Antifungal activity of Leptadenia reticulata Wight and Arn. aerial parts

The petroleum ether, chloroform, acetone, methanol and aqueous extracts of the aerial parts of Leptadenia reticulata Wight and Arn. (Asclepiadaceae) were studied for in vitro antifungal activity against Aspergillus flavus, Aspergillus ruantti, Candida tropicalis, Candida albicans, Trichodermata viride and Trichodermata koningii respectively. The methanolic extract exhibited prominent antifungal activity against all the selected strains. Minimum inhibitory concentration of the extracts was performed by broth dilution method and the zone of inhibition was studied by agar disc diffusion method at concentrations of 2, 5 and 10mg/ml in DMSO. Cotrimazole (25μg/ml) was used as reference control for antifungal studies. Results of MIC study revealed the antifungal activities of the extracts against the tested strains in between concentration ranges 50-400μg/ml. The present study indicates the potential usefulness of L. reticulata aerial parts as antifungal agent.Keywords: Leptadenia reticulata Wight and Arn., Antifungal activity, Minimum inhibitory concentration, Zone of inhibition, Clotrimazol

Dose-volume predictors for patient-reported late diarrhoea, faecal incontinence and urgency after pelvic radiotherapy

Aims Pelvic radiotherapy adds significantly to the curative treatment of many pelvic malignancies. However, this cure comes at a cost for many patients, where late bowel toxicities, such as faecal incontinence, urgency and diarrhoea, adversely affect quality of life. Despite the implementation of advanced radiotherapy techniques in many centres, there are deficiencies in our knowledge of how to make best use of these techniques to minimise these late toxicities, with dose–volume constraints specifically for late effects needing definition. The aims of this study were to establish dose–volume predictors for patient-reported late bowel toxicities and derive constraints for clinical use to reduce the risk of these toxicities. Materials and methods All radiotherapy patients treated in our institution between 2012 and 2014 for gynaecological and urological cancers (bladder, prostate where pelvic nodes are treated) were identified. Patients were sent patient-reported toxicity questionnaires at 12 and 24 months after treatment. Planning computed tomography scans were retrospectively contoured with different definitions of bowel as organs at risk (OARs). Dose–volume data for each OAR were collected and predictors of these toxicities found using multivariate analysis. For those dose–volume predictors found to be significant on multivariate analysis, statistically significant and clinically relevant dose–volume constraints were derived. Furthermore, data collected were used to validate constraints from published studies. Results Faecal urgency, incontinence and diarrhoea rates were found in 52, 23.5 and 18.7% of the 203 patients included at 12 months following radiotherapy. Dose–volume parameters for sigmoid colon and large bowel were significant for these toxicities, and constraints for these OARs were derived, which are promising. A previously published constraint for bowel loops was validated with our data. Conclusions The sigmoid colon and large bowel are important OARs for the development of faecal urgency, incontinence and diarrhoea. Promising constraints for these OARs were derived, which require further validation before prospective clinical use

Animal models and vaccines for SARS-CoV infection

We summarize findings of SARS-CoV infections in several animal models each of which support viral replication in lungs accompanied by histopathological changes and/or clinical signs of illness to varying degrees. New findings are reported on SARS-CoV replication and associated pathology in two additional strains (C57BL/6 and 129S6) of aged mice. We also provide new comparative data on viral replication and associated pathology following infection of golden Syrian hamsters with various SARS-CoV strains and report the levels of neutralizing antibody titers following these infections and the cross-protective efficacy of infection with these strains in protecting against heterologous challenge. Finally, we summarize findings of a variety of vaccine approaches and discuss the available in vitro and in vivo data addressing the potential for disease enhancement following re-infection in animals previously vaccinated against or infected with SARS-CoV

Protocol for the insight study: a randomised controlled trial of single-dose tocilizumab in patients with depression and low-grade inflammation.

INTRODUCTION: Observational studies indicate a potentially causal role for interleukin 6 (IL-6), a proinflammatory cytokine, in pathogenesis of depression, but interventional studies based on patients with depression have not been conducted. Tocilizumab, anti-inflammatory drug, is a humanised monoclonal antibody that inhibits IL-6 signalling and is licensed in the UK for treatment of rheumatoid arthritis. The main objectives of this study are to test whether IL-6 contributes to the pathogenesis of depression and to examine potential mechanisms by which IL-6 affects mood and cognition. A secondary objective is to compare depressed participants with and without evidence of low-grade systemic inflammation. METHODS AND ANALYSIS: This is a proof-of-concept, randomised, parallel-group, double-blind, placebo-controlled clinical trial. Approximately 50 participants with International Classification of Diseases 10th revision (ICD-10) diagnosis of depression who have evidence of low-grade inflammation, defined as serum high-sensitivity C reactive protein (hs-CRP) level ≥3 mg/L, will receive either a single intravenous infusion of tocilizumab or normal saline. Blood samples, behavioural and cognitive measures will be collected at baseline and after infusion around day 7, 14 and 28. The primary outcome is somatic symptoms score around day 14 postinfusion. In addition, approximately, 50 depressed participants without low-grade inflammation (serum hs-CRP level <3 mg/L) will complete the same baseline assessments as the randomised cohort. ETHICS AND DISSEMINATION: The study has been approved by the South Central-Oxford B Research Ethics Committee (REC) (Reference: 18/SC/0118). Study findings will be published in peer-review journals. Findings will be also disseminated by conference/departmental presentations and by social and traditional media. TRIAL REGISTRATION NUMBER: ISRCTN16942542; Pre-results

A live attenuated severe acute respiratory syndrome coronavirus is immunogenic and efficacious in Golden Syrian hamsters

The immunogenicity and protective efficacy of a live attenuated vaccine consisting of a recombinant severe acute respiratory syndrome (SARS) coronavirus lacking the E gene (rSARS-CoV-ΔE) were studied using hamsters. Hamsters immunized with rSARS-CoV-ΔE developed high serum-neutralizing antibody titers and were protected from replication of homologous (SARS-CoV Urbani) and heterologous (GD03) SARS-CoV in the upper and lower respiratory tract. rSARS-CoV-ΔE-immunized hamsters remained active following wild-type virus challenge, while mock-immunized hamsters displayed decreased activity. Despite being attenuated in replication in the respiratory tract, rSARS-CoV-ΔE is an immunogenic and efficacious vaccine in hamsters.This research was supported in part by the Intramural Research Program of the NIH, NIAID; by NIH AID AI059136; and by the European Community (projects DISSECT SP22-CT-2004-511060 and Rivigene SSPE-CT-2005-022639)

Examples of risk tools for pests in Peanut (Arachis hypogaea) developed for five countries using Microsoft Excel

Suppressing pest populations below economically-damaging levels is an important element of sustainable peanut (Arachis hypogaea L.) production. Peanut farmers and their advisors often approach pest management with similar goals regardless of where they are located. Anticipating pest outbreaks using field history and monitoring pest populations are fundamental to protecting yield and financial investment. Microsoft Excel was used to develop individual risk indices for pests, a composite assessment of risk, and costs of risk mitigation practices for peanut in Argentina, Ghana, India, Malawi, and North Carolina (NC) in the United States (US). Depending on pests and resources available to manage pests, risk tools vary considerably, especially in the context of other crops that are grown in sequence with peanut, cultivars, and chemical inputs. In Argentina, India, and the US where more tools (e.g., mechanization and pesticides) are available, risk indices for a wide array of economically important pests were developed with the assumption that reducing risk to those pests likely will impact peanut yield in a positive manner. In Ghana and Malawi where fewer management tools are available, risks to yield and aflatoxin contamination are presented without risk indices for individual pests. The Microsoft Excel platform can be updated as new and additional information on effectiveness of management practices becomes apparent. Tools can be developed using this platform that are appropriate for their geography, environment, cropping systems, and pest complexes and management inputs that are available. In this article we present examples for the risk tool for each country.Fil: Jordan, David L.. University of Georgia; Estados Unidos. North Carolina State University; Estados UnidosFil: Buol, Greg S.. North Carolina State University; Estados UnidosFil: Brandenburg, Rick L.. North Carolina State University; Estados UnidosFil: Reisig, Dominic. North Carolina State University; Estados UnidosFil: Nboyine, Jerry. Council for Scientific and Industrial Research Savanna Agricultural Research Institute; GhanaFil: Abudulai, Mumuni. Council for Scientific and Industrial Research Savanna Agricultural Research Institute; GhanaFil: Oteng Frimpong, Richard. Council for Scientific and Industrial Research Savanna Agricultural Research Institute; GhanaFil: Mochiah, Moses Brandford. Council for Scientific and Industrial Research Crops Research Institute; GhanaFil: Asibuo, James Y.. Council for Scientific and Industrial Research Crops Research Institute; GhanaFil: Arthur, Stephen. Council for Scientific and Industrial Research Crops Research Institute; GhanaFil: Akromah, Richard. Kwame Nkrumah University Of Science And Technology; GhanaFil: Mhango, Wezi. Lilongwe University Of Agriculture And Natural Resources; MalauiFil: Chintu, Justus. Chitedze Agricultural Research Service, Lilongwe; MalauiFil: Morichetti, Sergio. Aceitera General Deheza; ArgentinaFil: Paredes, Juan Andres. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Instituto de Patología Vegetal; Argentina. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Unidad de Fitopatología y Modelización Agrícola - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Unidad de Fitopatología y Modelización Agrícola; ArgentinaFil: Monguillot, Joaquín Humberto. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigaciones Agropecuarias. Instituto de Patología Vegetal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Singh Jadon, Kuldeep. Central Arid Zone Research Institute, Jodhpur; IndiaFil: Shew, Barbara B.. North Carolina State University; Estados UnidosFil: Jasrotia, Poonam. Indian Institute Of Wheat And Barley Research, Karnal; IndiaFil: Thirumalaisamy, P. P.. India Council of Agricultural Research, National Bureau of Plant Genetic Resources; IndiaFil: Harish, G.. Directorate Of Groundnut Research, Junagadh; IndiaFil: Holajjer, Prasanna. National Bureau Of Plant Genetic Resources, New Delhi; IndiaFil: Maheshala, Nataraja. Directorate Of Groundnut Research, Junagadh; IndiaFil: MacDonald, Greg. University of Florida; Estados UnidosFil: Hoisington, David. University of Georgia; Estados UnidosFil: Rhoads, James. University of Georgia; Estados Unido

The PROPER Study; A 48-week, pan-European, real-world study of biosimilar SB5 following transition from reference adalimumab in patients with immune-mediated inflammatory disease

Background: The non-interventional PROPER study generated real-world evidence on clinical outcomes following transition in routine practice from reference adalimumab to the EMA-approved SB5 biosimilar adalimumab in patients with immune-mediated inflammatory disease. Methods: Adults with rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), Crohn’s disease (CD), or ulcerative colitis (UC) were enrolled at 63 sites across Europe. Eligible patients received ≥ 16 weeks of routine treatment with reference adalimumab before transitioning to SB5, and were followed for 48 weeks post-transition. The primary objective was to evaluate candidate predictors (clinically relevant baseline variables with incidence ≥ 15% by indication cohort) associated with persistence on SB5 at 48 weeks post-initiation. Key primary outcome measures were persistence on SB5 (estimated by Kaplan–Meier methodology) and clinical characteristics and disease activity scores at the time of transition to SB5 treatment (baseline). Results: A total of 955 eligible patients were enrolled (RA, n = 207; axSpA, n = 127; PsA, n = 162; CD, n = 447; UC, n = 12), of whom 932 (97.6%) completed follow-up and 722 (75.6%) were still receiving SB5 at week 48. Kaplan–Meier estimates (95% confidence interval, CI) of persistence on SB5 at week 48 for RA, axSpA, PsA, and CD were 0.86 (0.80–0.90), 0.80 (0.71–0.86), 0.81 (0.74–0.86), and 0.72 (0.67–0.76), respectively. The single candidate predictor associated with probability of SB5 discontinuation before week 48 was female sex [RA, axSpA, and CD cohorts; HR (95% CI): 3.53 (1.07–11.67), 2.38 (1.11–5.14), and 2.21 (1.54–3.18), respectively]. Disease activity scores remained largely unchanged throughout the study, with proportions by cohort in remission at baseline versus week 48 being 59.2% versus 57.2%, 81.0% versus 78.0%, 94.7% versus 93.7%, and 84.0% versus 85.1% for patients with RA, axSpA, PsA, and CD, respectively. Similarly, the SB5 dosing regimen remained unchanged for the majority of patients from baseline to week 48, the most common regimen being 40 mg every 2 weeks. In total, 232 patients (24.3%) reported at least one adverse drug reaction, and most events were mild; eight patients (3.9%) in the RA cohort experienced nine serious adverse events (SAEs; two possibly related to SB5); eight patients (4.9%) in the PsA cohort experienced nine SAEs (one possibly related to SB5); 22 patients (4.9%) in the CD cohort experienced 27 SAEs (four possibly related to SB5); and no SAEs were observed in the UC cohort. Conclusions: With the exception of female sex in RA, axSpA, and CD, none of the candidate predictors were associated with SB5 discontinuation. Persistence on SB5 was high, treatment effectiveness was maintained, and no safety signals were detected. Trial Registration: This trial is registered with ClinicalTrials.gov: NCT04089514

Serum bone-turnover biomarkers are associated with the occurrence of peripheral and axial arthritis in psoriatic disease:a prospective cross-sectional comparative study

Abstract Background A recent systematic review identified four candidate serum-soluble bone-turnover biomarkers (dickkopf-1, Dkk-1; macrophage-colony stimulating factor, M-CSF; matrix metalloproteinase-3, MMP-3; osteoprotegerin, OPG) showing possible association with psoriatic arthritis (PsA). We aimed to: (i) confirm and determine if these four biomarkers are associated with PsA; (ii) differentiate psoriasis cases with and without arthritis; and (iii) differentiate PsA cases with and without axial arthritis. Methods A prospective cross-sectional comparative two-centre study recruited 200 patients with psoriasis without arthritis (PsC), 127 with PsA without axial arthritis (pPsA), 117 with PsA with axial arthritis (psoriatic spondyloarthritis, PsSpA), 157 with ankylosing spondylitis (AS) without psoriasis, and 50 matched healthy controls (HC). Serum biomarker concentrations were measured using ELISA. Multivariable regression and receiver operating characteristic analyses were performed. Results MMP-3 concentrations were significantly higher and M-CSF significantly lower in each arthritis disease group compared with HC (p ≤ 0.02). MMP-3 concentrations were significantly higher (adjusted odds ratio, ORadj 1.02 per ng/ml increase in concentration; p = 0.0004) and M-CSF significantly lower (ORadj 0.44 per ng/ml increase; p = 0.01) in PsA (pPsA and PsSpA combined) compared with PsC. Dkk-1 concentrations were significantly higher (ORadj 1.22 per ng/mL increase; p = 0.01), and OPG concentrations significantly lower (ORadj 0.20 per ng/mL increase; p = 0.02) in patients with axial arthritis (PsSpA and AS combined) than in those without (pPsA). Furthermore, Dkk-1 concentrations were significantly higher along a spectrum of increasing axial arthritis; Dkk-1 concentrations were higher in AS compared with PsSpA (ORadj 1.18 per ng/mL increase; p = 0.02). Receiver operating characteristic analysis showed MMP-3 to be the best single biomarker for differentiating PsA from PsC (AUC 0.70 for a cut-off of 14.51 ng/mL; sensitivity 0.76, specificity 0.60). Conclusions MMP-3 and M-CSF are biomarkers for the presence of arthritis in psoriatic disease, and could therefore be used to screen for PsA in psoriasis cohorts. Dkk-1 and OPG are biomarkers of axial arthritis; they could therefore be used to screen for the presence of axial disease in PsA cases, and help differentiate PsSpA from AS. High concentrations of Dkk-1 in AS and PsSpA compared with HC, support previous reports that Dkk-1 is dysfunctional in the spondyloarthritides

Axial Involvement in Psoriatic Arthritis cohort (AXIS): the protocol of a joint project of the Assessment of SpondyloArthritis international Society (ASAS) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA).

BACKGROUND: Involvement of the axial skeleton (sacroiliac joints and spine) is a relatively frequent manifestation associated with psoriatic skin disease, mostly along with involvement of peripheral musculoskeletal structures (peripheral arthritis, enthesitis, dactylitis), which are referred to as psoriatic arthritis (PsA). Data suggest that up to 30% of patients with psoriasis have PsA. Depending on the definition used, the prevalence of axial involvement varies from 25% to 70% of patients with PsA. However, there are currently no widely accepted criteria for axial involvement in PsA.Objective: The overarching aim of the Axial Involvement in Psoriatic Arthritis (AXIS) study is to systematically evaluate clinical and imaging manifestations indicative of axial involvement in patients with PsA and to develop classification criteria and a unified nomenclature for axial involvement in PsA that would allow defining a homogeneous subgroup of patients for research. DESIGN: Prospective, multicenter, multinational, cross-sectional study. METHODS AND ANALYSES: In this multicenter, multinational, cross-sectional study, eligible patients [adult patients diagnosed with PsA and fulfilling Classification Criteria for Psoriatic Arthritis (CASPAR) with musculoskeletal symptom duration of ⩽10 years not treated with biological or targeted synthetic disease-modifying anti-rheumatic drugs] will be recruited prospectively. They will undergo study-related clinical and imaging examinations. Imaging will include radiography and magnetic resonance imaging examinations of sacroiliac joints and spine. Local investigators will evaluate for the presence of axial involvement based on clinical and imaging information which will represent the primary outcome of the study. In addition, imaging will undergo evaluation by central review. Finally, the central clinical committee will determine the presence of axial involvement based on all available information. ETHICS: The study will be performed according to the ethical principles of the Declaration of Helsinki and International Council for Harmonisation Good Clinical Practice guidelines. The study protocol will be approved by the individual Independent Ethics Committee / Institutional Review Board of participating centers. Written informed consent will be obtained from all included patients.Registration: ClinicalTrials.gov ID: NCT04434885