Publications by authors named "Thomas O"

544 Publications

Reversible Shielding and Immobilization of Liposomes and Viral Vectors by Tailored Antibody-Ligand Interactions.

Small 2021 Dec 3:e2105157. Epub 2021 Dec 3.

Faculty of Biology II, University of Freiburg, 79104, Freiburg, Germany.

Controlling the time and dose of nanoparticulate drug delivery by administration of small molecule drugs holds promise for efficient and safer therapies. This study describes a versatile approach of exploiting antibody-ligand interactions for the design of small molecule-responsive nanocarrier and nanocomposite systems. For this purpose, antibody fragments (scFvs) specific for two distinct small molecule ligands are designed. Subsequently, the surface of nanoparticles (liposomes or adeno-associated viral vectors, AAVs) is modified with these ligands, serving as anchor points for scFv binding. By modifying the scFvs with polymer tails, they can act as a non-covalently bound shielding layer, which is recruited to the anchor points on the nanoparticle surface and prevents interactions with cultured mammalian cells. Administration of an excess of the respective ligand triggers competitive displacement of the shielding layer from the nanoparticle surface and restores nanoparticle-cell interactions. The same principle is applied for developing hydrogel depots that can release integrated AAVs or liposomes in response to small molecule ligands. The liberated nanoparticles subsequently deliver their cargoes to cells. In summary, the utilization of different antibody-ligand interactions, different nanoparticles, and different release systems validates the versatility of the design concept described herein.
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http://dx.doi.org/10.1002/smll.202105157DOI Listing
December 2021

Bacterial contamination of paediatric analgesic solutions mixed in the clinical setting: 'Time on our side?'

Eur J Anaesthesiol 2022 Jan;39(1):77-79

From the Department of Clinical Sciences, Anaesthesia and Intensive Care, Lund University, (ODT, MOJ, KS), Paediatric Anaesthesia and Intensive Care, Skåne University Hospital Lund (ODT, MOJ), Department of Clinical Sciences, Infectious Diseases, Lund University (GO), Department of Infectious Diseases (GO) and Paediatric Pain Unit, Skåne University Hospital Lund, Lund, Sweden (ODT).

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http://dx.doi.org/10.1097/EJA.0000000000001489DOI Listing
January 2022

Long-acting injectable buprenorphine - 'best practice' opioid agonist therapy for Australian prisoners.

Australas Psychiatry 2021 Dec 1:10398562211059086. Epub 2021 Dec 1.

Metro North Mental Health Alcohol and Drug Service, Brisbane, Queensland, Australia.

Objective: To consider opioid agonist therapy in prisons.

Conclusions: Given the substantial risks of substance misuse by prisoners, long-acting injectable buprenorphine should be adopted as 'best practice' treatment in Australian prison populations.
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http://dx.doi.org/10.1177/10398562211059086DOI Listing
December 2021

Antibacterial Activity and Amphidinol Profiling of the Marine Dinoflagellate (Subclade III).

Int J Mol Sci 2021 Nov 11;22(22). Epub 2021 Nov 11.

Centre for Environmental Research, Sustainability and Innovation, Department of Environmental Science, School of Science, Institute of Technology Sligo, Ash Ln, Ballytivnan, F91 YW50 Sligo, Ireland.

Microalgae have received growing interest for their capacity to produce bioactive metabolites. This study aimed at characterising the antimicrobial potential of the marine dinoflagellate strain LACW11, isolated from the west of Ireland. Amphidinolides have been identified as cytotoxic polyoxygenated polyketides produced by several species. Phylogenetic inference assigned our strain to subclade III, along with isolates interspersed in different geographic regions. A two-stage extraction and fractionation process of the biomass was carried out. Extracts obtained after stage-1 were tested for bioactivity against bacterial ATCC strains of , , and . The stage-2 solid phase extraction provided 16 fractions, which were tested against and Fractions I, J and K yielded minimum inhibitory concentrations between 16 μg/mL and 256 μg/mL for both Gram-positive. A targeted metabolomic approach using UHPLC-HRMS/MS analysis applied on fractions G to J evidenced the presence of amphidinol type compounds AM-A, AM-B, AM-22 and a new derivative dehydroAM-A, with characteristic masses of 1361, 1463, 1667 and 1343, respectively. Combining the results of the biological assays with the targeted metabolomic approach, we could conclude that AM-A and the new derivative dehydroAM-A are responsible for the detected antimicrobial bioactivity.
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http://dx.doi.org/10.3390/ijms222212196DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618426PMC
November 2021

Effect of type 1 tympanoplasty on the quality of life of patients suffering from chronic otitis media (safe type).

Niger J Clin Pract 2021 Nov;24(11):1641-1644

Department of Otorhinolaryngology, Government Medical College, Amritsar, Punjab, India.

Background: Chronic otitis media (COM) remains a major public health issue and is associated with relentless discharge from the ear, pain, significant functional limitation of hearing, leading to communication problems and frequent specialist visits.

Aims: To assess the improvement in quality of life of patients of COM (safe type) and surgical success in terms of graft uptake and improvement in hearing.

Patients And Methods: A prospective questionnaire-based outcome study was directed in 100 patients with COM who were treated with Type I Tympanoplasty at our institution between May 2018 and May 2020. All patients were asked to fill Modified Chronic Otitis Media 4 (COM-4) survey before operation and 3 months after operation. Preoperative and postoperative total ear scores, audiological results, postoperative graft uptake were assessed.

Results: The correlation between preoperative and postoperative assessment by questionnaire was statistically critical (P < 0.001). There was significant improvement in hearing postoperatively (P < 0.001). Effective graft uptake was seen in 80%.

Conclusion: The current study emphasizes that Type 1 Tympanoplasty fundamentally improves quality of life of patients in terms of physical suffering, hearing loss, emotional distress postoperatively.
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http://dx.doi.org/10.4103/njcp.njcp_23_21DOI Listing
November 2021

Tocophobia experience and its impact on birth choices among Nigerian women: a qualitative exploratory study.

Pan Afr Med J 2021 31;39:282. Epub 2021 Aug 31.

Department of Nursing Science, College of Medicine and Health Sciences, Afe Babalola University, Ado-Ekiti, Nigeria.

Introduction: while pregnancy is a very beautiful and memorable experience for most women, some women may experience apathy towards childbirth and have feelings of fear and anxiety (tocophobia). Tocophobia can be far reaching with adverse physiologic and emotional consequences for mothers, infants and families. This study therefore explored tocophobia experiences among primigravid women and explored its influence on birth choices among antenatal women.

Methods: the study employed a qualitative exploratory research design. Participants who were primigravida (women who had never experienced childbirth), were selected using purposive sampling technique on antenatal clinic days. Data was obtained using semi-structured interview questions. Data was analyzed using content analysis approach and thematic categorization.

Results: results showed that few of the women experienced tocophobia and these fears were not strong enough to make them opt for caesarian section. Reasons attributed to tocophobia experience among the participants included "horror stories" told in the neighborhood, "past experiences" of close acquaintance and "entertainment videos" broadcast. Furthermore, all the participants preferred to have vaginal delivery.

Conclusion: few of the primigravid women in Ekiti State, Nigeria, experience tocophobia and this experience does not influence their choice of delivery option, as all participant´s preferred vaginal delivery to caesarian section. It is important for midwives to be aware of their role in counselling and identifying women with tocophobia in order to promote good and safe transition from pregnancy to motherhood.
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http://dx.doi.org/10.11604/pamj.2021.39.282.27229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556740PMC
November 2021

Nascent chains can form co-translational folding intermediates that promote post-translational folding outcomes in a disease-causing protein.

Nat Commun 2021 11 8;12(1):6447. Epub 2021 Nov 8.

Institute of Structural and Molecular Biology, University College London, Gower Street, London, WC1E 6BT, UK.

During biosynthesis, proteins can begin folding co-translationally to acquire their biologically-active structures. Folding, however, is an imperfect process and in many cases misfolding results in disease. Less is understood of how misfolding begins during biosynthesis. The human protein, alpha-1-antitrypsin (AAT) folds under kinetic control via a folding intermediate; its pathological variants readily form self-associated polymers at the site of synthesis, leading to alpha-1-antitrypsin deficiency. We observe that AAT nascent polypeptides stall during their biosynthesis, resulting in full-length nascent chains that remain bound to ribosome, forming a persistent ribosome-nascent chain complex (RNC) prior to release. We analyse the structure of these RNCs, which reveals compacted, partially-folded co-translational folding intermediates possessing molten-globule characteristics. We find that the highly-polymerogenic mutant, Z AAT, forms a distinct co-translational folding intermediate relative to wild-type. Its very modest structural differences suggests that the ribosome uniquely tempers the impact of deleterious mutations during nascent chain emergence. Following nascent chain release however, these co-translational folding intermediates guide post-translational folding outcomes thus suggesting that Z's misfolding is initiated from co-translational structure. Our findings demonstrate that co-translational folding intermediates drive how some proteins fold under kinetic control, and may thus also serve as tractable therapeutic targets for human disease.
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http://dx.doi.org/10.1038/s41467-021-26531-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8576036PMC
November 2021

Modulation of impulsive behaviours using transcranial random noise stimulation.

Brain Stimul 2021 Nov 3;15(1):32-34. Epub 2021 Nov 3.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; R&D Department, Division of Mental Health Services, Akershus University Hospital, Lørenskog, Norway; Department of Psychiatry, University of Helsinki, Helsinki, Finland.

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http://dx.doi.org/10.1016/j.brs.2021.11.002DOI Listing
November 2021

Three strategies when physicians provide complex information in interactions with patients: How to recognize and measure them.

Patient Educ Couns 2021 Oct 13. Epub 2021 Oct 13.

Health Services Research Unit HØKH, Akershus University Hospital, Lørenskog, Norway.

Objective: To define and operationalize three taught strategies for providing information in interactions with patients using videos collected in a randomized controlled trial (RCT).

Methods: This was a qualitative exploratory study embedded in a randomized controlled design, using microanalysis of face-to-face dialogue as an inductive video analysis method to operationalize physicians' use of three information-provision strategies. Data were 34 video-recorded simulated (but unscripted) interactions between 17 physicians and 34 multiple sclerosis patients collected before and after a brief course on information provision. We operationalized (1) mapping the patient's preferences and (2) checking the patient's understanding, and pauses indicative of (3) portioning information.

Results: Results are detailed analytical definitions, criteria, and assessable, quantifiable outcomes for each of the three strategies. Patients responded to portioning pauses as expected: whereas 91% of these pauses elicited an immediate patient response, only 23% of non-portioning pauses did so.

Conclusion: Our methods revealed how to define and evaluate information sharing strategies physicians used within the contingencies of clinical interaction.

Practice Implications: Findings provide applicable methods to teach, analyze, and evaluate information sharing strategies and indications for further training.
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http://dx.doi.org/10.1016/j.pec.2021.10.013DOI Listing
October 2021

Marine Biodiscovery in a Changing World.

Prog Chem Org Nat Prod 2021 ;116:1-36

Marine Biodiscovery, School of Chemistry and Ryan Institute, NUI Galway, University Road, Galway, H91TK33, Ireland.

The term "marine biodiscovery" has been recently been adopted to describe the area of marine natural products dedicated to the search of new drugs. Several maritime countries such as Australia, New Zealand, South Korea, and Japan as well as some European countries have invested significantly in this area of research over the last 50 years. In the late 2000s, research in this field has received significant interest and support in Ireland for exploring new marine bioresources from the nutrient-rich waters of the Northeastern Atlantic Ocean. Despite undeniable success exemplified by the marketing of new drugs, especially in oncology, the integration of new technical but also environmental aspects should be considered. Indeed, global change, particularly in our oceans, such as climate change, biodiversity loss, and the emergence of microbial pathogens, not only affects the environment but ultimately contributes to social inequalities. In this contribution, new avenues and best practices are proposed, such as the development of biorepositories and shared data for the future of marine biodiscovery research. The extension of this type of scientific work will allow humanity to finally make the optimum use of marine bioresources.
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http://dx.doi.org/10.1007/978-3-030-80560-9_1DOI Listing
October 2021

Contemporary Approaches to the Discovery and Development of Broad-Spectrum Natural Product Prototypes for the Control of Coronaviruses.

J Nat Prod 2021 11 22;84(11):3001-3007. Epub 2021 Oct 22.

Departments of Drug Discovery and Biomedical Sciences and Public Health, Colleges of Pharmacy and Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, United States.

The pressing need for SARS-CoV-2 controls has led to a reassessment of strategies to identify and develop natural product inhibitors of zoonotic, highly virulent, and rapidly emerging viruses. This review article addresses how contemporary approaches involving computational chemistry, natural product (NP) and protein databases, and mass spectrometry (MS) derived target-ligand interaction analysis can be utilized to expedite the interrogation of NP structures while minimizing the time and expense of extraction, purification, and screening in BioSafety Laboratories (BSL)3 laboratories. The unparalleled structural diversity and complexity of NPs is an extraordinary resource for the discovery and development of broad-spectrum inhibitors of viral genera, including , which contains MERS, SARS, SARS-CoV-2, and the common cold. There are two key technological advances that have created unique opportunities for the identification of NP prototypes with greater efficiency: (1) the application of structural databases for NPs and target proteins and (2) the application of modern MS techniques to assess protein-ligand interactions directly from NP extracts. These approaches, developed over years, now allow for the identification and isolation of unique antiviral ligands without the immediate need for BSL3 facilities. Overall, the goal is to improve the success rate of NP-based screening by focusing resources on source materials with a higher likelihood of success, while simultaneously providing opportunities for the discovery of novel ligands to selectively target proteins involved in viral infection.
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http://dx.doi.org/10.1021/acs.jnatprod.1c00625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547502PMC
November 2021

Treatment and outcome of gastrointestinal bleeding due to peptic ulcers and erosions - (BLUE study).

Scand J Gastroenterol 2021 Oct 18:1-8. Epub 2021 Oct 18.

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Objectives: Peptic ulcers and erosions are the most common causes of upper gastrointestinal bleeding. The aim of this study was to investigate the management and outcomes of these patients.

Materials And Methods: A total of 543 patients with endoscopically confirmed bleeding from peptic ulcers and erosions were included from March 2015 to December 2017. The patient characteristics, endoscopic findings, Forrest classification and endoscopic treatment were recorded. Moreover, the rebleeding rates, repeated endoscopies and transcatheter angiographic embolization and surgery incidences were registered. A follow-up endoscopy after discharge from the hospital was scheduled.

Results: Among the patients, high-risk stigmata ulcers were present in 36% (198/543) and low-risk stigmata ulcers and erosions in 60% (327/543) at first endoscopy. Endoscopic therapy was performed in 30% (165/543) of the patients, and hemostasis was achieved in 94% (155/165). The incidence of rebleeding was 9% (49/543) for the whole cohort and 14.8% (23/155) for those patients who had received successful endoscopic treatment. Moreover, rebleeding was significantly more frequent in duodenal ulcers than in gastric ulcers (11.9% vs 4.0%,  = .004). In a multivariable analysis, rebleeding was significantly related to comorbidity and Forrest classification. Transcatheter angiographic embolization and surgery were required in 6% (34/543) and 0.07% (4/543) of patients, respectively. Complete peptic ulcer healing was found at follow-up in 73.3% (270/368) of patients.

Conclusions: Endoscopic hemostasis was achieved in the majority of patients with high-risk ulceration, although the occurrence of rebleeding is a significant challenge, especially in patients with duodenal ulcers. Bleeding Ulcer and Erosions Study (BLUE Study), ClinicalTrials.gov identifier: NCT03367897.
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http://dx.doi.org/10.1080/00365521.2021.1988701DOI Listing
October 2021

Twin boundary migration in an individual platinum nanocrystal during catalytic CO oxidation.

Nat Commun 2021 Sep 10;12(1):5385. Epub 2021 Sep 10.

Aix Marseille Université, Université de Toulon, CNRS, IM2NP, Marseille, France.

At the nanoscale, elastic strain and crystal defects largely influence the properties and functionalities of materials. The ability to predict the structural evolution of catalytic nanocrystals during the reaction is of primary importance for catalyst design. However, to date, imaging and characterising the structure of defects inside a nanocrystal in three-dimensions and in situ during reaction has remained a challenge. We report here an unusual twin boundary migration process in a single platinum nanoparticle during CO oxidation using Bragg coherent diffraction imaging as the characterisation tool. Density functional theory calculations show that twin migration can be correlated with the relative change in the interfacial energies of the free surfaces exposed to CO. The x-ray technique also reveals particle reshaping during the reaction. In situ and non-invasive structural characterisation of defects during reaction opens new avenues for understanding defect behaviour in confined crystals and paves the way for strain and defect engineering.
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http://dx.doi.org/10.1038/s41467-021-25625-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433154PMC
September 2021

Durability of Left Atrial Lesions After Ethanol Infusion in the Vein of Marshall.

JACC Clin Electrophysiol 2021 Aug 17. Epub 2021 Aug 17.

Laboratoire d'Electrophysiologie, Clinique Ambroise Paré, Neuilly-sur-Seine, France; Centre d'Explorations de Réanimation et d'Intervention Cardiaque, Clinique Ambroise Paré, Neuilly-sur-Seine, France. Electronic address:

Objectives: The aim of this study was to assess the persistence of left atrial (LA) lesions created by ethanol infusion in the vein of Marshall (EIVM) by electroanatomical mapping on repeat catheter ablation for recurrent atrial tachyarrhythmia.

Background: Little is known about the durability of LA lesions created by EIVM.

Methods: The study included consecutive patients who underwent EIVM for persistent atrial fibrillation or perimitral LA flutter (index procedure) and repeat catheter ablation for recurrent atrial tachyarrhythmia or atrial fibrillation at a single center between January 2019 and April 2020. The acute effect of EIVM was assessed at the index procedure by comparing the area of bipolar voltage <0.05 mV in the vein of Marshall (VOM) region before and immediately after EIVM. The long-term effect of EIVM was assessed by comparing this area in the VOM region between the redo procedure and the index procedure.

Results: Twenty-four consecutive patients (mean age 68.6 ± 6.1 years, 58% men) underwent redo procedures after previous EIVM for persistent atrial fibrillation (n = 21 [88%]) or perimitral LA flutter (n = 5 [21%]). In each patient, the EIVM-related lesion persisted, with a chronic scar in the VOM region (median 13.1 cm [interquartile range: 8.1-15.9 cm] vs 12.4 cm [interquartile range: 7.6-15.7 cm] acutely, respectively). One quarter of patients (9 of 20) had late mitral isthmus reconnection, which was located at the mitral annular edge or in the coronary sinus.

Conclusions: Atrial lesions created by EIVM are durable, which reinforces the efficacy profile of EIVM. Reconduction sites in the mitral isthmus are located at the edge of the scar and in the coronary sinus.
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http://dx.doi.org/10.1016/j.jacep.2021.06.019DOI Listing
August 2021

High lead level in the Alps in XIXth century, learning from the analysis of 138 historical hair stands.

Chemosphere 2022 Jan 2;286(Pt 3):131658. Epub 2021 Aug 2.

Univ Rennes, EHESP, Inserm, Irset (Institut de Recherche en Santé, Environnement et Travail) - UMR_S 1085, F-35000, Rennes, France.

Analysis of hair is known to provide useful information about environmental and toxic exposures. Very little historical use has been made of this type of investigation. Here we study 138 human hair samples from 19th century in France. In order to examine the potential association between contamination and historical health impacts, we characterized contamination by 33 elements in a set of hair strands sampled during the last quarter of the 19th century in the Savoy region of France. After a selected washing step on 138 hair strands conserved at the Museum National d'Histoire Naturelle in Paris (France), we assessed the presence of inorganics by ICP/MS, and lead level was higher than values reported in literature. We then compared concentrations and distributions between women and men, sampling locations and crossing gender and geographical origin. Hair lead level was high throughout Savoy at the end of the 19th century: significantly higher for people living in towns or industrial valleys, and lower for those of countryside and mountains areas. Environmental and economic changes (industrialization and urbanization with water adduction and leaded paints), living habits (kitchenware, cosmetics, wine, and tobacco), and local features (mines exploitation, railroad development, and industrialized narrow valleys) could be envisaged for explaining the level of lead contamination. In the same period, the two main industrial valleys of Savoy (Maurienne and Tarentaise) had high rates of endemic goiter and cretinism and among the highest hair lead levels. Other lines of evidence will need to be explore to investigate a possible link between historical Pb exposure and goiter in the study area.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131658DOI Listing
January 2022

Psychosis Biotypes: Replication and Validation from the B-SNIP Consortium.

Schizophr Bull 2021 Aug 19. Epub 2021 Aug 19.

Department of Psychiatry, UT Southwestern Medical Center, Dallas, TX, USA.

Current clinical phenomenological diagnosis in psychiatry neither captures biologically homologous disease entities nor allows for individualized treatment prescriptions based on neurobiology. In this report, we studied two large samples of cases with schizophrenia, schizoaffective, and bipolar I disorder with psychosis, presentations with clinical features of hallucinations, delusions, thought disorder, affective, or negative symptoms. A biomarker approach to subtyping psychosis cases (called psychosis Biotypes) captured neurobiological homology that was missed by conventional clinical diagnoses. Two samples (called "B-SNIP1" with 711 psychosis and 274 healthy persons, and the "replication sample" with 717 psychosis and 198 healthy persons) showed that 44 individual biomarkers, drawn from general cognition (BACS), motor inhibitory (stop signal), saccadic system (pro- and anti-saccades), and auditory EEG/ERP (paired-stimuli and oddball) tasks of psychosis-relevant brain functions were replicable (r's from .96-.99) and temporally stable (r's from .76-.95). Using numerical taxonomy (k-means clustering) with nine groups of integrated biomarker characteristics (called bio-factors) yielded three Biotypes that were virtually identical between the two samples and showed highly similar case assignments to subgroups based on cross-validations (88.5%-89%). Biotypes-1 and -2 shared poor cognition. Biotype-1 was further characterized by low neural response magnitudes, while Biotype-2 was further characterized by overactive neural responses and poor sensory motor inhibition. Biotype-3 was nearly normal on all bio-factors. Construct validation of Biotype EEG/ERP neurophysiology using measures of intrinsic neural activity and auditory steady state stimulation highlighted the robustness of these outcomes. Psychosis Biotypes may yield meaningful neurobiological targets for treatments and etiological investigations.
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http://dx.doi.org/10.1093/schbul/sbab090DOI Listing
August 2021

When More Is Less: Plastic Weakening of Single Crystalline Ag Nanoparticles by the Polycrystalline Au Shell.

ACS Nano 2021 Sep 11;15(9):14061-14070. Epub 2021 Aug 11.

Department of Materials Science and Engineering, Technion - Israel Institute of Technology, 3200003 Haifa, Israel.

It is well-known that in the case of bulk polycrystalline metals, a reduction in the grain size leads to material hardening, since the grain boundaries represent efficient barriers for slip transfer between the adjacent crystalline grains. Here, we show that coating single crystalline Ag nanoparticles with a thin polycrystalline Au layer leads to a weakening of the particles. Moreover, while the single crystalline Ag nanoparticles yield in a single large displacement burst when loaded in compression, their Ag-Au core-shell counterparts demonstrate a more homogeneous deformation with signs of strain hardening. Our molecular dynamics simulations demonstrate that particle weakening at low strains is attributed to the plasticity confinement in the polycrystalline shell, in which the grain boundaries play a dual role of dislocations sources and sinks. At higher strains, the plasticity within the Ag core is initiated by the dislocations nucleating at the Ag-Au interphase boundary. The widespread of energy barriers for dislocations nucleation at the interphase boundaries and their lower value as compared to the barriers for surface nucleation ensure particle weakening and more homogeneous deformation. The results of this study show that adding imperfect material to superstrong single crystalline metal nanoparticles makes them weaker. At the same time, thin nanocrystalline coatings can be employed to improve the formability of metals at the nanoscale.
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http://dx.doi.org/10.1021/acsnano.1c02976DOI Listing
September 2021

Correlation between MRI morphological response patterns and histopathological tumor regression after neoadjuvant endocrine therapy in locally advanced breast cancer: a randomized phase II trial.

Breast Cancer Res Treat 2021 Oct 6;189(3):711-723. Epub 2021 Aug 6.

Department of Diagnostic Imaging and Intervention, Akershus University Hospital (AHUS), Postboks 1000, 1478, Lørenskog, Norway.

Purpose: To correlate MRI morphological response patterns with histopathological tumor regression grading system based on tumor cellularity in locally advanced breast cancer (LABC)-treated neoadjuvant with third-generation aromatase inhibitors.

Methods: Fifty postmenopausal patients with ER-positive/HER-2-negative LABC treated with neoadjuvant letrozole and exemestane given sequentially in an intra-patient cross-over regimen for at least 4 months with MRI response monitoring at baseline as well as after at least 2 and 4 months on treatment. The MRI morphological response pattern was classified into 6 categories: 0/complete imaging response; I/concentric shrinkage; II/fragmentation; III/diffuse; IV/stable; and V/progressive. Histopathological tumor regression was assessed based on the recommendations from The Royal College of Pathologists regarding tumor cellularity.

Results: Following 2 and 4 months with therapy, the most common MRI pattern was pattern II (24/50 and 21/50, respectively). After 4 months on therapy, the most common histopathological tumor regression grade was grade 3 (21/50). After 4 months an increasing correlation is observed between MRI patterns and histopathology. The overall correlation, between the largest tumor diameter obtained from MRI and histopathology, was moderate and positive (r = 0.50, P-value = 2e-04). Among them, the correlation was highest in type IV (r = 0.53).

Conclusion: The type II MRI pattern "fragmentation" was more frequent in the histopathological responder group; and types I and IV in the non-responder group. Type II pattern showed the best endocrine responsiveness and a relatively moderate correlation between sizes obtained from MRI and histology, whereas type IV pattern indicated endocrine resistance but the strongest correlation between MRI and histology.
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http://dx.doi.org/10.1007/s10549-021-06343-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505284PMC
October 2021

Evaluating a training intervention for improving alignment between emergency medical telephone operators and callers: a pilot study of communication behaviours.

Scand J Trauma Resusc Emerg Med 2021 Jul 31;29(1):107. Epub 2021 Jul 31.

Health Services Research Unit, Akershus University Hospital, Sykehusveien 25, 1478, Lørenskog, Norway.

Background: Calls to emergency medical lines are an essential component in the chain of survival. Operators make critical decisions based on information they elicit from callers. Although smooth cooperation is necessary, the field lacks evidence-based guidelines for how to achieve it while adhering to strict parameters of index-driven questioning. We aimed to evaluate the effect of a training intervention for emergency medical operators at a call centre in Tønsberg, Norway. The course was designed to enhance operators' communication skills for smoothing cooperation with callers.

Methods: Calls were analyzed using inductively developed coding based on the course rationale and content. To evaluate whether the course generated consolidated behavioral change in everyday practice, the independent analyst evaluated 32 calls, selected randomly from eight operators, two calls before and two after course completion. To measure whether skill attainment delayed decision making, we compared the time to the first decision logged by intervention operators to eight control operators. Analysis included 3034 calls: 1375 to intervention operators (T1 = 815; T2 = 560) and 1659 to control operators (T1 = 683; T2 = 976).

Results: Operators demonstrated improved behaviours on how they greeted the caller (p < .001), acknowledged the caller (p < .001), and displayed empathy (p = 0.015). No change was found in the use of open-ended questions and agreeing with the caller. Contrary to expectations, operators who took the course logged first decisions more quickly than the control group (p < .001).

Conclusions: This pilot study demonstrated that the training intervention generated behavioural change in these operators, providing justification for scaling up the intervention.
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http://dx.doi.org/10.1186/s13049-021-00917-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325801PMC
July 2021

Crambescin C1 Acts as A Possible Substrate of iNOS and eNOS Increasing Nitric Oxide Production and Inducing Hypotensive Effect.

Front Pharmacol 2021 7;12:694639. Epub 2021 Jul 7.

Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.

Crambescins are guanidine alkaloids from the sponge . Crambescin C1 (CC) induces metallothionein genes and nitric oxide (NO) is one of the triggers. We studied and compared the , effects of some crambescine A and C analogs. HepG2 gene expression was analyzed using microarrays. Vasodilation was studied in rat aortic rings. hypotensive effect was directly measured in anesthetized rats. The targets of crambescines were studied . CC and homo-crambescine C1 (HCC), but not crambescine A1 (CA), induced metallothioneins transcripts. CC increased NO production in HepG2 cells. In isolated rat aortic rings, CC and HCC induced an endothelium-dependent relaxation related to eNOS activation and an endothelium-independent relaxation related to iNOS activation, hence both compounds increase NO and reduce vascular tone. analysis also points to eNOS and iNOS as targets of Crambescin C1 and source of NO increment. CC effect is mediated through crambescin binding to the active site of eNOS and iNOS. CC docking studies in iNOS and eNOS active site revealed hydrogen bonding of the hydroxylated chain with residues Glu377 and Glu361, involved in the substrate recognition, and explains its higher binding affinity than CA. The later interaction and the extra polar contacts with its pyrimidine moiety, absent in the endogenous substrate, explain its role as exogenous substrate of NOSs and NO production. Our results suggest that CC serve as a basis to develop new useful drugs when bioavailability of NO is perturbed.
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http://dx.doi.org/10.3389/fphar.2021.694639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312399PMC
July 2021

Immunomodulatory properties of characellide A on human peripheral blood mononuclear cells.

Inflammopharmacology 2021 Aug 9;29(4):1201-1210. Epub 2021 Jul 9.

Department of Translational Medical Sciences, Center for Basic and Clinical Immunology Research (CISI), WAO Center of Excellence, University of Naples Federico II, Via S. Pansini 5, 80131, Naples, Italy.

Marine sponges and their associated microbiota are multicellular animals known to produce metabolites with interesting pharmacological properties playing a pivotal role against a plethora of pathologic disorders such as inflammation, cancer and infections. Characellide A and B belong to a novel class of glycolipopeptides isolated from the deep sea marine sponge Characella pachastrelloides. In this study, we have evaluated the effects of characellide A and B on cytokine and chemokine release from human peripheral blood mononuclear cells (PBMC). Characellide A induces a concentration- and time-dependent CXCL8, IL-6 and TNF-α release from PBMC. This production is mediated by the induction of gene transcription. Moreover, cytokine/chemokine release induced by characellide A from PBMC is CD1d-dependent because a CD1d antagonist, 1,2-bis(diphenylphosphino)ethane [DPPE]-polyethylene glycolmonomethylether [PEG], specifically inhibits characellide A-induced activation of PBMC. In conclusion, characellide A is a novel modulator of adaptative/innate immune responses. Further studies are needed to understand its potential pharmacological application.
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http://dx.doi.org/10.1007/s10787-021-00836-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8298336PMC
August 2021

The International Parkinson Disease Genomics Consortium Africa.

Lancet Neurol 2021 05;20(5):335

Department of Neurology, Clinical Investigation Center of Neurosciences and Mental Health, Razi University Hospital, Tunis, Tunisia; Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis, Tunisia.

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http://dx.doi.org/10.1016/S1474-4422(21)00100-9DOI Listing
May 2021
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