Elevated fibroblast growth factor 23 in women with malignant ovarian tumors

OBJECTIVE: To determine whether fibroblast growth factor 23 (FGF23) concentrations are altered in women with ovarian cancers in which FGF physiology is known to be abnormal. PATIENTS AND METHODS: Between May 2002 and September 2003 at the Mayo Clinic in Rochester, Minn, plasma or serum FGF23 concentrations were measured in 39 healthy women and in 14 with benign ovarian tumors, 14 with early-stage ovarian cancer, and 13 with advanced-stage ovarian cancer. Immunohistochemistry using anti-human FGF23 antibodies was performed on tissue from benign masses and advanced-stage tumors. RESULTS: Serum or plasma FGF23 concentrations were significantly higher in women with advanced-stage ovarian cancer compared with concentrations in women with early-stage ovarian cancer or benign disease or in healthy women. A significant positive correlation was seen between serum iFGF23 and cFGF23 concentrations and stage of disease. Serum iFGF23 and cFGF23 concentrations were positively correlated with serum phosphorus among women with ovarian cancer. No patients with elevated iFGF23 or cFGF23 concentrations had hypophosphatemia. Immunohistochemistry detected FGF23 tissue staining in malignant ovarian cancer cells. CONCLUSION: Serum or plasma FGF23 concentrations are elevated in patients with advanced-stage epithellal ovarian cancer without reductions in serum phosphate concentrations. The presence of elevated FGF23 concentrations in patients with an ovarian mass should suggest advanced-stage disease.     

Mechanism of thioamide drug action against tuberculosis and leprosy

Thioamide drugs, ethionamide (ETH) and prothionamide (PTH), are clinically effective in the treatment of Mycobacterium tuberculosis, M. leprae, and M. avium complex infections. Although generally considered second-line drugs for tuberculosis, their use has increased considerably as the number of multidrug resistant and extensively drug resistant tuberculosis cases continues to rise. Despite the widespread use of thioamide drugs to treat tuberculosis and leprosy, their precise mechanisms of action remain unknown. Using a cell-based activation method, we now have definitive evidence that both thioamides form covalent adducts with nicotinamide adenine dinucleotide (NAD) and that these adducts are tight-binding inhibitors of M. tuberculosis and M. leprae InhA. The crystal structures of the inhibited M. leprae and M. tuberculosis InhA complexes provide the molecular details of target–drug interactions. The purified ETH-NAD and PTH-NAD adducts both showed nanomolar K_is against M. tuberculosis and M. leprae InhA. Knowledge of the precise structures and mechanisms of action of these drugs provides insights into designing new drugs that can overcome drug resistance.     

Phosphorylation-dependent translocation of sphingosine kinase to the plasma membrane drives its oncogenic signalling

Sphingosine kinase (SK) 1 catalyzes the formation of the bioactive lipid sphingosine 1-phosphate, and has been implicated in several biological processes in mammalian cells, including enhanced proliferation, inhibition of apoptosis, and oncogenesis. Human SK (hSK) 1 possesses high instrinsic catalytic activity which can be further increased by a diverse array of cellular agonists. We have shown previously that this activation occurs as a direct consequence of extracellular signal-regulated kinase 1/2-mediated phosphorylation at Ser225, which not only increases catalytic activity, but is also necessary for agonist-induced translocation of hSK1 to the plasma membrane. In this study, we report that the oncogenic effects of overexpressed hSK1 are blocked by mutation of the phosphorylation site despite the phosphorylation-deficient form of the enzyme retaining full instrinsic catalytic activity. This indicates that oncogenic signaling by hSK1 relies on a phosphorylation-dependent function beyond increasing enzyme activity. We demonstrate, through constitutive localization of the phosphorylation-deficient form of hSK1 to the plasma membrane, that hSK1 translocation is the key effect of phosphorylation in oncogenic signaling by this enzyme. Thus, phosphorylation of hSK1 is essential for oncogenic signaling, and is brought about through phosphorylation-induced translocation of hSK1 to the plasma membrane, rather than from enhanced catalytic activity of this enzyme.     

Adult anemia: determine clinical significance

Severity of adult anemia does not reliably indicate its origin or clinical significance. Causes range from dietary insufficiency to occult bleeding and from chronic disease processes to hemolysis. NPs can identify the different types of anemia with a thorough history, physical examination, and appropriate laboratory testing.     

Computer Modelling Using Prehospital Vitals Predicts Transfusion and Mortality

Objective: Test computer-assisted modeling techniques using prehospital vital signs of injured patients to predict emergency transfusion requirements, number of intensive care days, and mortality, compared to vital signs alone. Methods: This single-center retrospective analysis of 17,988 trauma patients used vital signs data collected between 2006 and 2012 to predict which patients would receive transfusion, require 3 or more days of intensive care, or die. Standard transmitted prehospital vital signs (heart rate, blood pressure, shock index, and respiratory rate) were used to create a regression model (PH-VS) that was internally validated and evaluated using area under the receiver operating curve (AUROC). Transfusion records were matched with blood bank records. Documentation of death and duration of intensive care were obtained from the trauma registry. Results: During the course of their hospital stay, 720 of the 17,988 patients in the study population died (4%), 2,266 (12.6%) required at least a 3-day stay in the intensive care unit (ICU), 1,171 (6.5%) required transfusions, and 210 (1.2%) received massive transfusions. The PH-VS model significantly outperformed any individual vital sign across all outcomes (average AUROC = 0.82), The PH-VS model correctly predicted that 512 of 777 (65.9%) and 580 of 931 (62.3%) patients in the study population would receive transfusions within the first 2 and 6 hours of admission, respectively. Conclusions: The predictive ability of individual vital signs to predict outcomes is significantly enhanced with the model. This could support prehospital triage by enhancing decision makers’ ability to match critically injured patients with appropriate resources with minimal delays.     

Experiences of health and well-being, a question of adjustment and compensation - views of older people dependent on community care

Most studies concerning older people's health and well-being have focused on their ill health, disease and complaints and have mainly been conducted with a quantitative design. Hence, there is still a need for qualitative studies in which these peoples' own views on health and well-being are shown, especially when they are dependent on health care in a community setting. A qualitative approach was used in the study reported here and aimed at obtaining a deeper understanding of older peoples' own views about their health and well-being. Interviews were carried out on two occasions with 19 older people living in their own homes and in sheltered accommodation. The data were analysed using content analysis. The findings suggested that the possibility to feel healthy was dependent both on the older person's own ability to adjust or compensate to their situation, and on how their caregivers, relatives and friends could compensate for the obstacles the older person faced. The subcategories that captured the informants' experiences of health and ill health were described as positive and negative poles of autonomy, togetherness, tranquillity and security in daily life. The significance of the caregivers was clearly evident. Their competence, commitment and treatment were prerequisites for the older person's ability to experience health in spite of being dependent on care.     

Implementation of the ANA report card.

A major challenge in healthcare today is measuring the quality of care. To explore nursing's contribution to patients in acute care settings, the American Nurses Association commissioned the development of the "Nursing Report Card." This study explored whether these report card indicators capture quality care. The convenience sample comprised 1,500 patients and 300 nurses from 16 units at an academic medical center. Using regression analysis, the most consistent predictor of outcome indicators was the percentage of RNs of the total staff.     

Mobilization-Observation-Behavior-Intensity-Dementia Pain Scale (MOBID): development and validation of a nurse-administered pain assessment tool for use in dementia

Pain assessment in older persons with severe cognitive impairment (SCI) is a challenge due to reduced self-report capacity and lack of movement-related pain assessment instruments. The purpose of this article was to describe the development of the Mobilization-Observation-Behaviour-Intensity-Dementia Pain Scale (MOBID) and to investigate aspects of reliability and validity. MOBID is a nurse-administered instrument developed for use in patients with SCI, where presence of pain behavior indicators (pain noises, facial expression, and defense) may be observed during standardized active, guided movements, and then inferred to represent pain intensity. Initially, the MOBID contained seven items (observing at rest, mobilization of the hands, arms, legs, turn over in bed, sitting on bedside, and teeth/mouth care). This was tested in 26 nursing home patients with SCI. Their primary caregivers, five registered nurses and six licensed practical nurses (LPNs), rated the patients' pain intensity during regular morning care, and by MOBID, both at bedside and from video uptakes. Three external raters (LPNs), not knowing the patients, also completed the MOBID by rating the videos. Internal consistency of the MOBID indicated high Cronbach's alpha (alpha=0.90) after deleting the items for observation at rest and observation of teeth/mouth care. MOBID disclosed significantly more pain than did pain scorings during regular morning care, and video observation demonstrated higher pain intensity than bedside scoring. Intertester reliability for inferred pain intensity was high to excellent (intraclass correlation coefficient=0.70-0.96), but varied between poor and excellent for pain behavior indicators (kappa=0.05-0.84). These results suggest that registration of pain behavior indicators during active, guided movements, as performed by the MOBID procedure, is useful to disclose reliable and valid pain intensity scores in patients with SCI.