 03-18-2014
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During the past 12 years, we have developed the zebrafish as a model for the study of tuberculosis pathogenesis and immunology. We have taken advantage of the optical transparency and the genetic and pharmacological tractability of the developing zebrafish to monitor infection in real time. Detailed information about the sequential interactions among the host and the pathogen, the cell types, and the molecules involved has yielded surprising insights into this ancient disease. We have identified a number of host evasion strategies deployed by pathogenic mycobacteria as well as host responses that provide broad insights into host immunity. Many of these discoveries have relevance to human tuberculosis and suggest new therapeutic avenues for tuberculosis as well as other inflammatory diseases.
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Identifying geographic hot spots of reassortment in a multipartite plant virus.
Evol Appl
PUBLISHED: 03-05-2014
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Reassortment between different species or strains plays a key role in the evolution of multipartite plant viruses and can have important epidemiological implications. Identifying geographic locations where reassortant lineages are most likely to emerge could be a valuable strategy for informing disease management and surveillance efforts. We developed a predictive framework to identify potential geographic hot spots of reassortment based upon spatially explicit analyses of genome constellation diversity. To demonstrate the utility of this approach, we examined spatial variation in the potential for reassortment among Cardamom bushy dwarf virus (CBDV; Nanoviridae, Babuvirus) isolates in Northeast India. Using sequence data corresponding to six discrete genome components for 163 CBDV isolates, a quantitative measure of genome constellation diversity was obtained for locations across the sampling region. Two key areas were identified where viruses with highly distinct genome constellations cocirculate, and these locations were designated as possible geographic hot spots of reassortment, where novel reassortant lineages could emerge. Our study demonstrates that the potential for reassortment can be spatially dependent in multipartite plant viruses and highlights the use of evolutionary analyses to identify locations which could be actively managed to facilitate the prevention of outbreaks involving novel reassortant strains.
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Analysis of breast thermograms using Gabor wavelet anisotropy index.
J Med Syst
PUBLISHED: 02-21-2014
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In this study, an attempt is made to distinguish the normal and abnormal tissues in breast thermal images using Gabor wavelet transform. Thermograms having normal, benign and malignant tissues are considered in this study and are obtained from public online database. Segmentation of breast tissues is performed by multiplying raw image and ground truth mask. Left and right breast regions are separated after removing the non-breast regions from the segmented image. Based on the pathological conditions, the separated breast regions are grouped as normal and abnormal tissues. Gabor features such as energy and amplitude in different scales and orientations are extracted. Anisotropy and orientation measures are calculated from the extracted features and analyzed. A distinctive variation is observed among different orientations of the extracted features. It is found that the anisotropy measure is capable of differentiating the structural changes due to varied metabolic conditions. Further, the Gabor features also showed relative variations among different pathological conditions. It appears that these features can be used efficiently to identify normal and abnormal tissues and hence, improve the relevance of breast thermography in early detection of breast cancer and content based image retrieval.
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Verapamil, and its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pump-mediated tolerance to multiple anti-tubercular drugs.
J. Infect. Dis.
PUBLISHED: 02-14-2014
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Drug tolerance likely represents an important barrier to tuberculosis treatment shortening. We previously implicated the Mycobacterium tuberculosis efflux pump Rv1258c as mediating macrophage-induced tolerance to rifampicin and intracellular growth. In this study, we infected the human macrophage-like cell line THP-1 with drug-sensitive and drug-resistant M. tuberculosis strains and found that tolerance developed to most antituberculosis drugs, including the newer agents moxifloxacin, PA-824, linezolid, and bedaquiline. Multiple efflux pump inhibitors in clinical use for other indications reversed tolerance to isoniazid and rifampicin and slowed intracellular growth. Moreover, verapamil reduced tolerance to bedaquiline and moxifloxacin. Verapamil's R isomer and its metabolite norverapamil have substantially less calcium channel blocking activity yet were similarly active as verapamil at inhibiting macrophage-induced drug tolerance. Our finding that verapamil inhibits intracellular M. tuberculosis growth and tolerance suggests its potential for treatment shortening. Norverapamil, R-verapamil, and potentially other derivatives present attractive alternatives that may have improved tolerability.
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Complete mitochondrial genome analysis and clinical documentation of a five-generational Indian family with mitochondrial 1555A>G mutation and postlingual hearing loss.
Ann. Hum. Genet.
PUBLISHED: 02-11-2014
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Hearing loss is the most common sensory disorder and is genetically heterogeneous. Apart from nuclear gene mutations, a number of inherited mitochondrial mutations have also been implicated. The m.1555A>G mutation in the mitochondrial MT-RNR1 gene is reported as the most common mutation causing nonsyndromic hearing loss in various ethnic populations. We report here for the first time the clinical, genetic and molecular characterisation of a single large five-generational Tamil-speaking South Indian family with maternally inherited nonsyndromic postlingual hearing loss. Molecular analysis led to identification of m.1555A>G in 28 maternal relatives with variable degree of phenotypic expression. The penetrance of hearing loss among the maternal relatives in this family was 55%. Sequence analysis of the complete mitochondrial genome in 36 members of this pedigree identified 25 known variants and one novel variant co-transmitted along with m.1555A>G mutation. The mtDNA haplotype analysis revealed that the maternal relatives carry the R*T2 haplotype similar to Europeans and South Asians. Sequencing of the coding exon of GJB2 nuclear gene did not show any pathogenic mutations. The results suggest that other nuclear or environmental modifying factors could have played a role in the differential expression of mutation m.1555A>G in postlingual hearing loss in this family.
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Analysis of sub-anatomic diffusion tensor imaging indices in white matter regions of Alzheimer with MMSE score.
Comput Methods Programs Biomed
PUBLISHED: 02-10-2014
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In this study, an attempt has been made to find the correlation between diffusion tensor imaging (DTI) indices of white matter (WM) regions and mini mental state examination (MMSE) score of Alzheimer patients. Diffusion weighted images are obtained from the ADNI database. These are preprocessed for eddy current correction and removal of non-brain tissue. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (DA) indices are computed over significant regions (Fornix left, Splenium of corpus callosum left, Splenium of corpus callosum right, bilateral genu of the corpus callosum) affected by Alzheimer disease (AD) pathology. The correlation is computed between diffusion indices of the significant regions and MMSE score using linear fit technique so as to find the relation between clinical parameters and the image features. Binary classification has been employed using support vector machine, decision stumps and simple logistic classifiers on the extracted DTI indices along with MMSE score to classify Alzheimer patients from healthy controls. It is observed that distinct values of DTI indices exist for the range of MMSE score. However, there is no strong correlation (Pearson's correlation coefficient 'r' varies from 0.0383 to -0.1924) between the MMSE score and the diffusion indices over the significant regions. Further, the performance evaluation of classifiers shows 94% accuracy using SVM in differentiating AD and control. In isolation clinical and image features can be used for prescreening and diagnosis of AD but no sub anatomic region correlation exist between these features set. The discussion on the correlation of diffusion indices of WM with MMSE score is presented in this study.
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Ground beetle, Opatroides frater (Coleoptera) as natural intermediate host for the poultry tapeworm, Raillietina cesticillus.
J Parasit Dis
PUBLISHED: 02-08-2014
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Poultry farms in and around Namakkal with a history of tapeworm infection were surveyed for the presence of beetles which could act as intermediate host for the tapeworms. Beetles collected from different poultry farms with suspected tapeworm infection were examined for the presence of metacestode stage of the parasite. A total of 1,880 beetles were collected from 12 poultry farms with suspected tapeworm infection to study the vector potentiality. Out of these, 205 beetles (10.9 %) from nine farms were found to harbour cysticercoids. The percentage of cysticercoid infection in beetles was 8.24, 10.34 and 16.66 % respectively in three different surveys. The beetles harbouring the cysticercoids were identified as Opatroides frater, which may be a natural intermediate host for Raillietina cesticillus. Infection free young chicks (4 weeks old) were experimentally infected with specific number of cysticercoids and prepatent period of tapeworms was found to be between 12 and 13 days. Gravid segments were expelled between 3 and 4 p.m. consistently. The results of this study would help to formulate suitable control measures against the above tapeworm infection.
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Vascular endothelial growth factor signaling in hypoxia and inflammation.
J Neuroimmune Pharmacol
PUBLISHED: 02-03-2014
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Infection, cancer and cardiovascular diseases are the major causes for morbidity and mortality in the United States according to the Center for Disease Control. The underlying etiology that contributes to the severity of these diseases is either hypoxia induced inflammation or inflammation resulting in hypoxia. Therefore, molecular mechanisms that regulate hypoxia-induced adaptive responses in cells are important areas of investigation. Oxygen availability is sensed by molecular switches which regulate synthesis and secretion of growth factors and inflammatory mediators. As a consequence, tissue microenvironment is altered by re-programming metabolic pathways, angiogenesis, vascular permeability, pH homeostasis to facilitate tissue remodeling. Hypoxia inducible factor (HIF) is the central mediator of hypoxic response. HIF regulates several hundred genes and vascular endothelial growth factor (VEGF) is one of the primary target genes. Understanding the regulation of HIF and its influence on inflammatory response offers unique opportunities for drug development to modulate inflammation and ischemia in pathological conditions.
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Periodically clickable polyesters: study of intrachain self-segregation induced folding, crystallization, and mesophase formation.
J. Am. Chem. Soc.
PUBLISHED: 01-28-2014
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A series of polyesters based on 2-propargyl-1,3-propanediol or 2,2-dipropargyl-1,3-propanediol or 2-allyl-2-propargyl-1,3-propanediol and 1,20-eicosanedioic acid were prepared by solution polycondensation using the corresponding diacid chloride; these polyesters were quantitatively "clicked" with a fluoroalkyl azide, namely CF3(CF2)7CH2CH2N3, to yield polyesters carrying long-chain alkylene segments in the backbone and either one or two perfluoroalkyl segments located at periodic intervals along the polymer chain. The immiscibility of the alkylene and fluoroalkyl segments causes the polymer chains to fold in a zigzag fashion to facilitate the segregation of these segments; the folded chains further organize in the solid state to form a lamellar structure with alternating domains of alkyl (HC) and fluoroalkyl (FC) segments. Evidence for the self-segregation is provided by DSC, SAXS, WAXS, and TEM studies; in two of the samples, the DSC thermograms showed two distinct endotherms associated with the melting of the individual domains, while the WAXS patterns confirm the existence of two separate peaks corresponding to the interchain distances within the crystalline lattices of the HC and FC domains. SAXS data, on the other hand, reveal the formation of an extended lamellar morphology with an interlamellar spacing that matches reasonably well with those estimated from TEM studies. Interestingly, a smectic-type liquid crystalline phase is observed at temperatures between the two melting transitions. These systems present a unique opportunity to develop interesting nanostructured polymeric materials with precise control over both the domain size and morphology; importantly, the domain sizes are far smaller than those typically observed in traditional block copolymers.
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Methamphetamine induces autophagy as a pro-survival response against apoptotic endothelial cell death through the Kappa opioid receptor.
Cell Death Dis
PUBLISHED: 01-27-2014
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Methamphetamine (METH) is a psychostimulant with high abuse potential and severe neurotoxicity. Recent studies in animal models have indicated that METH can impair the blood-brain barrier (BBB), suggesting that some of the neurotoxic effects resulting from METH abuse could be due to barrier disruption. We report here that while chronic exposure to METH disrupts barrier function of primary human brain microvascular endothelial cells (HBMECs) and human umbilical vein endothelial cells (HUVECs), an early pro-survival response is observed following acute exposure by induction of autophagic mechanisms. Acute METH exposure induces an early increase in Beclin1 and LC3 recruitment. This is mediated through inactivation of the protein kinase B (Akt)/mammalian target of rapamycin (mTOR)/p70S6K pathway, and upregulation of the ERK1/2. Blockade of Kappa opioid receptor (KOR), and treatment with autophagic inhibitors accelerated METH-induced apoptosis, suggesting that the early autophagic response is a survival mechanism for endothelial cells and is mediated through the kappa opioid receptor. Our studies indicate that kappa opioid receptor can be therapeutically exploited for attenuating METH-induced BBB dysfunction.
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Reasons for phosphate binder discontinuation vary by binder type.
J Ren Nutr
PUBLISHED: 01-24-2014
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Nonadherence to phosphate binder regimen is common among end-stage renal disease patients and contributes to elevated phosphorus levels. Pill burden, side effects, complex regimens, and cost all contribute to nonadherence. We retrospectively analyzed reasons for discontinuation in hemodialysis patients receiving treatment at a large U.S. dialysis organization to better understand the drivers of nonadherence for particular phosphate binders.
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Treosulfan, fludarabine, and 2-Gy total body irradiation followed by allogeneic hematopoietic cell transplantation in patients with myelodysplastic syndrome and acute myeloid leukemia.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-10-2014
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Allogeneic hematopoietic cell transplantation (HCT) offers curative therapy for many patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML). However, post-HCT relapse remains a major problem, particularly in patients with high-risk cytogenetics. In this prospective phase II trial, we assessed the efficacy and toxicity of treosulfan, fludarabine, and 2 Gy total body irradiation (TBI) as conditioning for allogeneic HCT in patients with MDS or AML. Ninety-six patients with MDS (n = 36: 15 refractory cytopenia with multilineage dysplasia, 10 refractory anemia with excess blasts type 1, 10 refractory anemia with excess blasts type 2, 1 chronic myelomonocytic leukemia type 1) or AML (n = 60: 35 first complete remission [CR], 18 second CR, 3 advanced CR, 4 refractory relapse) were enrolled; median age was 51 (range, 1 to 60) years. Twelve patients had undergone a prior HCT with high-intensity conditioning. Patients received 14 g/m(2)/day treosulfan i.v. on days -6 to -4, 30 mg/m(2)/day fludarabine i.v. on days -6 to -2, and 2 Gy TBI on day 0, followed by infusion of hematopoietic cells from related (n = 27) or unrelated (n = 69) donors. Graft-versus-host disease prophylaxis consisted of tacrolimus and methotrexate. With a median follow-up of 30 months, the 2-year overall survival (OS), relapse incidence, and nonrelapse mortality were 73%, 27%, and 8%, respectively. The incidences of grades II to IV (III to IV) acute and chronic graft-versus-host disease were 59% (10%) and 47%, respectively. Two-year OS was not significantly different between MDS patients with poor-risk and good/intermediate-risk cytogenetics (69% and 85%, respectively) or between AML patients with unfavorable and favorable/intermediate-risk cytogenetics (64% and 76%, respectively). In AML patients, minimal residual disease (MRD; n = 10) at the time of HCT predicted higher relapse incidence (70% versus 18%) and lower OS (41% versus 79%) at 2 years, when compared with patients without MRD. In conclusion, treosulfan, fludarabine, and low-dose TBI provided effective conditioning for allogeneic HCT in patients with MDS or AML and resulted in low relapse incidence, regardless of cytogenetic risk. In patients with AML, MRD at the time of HCT remained a risk factor for post-HCT relapse.
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Diagnostic imaging for dental implant therapy.
J Clin Imaging Sci
PUBLISHED: 01-01-2014
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Dental implant is a device made of alloplastic (foreign) material implanted into the jaw bone beneath the mucosal layer to support a fixed or removable dental prosthesis. Dental implants are gaining immense popularity and wide acceptance because they not only replace lost teeth but also provide permanent restorations that do not interfere with oral function or speech or compromise the self-esteem of a patient. Appropriate treatment planning for replacement of lost teeth is required and imaging plays a pivotal role to ensure a satisfactory outcome. The development of pre-surgical imaging techniques and surgical templates helps the dentist place the implants with relative ease. This article focuses on various types of imaging modalities that have a pivotal role in implant therapy.
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The application of gaussian mixture models for signal quantification in maldi-tof mass spectrometry of peptides.
PLoS ONE
PUBLISHED: 01-01-2014
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Matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) coupled with stable isotope standards (SIS) has been used to quantify native peptides. This peptide quantification by MALDI-TOF approach has difficulties quantifying samples containing peptides with ion currents in overlapping spectra. In these overlapping spectra the currents sum together, which modify the peak heights and make normal SIS estimation problematic. An approach using Gaussian mixtures based on known physical constants to model the isotopic cluster of a known compound is proposed here. The characteristics of this approach are examined for single and overlapping compounds. The approach is compared to two commonly used SIS quantification methods for single compound, namely Peak Intensity method and Riemann sum area under the curve (AUC) method. For studying the characteristics of the Gaussian mixture method, Angiotensin II, Angiotensin-2-10, and Angiotenisn-1-9 and their associated SIS peptides were used. The findings suggest, Gaussian mixture method has similar characteristics as the two methods compared for estimating the quantity of isolated isotopic clusters for single compounds. All three methods were tested using MALDI-TOF mass spectra collected for peptides of the renin-angiotensin system. The Gaussian mixture method accurately estimated the native to labeled ratio of several isolated angiotensin peptides (5.2% error in ratio estimation) with similar estimation errors to those calculated using peak intensity and Riemann sum AUC methods (5.9% and 7.7%, respectively). For overlapping angiotensin peptides, (where the other two methods are not applicable) the estimation error of the Gaussian mixture was 6.8%, which is within the acceptable range. In summary, for single compounds the Gaussian mixture method is equivalent or marginally superior compared to the existing methods of peptide quantification and is capable of quantifying overlapping (convolved) peptides within the acceptable margin of error.
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The KDM2B- let-7b -EZH2 axis in myelodysplastic syndromes as a target for combined epigenetic therapy.
PLoS ONE
PUBLISHED: 01-01-2014
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Both DNA and histone methylation are dysregulated in the myelodysplastic syndromes (MDS). Based on preliminary data we hypothesized that dysregulated interactions of KDM2B, let-7b and EZH2 signals lead to an aberrant epigenetic landscape. Gene expression in CD34+ cells from MDS marrows was analyzed by NanoString miR array and validated by real-time polymerase chain reaction (PCR). The functions of KDM2B, let-7b and EZH2 were characterized in myeloid cell lines and in primary MDS cells. Let-7b levels were significantly higher, and KDM2B and EZH2 expression was lower in primary CD34+ MDS marrow cells (n = 44) than in healthy controls (n = 21; p<0.013, and p<0.0001, respectively). Overexpression of let-7b reduced EZH2 and KDM2B protein levels, and decreased cells in S-phase while increasing G0/G1 cells (p = 0.0005), accompanied by decreased H3K27me3 and cyclin D1. Silencing of KDM2B increased let-7b expression. Treatment with the cyclopentanyl analog of 3-deazaadenosine, DZNep, combined with the DNA hypomethylating agent 5-azacitidine, decreased levels of EZH2, suppressed methylation of di- and tri-methylated H3K27, and increased p16 expression, associated with cell proliferation. Thus, KDM2B, via let-7b/EZH2, promotes transcriptional repression. DZNep bypassed the inhibitory KDM2B/let-7b/EZH2 axis by preventing H3K27 methylation and reducing cell proliferation. DZNep might be able to enhance the therapeutic effects of DNA hypomethylating agents such as 5-azacitidine, currently considered standard therapy for patients with MDS.
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Inhibition of Hsp90 augments docetaxel therapy in castrate resistant prostate cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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First line treatment of patients with castrate resistant prostate cancer (CRPC) primarily involves administration of docetaxel chemotherapy. Unfortunately, resistance to docetaxel therapy is an ultimate occurrence. Alterations in androgen receptor (AR) expression and signaling are associated mechanisms underlying resistance to docetaxel treatment in CRPC. Heat shock protein 90 (Hsp90) is a molecular chaperone, which regulates the activation, maturation and stability of critical signaling proteins involved in prostate cancer, including the AR. This knowledge and recent advances in compound design and development have highlighted Hsp90 as an attractive therapeutic target for the treatment of CRPC. We recently reported the development of a MYC-CaP castrate resistant (MYC-CaP/CR) transplant tumor model, which expresses amplified wild type AR. Within, we report that a second generation Hsp90 inhibitor, NVP-AUY922, inhibits cell growth and significantly induces cell death in MYC-CaP/CR and Pten-CaP/cE2 cell lines. NVP-AUY922 induced proteasome degradation of AR, though interestingly does not require loss of AR protein to inhibit AR transcriptional activity. Further, NVP-AUY922 increased docetaxel toxicity in MYC-CaP/CR and Pten-CaP/cE2 cell lines in vitro. Finally, NVP-AUY922/docetaxel combination therapy in mice bearing MYC-CaP/CR tumors resulted in greater anti-tumor activity compared to single treatment. This study demonstrates that NVP-AUY922 elicits potent activity towards AR signaling and augments chemotherapy response in a mouse model of CRPC, providing rationale for the continued clinical development of Hsp90 inhibitors in clinical trials for treatment of CRPC patients.
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Mixed fortunes: ancient expansion and recent decline in population size of a subtropical montane primate, the Arunachal macaque Macaca munzala.
PLoS ONE
PUBLISHED: 01-01-2014
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Quaternary glacial oscillations are known to have caused population size fluctuations in many temperate species. Species from subtropical and tropical regions are, however, considerably less studied, despite representing most of the biodiversity hotspots in the world including many highly threatened by anthropogenic activities such as hunting. These regions, consequently, pose a significant knowledge gap in terms of how their fauna have typically responded to past climatic changes. We studied an endangered primate, the Arunachal macaque Macaca munzala, from the subtropical southern edge of the Tibetan plateau, a part of the Eastern Himalaya biodiversity hotspot, also known to be highly threatened due to rampant hunting. We employed a 534 bp-long mitochondrial DNA sequence and 22 autosomal microsatellite loci to investigate the factors that have potentially shaped the demographic history of the species. Analysing the genetic data with traditional statistical methods and advance Bayesian inferential approaches, we demonstrate a limited effect of past glacial fluctuations on the demographic history of the species before the last glacial maximum, approximately 20,000 years ago. This was, however, immediately followed by a significant population expansion possibly due to warmer climatic conditions, approximately 15,000 years ago. These changes may thus represent an apparent balance between that displayed by the relatively climatically stable tropics and those of the more severe, temperate environments of the past. This study also draws attention to the possibility that a cold-tolerant species like the Arunachal macaque, which could withstand historical climate fluctuations and grow once the climate became conducive, may actually be extremely vulnerable to anthropogenic exploitation, as is perhaps indicated by its Holocene ca. 30-fold population decline, approximately 3,500 years ago. Our study thus provides a quantitative appraisal of these demographically important events, emphasising the ability to potentially infer the occurrence of two separate historical events from contemporary genetic data.
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Evidence of a novel mechanism for partial ?-secretase inhibition induced paradoxical increase in secreted amyloid ? protein.
PLoS ONE
PUBLISHED: 01-01-2014
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BACE1 (?-secretase) and ?-secretase cleave the Alzheimer's amyloid ? protein (A?) precursor (APP) to C-terminal fragments of 99 aa (CTF?) and 83 aa (CTF?), respectively, which are further cleaved by ?-secretase to eventually secrete A? and A? (a.k.a. P3) that terminate predominantly at residues 40 and 42. A number of ?-secretase inhibitors (GSIs), such as N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester (DAPT), have been developed with the goal of reducing A? to treat Alzheimer's disease (AD). Although most studies show that DAPT inhibits A? in a dose-dependent manner several studies have also detected a biphasic effect with an unexpected increase at low doses of DAPT in cell cultures, animal models and clinical trials. In this article, we confirm the increase in A?40 and A?42 in SH-SY5Y human neuroblastoma cells treated with low doses of DAPT and identify one of the mechanisms for this paradox. We studied the pathway by first demonstrating that stimulation of A?, a product of ?-secretase, was accompanied by a parallel increase of its substrate CTF?, thereby demonstrating that the inhibitor was not anomalously stimulating enzyme activity at low levels. Secondly, we have demonstrated that inhibition of an A? degrading activity, endothelin converting enzyme (ECE), yielded more A?, but abolished the DAPT-induced stimulation. Finally, we have demonstrated that A?, which is generated in the secretory pathway before endocytosis, is not subject to the DAPT-mediated stimulation. We therefore conclude that impairment of ?-secretase can paradoxically increase A? by transiently skirting A? degradation in the endosome. This study adds to the growing body of literature suggesting that preserving ?-secretase activity, rather than inhibiting it, is important for prevention of neurodegeneration.
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Clinical characteristics and outcomes of end-stage renal disease patients with self-reported pruritus symptoms.
Int J Nephrol Renovasc Dis
PUBLISHED: 12-19-2013
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One of the most common conditions affecting end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) is pruritus. Studies report that itchy and dry skin, symptoms of pruritus, affect 40%-90% of ESRD patients. Yet, in clinical practice the condition is often underdiagnosed resulting in inadequate management and an underappreciated impact on patient outcomes. Two retrospective analyses were conducted: a preliminary analysis of ESRD patients with pruritus symptoms (n=73,124) undergoing HD or peritoneal dialysis at a large dialysis provider and a subsequent detailed analysis of a homogenous subset of patients undergoing in-center HD (n=38,315). The goal was to better understand the clinical burden of pruritus as it relates to patient characteristics, quality of life, medication use, and HD compliance. This population is commonly burdened by multiple comorbidities and related polypharmaceutical management; identifying the relationship of pruritus to these ailments can help guide future research and resource allocation. The detailed analysis confirmed trends observed in the preliminary analysis: 30% reported being "moderately" to "extremely bothered" by itchiness. The HD patient population with the highest severity of self-reported pruritus also had a consistent trend in overall increased resource utilization - higher monthly doses of erythropoietin-stimulating agents (53,397.1 to 63,405.4 units) and intravenous (IV) iron (237.2 to 247.6 units) and higher use of IV antibiotics (14.1% to 20.7%), as well as poorer quality-of-life measures (25-point reductions in Burden of Disease Score and Effects on Daily Life subscales of the Kidney Disease Quality of Life-36 survey). These results highlight the need to better identify and manage ESRD patients impacted by pruritus, as this symptom is associated with negative clinical outcomes and increased resource utilization. Further studies are needed to evaluate the current economic burden of pruritus in ESRD patients and create possible options for an improved pharmacoeconomic profile in this patient population.
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Use of ?-Blockade and Levosimendan for Separation From Extracorporeal Life Support in an Infant With Postoperative Diastolic Dysfunction.
World J Pediatr Congenit Heart Surg
PUBLISHED: 12-12-2013
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Diastolic dysfunction is common in infants and neonates with left ventricular (LV) outflow tract obstruction and may lead to low-cardiac output in the postoperative period. We present a management strategy for severe postrepair diastolic dysfunction in an infant with critical congenital aortic stenosis and LV hypertrophy, employing ?-blockade and levosimendan.
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A Call for Tiger Management Using "Reserves" of Genetic Diversity.
J. Hered.
PUBLISHED: 12-11-2013
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Tigers (Panthera tigris), like many large carnivores, are threatened by anthropogenic impacts, primarily habitat loss and poaching. Current conservation plans for tigers focus on population expansion, with the goal of doubling census size in the next 10 years. Previous studies have shown that because the demographic decline was recent, tiger populations still retain a large amount of genetic diversity. Although maintaining this diversity is extremely important to avoid deleterious effects of inbreeding, management plans have yet to consider predictive genetic models. We used coalescent simulations based on previously sequenced mitochondrial fragments (n = 125) from 5 of 6 extant subspecies to predict the population growth needed to maintain current genetic diversity over the next 150 years. We found that the level of gene flow between populations has a large effect on the local population growth necessary to maintain genetic diversity, without which tigers may face decreases in fitness. In the absence of gene flow, we demonstrate that maintaining genetic diversity is impossible based on known demographic parameters for the species. Thus, managing for the genetic diversity of the species should be prioritized over the riskier preservation of distinct subspecies. These predictive simulations provide unique management insights, hitherto not possible using existing analytical methods.
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Stretching single polymer chains of donor-acceptor foldamers: toward the quantitative study on the extent of folding.
Langmuir
PUBLISHED: 11-14-2013
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Single-molecule force spectroscopy has proven to be an efficient tool for the quantitative characterization of flexible foldamers on the single-molecule level in this study. The extent of folding has been estimated quantitatively for the first time to the best of our knowledge, which is crucial for a better understanding of the "folding-process" on single-molecule level. Therefore, this study may provide a guidance to regulate folding for realizing rational control over the functions of bulk materials.
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Antimicrobial Efflux Pumps and Mycobacterium tuberculosis Drug Tolerance: Evolutionary Considerations.
Curr. Top. Microbiol. Immunol.
PUBLISHED: 11-08-2013
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The need for lengthy treatment to cure tuberculosis stems from phenotypic drug resistance, also known as drug tolerance, which has been previously attributed to slowed bacterial growth in vivo. We discuss recent findings that challenge this model and instead implicate macrophage-induced mycobacterial efflux pumps in antimicrobial tolerance. Although mycobacterial efflux pumps may have originally served to protect against environmental toxins, in the pathogenic mycobacteria, they appear to have been repurposed for intracellular growth. In this light, we discuss the potential of efflux pump inhibitors such as verapamil to shorten tuberculosis treatment by their dual inhibition of tolerance and growth.
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Combinatorial antitumor effect of HDAC and the PI3K-Akt-mTOR pathway inhibition in a Pten defecient model of prostate cancer.
Oncotarget
PUBLISHED: 10-29-2013
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Increased expression of histone deacetylases (HDACs) and activation of the PI3K-Akt-mTORC1 pathway are common aberrations in prostate cancer (PCa). For this reason, inhibition of such targets is an exciting avenue for the development of novel therapeutic strategies to treat patients with advanced PCa. Previous reports demonstrated that HDAC inhibitors (HDACi) increases DNA damage and induce greater apoptosis in PCa cell lines that express androgen receptor (AR). In this study we utilized the AR negative PCa cell line and observed that re-expression of AR (PC3-AR) results in greater levels of apoptosis when treated with the pan-DACi, panobinostat (PAN). PAN mediated apoptosis in PC3 and PC3-AR cells was associated with increased levels of double strand DNA breaks, indicated by p-?H2AX. Further, PAN treatment in PC3-AR cells resulted in moderate attenuation of the ATM-Akt-ERK DNA damage response pathway. For this reason, we combined PAN with the dual PI3K-mTOR inhibitor, BEZ235. Combination of PAN with BEZ235 resulted in significant attenuation of the DNA damage repair protein ATM and significantly increased anti-tumor activity compared to each single treatment. Overall, superior anti-tumor activity with combination of PAN with BEZ235 was independent of AR status. These findings suggest that this therapeutic strategy should be further developed in clinical trials.
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A novel photodegradable hyperbranched polymeric photoresist.
Chem. Commun. (Camb.)
PUBLISHED: 10-22-2013
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We report the first synthesis of a photodegradable hyperbranched polyacetal, wherein every repeat unit carries a photo-labile 2-nitrobenzyloxy moiety. The pristine HBP serves as a positive photoresist to create micron-size patterns; furthermore, by changing the terminal groups to dipropargyl acetal, clickable photo-patterned substrates can be generated.
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Identification of brain white matter regions for diagnosis of Alzheimer using Diffusion Tensor Imaging.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Diffusion Tensor Imaging (DTI) technique is widely used to probe the white matter (WM) tracts, which is affected most by neurological disorders. The fractional anisotropy (FA) metric has been used predominantly to study changes in the WM tracts. Here an attempt is made to delineate specific regions of interest in the WM that may be probable indicators for the diagnosis of Alzheimer disease (AD). Genetic algorithm has been used as feature reduction method along with Adaptive Boosting (AdaBoost) machine learning technique to determine the most prominent regions in the WM that are indicators of AD. It is found in this study that Fornix region of WM is most affected by Alzheimer. Further, classification was done to differentiate between Alzheimer and Normal controls with accuracy of 84.5%. The results obtained were validated by comparing with the existing literature on Alzheimer.
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Serum phosphorus levels and pill burden are inversely associated with adherence in patients on hemodialysis.
Nephrol. Dial. Transplant.
PUBLISHED: 09-05-2013
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Phosphate binders (PBs) account for about one half of the daily pill burden for US hemodialysis (HD) patients, which may reduce adherence. Adherence can be estimated by the medication possession ratio (MPR), which is defined as the proportion of time a patient had sufficient medication to have taken it as prescribed. Gaps of time between prescription fills lower the patients MPR. We assessed the association of PB pill burden and adherence (MPR) with phosphorus goal attainment.
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Primary marrow-derived stromal cells: isolation and manipulation.
Methods Mol. Biol.
PUBLISHED: 08-21-2013
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Marrow stromal cells (MSCs) are relatively rare cells difficult to visualize in marrow biopsies or detect in aspirated marrow. Under specific conditions MSC can be expanded in vitro and the population can give rise to several mesenchymal lineages. "MSC" also refers to mesenchymal stem cells which implies that all cells in the population are multipotent. It is generally agreed that while there may be a few multipotent stem cells in an MSC population the majority are not stem cells. In either case MSCs do not produce hematopoietic cells. Although MSCs have been isolated and characterized from several tissues, bone marrow is their most common source for research and clinical use. Primary MSC populations can be derived from bone marrow mononuclear cells with relative ease, but it is important to recognize the cellular heterogeneity within a culture and how this may vary from donor to donor. In this chapter, we describe methodology to derive primary MSCs from bone marrow screens, an otherwise discarded by-product of bone marrow harvests used for clinical transplantation. We also describe some useful techniques to characterize and manipulate MSCs-both primary and immortalized cell lines.
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Histone modifications: implications in renal cell carcinoma.
Epigenomics
PUBLISHED: 07-31-2013
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In 2012, an estimated 64,770 men and women were diagnosed with malignancy of the kidney and renal pelvis, of which 13,570 succumbed to their disease. Common genetic aberrations in renal cell carcinomas (RCCs) include loss of function of the VHL gene in clear-cell RCC, overexpression of the c-MET gene in papillary RCC type I, deficiency in the FH gene in papillary RCC type II and loss of heterozygozity of the BHD gene in chromophobe RCC. Recent studies illustrate epigenetic silencing of VHL, as well as alterations in histone modifications and their governing enzymes. The possibility of reversing these epigenetic marks has resulted in efforts to target these changes by utilizing inhibitors of HDACs, DNA methyltransferases and, recently, histone methyltransferases in preclinical and clinical studies. This article focuses on potential therapeutic interventions, and the implications of histone modifications and related enzyme alterations in RCC.
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Histone deacetylase inhibitors and epigenetic modifications as a novel strategy in renal cell carcinoma.
Cancer J
PUBLISHED: 07-23-2013
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Recent investigations of renal cell carcinoma (RCC) have revealed several epigenetic modifications, as well as alterations in the genes and enzymes that regulate these changes. Preclinical models have revealed that histone gene modifiers and epigenetic alterations may play a critical role in RCC tumorigenesis. Specific changes in DNA methylation and mutations of histone modifiers have been identified and may be associated with an aggressive phenotype. In addition, the potential of reversing the effects of these enzymes and hence reversing the cellular epigenetic landscape to a "normal phenotype" have led to an increasing interest in developing targeted chromatin remodeling agents. However, the translation of the understanding of these changes to the clinic for the treatment of RCC has posed significant challenges, partly due to tumor heterogeneity. This review describes the aberrant histone and DNA alterations recently reported in RCC and highlights the potential targeted chromatin remodeling therapies in the management of this disease.
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A comparative clinical study of the efficacy of subepithelial connective tissue graft and acellular dermal matrix graft in root coverage: 6-month follow-up observation.
J Indian Soc Periodontol
PUBLISHED: 07-18-2013
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The purpose of this study was to compare the clinical efficacy of subepithelial connective tissue graft and acellular dermal matrix graft associated with coronally repositioned flap in the treatment of Millers class I and II gingival recession, 6 months postoperatively.
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A learning-enabled neuron array IC based upon transistor channel models of biological phenomena.
IEEE Trans Biomed Circuits Syst
PUBLISHED: 07-16-2013
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We present a single-chip array of 100 biologically-based electronic neuron models interconnected to each other and the outside environment through 30,000 synapses. The chip was fabricated in a standard 350 nm CMOS IC process. Our approach used dense circuit models of synaptic behavior, including biological computation and learning, as well as transistor channel models. We use Address-Event Representation (AER) spike communication for inputs and outputs to this IC. We present the IC architecture and infrastructure, including IC chip, configuration tools, and testing platform. We present measurement of small network of neurons, measurement of STDP neuron dynamics, and measurement from a compiled spiking neuron WTA topology, all compiled into this IC.
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Baseline regional perfusion impacts exercise response to endobronchial valve therapy in advanced pulmonary emphysema.
Chest
PUBLISHED: 07-06-2013
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Advanced heterogeneous emphysema with hyperinflation impacts exercise tolerance in COPD. Bronchoscopic lung volume reduction using Zephyr endobronchial valves (EBVs) has been shown to improve lung function in patients with heterogeneous emphysema. It is unclear whether the target lobe perfusion of patients receiving EBV therapy impacts exercise tolerance as measured by the 6-min walk test distance (6MWTD).
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Native valve Escherichia coli endocarditis following urosepsis.
Indian J Nephrol
PUBLISHED: 07-02-2013
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Gram-negative organisms are a rare cause of infective endocarditis. Escherichia coli, the most common cause of urinary tract infection and gram-negative septicemia involves endocardium rarely. In this case report, we describe infection of native mitral valve by E. coli following septicemia of urinary tract origin in a diabetic male; subsequently, he required prosthetic tissue valve replacement indicated by persistent sepsis and congestive cardiac failure.
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Regression analysis of ordinal stroke clinical trial outcomes: An application to the NINDS t-PA trial.
Int J Stroke
PUBLISHED: 06-27-2013
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The modified Rankin scale (mRS) is the most common functional outcome assessed in stroke trials. The proportional odds model is commonly used to analyze this ordinal outcome but it requires a restrictive assumption that a single odds ratio applies across the entire outcome scale.
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TB: the Yin and Yang of lipid mediators.
Curr Opin Pharmacol
PUBLISHED: 06-18-2013
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There is a growing appreciation of the diverse roles that lipid mediators play in modulating inflammatory responses during infection. In the case of tuberculosis, virulent mycobacteria induce host production of anti-inflammatory mediators, including lipoxins, which limit the host inflammatory response and lead to necrotic cell death of infected macrophages. Recent work using the zebrafish model suggests that, while excess anti-inflammatory lipoxins are host detrimental during mycobacterial infections, excess pro-inflammatory lipids also drive host susceptibility. The balance of these inflammatory states is influenced by common human genetic variation in Asia. Fuller understanding of the mechanisms of eicosanoid-mediated inflammatory imbalance during tuberculosis infection has important implications for the development of adjunctive therapies.
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Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids.
Nature
PUBLISHED: 05-21-2013
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The evolutionary survival of Mycobacterium tuberculosis, the cause of human tuberculosis, depends on its ability to invade the host, replicate, and transmit infection. At its initial peripheral infection site in the distal lung airways, M. tuberculosis infects macrophages, which transport it to deeper tissues. How mycobacteria survive in these broadly microbicidal cells is an important question. Here we show in mice and zebrafish that M. tuberculosis, and its close pathogenic relative Mycobacterium marinum, preferentially recruit and infect permissive macrophages while evading microbicidal ones. This immune evasion is accomplished by using cell-surface-associated phthiocerol dimycoceroserate (PDIM) lipids to mask underlying pathogen-associated molecular patterns (PAMPs). In the absence of PDIM, these PAMPs signal a Toll-like receptor (TLR)-dependent recruitment of macrophages that produce microbicidal reactive nitrogen species. Concordantly, the related phenolic glycolipids (PGLs) promote the recruitment of permissive macrophages through a host chemokine receptor 2 (CCR2)-mediated pathway. Thus, we have identified coordinated roles for PDIM, known to be essential for mycobacterial virulence, and PGL, which (along with CCR2) is known to be associated with human tuberculosis. Our findings also suggest an explanation for the longstanding observation that M. tuberculosis initiates infection in the relatively sterile environment of the lower respiratory tract, rather than in the upper respiratory tract, where resident microflora and inhaled environmental microbes may continually recruit microbicidal macrophages through TLR-dependent signalling.
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Segmentation of ct liver images using phase based level set method - biomed 2013.
Biomed Sci Instrum
PUBLISHED: 05-21-2013
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Segmentation of Liver from Abdominal CT images has received much importance due to its complexity, as the intensity of the liver is quite similar to those of other organs surrounding it. Hence, intensity based edge operators fail to segment the liver accurately. In this work, an attempt has been made to segment liver from abdominal CT images using phase-based level set method. CT images used in this work were acquired from open source online database MIDAS and nearby hospitals. These images were subjected to phase-based distance regularized level set segmentation. A distance regularization term proposed by Chumming Li et al. was used in the energy function of level set method, to maintain stability of the evolving contour. This energy function was minimized to obtain the final contour. The phase congruency measure proposed by Kovesi was used as an edge detector for the evolution of level set function. The segmentation results were compared with the ground truth using similarity measures. It was observed that the implemented technique resulted in better similarity index and they were close to the ideal values. Leakage of contour was avoided as phase information lead to robust convergence at edges. Edges and lines were found to be well distinguished using phase congruency information. As CT images are found to be helpful in detection and characterization of abnormalities in liver like hepatoma, cysts and tumors, the proposed study seems to be clinically relevant.
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Evaluation of human hand thermal images using wavelet transform based local spatial features - biomed 2013.
Biomed Sci Instrum
PUBLISHED: 05-21-2013
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Transform-based spatial analyses of medical Infrared (IR) images are found to be useful to extract local information, which can be used to identify the abnormalities associated with in region of interest. In this work, human hand infrared images are analyzed by extracting local spatial features using wavelet transform method. The images for this study were acquired using uncooled micro bolometer with focal plane array technology based medical IR camera with dedicated software having high array resolution and spectral response under controlled protocol. The acquired images were decomposed into Intrinsic Mode Functions (IMFs) using bidimensional empirical mode decomposition. Extrema points were detected using eight connected neighbor window method and interpolated using thin plate spline interpolation technique to generate IMFs. The edge information were extracted from local phase of the first IMF. Edges were detected using phase congruency measure by applying Gabor function based wavelet transform. The results showed that it was possible to detect edges from only the first IMF without being influenced by other IMFs. It was further observed that the edge intermittence that arises due to noise component was reduced by treating images with local phase distributions. Hence, it appears that the edge information extraction could enhance the diagnostic relevance of thermal image analysis.
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Evaluation of the pathogenesis and treatment of Mycobacterium marinum infection in zebrafish.
Nat Protoc
PUBLISHED: 05-16-2013
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Mycobacterium marinum-infected zebrafish are used to study tuberculosis pathogenesis, as well as for antitubercular drug discovery. The small size of zebrafish larvae coupled with their optical transparency allows for rapid analysis of bacterial burdens and host survival in response to genetic and pharmacological manipulations of both mycobacteria and host. Automated fluorescence microscopy and automated plate fluorimetry (APF) are coupled with facile husbandry to facilitate large-scale, repeated analysis of individual infected fish. Both methods allow for in vivo screening of chemical libraries, requiring only 0.1 ?mol of drug per fish to assess efficacy; they also permit a more detailed evaluation of the individual stages of tuberculosis pathogenesis. Here we describe a 16-h protocol spanning 22 d, in which zebrafish larvae are infected via the two primary injection sites, the hindbrain ventricle and caudal vein; this is followed by the high-throughput evaluation of pathogenesis and antimicrobial efficacy.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.