Evaluation of the electrostatic properties of biomolecules has become a standard practice in molecular biophysics. Foremost among the models used to elucidate the electrostatic potential is the Poisson-Boltzmann equation; however, existing methods for solving this equation have limited the scope of accurate electrostatic calculations to relatively small biomolecular systems. Here we present the application of numerical methods to enable the trivially parallel solution of the Poisson-Boltzmann equation for supramolecular structures that are orders of magnitude larger in size. As a demonstration of this methodology, electrostatic potentials have been calculated for large microtubule and ribosome structures. The results point to the likely role of electrostatics in a variety of activities of these structures.

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Electrostatics of nanosystems: Application to microtubules and the ribosome

Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Resistance to chemotherapy and molecularly targeted therapies is a major problem facing current cancer research. The mechanisms of resistance to 'classical' cytotoxic chemotherapeutics and to therapies that are designed to be selective for specific molecular targets share many features, such as alterations in the drug target, activation of prosurvival pathways and ineffective induction of cell death. With the increasing arsenal of anticancer agents, improving preclinical models and the advent of powerful high-throughput screening techniques, there are now unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive biomarkers to enable patient stratification.

Cancer drug resistance: an evolving paradigm

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise . The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

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European Position Paper on Rhinosinusitis and Nasal Polyps 2020

https://cyberleninka.org/article/n/148766.pdf

Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation

Meteorological conditions and the distribution of pollen sources are the two most decisive factors influencing the concentration of airborne grass pollen. However, knowledge about land-use types, their potential pollen emission, and the importance of local sources remains limited. In this study, wild grass pollen concentrations from 27 stations in Bavaria, Germany, were linked to potential pollen within a 30 km radius. Agricultural grass pollen sources were derived from the InVeKos database, which contains detailed information on agricultural land-use types and their spatial distribution. Non-agricultural grassland was identified by OpenStreetMap. Further source classification was conducted using a cultivation intensity indicator and wind direction. We show that the grassland percentage and pollen concentrations, specified as annual pollen integral and pollen peak vary strongly between pollen stations. Correlation analyses indicated that the impact of the grassland on pollen concentration was greater within 10 km of the pollen traps. At greater distances, the correlation coefficient between the grassland percentage and pollen indicators steadily declined.

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Impact of Local Grasslands on Wild Grass Pollen Emission in Bavaria, Germany

Background: Clinical efficacy of pollen allergen immunotherapy (AIT) has been broadly documented in randomized controlled trials. The underlying clinical endpoints are analysed in seasonal time periods predefined based on the background pollen concentration. However, any validated or generally accepted definition from academia or regulatory authorities for this relevant pollen exposure intensity or period of time (season) is currently not available. Therefore, this Task Force initiative of the European Academy of Allergy and Clinical Immunology (EAACI) aimed to propose definitions based on expert consensus. Methods: A Task Force of the Immunotherapy and Aerobiology and Pollution Interest Groups of the EAACI reviewed the literature on pollen exposure in the context of defining relevant time intervals for evaluation of efficacy in AIT trials. Underlying principles in measuring pollen exposure and associated methodological problems and limitations were considered to achieve a consensus. Results: The Task Force achieved a comprehensive position in defining pollen exposure times for different pollen types. Definitions are presented for “pollen season”, “high pollen season” (or “peak pollen period”) and “high pollen days”. Conclusion: This EAACI position paper provides definitions of pollen exposures for different pollen types for use in AIT trials. Their validity as standards remains to be tested in future studies.

Definition von Pollenexpositionszeiten für klinische Studien zur Allergen-Immuntherapie bei polleninduzierter Rhinokonjunktivitis – ein EAACI-Positionspapier

Il progetto europeo HIALINE (Health Impacts of Airborne Allergen Information Network): risultati del monitoraggio del polline di betulla e allergene Bet v1 a Parma nell'anno 2009

Allergien und im speziellen hier atopieassoziierte Typ-I-Reaktionen sind klassische Umwelterkrankungen, wobei die auslosenden Substanzen (das sind die Allergene) grosteils bereits charakterisiert und in rekombinanter Form erhaltlich sind. Neben dieser Kausalkette, Allergen und Sensibilisierung gegenuber diesem Allergen, wirken Umwelteinflusse unterschiedlichster Art modulierend – verstarkend oder protektiv – auf die Allergieentwicklung ein. Dabei muss zwischen biogenen und anthropogenen Umweltfaktoren unterschieden werden. Unter den allergiefordernden Faktoren kommt im Innenraum dem Tabakrauch, in der Ausenluft der Exposition durch Verkehrsbelastung eine entscheidende Rolle zu. In der Ausenluft bestehen Interaktionen zwischen den Allergentragern (z. B. Pollen) und Luftschadstoffen, die u. U. zur weiteren Verstarkung allergischer Reaktionen, insbesondere in der Symptomverschlechterung, eine Rolle spielen. Durch den Klimawandel mit zunehmender globaler Erwarmung wird eine Veranderung der saisonalen Verteilung und weitere Haufung von allergischen Erkrankungen mit regional neuen bzw. veranderten Allergenen zu erwarten sein.

Allergie und Umwelt

In this issue, Charles et al. ([1][1]) showed in vivo that cytokines secreted by tumors, such as interleukin-6, down-regulate the transcription of cytochrome P450 CYP3A4 in liver and consequently the metabolism of CYP3A4 substrates. Reduced metabolism of chemotherapeutic agents could be responsible

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Jeroen Buters

Papers

Impact of Local Grasslands on Wild Grass Pollen Emission in Bavaria, Germany

Definition von Pollenexpositionszeiten für klinische Studien zur Allergen-Immuntherapie bei polleninduzierter Rhinokonjunktivitis – ein EAACI-Positionspapier

Il progetto europeo HIALINE (Health Impacts of Airborne Allergen Information Network): risultati del monitoraggio del polline di betulla e allergene Bet v1 a Parma nell'anno 2009

Allergie und Umwelt

Effective strategies for tumors affecting chemopreventive metabolism.