The essential synergy of MD simulation and NMR in understanding amorphous drug forms.

Molecular dynamics (MD) simulations and chemical shifts from machine learning are used to predict N, C and H chemical shifts for the amorphous form of the drug irbesartan. The local environments are observed to be highly dynamic well below the glass transition, and averaging over the dynamics is essential to understanding the observed NMR shifts. Predicted linewidths are about 2 ppm narrower than observed experimentally, which is hypothesised to largely result from susceptibility effects.

Glyphosate and its formulations Roundup Bioflow and RangerPro alter bacterial and fungal community composition in the rat caecum microbiome.

The potential health consequences of glyphosate-induced gut microbiome alterations have become a matter of intense debate. As part of a multifaceted study investigating toxicity, carcinogenicity and multigenerational effects of glyphosate and its commercial herbicide formulations, we assessed changes in bacterial and fungal populations in the caecum microbiota of rats exposed prenatally until adulthood (13 weeks after weaning) to three doses of glyphosate (0.5, 5, 50 mg/kg body weight/day), or to the formulated herbicide products Roundup Bioflow and RangerPro at the same glyphosate-equivalent doses.

Synergy of Turbulent Momentum Drive and Magnetic Braking.

In absence of external torque, plasma rotation in tokamaks results from a balance between collisional magnetic braking and turbulent drive. The outcome of this competition and cooperation is essential to determine the plasma flow. A reduced model, supported by gyrokinetic simulations, is first used to explain and quantify the competition only.

Comparative Toxicogenomics of Glyphosate and Roundup Herbicides by Mammalian Stem Cell-Based Genotoxicity Assays and Molecular Profiling in Sprague-Dawley Rats.

Whether glyphosate-based herbicides (GBHs) are more potent than glyphosate alone at activating cellular mechanisms, which drive carcinogenesis remain controversial. As GBHs are more cytotoxic than glyphosate, we reasoned they may also be more capable of activating carcinogenic pathways. We tested this hypothesis by comparing the effects of glyphosate with Roundup GBHs both in vitro and in vivo.

Evidence for Lignocellulose-Decomposing Enzymes in the Genome and Transcriptome of the Aquatic Hyphomycete .

Fungi are ecologically outstanding decomposers of lignocellulose. Fungal lignocellulose degradation is prominent in saprotrophic Ascomycota and Basidiomycota of the subkingdom Dikarya. Despite ascomycetes dominating the Dikarya inventory of aquatic environments, genome and transcriptome data relating to enzymes involved in lignocellulose decay remain limited to terrestrial representatives of these phyla.

Clinical educators can supervise students without increased stress: a study of interacting factors using insights from complexity theory.

Supervising students in healthcare settings is complex and can be stressful for clinical educators. However, it is unclear how to design student placements without clinical educator stress. Using complexity theory as a lens, fuzzy set Qualitative Comparative Analysis (fsQCA) was used to explore factors associated with no increased stress for clinical educators during speech pathology (SP) placements.

The genomic loci of specific human tRNA genes exhibit ageing-related DNA hypermethylation.

The epigenome has been shown to deteriorate with age, potentially impacting on ageing-related disease. tRNA, while arising from only ˜46 kb (<0.002% genome), is the second most abundant cellular transcript.

Multi-omics phenotyping of the gut-liver axis reveals metabolic perturbations from a low-dose pesticide mixture in rats.

Health effects of pesticides are not always accurately detected using the current battery of regulatory toxicity tests. We compared standard histopathology and serum biochemistry measures and multi-omics analyses in a subchronic toxicity test of a mixture of six pesticides frequently detected in foodstuffs (azoxystrobin, boscalid, chlorpyrifos, glyphosate, imidacloprid and thiabendazole) in Sprague-Dawley rats. Analysis of water and feed consumption, body weight, histopathology and serum biochemistry showed little effect.

Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Improves Exacerbation Outcomes in Patients with COPD without a Recent Exacerbation History: A Subgroup Analysis of KRONOS.

Purpose: In the Phase III, 24-week KRONOS study (NCT02497001), triple therapy with budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) reduced exacerbation rates versus glycopyrrolate/formoterol fumarate (GFF) MDI in patients with moderate-to-very severe chronic obstructive pulmonary disease (COPD) and no requirement for a history of exacerbations. We report a post hoc analysis investigating whether the benefits observed were driven by patients with ≥1 exacerbation in the 12 months prior to the study.

Patients And Methods: Patients received BGF MDI 320/18/9.

Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler in Chinese Patients with COPD: A Subgroup Analysis of KRONOS.

Introduction: This pre-specified subgroup analysis evaluated the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) triple therapy versus corresponding dual therapies in the China subgroup of the phase III, double-blind KRONOS study in patients with moderate to very severe chronic obstructive pulmonary disease (COPD).

Methods: Patients were randomized 2:2:1:1 to BGF MDI 320/18/9.6 μg, glycopyrrolate/formoterol fumarate (GFF) MDI 18/9.

Long-Term Safety and Efficacy of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD.

Background: Budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) is a triple fixed-dose combination for COPD. The long-term safety of triple therapy for COPD has not been investigated in Japanese patients. In this 28-week extension study (NCT03262012), we investigated the long-term safety and tolerability of BGF MDI in Japanese patients with moderate-to-very severe COPD who completed the 24-week Phase III randomized, double-blind, multicenter KRONOS study (NCT02497001).

Efficacy and Safety of Budesonide/Glycopyrrolate/Formoterol Fumarate Metered Dose Inhaler Formulated Using Co-Suspension Delivery Technology in Japanese Patients with COPD: A Subgroup Analysis of the KRONOS Study.

Background: KRONOS, a Phase III, multicenter, randomized, double-blind study (NCT02497001) conducted in Canada, China, Japan, and the USA, assessed the efficacy and safety of budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI), a triple fixed-dose combination therapy, relative to dual therapies in patients with moderate-to-very severe COPD. Here we present findings from the Japanese subgroup of KRONOS.

Methods: Patients received BGF MDI 320/18/9.

Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS): a double-blind, parallel-group, multicentre, phase 3 randomised controlled trial.

Background: Inhaled corticosteroids have been used in patients with chronic obstructive pulmonary disease (COPD), but the potential benefits of their use in triple therapy are not well known. We aimed to compare the efficacy of a triple therapy with corresponding dual therapies in symptomatic patients with moderate to very severe COPD, without a requirement for a history of exacerbations.

Methods: In this double-blind, parallel-group, multicentre phase 3 randomised controlled trial, we recruited patients from hospitals and care centres in Canada, China, Japan, and the USA.

Long-read DNA metabarcoding of ribosomal RNA in the analysis of fungi from aquatic environments.

DNA metabarcoding is widely used to study prokaryotic and eukaryotic microbial diversity. Technological constraints limit most studies to marker lengths below 600 base pairs (bp). Longer sequencing reads of several thousand bp are now possible with third-generation sequencing.

The effect of speech-language pathology students on clinician time use and activity.

Purpose: This prospective study investigated the impact of supervising students on public health speech-language pathologists' (SLPs) time and patient activity levels in order to broaden evidence in the profession.

Method: Thirty-four SLPs supervising students collected data profiling their time use and activity during the first, middle and penultimate placement week. They also collected data for a week when not supervising students.

Integrating chytrid fungal parasites into plankton ecology: research gaps and needs.

Chytridiomycota, often referred to as chytrids, can be virulent parasites with the potential to inflict mass mortalities on hosts, causing e.g. changes in phytoplankton size distributions and succession, and the delay or suppression of bloom events.

Determination of the True Inclination Angle of the Main Bronchi Relative to the Median Sagittal Plane for Placement of a Left-Sided Double-Lumen Tube.

Objectives: This study aimed to determine the true inclination angle of the main bronchi relative to the median sagittal plane, using CT imaging to help increase accuracy of double-lumen tube (DLT) placement.

Design: In this retrospective study, 2 investigators independently measured normal chest CT scans from 50 male and 50 female patients. To determine the true AP axis, a mid-sagittal plane reference line (MSPRL) was drawn, intersecting the midsternum and the vertebral spinous process at the level of mid-carina.

Invasive central nervous system aspergillosis in a patient with Crohn's disease after treatment with infliximab and corticosteroids.

Aspergillus species are emerging as a significant cause of pneumonia mortality in immune compromised hosts, with haematological spread being a rare and life-threatening complication. The central nervous system (CNS) as a site for extrapulmonary spread is rarer still. We report a case of CNS disseminated aspergillosis in a patient treated with corticosteroids and infliximab, an immunomodulatory agent commonly used in the treatment of inflammatory bowel disease, and review the available literature regarding this rare pathology.

Between migration load and evolutionary rescue: dispersal, adaptation and the response of spatially structured populations to environmental change.

The evolutionary potential of populations is mainly determined by population size and available genetic variance. However, the adaptability of spatially structured populations may also be affected by dispersal: positively by spreading beneficial mutations across sub-populations, but negatively by moving locally adapted alleles between demes. We develop an individual-based, two-patch, allelic model to investigate the balance between these opposing effects on a population's evolutionary response to rapid climate change.

Large and variable genome size unrelated to serpentine adaptation but supportive of cryptic sexuality in Cenococcum geophilum.

Estimations of genome size and its variation can provide valuable information regarding the genetic diversity of organisms and their adaptation potential to heterogeneous environments. We used flow cytometry to characterize the variation in genome size among 40 isolates of Cenococcum geophilum, an ectomycorrhizal fungus with a wide ecological and geographical distribution, obtained from two serpentine and two non-serpentine sites in Portugal. Besides determining the genome size and its intraspecies variation, we wanted to assess whether a relationship exists between genome size and the edaphic background of the C.

Limited evolutionary rescue of locally adapted populations facing climate change.

Dispersal is a key determinant of a population's evolutionary potential. It facilitates the propagation of beneficial alleles throughout the distributional range of spatially outspread populations and increases the speed of adaptation. However, when habitat is heterogeneous and individuals are locally adapted, dispersal may, at the same time, reduce fitness through increasing maladaptation.