How leukemia stem cells gained resistance to radiation and chemotheraphy is poorly defined, yet critically determines how leukemia cells tolerate conventional leukemia therapy. Normal hematopoietic stem cells and leukemia initiating cells are known to share many functional properties. Therefore, they are supposed to utilize many common mechanistic pathways for their survival and migration. Using genetically engineered mice we demonstrated the functional roles of P2Y14 in preserving regenerative capacity by constraining senescence induction and molecular events governing it. Since P2Y14 is highly expressed in differentiation-resistant leukemia cells, P2Y14 expression in leukemia cells may also function in modulating the resistance to conventional cancer treatment. Our results strongly suggest that P2Y14/UDP-Glc axis plays an important role in stress-induced senescence and motility of HSPCs. As the expression of P2Y14 is preferentially high in drug-resistant leukemia cells, we anticipate that P2Y14/UDP-Glc axis governs the resistance and motility also in leukemia stem/progenitor cells.

关键词：白血病;干细胞;老化(生理学);血液细胞,癌症;化疗;造血细胞

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Rising health care costs in general and prescribed medicine costs in particular continue to be a concern for U.S. policymakers and consumers of care. Analyzing total prescription drug costs by therapeutic classes and subclasses provides decision makers and the public with an understanding of the costs and extent to which specific therapeutic classes and subclasses of drugs are contributing to the upturn in total costs. This Statistical Brief provides trends for one therapeutic subclass of prescribed drugs--urinary antispasmodics. This Brief presents trends in utilization and expenditures for outpatient prescription urinary antispasmodics for the years 2000 and 2010. The estimates are for the U.S. civilian noninstitutionalized population and are derived from the 2000 and 2010 Household Component of the Medical Expenditure Panel Survey (MEPS-HC). The Brief compares outpatient prescription urinary antispasmodics for 2000 and 2010, using the number of persons obtaining at least one prescription, total expenditures, and total number of prescriptions, as well as average annual cost per person and average drug cost. Only prescriptions purchased or obtained in an outpatient setting are included in these estimates. Prescription medicines administered in an inpatient setting or in a clinic or physician's office are excluded.

关键词：卫生保健支出;尿抗痉挛;成本;医疗利用率

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This Technical Assistance Publication (TAP), Clinical Drug Testing in Primary Care, is for clinical practitioners-physicians, nurse practitioners, and physician assistants who provide primary care in office settings and community health centers. The publication provides information that practitioners need when deciding whether to introduce drug-testing in their practices and gives guidance on implementing drug testing. The TAP does not address drug testing for law enforcement or legal purposes, nor does it include testing for the use of anabolic steroids or performance-enhancing substances. This TAP describes some of the ways that drug testing cancontribute to the assessment, diagnosis, and treatment of patients seen in primary care, the management of the treatment of chronic pain, and the identification and treatment of substance use disorders.

关键词：药物;初级护理;临床医学;社区卫生中心;诊断

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The objective of this research is to design and develop a nanocarrier that is able to evade the immune system, circulate in the blood stream, find its target prostate cancer cells, and transfer therapeutic genes into prostate cancer cells efficiently. The gene carrier is composed of: a) histone H2A peptide to condense pDNA into nano-size particles, b) a PC-3 specific targeting motif (TM) to target prostate cancer cells, c) an endosomolytic motif to disrupt endosome membrane, and d) a nuclear localization signal (NLS) to actively translocate pDNA towards the nucleus of cancer cells. The gene delivery system was synthesized in E.coli. The vector was then complexed with plasmid DNA (pDNA) to form stable nanoparticles with sizes below 100nm. The nanoparticles were used to deliver reporter genes (pEGFP) to target PC-3 prostate cancer cells and RWPE-1 normal epithelial prostate cells. The induction of immune response by the vector was studied in BALB/c immune-competent mice. The results demonstrated that the gene delivery system is able to target and efficiently transfect PC-3 cancer cells with minimum cross-reactivity with normal epithelial prostate cells. An animal protocol was prepared and approved by IACUC and DOD ACURO. The immunogenicity studies showed that the vector does not induce production IgG or IgM after repeated systemic injection.

关键词：前列腺癌;染色体;脱氧核糖核的酸;基因治疗;基因;治疗

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The function of the kidney system is to remove waste products of human metabolism and to eliminate extra fluids. When end-stage renal disease (ESRD) occurs, renal replacement therapy (RRT) - dialysis, transplantation - is required. There are two types of dialysis treatment: extracorporeal blood purification (mainly hemodialysis) and intracorpo-real blood purification (peritoneal dialysis). All patients with ESRD should be considered for kidney transplantation. Patients without absolute contraindications should be placed on the transplant waiting list, and receive a kidney, if possible. Patients should be educated about each procedure of RRT.

关键词：肾功能;急性肾损伤(AKI);慢性肾脏疾病(CKD);血液透析(HD)

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This report is based on research conducted by the Tufts Evidence-based Practice Center under contract to the Agency for Healthcare Research and Quality (AHRQ), Rockville, MD (Contract No. 290 2007 10055 I). The findings and conclusions in this document are those of the author(s) who are responsible for its contents; the findings and conclusions do not necessarily represent the views of AHRQ. No statement in this article should be construed as an official position of the Agency for Healthcare Research and Quality or of the U.S. Department of Health and Human Services.

关键词：心血管疾病;医疗设备;技术评估;心脏病;死亡;预防;心律;监测

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This study is a follow up to two projects, funded by the Office of Naval Research, which demonstrated that Virtual Reality (VR) Exposure Therapy was safe for the treatment of combat PTSD Disorder, and that it worked better than treatment as usual. In this study, we are attempting to discover if the Virtual Reality is actually the active component of the treatment. Participants with PTSD are randomized to receive the same treatment that was successful in the previous projects, or the same treatment in which a simple, still computer image replaces the VR. At the last annual review, our findings were indicating that VR treatment and the control condition resulted in similar improvements, but that improvements in the VR condition persisted whereas those in the control condition did not. In the last year, we have continued to recruit, assess, and treat individuals with combat related PTSD. Results with our larger sample size continue to demonstrate similar findings as last year s analysis. We have presented these findings at the American Psychiatric Association and will be presenting them at the International Society for Traumatic Stress Studies meeting. Sample size has not yet reached our original target, and we do not yet have enough data to examine particular predictors of treatment success. We hope to reach these goals in our final year of study.

关键词：暴露(生理学);创伤后应激障碍;虚拟现实

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This article presents the design of an intelligent agent application aimed at supporting people with a cognitive vulnerability to prevent the onset of a depression. For this, a computational model of the cognitive processes around depression is used. The agent application uses the principles of Rational Emotive Behavioural Therapy (RBET). The effect of the application is studied using software simulation. The simulation shows that a person that responds to REBT therapy develops less cognitive vulnerability than people that are not supported.

关键词：智能代理应用程序；抑郁症；理情行为疗法

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Despite recent advances in deciphering the molecular pathways that trigger cancer and its progression, progress in developing therapies that effectively target those pathways has been hampered by their complexity. Researchers are finding that many cancer pathways have backup or bypass pathways that foster drug resistance. Consequently, targeted therapies that initially are quite effective in certain patients eventually stop working. In addition, many therapies appear to work best when they are used in combination with various treatment modalities. Combining investigational cancer therapies early in their development is thought to be a promising strategy for identifying cancer treatments that will be effective in the long term, especially when a combination targets multiple pathways and byways in the development or progression of cancer, or more than one step in a pathway, potentially conferring greater benefit than a therapy directed at a single target.

关键词：癌症;治疗;药物;治疗;分子生物学;患者;临床研究

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Vascular pattern may serve as a useful new biomarker principle of complex, multi-scale signaling in pathological,physiological angiogenesis and microvascular remodeling. Each angiogenesis stimulator or inhibitor we have analyzed,including VEGF, bFGF, TGF-beta1, angiostatin and triamcinolone acetonide, has induced a novel ‘fingerprint’ or ‘signature’ biomarker vascular pattern that is spatio-temporally unique. Remodeling vasculature thereby provides an informative read-out of dominant molecular signaling, when analyzed by innovative, fractal-based VESsel GENeration (VESGEN) Analysis software. Using VESGEN to analyze ophthalmic clinical vascular images, we recently introduced a potential paradigm shift to the understanding of early-stage progression that suggests new regenerative opportunities for human diabetic retinopathy (DR), the major blinding disease for working-aged adults. In a pilot study, we discovered that angiogenesis oscillates as a surprising, homeostatic-like regeneration of retinal vessels during early progression of DR (IOVS 51(1):498). Results suggest that the term ‘non-proliferative DR’ may be a misnomer. In new studies,normalization of the vasculature will be determined from the response of vascular pattern to therapeutic monitoring and treatment. We have mapped and quantified in vivo experimental models of angiogenesis, lymphangiogenesis and intravital blood flow from cellular/molecular to higher systems levels that include a murine model of infant retinopathy of prematurity (ROP); developing and pathological coronary and placental-like vessel models; progressive intestinal inflammation, growing murine tumors, and other pathological, physiological and therapeutically treated tissues of transgenic mice and avian embryos.

关键词：生物标志物;心血管系统;眼科;生理学

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