Autocrine production of prostaglandin F\u3csub\u3e2α\u3c/sub\u3e enhances phenotypic transformation of normal rat kidney fibroblasts

\u3cp\u3eWe have used normal rat kidney (NRK) fibroblasts as an in vitro model system to study cell transformation. These cells obtain a transformed phenotype upon stimulation with growth-modulating factors such as retinoic acid (RA) or transforming growth factor-β (TGF-β). Patch-clamp experiments showed that transformation is paralleled by a profound membrane depolarization from around -70 to -20 mV. This depolarization is caused by a compound in the medium conditioned by transformed NRK cells, which enhances intracellular Ca \u3csup\u3e2+\u3c/sup\u3e levels and thereby activates Ca\u3csup\u3e2+\u3c/sup\u3e-dependent Cl \u3csup\u3e-\u3c/sup\u3e channels. This compound was identified as prostaglandin F \u3csub\u3e2α\u3c/sub\u3e (PGF\u3csub\u3e2α\u3c/sub\u3e) using electrospray ionization mass spectrometry. The active concentration in the medium conditioned by transformed NRK cells as determined using an enzyme immunoassay was 19.7 ± 2.5 nM (n = 6), compared with 1.5 ± 0.1 nM (n = 3) conditioned by nontransformed NRK cells. Externally added PGF\u3csub\u3e2α\u3c/sub\u3e was able to trigger NRK cells that had grown to density arrest to restart their proliferation. This proliferation was inhibited when the FP receptor (i.e., natural receptor for PGF\u3csub\u3e2\u3c/sub\u3eα) was blocked by AL-8810. RA-induced phenotypic transformation of NRK cells was partially (∼25%) suppressed by AL-8810. Our results demonstrate that PGF\u3csub\u3e2α\u3c/sub\u3e acts as an autocrine enhancer and paracrine inducer of cell transformation and suggest that it may play a crucial role in carcinogenesis in general.\u3c/p\u3

Cultural orientations and information systems success in public and private hospitals: preliminary evidences from Italy

Abstract Background The effective adoption and use of digital and computerized systems and records in hospitals are crucial for increasing the overall quality, safety and outcomes of any national health community. Prior research found that hospitals’ dominant cultural orientation affects the adoption of new technology. However, the organizational culture of hospitals can greatly vary between public and private hospitals. Thus, the ownership type of the hospital is likely to affect, to some extent, the aforementioned relationship between culture and information system success. The present article focuses in detail on this issue and attempts to answer the following research question: which cultural orientations are promoting information system success in public and private hospitals? Methods The authors develop and test two hypotheses about this relationship via two regression approaches (single-level and multi-level). The authors collected data from 172 respondents—clinicians and non-clinicians—working in two (one public and one private) hospitals in Campania, one of the largest regions in Italy. Results The findings of this study show clear differences between private and public hospitals. First, a dominant cultural orientation that emphasizes flexibility values (clan and adhocracy cultures) positively influences information systems success in terms of individual impact. Second, the influence of a clan orientation on individual impact is stronger in the public hospital. Third, the influence of an adhocracy orientation is stronger in the private hospital. Overall, the type of ownership—either public or private—of these healthcare organizations affects the link between cultural orientations and IS success. Conclusion Managers of private hospitals should offer to their employees the opportunity to adopt and implement new information systems processes driven by openness towards the external environment in order to benchmark and learn from what was done previously in other organizations. Managers of public hospitals should set up human resource management practices, knowledge creation mechanisms, and internal communication capable of generating a friendly learning environment for their employees when adopting new technology

Elucidating the burden of recurrent and chronic digital ulcers in systemic sclerosis: long-term results from the DUO Registry

Objectives Digital ulcers (DUs) occur in up to half of patients with systemic sclerosis (SSc) and may lead to infection, gangrene and amputation with functional disability and reduced quality of life. This study has elucidated the burden of SSc-associated DUs through identification of four patient categories based on the pattern of DU recurrence over a 2-year observation period.Methods Patients with SSc-associated DUs enrolled in the Digital Ulcers Outcome Registry between 1 April 2008 and 19 November 2013, and with 2years of observation and 3 follow-up visits during the observation period were analysed. Incident DU-associated complications were recorded during follow-up. Work and daily activity impairment were measured using a functional assessment questionnaire completed by patients after the observation period. Potential factors that could predict incident complications were identified in patients with chronic DUs.Results From 1459 patients, four DU occurrence categories were identified: 33.2% no-DU; 9.4% episodic; 46.2% recurrent; 11.2% chronic. During the observation period, patients from the chronic category had the highest rate of incident complications, highest work impairment and greatest need for help compared with the other categories. Independent factors associated with incident complications included gastrointestinal manifestations (OR 3.73, p=0.03) and previous soft tissue infection (OR 5.86, p=0.01).Conclusions This proposed novel categorisation of patients with SSc-associated DUs based on the occurrence of DUs over time may help to identify patients in the clinic with a heavier DU burden who could benefit from more complex management to improve their functioning and quality of life