Global hemostatic status in patients with acute-on-chronic liver failure and septics without underlying liver disease

Background Even the sickest patients with chronic liver disease (CLD), such as those with acute-on-chronic liver failure (ACLF) remain in hemostatic balance due to a concomitant decline in pro- and antihemostatic factors. Objectives We aimed to study whether the hemostatic status in ACLF is merely an exaggeration from the status in patients with compensated and acutely decompensated cirrhosis, or whether sepsis-associated hemostatic changes contribute. Methods We performed extensive hemostatic profiling in 31 adult patients with ACLF, 20 patients with sepsis without underlying CLD, and 40 healthy controls. Results We found similarly elevated plasma levels of the platelet adhesive protein von Willebrand factor (VWF) and decreased levels of the VWF-regulating protease ADAMTS13 in both groups compared to healthy controls. In vivo markers of activation of coagulation (thrombin-antithrombin III, D-dimer) were similarly elevated in both groups compared to controls, but ex vivo thrombin-generating capacity was similar between patients and controls, despite a much more profound international normalized ratio elevation in ACLF. Plasma fibrinogen levels were much higher in septics, which was accompanied by a decreased ex vivo clot permeability and an increase in ex vivo resistance to clot lysis. All hemostatic parameters were remarkably stable over the first 10 days after admission. Conclusions We have found hemostatic changes in ACLF to partially overlap with that of patients with sepsis, and evidence of preserved hemostatic capacity in both patient groups. The notable difference was a profound hyperfibrinogenemia, associated with a thrombogenic clot structure and a marked ex vivo resistance to fibrinolysis in patients with sepsis

The Delphi technique in ecology and biological conservation: Applications and guidelines

1. Many areas of science, including conservation and environmental management, regularly require engaging stakeholders or experts to produce consensus or technical inputs. The Delphi technique is an iterative and anonymous participatory method used for gathering and evaluating such expert-based knowledge. 2. We outline the methodology of the Delphi technique and provide a taxonomy of its main variants. In addition, we refine the technique by providing suggestions to address common limitations (e.g. time consumption, attrition rate) in order tomake the method more suitable for application in ecology and conservation. 3. A comprehensive search for studies that have applied the Delphi technique in conservation and environmental management resulted in 36 papers. The Delphi technique has been applied to a range of issues, including developing decision support systems and predicting ecological impacts of climate change. 4. The papers reviewed suggest that the Delphi technique is an efficient, inclusive, systematic and structured approach that can be used to address complex issues. A major strength compared to other group-based techniques is the reduced influence of social pressures among respondents. 5. The Delphi technique is relatively little used and seems undervalued. Given its wide range of possible applications, it could be applied more widely in evaluating evidence and providing expert judgments.The authors would like to thank Pinaki Bhattacharya, Maria Voigt, Francisco Benitez-Capistros and the three anonymous reviewers for their significant contributions in improving the earlier manuscript. WJS is funded by Arcadia. NM and JH were funded by the Belgian National Science Foundation (FNRS), MIS ID 1765914 project. NM was also funded by the Fondation Weiner Anspach (FWA) postdoctoral fellowship.This is the author accepted manuscript. The final version is available from Wiley at http://dx.doi.org/10.1111/2041-210X.1238

The Large Aperture GRB Observatory

The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the high energy (around 100 GeV) component of Gamma Ray Bursts, using the single particle technique in arrays of Water Cherenkov Detectors (WCD) in high mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range. The status of the Observatory and data collected from 2007 to date will be presented.Comment: 4 pages, proceeding of 31st ICRC 200

Water Cherenkov Detectors response to a Gamma Ray Burst in the Large Aperture GRB Observatory

In order to characterise the behaviour of Water Cherenkov Detectors (WCD) under a sudden increase of 1 GeV - 1 TeV background photons from a Gamma Ray Burst (GRB), simulations were conducted and compared to data acquired by the WCD of the Large Aperture GRB Observatory (LAGO). The LAGO operates arrays of WCD at high altitude to detect GRBs using the single particle technique. The LAGO sensitivity to GRBs is derived from the reported simulations of the gamma initiated particle showers in the atmosphere and the WCD response to secondaries.Comment: 5 pages, proceeding of the 31st ICRC 200

Rpgrip1 is required for rod outer segment development and ciliary protein trafficking in zebrafish

The authors would like to thank the Royal Society of London, the National Eye Research Centre, the Visual Research Trust, Fight for Sight, the W.H. Ross Foundation, the Rosetrees Trust, and the Glasgow Children’s Hospital Charity for supporting this work. This work was also supported by the Deanship of Scientific Research at King Saud University for funding this research (Research Project) grant number ‘RGP – VPP – 219’.Mutations in the RPGR-interacting protein 1 (RPGRIP1) gene cause recessive Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa (RP) and cone-rod dystrophy. RPGRIP1 interacts with other retinal disease-causing proteins and has been proposed to have a role in ciliary protein transport; however, its function remains elusive. Here, we describe a new zebrafish model carrying a nonsense mutation in the rpgrip1 gene. Rpgrip1homozygous mutants do not form rod outer segments and display mislocalization of rhodopsin, suggesting a role for RPGRIP1 in rhodopsin-bearing vesicle trafficking. Furthermore, Rab8, the key regulator of rhodopsin ciliary trafficking, was mislocalized in photoreceptor cells of rpgrip1 mutants. The degeneration of rod cells is early onset, followed by the death of cone cells. These phenotypes are similar to that observed in LCA and juvenile RP patients. Our data indicate RPGRIP1 is necessary for rod outer segment development through regulating ciliary protein trafficking. The rpgrip1 mutant zebrafish may provide a platform for developing therapeutic treatments for RP patients.Publisher PDFPeer reviewe

Diagnostic Accuracy of Adenosine Deaminase and Lymphocyte Proportion in Pleural Fluid for Tuberculous Pleurisy in Different Prevalence Scenarios

BACKGROUND: Tuberculous pleural effusion (TPE) is a paucibacillary manifestation of tuberculosis, so isolation of Mycobacterium tuberculosis is difficult, biomarkers being an alternative for diagnosis. Adenosine deaminase (ADA) is the most cost-effective pleural fluid marker and is routinely used in high prevalence settings, whereas its value is questioned in areas with low prevalence. The lymphocyte proportion (LP) is known to increase the specificity of ADA for this diagnosis. We analyse the diagnostic usefulness of ADA alone and the combination of ADA ≥ 40 U/l (ADA(40)) and LP ≥ 50% (LP(50)) in three different prevalence scenarios over 11 years in our area. MATERIALS AND METHODS: Biochemistry, cytology and microbiology studies from 472 consecutive pleural fluid samples were retrospectively analyzed. ADA and differential cell count were determined in all samples. We established three different prevalence periods, based on percentage of pleural effusion cases diagnosed as tuberculosis: 1998-2000 (31.3%), 2001-2004 (11.8%), and 2005-2008 (7.4%). ROC curves, dispersion diagrams and pre/post-test probability graphs were produced. TPE accounted for 73 episodes (mean prevalence: 15.5%). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for ADA(40) were 89%, 92.7%, 69.2% and 97.9%, respectively. For ADA(40)+LP(50) the specificity and PPV increased (98.3% and 90%) with hardly any decrease in the sensitivity or NPV (86.3% and 97.5%). No relevant differences were observed between the three study periods. CONCLUSIONS/SIGNIFICANCE: ADA remains useful for the diagnosis of TPE even in low-to-intermediate prevalence scenarios when combined with the lymphocyte proportion

Interaction of retinitis pigmentosa GTPase regulator (RPGR) with RAB8A GTPase: implications for cilia dysfunction and photoreceptor degeneration

Defects in biogenesis or function(s) of primary cilia are associated with numerous inherited disorders (called ciliopathies) that may include retinal degeneration phenotype. The cilia-expressed gene RPGR (retinitis pigmentosa GTPase regulator) is mutated in patients with X-linked retinitis pigmentosa (XLRP) and encodes multiple protein isoforms with a common N-terminal domain homologous to regulator of chromosome condensation 1 (RCC1), a guanine nucleotide exchange factor (GEF) for Ran GTPase. RPGR interacts with several ciliopathy proteins, such as RPGRIP1L and CEP290; however, its physiological role in cilia-associated functions has not been delineated. Here, we report that RPGR interacts with the small GTPase RAB8A, which participates in cilia biogenesis and maintenance. We show that RPGR primarily associates with the GDP-bound form of RAB8A and stimulates GDP/GTP nucleotide exchange. Disease-causing mutations in RPGR diminish its interaction with RAB8A and reduce the GEF activity. Depletion of RPGR in hTERT-RPE1 cells interferes with ciliary localization of RAB8A and results in shorter primary cilia. Our data suggest that RPGR modulates intracellular localization and function of RAB8A. We propose that perturbation of RPGR–RAB8A interaction, at least in part, underlies the pathogenesis of photoreceptor degeneration in XLRP caused by RPGR mutations

Medicinal plants and functional foods used as resources against Covid-19 by an andean population in Peru

Abstract The objective of this research was to identify those medicinal plants and functional foods that the population of Cusco, located in the Peruvian Andes, use as resources to cope with COVID-19 either for prevention or as an adjuvant to treatment with drugs. A descriptive, non-experimental and cross-sectional research was developed. The study population consisted of inhabitants over 20 and under 70 years of age, of both exes from the districts of Cusco, San Jeronimo, San Sebastian, Santiago and Wanchaq in the city of Cusco, Peru. A virtual survey was applied to 1747 inhabitants, for which a questionnaire was designed and elaborated with 07 items whose content was validated by 10 expert judges using Aiken’s V (Aiken’s V > 0.90). The data collected were exported to a database in Microsoft Excel. This research work was reviewed and approved by the Research Bioethics Committee of the National University of San Antonio Abad del Cusco. The results obtained show that the medicinal plants most used by the population studied were eucalyptus (70.2%), kion (68.3%), garlic (58.8%), matico (49.6%), chamomile (34.0%) and coca (21.6%). The functional foods consumed by the population include lemon (79.1%), kion (65.3%), orange (62.2%), honey (63.5%), onion (52.4%), avocado (40.2%), broccoli (35.8%),fish (35.5%) and tarwi (32.5%) for prevention, symptom relief and as an adjuvant in the treatment with drugs for COVID-19.ResumenLa presente investigación, tuvo como objetivo identificar aquellas plantas medicinales y alimentos funcionales que la población del Cusco ubicada en los Andes del Perú, hace uso como recursos para hacer frente a la COVID-19 ya sea para la prevención o como coadyuvante al tratamiento con medicamentos. Se desarrolló una investigación descriptiva, no xperimental y transversal. La población de estudio estuvo constituida por los habitantes mayores de 20 y menores de 70 años, de ambos sexos de los distritos de Cusco, San Jerónimo, San Sebastián, Santiago y Wanchaq de la ciudad del Cusco., Perú. Se aplicó una encuesta virtual a 1747 pobladores, para lo cual se diseñó y elaboró un cuestionario con 07 ítems cuyo contenido fue validado por 10 jueces expertos utilizando la V de Aiken (V de Aiken > 0,90). Los datos recopilados fueron exportados a una base de datos en el programa Microsoft Excel. Este trabajo de investigación fue revisado y aprobado por el Comité de Bioética en Investigación de la Universidad Nacional de San Antonio Abad del Cusco. Los resultados obtenidos muestran que las plantas medicinales más utilizadas por la población estudiada fueron eucalipto (70,2%), kión (68,3%), ajo (58,8%), matico (49,6%), manzanilla (34,0%) y coca (21,6%). En relación a los alimentos funcionales que la población consume se encuentran limón (79,1%), kión (65,3%), naranja (62,2%), miel (63,5%), cebolla (52,4%), palta (40,2%), brócoli (35,8%), pescado (35,5%) y tarwi (32,5%) con fines de prevención, alivio de síntomas y coadyuvante en el tratamiento con medicamentos para la COVID-19