25 research outputs found
The Marble Man: Images Depict Lee, His Friends, And His Legend
No full textRobert E. Lee: An Album tells of Lee\u27s life through images. This book is an album in the literal sense, author Emory M. Thomas explains. It contains pictures, contemporary with Lee and with us, of places associated with Lee. It includes pictures of people Lee knew and pictures of Lee. Here...
Causes of Death in the United States, 1999 to 2014
No full textStatistical methods have been widely used in studies of public health. Although useful in clinical research and public health policy making, these methods could not find correlation among health conditions automatically, or capture the temporal evolution of causes of death correctly. To cope with two challenges above, we implement the unsupervised machine learning method "topic model" to study the United States death reporting data. Our model successfully groups morbidities based on their correlation, and reveals the temporal evolution of these groups from 1999 to 2014. This result is validated by existing literature, and provides a novel view that enables clinical practitioners to make more accurate healthcare decisions, and public health policymakers to make better policy.Department of Biomedical Engineering, Peking University, ChinaCPCI-S(ISTP)177-18
Identification of a Novel UT-B Urea Transporter in Human Urothelial Cancer
No full textThe urea transporter UT-B is widely expressed and has been studied in erythrocyte, kidney, brain and intestines. Interestingly, UT-B gene has been found more abundant in bladder than any other tissue. Recently, gene analyses demonstrate that SLC14A1 (UT-B) gene mutations are associated with bladder cancer, suggesting that urea transporter UT-B may play an important role in bladder carcinogenesis. In this study, we examined UT-B expression in bladder cancer with human primary bladder cancer tissues and cancer derived cell lines. Human UT-B has two isoforms. We found that normal bladder expresses long form of UT-B2 but was lost in 8 of 24 (33%) or significantly downregulated in 16 of 24 (67%) of primary bladder cancer patients. In contrast, the short form of UT-B1 lacking exon 3 was detected in 20 bladder cancer samples. Surprisingly, a 24-nt in-frame deletion in exon 4 in UT-B1 (UT-B1 1 24) was identified in 11 of 20 (55%) bladder tumors. This deletion caused a functional defect of UT-B1. Immunohistochemistry revealed that UT-B protein levels were significantly decreased in bladder cancers. Western blot analysis showed a weak UT-B band of 40 kDa in some tumors, consistent with UT-B1 gene expression detected by RT-PCR. Interestingly, bladder cancer associate UT-B1 1 24 was barely sialylated, reflecting impaired glycosylation of UT-B1 in bladder tumors. In conclusion, SLC14A1 gene and UT-B protein expression are significantly changed in bladder cancers. The aberrant UT-B expression may promote bladder cancer development or facilitate carcinogenesis induced by other carcinogens.Emory URC grant; NIH [R01-DK087838, R01-DK89828, R01-DK41707]; China Scholarship Council (CSC) under the State Scholarship FundSCI(E)ARTICLE
Urea transporter physiology studied in knockout mice
No full textIn mammals, there are two types of urea transporters (UTs), UT-A and UT-B. The UT-A transporter is mainly expressed in kidney epithelial cells; while UT-B demonstrates a broader distribution in kidney, heart, brain, testis, urinary tract and other tissues. Over the past few years, multiple UT knockout mouse models have been generated enabling us to explore the physiological roles of the different UTs. In the kidney, deletion of UTA1/A3 results in polyuria and a severe urine concentrating defect, indicating that intrarenal recycling of urea plays a crucial role in the overall capacity to concentrate urine. Since UT-B has a wide distribution, multiple phenotypic abnormalities were found in UT-B null mice, such as defective urine concentration, heart block with aging, depression-like behavior and earlier male sexual maturation. This review summarizes the new insights of urea transporter functions in different organs from UT knockout mice. Finally, we take a glance at the pharmacological prospect of UTs
Early Life Exposure to the 1959-1961 Chinese Famine Has Long-Term Health Consequences
No full textThe Chinese famine of 1959-1961 was the largest in human history. We used data on 35,025 women born in 1957-1963 to assess the impact of famine exposure on height, BMI, and hypertension at similar to 32 y of age. The data were from the China-U.S. Collaborative Project for Neural Tube Defect Prevention. The famine varied in intensity across provinces and counties and affected rural areas disproportionately. We used a measure of famine intensity at the county level based on the size of birth year cohorts in a difference-in-difference model, which compared each cohort to the unexposed 1963 cohort, after correcting for age and time trends, and estimated impact for the average level of intensity across counties. The impact was confined to rural areas, but this could be due to small sample sizes in urban areas. Height was reduced in the 1958 and 1959 cohorts by 1.7 and 1.3 cm, respectively. This corresponded to exposures during 0.5-3.5 y for the 1958 cohort and late pregnancy and 0-2.5 y for the 1959 cohort. BMI increased by 0.92 kg/m(2) in the 1957 cohort, exposed from 1.5 to 4.5 y, but decreased by 0.3 kg/m(2) in the 1960-1961 cohorts, exposed during pregnancy and infancy. Famine exposure was associated with a 3-fold increase in the odds of hypertension for the 1958 cohort. In general, postnatal exposure during the first 2-3 y of life reduced height and increased BMI and hypertension, whereas exposure during pregnancy and infancy reduced BMI. J. Nutr. 140: 1874-1878, 2010.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000286086300025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701Nutrition & DieteticsSCI(E)SSCI52ARTICLE101874-187814
NSAIDs Alter Phosphorylated Forms of AQP2 in the Inner Medullary Tip.
No full textVasopressin increases urine concentration through activation of aquaporin-2 (AQP2) in the collecting duct. Nonsteroidal anti-inflammatory drugs (NSAIDs) block prostaglandin E2 synthesis, and may suppress AQP2 producing a urine concentrating defect. There are four serines in AQP2 that are phosphorylated by vasopressin. To determine if chronic use of NSAIDs changes AQP2's phosphorylation at any of these residues, the effects of a non-selective NSAID, ibuprofen, and a COX-2-selective NSAID, meloxicam, were investigated. Daily ibuprofen or meloxicam increased the urine output and decreased the urine osmolality significantly by days 7 through 14. Concomitantly, meloxicam significantly reduced total AQP2 protein abundance in inner medulla (IM) tip to 64% of control and base to 63%, respectively. Ibuprofen significantly decreased total AQP2 in IM tip to 70% of control, with no change in base. Meloxicam significantly increased the ratios of p256-AQP2 and p261-AQP2 to total AQP2 in IM tip (to 44% and 40%, respectively). Ibuprofen increased the ratio of p256-AQP2 to total AQP2 in IM tip but did not affect p261-AQP2/total AQP2 in tip or base. Both ibuprofen and meloxicam increased p264-AQP2 and p269-AQP2 ratios in both tip and base. Ibuprofen increased UT-A1 levels in IM tip, but not in base. We conclude that NSAIDs reduce AQP2 abundance, contributing to decreased urine concentrating ability. They also increase some phosphorylated forms of AQP2. These changes may partially compensate for the decrease in AQP2 abundance, thereby lessening the decrease in urine osmolality
<sup>64</sup>Cu-Doped PdCu@Au Tripods: A Multifunctional Nanomaterial for Positron Emission Tomography and Image-Guided Photothermal Cancer Treatment
No full textThis article reports a facile synthesis
of radiolabeled PdCu@Au
core–shell tripods for use in positron emission tomography
(PET) and image-guided photothermal cancer treatment by directly incorporating
radioactive <sup>64</sup>Cu atoms into the crystal lattice. The tripod
had a unique morphology determined by the PdCu tripod that served
as a template for the coating of Au shell, in addition to well-controlled
specific activity and physical dimensions. The Au shell provided the
nanostructure with strong absorption in the near-infrared region and
effectively prevented the Cu and <sup>64</sup>Cu atoms in the core
from oxidization and dissolution. When conjugated with d-Ala<sub>1</sub>-peptide T-amide (DAPTA), the core–shell tripods showed
great enhancement in targeting the C–C chemokine receptor 5
(CCR5), a newly identified theranostic target up-regulated in triple
negative breast cancer (TNBC). Specifically, the CCR5-targeted tripods
with an arm length of about 45 nm showed 2- and 6-fold increase in
tumor-to-blood and tumor-to-muscle uptake ratios, respectively, relative
to their nontargeted counterpart in an orthotopic mouse 4T1 TNBC model
at 24 h postinjection. The targeting specificity was further validated <i>via</i> a competitive receptor blocking study. We also demonstrated
the use of these targeted, radioactive tripods for effective photothermal
treatment in the 4T1 tumor model as guided by PET imaging. The efficacy
of treatment was confirmed by the significant reduction in tumor metabolic
activity revealed through the use of <sup>18</sup>F-fluorodeoxyglucose
PET/CT imaging. Taken together, we believe that the <sup>64</sup>Cu-doped
PdCu@Au tripods could serve as a multifunctional platform for both
PET imaging and image-guided photothermal cancer therapy
Minor physical anomalies: potentially informative vestiges of fetal developmental disruptions in schizophrenia
No full textMinor physical anomalies (MPAs) are subtle signs of developmental deviation that are observed at anelevated frequency among patients with schizophrenia. These minor morphological abnormalities of the craniofacial region and limbs arise during fetal development and represent a set of risk markers for schizophrenia. Although MPAs are not specific to schizophrenia, established findings about MPAs vis-a-vis schizophrenia include the replicated findings that MPAs are more prevalent among individuals with schizophrenia than healthy controls, MPAs are more prevalent among individuals with schizophrenia than unaffected relatives, and MPAs are not consistently associated with symptom domains or other risk markers, such as neurological soft signs. Unresolved questions include whether or not MPAs are more prevalent among unaffected relatives than healthy controls, and which specific MPAs are most associated with schizophrenia. This overview presents three promising avenues of further research on MPAs, including: (1) studies relying on traditional summary scores that combine multiple MPAs, which may have a role in prospective risk stratification in conjunction with other risk markers and endophenotypes; (2) research on specific, quantitatively assessed MPAs (especially in specific craniofacial structures) that may inform neurodevelopmental understandings of schizophrenia; and (3) genetic studies aimed at identifying the heritable and nonheritable determinants of specific MPAs, which may increase the field's understanding of the origins of MPAs and the nature of their association with schizophrenia. (C) 2010 ISDN. Published by Elsevier Ltd. All rights reserved
Novel Osteogenic Ti-6Al-4V Device For Restoration Of Dental Function In Patients With Large Bone Deficiencies: Design, Development And Implementation
No full textCustom devices supporting bone regeneration and implant placement are needed for edentulous patients with large mandibular deficiencies where endosteal implantation is not possible. We developed a novel subperiosteal titanium-aluminum-vanadium bone onlay device produced by additive manufacturing (AM) and post-fabrication osteogenic micro-/nano-scale surface texture modification. Human osteoblasts produced osteogenic and angiogenic factors when grown on laser-sintered nano-/micro-textured surfaces compared to smooth surfaces. Surface-processed constructs caused higher bone-to-implant contact, vertical bone growth into disk pores (microCT and histomorphometry), and mechanical pull-out force at 5 and 10 w on rat calvaria compared to non surface-modified constructs, even when pre-treating the bone to stimulate osteogenesis. Surface-modified wrap-implants placed around rabbit tibias osseointegrated by 6 w. Finally, patient-specific constructs designed to support dental implants produced via AM and surface-processing were implanted on edentulous mandibular bone. 3 and 8 month post-operative images showed new bone formation and osseointegration of the device and indicated stability of the dental implants
Putting gold nanocages to work for optical imaging, controlled release and cancer theranostics
No full textGold nanocages are hollow nanostructures with ultrathin, porous walls. They are bio-inert and their surface can be readily modified with functional groups to specifically interact with the biological system of interest. They have remarkable optical properties, including localized surface plasmon resonance peaks tunable to the near-infrared region, strong absorption and scattering, as well as two-and three-photon luminescence. With the establishment of robust protocols for both synthesis and surface functionalization, Au nanocages have been extensively explored for various biomedical applications. In this review, we begin with a brief account of the synthesis and properties of Au nanocages, and then highlight some of the recent developments in applying them to an array of biomedical applications related to optical imaging, controlled release and cancer theranostics.National Cancer Institute [1R01 CA 138527]; NIH Director's Pioneer Award [DP1 OD000798]; Georgia Institute of Technology; China Scholarship CouncilSCI(E)[email protected]
