Conectar
by Andreas Michalsen, Kim Goldenstein, Peter Kardos, Ludger Klimek, Jürgen Palm, Dajana Parganlija, Johannes Stöckl
IntroductionCommon cold (CC) symptoms arise from an inflammatory response treatable with cineole and generally peak within two days, which complicates research implementation. We therefore explored the benefits of early cineole administration with enrolment of participants prior to CC onset.
MethodsOut of 522 adults enrolled in our phase IV, open-label, non-randomized, exploratory clinical trial (EudraCT No. 2020-000860-51), 329 developed a CC and used 200 mg cineole (Soledum®, CNL-1976) t.i.d. for max. 15 (± 2) days. Primary endpoint was burden of disease based on the Wisconsin Upper Respiratory Symptom Survey (WURSS-11).
ResultsComparing three strata based on time to treatment (≤ 12 h, > 12 to ≤ 24 h and > 24 h), earliest treatment resulted in lowest AUC-WURSS (Spearman correlation coefficient of 0.36) and reduced the overall burden of disease by 38% (p Conclusions
Early intervention shows clinical benefits relevant for the effective treatment of CC with cineole.
by Ursula Just, Helmut Burtscher, Sylvia Jeratsch, Meike Fischer, Carol Stocking, Jens Preussner, Mario Looso, Ralf Schwanbeck, Stefan Günther, Ralf Huss, Lynne Mullen, Thomas Braun
Brain metastasis leads to increased mortality and is a major site of relapse for several cancers, yet the molecular mechanisms of brain metastasis are not well understood. In this study, we established and characterized a new leukemic cell line, FIA10, that metastasizes into the central nervous system (CNS) following injection into the tail vein of syngeneic mice. Mice injected with FIA10 cells developed neurological symptoms such as loss of balance, tremor, ataxic gait and seizures, leading to death within 3 months. Histopathology coupled with PCR analysis clearly showed infiltration of leukemic FIA10 cells into the brain parenchyma of diseased mice, with little involvement of bone marrow, peripheral blood and other organs. To define pathways that contribute to CNS metastasis, global transcriptome and proteome analysis was performed on FIA10 cells and compared with that of the parental stem cell line FDCP-Mix and the related FIA18 cells, which give rise to myeloid leukemia without CNS involvement. 188 expressed genes (RNA level) and 189 proteins were upregulated (log2 ratio FIA10/FIA18 ≥ 1) and 120 mRNAs and 177 proteins were downregulated (log2 ratio FIA10/FIA18 ≤ 1) in FIA10 cells compared with FIA18 cells. Major upregulated pathways in FIA10 cells revealed by biofunctional analyses involved immune response components, adhesion molecules and enzymes implicated in extracellular matrix remodeling, opening and crossing the blood-brain barrier (BBB), molecules supporting migration within the brain parenchyma, alterations in metabolism necessary for growth within the brain microenvironment, and regulators for these functions. Downregulated RNA and protein included several tumor suppressors and DNA repair enzymes. In line with the function of FIA10 cells to specifically infiltrate the brain, FIA10 cells have acquired a phenotype that permits crossing the BBB and adapting to the brain microenvironment thereby escaping immune surveillance. These data and our model system FIA10 will be valuable resources to study the occurrence of brain metastases and may help in the development of potential therapies against brain invasion.by Irene Boateng, Beth Stuart, Taeko Becque, Bruce Barrett, Jennifer Bostock, Robin Bruyndonckx, Lucy Carr-Knox, Emily J. Ciccone, Samuel Coenen, Mark Ebell, David Gillespie, Gail Hayward, Katarina Hedin, Kerenza Hood, Tin Man Mandy Lau, Paul Little, Dan Merenstein, Edgar Mulogo, Jose Ordóñez-Mena, Peter Muir, Kirsty Samuel, Nader Shaikh, Sharon Tonner, Alike W. van der Velden, Theo Verheij, Kay Wang, Alastair D. Hay, Nick Francis
BackgroundResistance to antibiotics is rising and threatens future antibiotic effectiveness. ‘Antibiotic targeting’ ensures patients who may benefit from antibiotics receive them, while being safely withheld from those who may not. Point-of-care tests may assist with antibiotic targeting by allowing primary care clinicians to establish if symptomatic patients have a viral, bacterial, combined, or no infection. However, because organisms can be harmlessly carried, it is important to know if the presence of the virus/bacteria is related to the illness for which the patient is being assessed. One way to do this is to look for associations with more severe/prolonged symptoms and test results. Previous research to answer this question for acute respiratory tract infections has given conflicting results with studies has not having enough participants to provide statistical confidence.
AimTo undertake a synthesis of IPD from both randomised controlled trials (RCTs) and observational cohort studies of respiratory tract infections (RTI) in order to investigate the prognostic value of microbiological data in addition to, or instead of, clinical symptoms and signs.
MethodsA systematic search of Cochrane Central Register of Controlled Trials, Ovid Medline and Ovid Embase will be carried out for studies of acute respiratory infection in primary care settings. The outcomes of interest are duration of disease, severity of disease, repeated consultation with new/worsening illness and complications requiring hospitalisation. Authors of eligible studies will be contacted to provide anonymised individual participant data. The data will be harmonised and aggregated. Multilevel regression analysis will be conducted to determine key outcome measures for different potential pathogens and whether these offer any additional information on prognosis beyond clinical symptoms and signs.
Trial registrationPROSPERO Registration number: CRD42023376769.
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