4-Phenyl tetrahydroisoquinolines as dual norepinephrine and dopamine reuptake inhibitors.

Novel 4-phenyl tetrahydroisoquinolines that inhibit both dopamine and norepinephrine transporters were designed and prepared. In this Letter, we describe the synthesis, in vitro activity and associated structure-activity relationships of this series. We also report the ex vivo NET occupancy of a representative compound, 41.

Hospital-acquired pressure ulcers: results from the national Medicare Patient Safety Monitoring System study.

Objectives: To determine the national and state incidence levels of newly hospital-acquired pressure ulcers (PUs) in Medicare beneficiaries and to describe the clinical and demographic characteristics and outcomes of these individuals.

Design: Retrospective secondary analysis of the national Medicare Patient Safety Monitoring System (MPSMS) database.

Setting: Medicare-eligible hospitals across the United States and select territories.

Objective assessment in residency-based training for transoral robotic surgery.

Objectives/hypothesis: To develop a robotic surgery training regimen integrating objective skill assessment for otolaryngology and head and neck surgery trainees consisting of training modules of increasing complexity leading up to procedure-specific training. In particular, we investigated applications of such a training approach for surgical extirpation of oropharyngeal tumors via a transoral approach using the da Vinci robotic system.

Study Design: Prospective blinded data collection and objective evaluation (Objective Structured Assessment of Technical Skills [OSATS]) of three distinct phases using the da Vinci robotic surgical system in an academic university medical engineering/computer science laboratory setting.

Distinct regulation of cytoplasmic calcium signals and cell death pathways by different plasma membrane calcium ATPase isoforms in MDA-MB-231 breast cancer cells.

Plasma membrane calcium ATPases (PMCAs) actively extrude Ca(2+) from the cell and are essential components in maintaining intracellular Ca(2+) homeostasis. There are four PMCA isoforms (PMCA1-4), and alternative splicing of the PMCA genes creates a suite of calcium efflux pumps. The role of these different PMCA isoforms in the control of calcium-regulated cell death pathways and the significance of the expression of multiple isoforms of PMCA in the same cell type are not well understood.

Liver transplant center risk tolerance.

Recent changes in Center for Medicare & Medicaid Services (CMS) condition for participation, using benchmark volume/outcomes requirements for certification, have been implemented. Consequently, the ability of a transplant center to assess its risk tolerance is important in successful management. An analysis of SRTR data was performed to determine donor/recipient risk factors for graft loss or patient death in the first year.

A selective, orally bioavailable 1,2,4-triazolo[1,5-a]pyridine-based inhibitor of Janus kinase 2 for use in anticancer therapy: discovery of CEP-33779.

Members of the JAK family of nonreceptor tyrosine kinases play a critical role in the growth and progression of many cancers and in inflammatory diseases. JAK2 has emerged as a leading therapeutic target for oncology, providing a rationale for the development of a selective JAK2 inhibitor. A program to optimize selective JAK2 inhibitors to combat cancer while reducing the risk of immune suppression associated with JAK3 inhibition was undertaken.

Discovery of an orally efficacious inhibitor of anaplastic lymphoma kinase.

Anaplastic lymphoma kinase (ALK) is a promising therapeutic target for the treatment of cancer, supported by considerable favorable preclinical and clinical activities over the past several years and culminating in the recent FDA approval of the ALK inhibitor crizotinib. Through a series of targeted modifications on an ALK inhibitor diaminopyrimidine scaffold, our research group has driven improvements in ALK potency, kinase selectivity, and overall pharmaceutical properties. Optimization of this scaffold has led to the identification of a potent and efficacious inhibitor of ALK, 25b.

A framework for the analysis of phantom data in multicenter diffusion tensor imaging studies.

Diffusion tensor imaging (DTI) is commonly used for studies of the human brain due to its inherent sensitivity to the microstructural architecture of white matter. To increase sampling diversity, it is often desirable to perform multicenter studies. However, it is likely that the variability of acquired data will be greater in multicenter studies than in single-center studies due to the added confound of differences between sites.

A robotic assistant for trans-oral surgery: the robotic endo-laryngeal flexible (Robo-ELF) scope.

This paper describes the continued development of the Robotic EndoLaryngeal (Robo-ELF) Scope System, a simple clinically usable robot for manipulating flexible endoscopes, particularly in laryngeal surgery. The system includes a robot with three active and two passive degrees of freedom, a five degree of freedom passive positioning arm, a malleable scope shaft support, and a custom joystick controller. The Robo-ELF Scope allows a surgeon to control a flexible endoscope with only one hand and also to release the controls and perform bimanual surgery if desired.

Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon.

Background & Aims: Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection.

Methods: We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104).

Evaluation of native kidney recovery after simultaneous liver-kidney transplantation.

Background: Debate continues about which liver transplantation candidates with impaired renal function should undergo liver transplant alone versus simultaneous liver-kidney transplantation (SLK). Identifying predictors of native kidney function recovery after SLK requires an accurate measure of the relative function of all three kidneys in patients with SLK.

Methods: The distance of a transplanted kidney from the renal scan camera can be substantially different from that of native kidneys.

Transient elastography for predicting clinical outcomes in patients with chronic liver disease.

There is increasing interest in developing noninvasive means to evaluate liver fibrosis in patients with chronic liver disease to determine disease severity, prognosis and optimal treatment. Transient elastography (TE) has previously been demonstrated to predict the presence or absence of advanced fibrosis. The current study was conducted to determine whether TE can identify patients with chronic liver disease at risk of clinical decompensation.

Pediatric educational needs assessment for urban and rural emergency medical technicians.

Objective: The objective of the study was to identify past experiences, present needs, barriers, and desired methods of training for urban and rural emergency medical technicians.

Methods: This 62-question pilot-tested written survey was administered at the 2008 Oregon EMS and 2009 EMS for Children conferences. Respondents were compared with registration lists and the state emergency medical services (EMS) database to assess for nonresponder bias.

Prevalence of interpersonal violence against community-living adults with disabilities: a literature review.

Objective: To review the empirical literature on the prevalence of interpersonal violence (IPV) against people with disabilities.

Method: The authors searched for, obtained, and reviewed 6,000 abstracts published between January, 2000 and August, 2010 via searches in PsycINFO and PubMed. Subsequently, 177 potentially applicable full-text articles were independently assessed for inclusion; 22 articles describing 21 individual studies were included in this review.

A comprehensive evaluation of a diabetes quality improvement project in privately owned primary care practices that serve minority patients.

The authors conducted a diabetes quality improvement project in 5 privately owned primary care practices serving at least 25% minority patients. Interventions included group-specific and practice-specific training on an electronic patient registry, cultural competency practices and tools, and selected quality improvement strategies. The authors conducted a comprehensive evaluation involving quantitative and qualitative data to assess project impact.

Spectrum of cancer risk among US solid organ transplant recipients.

Context: Solid organ transplant recipients have elevated cancer risk due to immunosuppression and oncogenic viral infections. Because most prior research has concerned kidney recipients, large studies that include recipients of differing organs can inform cancer etiology.

Objective: To describe the overall pattern of cancer following solid organ transplantation.

Robotic endolaryngeal flexible (Robo-ELF) scope: a preclinical feasibility study.

Objectives/hypothesis: This article presents a novel robotic endolaryngeal flexible (Robo-ELF) scope driver for minimally invasive laryngeal surgery. The Robo-ELF consists of a simple, robust robotic scope driver with three active and two passive degrees of freedom, allowing it to manipulate any standard flexible endoscope. The system is controlled by a joystick-like three dimensional mouse that interfaces with the scope driver via a laptop.

Is Model for End-Stage Liver Disease score associated with quality of life after liver transplantation?

Context: The Model for End-Stage Liver Disease (MELD) is used to predict short-term mortality of patients on the liver transplant waiting list and to allocate deceased donor livers for transplantation.

Objective: To examine the relationship between MELD score before transplant and quality of life and other functional status indicators after transplant.

Design, Setting, And Patients: Two-hundred sixty-five adults from 2 transplant programs completed quality-of-life measures 1 year after transplantation.

Facilitators and barriers to disclosing abuse among women with disabilities.

An anonymous audio computer-assisted self-interview (A-CASI) designed to increase awareness of abuse was completed by 305 women with diverse disabilities. Data were also collected about lifetime and past year abuse; perpetrator risk characteristics; facilitators and barriers to disclosing abuse; abuse disclosure to a health provider, case manager, or police officer; and whether a health provider had ever discussed abuse or personal safety. A total of 276 (90%) women reported abuse, 208 (68%) reported abuse within the past year.

Challenges in recruiting minority-serving private practice primary care physicians to a quality improvement project.

The objectives of this study were the following: (1) describe one organization's experience with recruiting minority-serving private practice primary care physicians to an ambulatory quality improvement (QI) project; (2) compare and contrast physicians who agreed to participate with those who declined; and (3) list incentives and barriers to participation. The authors identified eligible physicians by analyzing Medicare Part B claims data, a publicly available physician database, and office staff responses to telephone inquiries. The recruitment team had difficulty identifying, contacting, and recruiting eligible physicians.

Plasma membrane calcium ATPases and cancer.

The plasma membrane calcium ATPases (PMCAs) are vital regulators of basal Ca(2+) and shape the nature of intracellular free Ca(2+) transients after cellular stimuli and are thus regulators of a plethora of cellular processes. Studies spanning many years have identified that at least some cancers are associated with a remodeling of PMCA isoform expression. This alteration in Ca(2+) efflux capacity may have a variety of consequences including reduced sensitivity to apoptosis and increases in the responsiveness of cancer cells to proliferative stimuli.

Patients' willingness to accept expanded criteria donor liver transplantation.

Utilization of livers from expanded criteria donors (ECD) is one strategy to overcome the severe organ shortage. The decision to utilize an ECD liver is complex and fraught with uncertainty for both providers and patients. We assessed patients' willingness to accept ECD liver transplantation (LTx) and acceptable 1-year mortality risk.