The traditional control of the dialysis session comes about by means of an open-loop system. At the beginning of the session some parameters are set, such as the kind of dialyzer, the blood flow, the ultrafiltration rate, the dialysate conductivity and the dialysate temperature. Generally speaking, these parameters are not modified unless there occur complications in the patient that call for adjustments to be made. The biofeedback concept, which is synonymous with a closed-loop control of biological variables, presupposes, on the other hand: the continuous measurement of a variable thanks to a specific sensor its evaluation by a sort of expert system - the so-called controller and a series of means - the actuators - that allow the behavior of the variable to be directly or indirectly influenced. In clinical practice, different biofeedback systems are emerging, addressed to the control of blood volume, body temperature, and blood pressure. Each one of these systems has been successfully utilized, especially in the management of "difficult" patients unstable from the hemodynamic point of view. However, the future will be an integrated system that sees a complex adaptive, multi-input, multi-output controller which, with a great simplicity of use and low costs, will allow renal replacement therapy to be increasingly physiological and more efficient.

关键词：医药；治疗技术；生物反馈；血液透析

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The circadian system in humans encompasses all organs, tissues and cells. Coordination of central and peripheral clocks and synchronization of cellular clocks within the brain regulate daily phases, neurophysiology and behavior. The mechanism of action of the circadian system is complex, but is centered on the paired structure of the suprachiasmatic nuclei (SCN) that serves as a pacemaker in humans. Light adjusts the phase of the SCN oscillator to the environmental light-dark cycle. Light therapy has been developed for clinical use and many apparatus and parameters have been extensively studied. Bright light therapy is the treatment of choice for seasonal affective disorder and circadian rhythm sleep disorders. Cumulative studies support the efficacy of light therapy for some clinical conditions which are characterized by seasonality or disrupted circadian rhythms. The benefit of light therapy is significant and warrants further clinical studies to optimize the treatment effect.

关键词：医药；治疗技术；光线疗法；睡眠障碍

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关键词：肿瘤乙肝；生物制药；单抗；药物金矿

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A major impediment to effective prostate cancer treatment involves the acquired resistance to cytotoxic therapies. Components of the tissue microenvironment are increasingly recognized to profoundly influence tumor cell phenotypes that include susceptibilities to toxic insults. Using a genome-wide analysis of transcriptional responses to genotoxic stress induced by cancer therapeutics, we have identified a spectrum of secreted proteins derived from the tumor microenvironment (TME) that have the potential to modify tumor growth and enhance resistance to DNA-damaging cancer therapeutics. These results suggest a mechanism by which genotoxic therapies given in a cyclical fashion can enhance subsequent treatment resistance through cell non-autonomous effects contributed by the TME. To date, the contributions of individual members of this DNA Damage-associated Secretory Program (DDSP) have not been defined, nor have the signaling mechanisms responsible for propagating the DNA-damage signal(s) been determined. Our objective during this grant period is to test whether treatment-associated DNA damage responses in cells comprising the prostate TME promote tumor growth and subsequent therapy resistance. During this funding period we have: (1) Generated a prostate fibroblast cell line stably expressing SPINK1; (2) Evaluated the impact which SPINK1 activation has upon the growth characteristics of prostate cancer cells lines; (3) Examined how SPINK1 secretion from the microenvironment modulates the response of prostate cancer cells to chemotherapeutics: (4) Begun the evaluation of SPINK1 regulatory pathway.

关键词：治疗技术；治疗抵抗；损伤反应

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Although the combination of radiation therapy and androgen deprivation therapy (ADT) is initially effective in many patients, biochemical failure rates of 20at 5-years to 50at 10-years have been reported, highlighting the need for improved treatments, particularly for men with high- risk prostate cancer. ADT in the neo-adjuvant setting is used to reduce tumor volume and improve the response to radiation. Additionally, ADT causes infiltration of lymphocytes into the prostate. B cell infiltrates may promote prostate cancer progression and development of castration resistant prostate cancer by the production of inflammatory cytokines and skewing CD4+ T cell responses towards Th2. We hypothesized that depletion of B cells at the time of castration would improve tumor control. Our results demonstrate that the depletion of B cells at the time of castration improves tumor latency.

关键词：治疗技术；前列腺癌；免疫反应

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Therapeutic options for patients suffering from end-stage renal disease have improved tremendously over the last decades and can be divided into three categories: hemodialysis, peritoneal dialysis and kidney transplantation. Transplantation remains the treatment of choice, however, lack of donor organs results in the necessity of performing -temporary-dialysis therapies of which hemodialysis is carried out in the majority of patients. To facilitate adequate hemodialysis therapy a reliable vascular access is mandatory and can be provided by either surgically connecting an artery with a vein (arteriovenous fistula), surgically connecting an artery with a vein using an interposition of prosthetic graft material (arterioven-ous graft) or a central venous catheter. This chapter shortly reviews the condition of end-stage renal disease after which history of vascular access, different options to create a vascular access, pre-operative work-up, surgical procedure, monitoring and usage, post-operative complications and the role of hemodynamics will be discussed. Finally, some future directions for vascular access creation and management will be identified.

关键词：治疗技术；透析；血管

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Tamoxifen, the first targeted therapy, has shown great success in treating estrogen receptor (ER) positive breast cancer. However, both acquired and de novo resistance to this therapy prevents it from being effective in all situations. Multiple lines of evidence indicate that increased signaling through growth factor pathways, such as the IGF pathway, mediates resistance to tamoxifen. The link between ER and ICGF1R leads us to hypothesize that IGF system crosstalk with the ER contributes to tamoxifen resistance. Tamoxifen resistance has thus provided researchers with a reason to investigate other growth factor pathways involved in breast cancer. As new targeted therapies are being developed, it will be important to examine their benefit with existing therapies. In order to examine the effectiveness of anti-IGF1R inhibitors in vitro, tamoxifen resistant (TamR) cells were generated by culturing MCF-7L and T47D cells in the presence of 4-OH-tamoxifen for >6 months. TamR cells had dimished levels of IGF1R, with unchanged levels of insulin receptor (IR). Further, TamR cells failed to respond to IGF-I induced p-AKT activation, while retaining responsiveness to both insulin and IGF-II. Additionally, IGF-I failed to enhance the proliferation and anchorage-independent growth of TamR cells; however, both insulin and IGF-II were able to enhance proliferation in MCF
anchorage-independent growth. An IGF1R antibody was effective in inhibiting signaling, anchorage-independent growth, and proliferation in MCF-7L cells, but had no effect in TamR cells. In contract, an IGF1R/TR tyrosine kinase inhibitor was effective in both MCF-7L and TamR cells. In a xenograft model, an IGF1R antibody was able to inhibit estrogen stimulated tumor growth, but had no additive effect when combined with tamoxifen treatment. Further, tamoxifen-treated xenografts had diminished IGF1R levels.

关键词：治疗技术；胰岛素；乳腺癌细胞

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Despite the elevated rates of psychiatric problems among returning combat veterans, available evidence suggests that as many as half of soldiers screening positive for mental health problems never seek treatment for these issues (Fikretoglu et al., 2008, Hoge et al., 2006). One promising treatment approach that has shown efficacy in preliminary research and which may address issues related to stigma and barriers to care, is the used of web-based treatment interventions. In particular, internet-based cognitive behavioral therapy (iCBT) is rapidly emerging as a potentially efficacious treatment option for many individuals with mild to moderate depression (Andersson and Cuijpers, 2009). Emerging evidence suggests that iCBT is a particularly promising and well-accepted approach for treating large numbers of individuals while minimizing cost and clinicians time demand. Recently, researchers from the School of Psychiatry at the University of New South Wales (UNSW) developed and validated several, clinician-assisted iCBT programs that have shown remarkable success in treating major depressive disorder (MDD), generalized anxiety disorder, social phobia, and panic disorder (Robinson et al., 2010, Titov et al., 2010, Titov et al., 2009).

关键词：治疗技术；互联网；精神治疗

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The endocytic trafficking pathway is the site of action for receptor- targeted drug-delivery strategies, including Antibody-Drug- Conjugates (ADCs) and nanoparticle drug-delivery systems. Effective drug-release requires trafficking of the endocytosed receptor-bound cargo into the lysosomes for efficient disintegration. However, cancer-cell specific alterations that lead to receptor recycling, instead of lysosomal-degradation, can dampen the efficiency of drug delivery. Such changes include receptor overexpression, increased association with the molecular chaperone, chaperones such as HSP90 or alterations in regulators of recycling versus lysosomal pathways (Rab GTPases, c-Src, deubiquitinases). While substantial effort has gone into designing receptor-targeted drug delivery systems, the consequence of factors leading to altered recycling versus lysosomal trafficking on the efficiency of drug delivery have not been considered. The receptor tyrosine kinases ErbB2 and EGFR, which are often overexpressed in breast cancer, are examples of cell surface receptors used for evaluating nanoparticle-based targeted drug delivery systems. However, several studies have established that the ErbB2 receptor is either endocytosis-impaired or undergoes rapid recycling, suggesting that the strategies to enhance receptor internalization and lysosomal routing could further enhance the efficacy of cytotoxic drug being delivered. While, the molecular chaperone HSP90 is critical for maintaining oncogenic ErbB2-activity, it also is thought to be responsible for the altered trafficking of the receptor. The objective of this synergistic DOD-IDEA grant proposal was to evaluate our innovative hypothesis that HSP90 inhibitors can facilitate ErbB2- targeted delivery of chemotherapeutic payloads.

关键词：治疗技术；纳米粒子；乳腺癌

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The Tulane/Xavier Biodefense Vaccine Development/Engineering project will develop new vaccines against biological threat agents to aid the war- fighter. Through the innovative use of nanotechnology, researchers and engineers from the Tulane University Schools of Medicine and Science & Engineering and the Xavier College of Pharmacy will fabricate nanoparticulate systems that are effective for transdermal and mucosal delivery of life-saving vaccines. One aim of this project will be to compare different nanocarriers (i.e., nanohydrogels, star copolymers, and spray-dried PLGA nanoparticles) for the ability to incorporate biological threat-relevant vaccine antigens and deliver those antigens through the stratum corneum to immuneresponsive cells in the epidermis. The specialized assembly of each type of nanocarrier gives each unique properties and different interactions within the lipid channels of the stratum corneum. The use of nanocarriers for vaccine delivery is a platform technology, applicable to delivery of a variety of existing and potential vaccines.

关键词：疫苗；抗原；纳米技术

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