Variabilin: A dual inhibitor of human secretory and cytosolic phospholipase A2 with antiinflammatory activity

ABSTRACT The marine product variabilin was identified as a novel inhibitor of phospholipase A 2 (PLA 2 ), which exhibited IC 50 values of 6.9 M and 7.9 M for human synovial secretory PLA 2 and U937 cells cytosolic PLA 2 activities, respectively. This compound was less potent on bee venom or zymosan-injected rat air pouch enzymes and failed to affect Naja naja venom PLA 2 . The production of leukotriene B 4 by human neutrophils stimulated with calcium ionophore A23187 was also inhibited by variabilin, which was without effect on 5-lipoxygenase, cyclo-oxygenase 1 and cyclo-oxygenase 2 activities in cell-free assays. Other functions of human neutrophils, such as degranulation and superoxide generation, were also significantly reduced in vitro. Variabilin administered topically suppressed the mouse ear edema induced by 12-O-tetradecanoylphorbol 13-acetate, whereas the ear edema induced by arachidonic acid was unaffected; this suggests an action previous to arachidonic acid metabolism. This compound administered p.o. at 30 mg/kg and 45 mg/kg significantly inhibited mouse paw edema induced by carrageenan and, at 0.01 to 1.0 mol/pouch in the mouse air pouch injected with zymosan, exerted a marked inhibition on PGE 2 and leukotriene B 4 levels in exudates (ID 50 values of approximately 0.028 -0.029 mol/pouch), without affecting cell migration. Our results indicate that variabilin is an inhibitor of human secretory and cytosolic PLA 2 activities that controls eicosanoid production in vitro and in vivo, inhibits neutrophil degranulation and superoxide generation in vitro and shows anti-inflammatory activity after topical or p.o. administration to mice

Impact of observing hand hygiene in practice and research: a methodological reconsideration

The purpose of hand hygiene is to break the chain of healthcare-associated infection. In many countries hand hygiene is regularly audited as part of quality assurance based on recommendations from the World Health Organization. Direct observation is the recommended audit method but is associated with disadvantages, including potential for being observed to alter usual behaviour. The Hawthorne effect in relation to hand hygiene is analogous with productivity improvement by increasing the frequency with which hand hygiene is undertaken. Unobtrusive and/or frequent observation to accustom staff to the presence of observers is considered an acceptable way of reducing the Hawthorne effect, but few publications have discussed how to implement these techniques or examine their effectiveness. There is evidence that awareness of being watched can disrupt the usual behaviour of individuals in complex and unpredictable ways other than simple productivity effect. In the presence of auditors, health workers might defer or avoid activities that require hand hygiene, but these issues are not addressed in guidelines for practice or research studies. This oversight has implications for the validity of hand hygiene audit findings. Measuring hand hygiene product use overcomes avoidance tactics. It is cheaper and generates data continuously to assess the compliance of all clinicians without disrupting patient care. Disadvantages are the risk of overestimating uptake through spillage, wastage, or use by visitors and non-clinical staff entering patient care areas. Electronic devices may overcome the Hawthorne and avoidance effects but are costly and are not widely used outside research studies

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

Resultados experimentales y simulación con TRNSYS de un sistema fotovoltaico conectado a la red de 7.2kWp

This paper presents a dynamic model and experimental results of a 7.2 kWp photovoltaic (PV) installation located at the Polytechnic University of Valencia (Spain). The modelling of the monocrystalline cells has been realised in TRNSYS and has been validated during an extensive experimental campaign from January 2001 to March 2003, using the data of a fully monitored PV field. The simulation results with TRNSYS provide an accurate prediction of the long-term performance. In addition to the dynamic models, algebraic methods such as the constant fill factor have also been applied. In the design of PV systems, there are several important uncertainties which have to be taken into account, such as the reduction of power with respect to the nominal power under Standard Test Conditions (STC), the choice of the meteorological database, and the models for the calculation of the radiation on tilted surface and of the cell temperature. These aspects are analyzed thoroughly in this paper, as well as the problems inherent to the PV power injection into the grid

Reccurrence Pattern After Adjuvant Customized Chemotherapy Based on BRCA Expression Level (SCAT Trial)

Background Postop platinum-based CT improves outcomes in completely resected NSCLC with nodal involvement, (St II-IIIA). Customization is feasible in adjuvant setting (tissue availability) . Analysis of expressionin genes involved in DNA repair could be use to select CT regiment. •BRCA1 plays an important role in DNA repair pathways and functions as a differential regulator of response to cisplatin and antimicrotubuleagents. SCAT trial results found that for low BRCA1 levels subgroup Cis-Gemcitabine was superior to Cis-Docetaxel and in high BRCA1 levels subgroup Docetaxel single agent without platinum achieved similar survival to Cis-Doc. Analysis of recurrence pattern in different subgroups of the trials has been performed. Method From Jun/2007 to May/2013 591 patients were screened and 500 p were included (108 in Control arm treated with Cisplatin-Docetaxel and 392 in Experimental arm treated with Cisplatin-Gemcitabine, Cisplatin-Docetaxel or Docetaxel alone according terciles BRCA1 expression level). With a cut-off September 30th 2018 and a median follow-up of 60 months, recurrence pattern are analysed in each arm and subgroup treatment and comparison are made for incidence of risk of recurrence, single/multiple recurrence, thoracic/extrathoracic and site of metastases (liver, bone, brain). Result Cumulative recurrence 232/456 evaluable patients (p) (50.8%). Recurrence were seen in 182/354 patients treated in experimental arm and in 50/102 p treated in the control arm (RR 1.04; 0.83-1.30) (p=0.672). Majority of recurrences 159/232 (68.5%) were single site recurrence. Intrathoracic recurrences in 121/232 (52%) while extrathoracic metastatic disease 111/232 (47.8%). No significant differences were seen for single/multiple, intra/extrathoracic recurrences between experimental and control arm. More frequent distant metastatic sites were: bone (42 p), brain (38 p) and liver (11 p) In the experimental group between different treatments no significant differences were found for the overall metastatic rate or for the single/multiple, intrathoracic/extrathoracic recurrences. For specific metastatic sites related to experimental treatment a significant reduction of risk of brain metastases were found in the experimental group with high level BRCA1 treated with Docetaxel single agent (p=0.0016). Conclusion For NSCLC resected patients with lymph node involvement (Stages II-IIIA) risk of recurrence remains high with cumulative rate >50%. There were no differences in the Relative Risk (1.04) of recurrence when control and experimental arm are compared. Majority of recurrences were single site (68.5%) and intrathoracic (52%) but distant metastases developed in 47.8% os p. More frequent metastatic site was bone, followed by brain and liver. Brain metastases risk were significant lower for patients with low BRCA1 expression treated with single agent Docetaxel