Low potency toxins reveal dense interaction networks in metabolism

Background The chemicals of metabolism are constructed of a small set of atoms and bonds. This may be because chemical structures outside the chemical space in which life operates are incompatible with biochemistry, or because mechanisms to make or utilize such excluded structures has not evolved. In this paper I address the extent to which biochemistry is restricted to a small fraction of the chemical space of possible chemicals, a restricted subset that I call Biochemical Space. I explore evidence that this restriction is at least in part due to selection again specific structures, and suggest a mechanism by which this occurs. Results Chemicals that contain structures that our outside Biochemical Space (UnBiological groups) are more likely to be toxic to a wide range of organisms, even though they have no specifically toxic groups and no obvious mechanism of toxicity. This correlation of UnBiological with toxicity is stronger for low potency (millimolar) toxins. I relate this to the observation that most chemicals interact with many biological structures at low millimolar toxicity. I hypothesise that life has to select its components not only to have a specific set of functions but also to avoid interactions with all the other components of life that might degrade their function. Conclusions The chemistry of life has to form a dense, self-consistent network of chemical structures, and cannot easily be arbitrarily extended. The toxicity of arbitrary chemicals is a reflection of the disruption to that network occasioned by trying to insert a chemical into it without also selecting all the other components to tolerate that chemical. This suggests new ways to test for the toxicity of chemicals, and that engineering organisms to make high concentrations of materials such as chemical precursors or fuels may require more substantial engineering than just of the synthetic pathways involved

Evaluation of a new, rapid, simple test for the detection of influenza virus

BACKGROUND: Influenza virus infections are responsible for significant morbidity and mortality in both pediatric and adult populations worldwide. Rapid and accurate diagnosis of influenza is necessary for appropriate patient management during the influenza season and for optimal utilization of anti-influenza therapy. We prospectively tested the accuracy of a simple and rapid diagnostic method. METHODS: Ninety-eight samples (nasal and pharyngeal swabs) from patients with upper respiratory tract infection symptoms who presented to primary healthcare centres in Barcelona (Spain) were prospectively analyzed. The samples were collected as part of influenza surveillance program. Samples that had enough volume to make the new test after aliquoting the amount needed to perform routine tests were included. None of the samples were pre-selected as a result of their status in relation to influenza virus. Samples were analyzed by in-house real-time PCR and Alere™ i Influenza A & B (Alere™ i), which uses isothermal amplification of nucleic acids for the qualitative detection of influenza A and B in nasal swabs transported in viral transport media. The two techniques were compared by positive percent agreement (PPA) and negative percent agreement (NPA). Statistical analysis was performed with Stata. RESULTS: Of the 98 samples analysed 90 were concordant; 46 (46.9%) were positive and 44 (44.9%) were negative. Five samples showed invalid results with the Alere™ i test and could be not re-tested due to insufficient sample volume and were not included in the final statistical analysis. In the 93 remaining samples, the Alere™ i test showed 97% of accuracy having correctly classified 90 samples. We obtained discordant results in 3 samples (3%). The PPA was 93.8% for influenza A and 94.1% for influenza B, and NPA was 100% for influenza A and influenza B virus. In addition, the Alere™ i was very rapid (15 minutes or less) and extremely easy to use. CONCLUSIONS: The Alere™ i test provided a good correlation compared to the real-time PCR test for the diagnosis of influenza. Since this method can be performed in minutes, it allows immediate, accurate clinical decisions to prescribe appropriate antiviral treatment or isolation of patients

Deconstructing adverse reactions to Amoxicillin-Clavulanic Acid: the importance of time of onset

Background: Amoxicillin-clavulanic acid (AX-CL) is the most consumed betalactam antibiotic worldwide. We aimed to establish the different phenotypes of betalactam allergy in those referring a reaction with AX-CL and to investigate the differences between immediate and non-immediate onset. Methods: Cross-sectional retrospective study performed at Hospital Clínico San Carlos (HCSC) and Hospital Regional Universitario de Málaga (HRUM) in Spain. Patients reporting reactions with AX-CL who completed the allergy workup between 2017 and 2019 were included. Data of reported reaction and allergy workup were collected. Reactions were classified as immediate and non-immediate with 1hour cut-off point. Results: We included 372 patients (HCSC 208, HRUM 164). There were 90 (24.2%) immediate, 252 (67.7%) non-immediate reactions, and 30 (8.1%) with unknown latency. Allergy to betalactams was ruled-out in 266 (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population were allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%) and to betalactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and non-immediate reactions respectively, with a relative risk of 5.06 (95%CI 3.64-7.02) of an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with late-positive intradermal test (IDT) to CL were diagnosed of CL allergy. Conclusion: Allergy diagnosis was confirmed in a minority of the whole study population, but 5 times more frequently in those reporting immediate reactions, making this classification useful in risk stratification. Late-positive IDT for CL has no diagnostic value and its late reading could be retrieved from the diagnosis work-up.</jats:p