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

Choice of the initial antiretroviral treatment for HIV-positive individuals in the era of integrase inhibitors

BACKGROUND: We aimed to describe the most frequently prescribed initial antiretroviral therapy (ART) regimens in recent years in HIV-positive persons in the Cohort of the Spanish HIV/AIDS Research Network (CoRIS) and to investigate factors associated with the choice of each regimen. METHODS: We analyzed initial ART regimens prescribed in adults participating in CoRIS from 2014 to 2017. Only regimens prescribed in >5% of patients were considered. We used multivariable multinomial regression to estimate Relative Risk Ratios (RRRs) for the association between sociodemographic and clinical characteristics and the choice of the initial regimen. RESULTS: Among 2874 participants, abacavir(ABC)/lamivudine(3TC)/dolutegavir(DTG) was the most frequently prescribed regimen (32.1%), followed by tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)/elvitegravir(EVG)/cobicistat(COBI) (14.9%), TDF/FTC/rilpivirine (RPV) (14.0%), tenofovir alafenamide (TAF)/FTC/EVG/COBI (13.7%), TDF/FTC+DTG (10.0%), TDF/FTC+darunavir/ritonavir or darunavir/cobicistat (bDRV) (9.8%) and TDF/FTC+raltegravir (RAL) (5.6%). Compared with ABC/3TC/DTG, starting TDF/FTC/RPV was less likely in patients with CD4100.000 copies/mL. TDF/FTC+DTG was more frequent in those with CD4100.000 copies/mL. TDF/FTC+RAL and TDF/FTC+bDRV were also more frequent among patients with CD4<200 cells//muL and with transmission categories other than men who have sex with men. Compared with ABC/3TC/DTG, the prescription of other initial ART regimens decreased from 2014-2015 to 2016-2017 with the exception of TDF/FTC+DTG. Differences in the choice of the initial ART regimen were observed by hospitals' location. CONCLUSIONS: The choice of initial ART regimens is consistent with Spanish guidelines' recommendations, but is also clearly influenced by physician's perception based on patient's clinical and sociodemographic variables and by the prescribing hospital location

Immunological response against SARS-CoV-2 following full-dose administration of Comirnaty® COVID-19 vaccine in nursing home residents

6 páginas, 2 figuras, 3 tablas. Se puede acceder al texto completo de este artículo desde PubMedCentral: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8490129 . Los datos de investigación utilizados en el mismo, se encuentran disponibles en: https://doi.org/10.1016/j.cmi.2021.09.031.Objectives: The current study was aimed at examining SARS-CoV-2 immune responses following two doses of Comirnaty® COVID-19 vaccine among elderly people in nursing homes. Methods: A prospective cohort study in a representative sample from nursing homes in Valencia (n = 881; males: 271, females 610; median age, 86 years) recruited residents using a random one-stage cluster sampling approach. A lateral flow immunochromatography device (LFIC) (OnSite COVID-19 IgG/IgM Rapid Test; CTK BIOTECH, Poway, CA, USA) was used as the front-line test for detecting SARS-CoV-2-Spike (S)-specific antibodies in whole blood obtained using a fingerstick. Residents returning negative LFIC results underwent venipuncture and testing for presence of SARS-CoV-2-S-reactive antibodies and T cells using the Roche Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics, Pleasanton, CA, USA), the LIAISON® SARS-CoV-2 TrimericS IgG assay (Diasorin S.p.A, Saluggia, Italy) and by flow cytometry, respectively. Results: The SARS-CoV-2-S antibody detection rate in nursing home residents was 99.6% (283/284) and 98.3% (587/597) for SARS-CoV-2 recovered and naïve residents, respectively, within a median of 99 days (range 17-125 days) after full vaccination. Three out of five residents lacking SARS-CoV-2-S antibodies had detectable S-reactive CD8+ and/or CD4+ T cells. In addition, 50/50 and 40/50 participants with detectable SARS-CoV-2 antibodies also had SARS-CoV-2-S-reactive interferon-γ-producing CD4+ and CD8+ T cells, respectively. Discussion: The Comirnaty® COVID-19 vaccine is highly immunogenic in nursing home residents. Keywords: Comirnaty®COVID-19 vaccine; Nursing home residents; SARS-CoV-2; SARS-CoV-2-S antibodies.Ignacio Torres (Río Hortega Contract; CM20/00090), Eliseo Albert (Juan Rodes Contract; JR20/00011) and Estela Gimenez (Juan Rod es Contract, JR18/00053) hold contracts funded by the Health Institute Carlos III (co-financed by the European Regional Development Fund, ERDF/FEDER).Peer reviewe

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&lt;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&lt;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