| 1. |
- Mercuri, E., et al.
(författare)
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Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study
- 2020
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Ingår i: Journal of Comparative Effectiveness Research. - : Becaris Publishing Limited. - 2042-6305 .- 2042-6313. ; 9:5, s. 341-360
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Tidskriftsartikel (refereegranskat)abstract
- Aim: Strategic Targeting of Registries and International Database of Excellence (STRIDE) is an ongoing, multicenter registry providing real-world evidence regarding ataluren use in patients with nonsense mutation Duchenne muscular dystrophy (nmDMD). We examined the effectiveness of ataluren + standard of care (SoC) in the registry versus SoC alone in the Cooperative International Neuromuscular Research Group (CINRG) Duchenne Natural History Study (DNHS), DMD genotype-phenotype/-ataluren benefit correlations and ataluren safety. Patients & methods: Propensity score matching was performed to identify STRIDE and CINRG DNHS patients who were comparable in established disease progression predictors (registry cut-off date, 9 July 2018). Results & conclusion: Kaplan-Meier analyses demonstrated that ataluren + SoC significantly delayed age at loss of ambulation and age at worsening performance in timed function tests versus SoC alone (p <= 0.05). There were no DMD genotype-phenotype/ataluren benefit correlations. Ataluren was well tolerated. These results indicate that ataluren + SoC delays functional milestones of DMD progression in patients with nmDMD in routine clinical practice. ClinicalTrials.gov identifier: NCT02369731. ClinicalTrials.gov identifier: NCT02369731.
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| 2. |
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| 3. |
- Sungnak, W., et al.
(författare)
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SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes
- 2020
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Ingår i: Nature Medicine. - : Nature Research. - 1078-8956 .- 1546-170X. ; 26:5, s. 681-687
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Tidskriftsartikel (refereegranskat)abstract
- We investigated SARS-CoV-2 potential tropism by surveying expression of viral entry-associated genes in single-cell RNA-sequencing data from multiple tissues from healthy human donors. We co-detected these transcripts in specific respiratory, corneal and intestinal epithelial cells, potentially explaining the high efficiency of SARS-CoV-2 transmission. These genes are co-expressed in nasal epithelial cells with genes involved in innate immunity, highlighting the cells’ potential role in initial viral infection, spread and clearance. The study offers a useful resource for further lines of inquiry with valuable clinical samples from COVID-19 patients and we provide our data in a comprehensive, open and user-friendly fashion at www.covid19cellatlas.org.
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| 4. |
- Woitowich, N. C., et al.
(författare)
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Structural basis for light control of cell development revealed by crystal structures of a myxobacterial phytochrome
- 2018
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Ingår i: Iucrj. - : International Union of Crystallography (IUCr). - 2052-2525. ; 5:Part 5, s. 619-634
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Tidskriftsartikel (refereegranskat)abstract
- Phytochromes are red-light photoreceptors that were first characterized in plants, with homologs in photosynthetic and non-photosynthetic bacteria known as bacteriophytochromes (BphPs). Upon absorption of light, BphPs interconvert between two states denoted Pr and Pfr with distinct absorption spectra in the red and far-red. They have recently been engineered as enzymatic photoswitches for fluorescent-marker applications in non-invasive tissue imaging of mammals. This article presents cryo- and room-temperature crystal structures of the unusual phytochrome from the non-photosynthetic myxobacterium Stigmatella aurantiaca (SaBphP1) and reveals its role in the fruitingbody formation of this photomorphogenic bacterium. SaBphP1 lacks a conserved histidine (His) in the chromophore-binding domain that stabilizes the Pr state in the classical BphPs. Instead it contains a threonine (Thr), a feature that is restricted to several myxobacterial phytochromes and is not evolutionarily understood. SaBphP1 structures of the chromophore binding domain (CBD) and the complete photosensory core module (PCM) in wild-type and Thr-to-His mutant forms reveal details of the molecular mechanism of the Pr/Pfr transition associated with the physiological response of this myxobacterium to red light. Specifically, key structural differences in the CBD and PCM between the wild-type and the Thr-to-His mutant involve essential chromophore contacts with proximal amino acids, and point to how the photosignal is transduced through the rest of the protein, impacting the essential enzymatic activity in the photomorphogenic response of this myxobacterium.
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| 5. |
- Ayeni, O. R., et al.
(författare)
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Clinical and Radiographic Criteria Define "Acceptable" Surgical Correction of Hip Femoroacetabular Impingement Syndrome as Well as Postoperative Complications: An International Modified Delphi Study
- 2023
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Ingår i: Arthroscopy-the Journal of Arthroscopic and Related Surgery. - : Elsevier BV. - 0749-8063. ; 39:5, s. 1198-1210
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To develop recommendations for clinical and radiographic criteria to help define the "acceptable" surgical correction of femoroacetabular impingement syndrome (FAIS) and identify/define complications postoperatively. Methods: A 3-phase modified Delphi study was conducted involving a case-based survey; a Likert/multiple choice-based survey concerning radiographic and physical examination characteristics to help define FAIS correction, as well as the prevalence and definition of potential postoperative complications; and 2 consensus meetings. Results: Of the 75 experts invited, 54 completed the Phase I survey, 50 completed the Phase II survey (72% and 67% response rate), and 50 participated in the Phase III consensus meetings. For both typical and atypical (complex) cases, there was consensus that fluoroscopy with multiple views and dynamic hip assessment should be used intraoperatively (96% and 100%, respectively). For typical FAIS cases, the Expert Panel agreed that Dunn lateral and anteroposterior radiographs were the most important radiographs to evaluate the hip postoperatively (88%, consensus). When asked about evaluating the correction of cam impingement postoperatively, 87% voted that they use subjective evaluation of the "sphericity" of the femoral head. In the case of focal and global pincer-type FAIS, there was consensus that the reduction or elimination of the crossover sign (84%) and lateral center-edge angle (91%) were important to inform the extent of the FAIS correction. There was consensus for recommending further investigation at 6 months postoperatively if hip pain had increased/plateaued (92% agreed); that additional investigation and treatment should occur between 6 and 12 months (90% agreed); and that a reoperation may be recommended at 12 months or later following this investigation period (89% agreed). Conclusions: This consensus project identified the importance of using fluoroscopy and dynamic hip assessment intraoperatively; Dunn lateral and anteroposterior view radiographs postoperatively; evaluating the "sphericity" of the femoral head for cam-type correction and the use of dynamic hip assessment; reducing/eliminating the crossover sign for focal pincertype FAIS; evaluating the lateral center-edge angle for global pincer-type FAIS; and avoiding overcorrection of pincer-type FAIS. In cases in which postoperative hip pain increased/plateaued, further investigation and treatment is warranted between 6 and 12 months, and a reoperation may be recommended at a minimum of 12 months depending on the cause of the hip pain. Clinical Relevance: Hip arthroscopy surgeons have yet to reach a firm agreement on what constitutes an "acceptable" or "good" surgery radiographically and how they can achieve desired clinical outcomes. Although this was a comprehensive effort, more study is needed to determine therapeutic thresholds that can be universally applied.
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| 6. |
- Lacour, S., et al.
(författare)
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The mass of β Pictoris c from β Pictoris b orbital motion
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 654
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Tidskriftsartikel (refereegranskat)abstract
- Aims. We aim to demonstrate that the presence and mass of an exoplanet can now be effectively derived from the astrometry of another exoplanet.Methods. We combined previous astrometry of β Pictoris b with a new set of observations from the GRAVITY interferometer. The orbital motion of β Pictoris b is fit using Markov chain Monte Carlo simulations in Jacobi coordinates. The inner planet, β Pictoris c, was also reobserved at a separation of 96 mas, confirming the previous orbital estimations.Results. From the astrometry of planet b only, we can (i) detect the presence of β Pictoris c and (ii) constrain its mass to 10.04(-3.10)(+4.53) M-Jup. If one adds the astrometry of β Pictoris c, the mass is narrowed down to 9.15(-1.06)(+1.08) M-Jup. The inclusion of radial velocity measurements does not affect the orbital parameters significantly, but it does slightly decrease the mass estimate to 8.89(-0.75)(+0.75) M-Jup. With a semimajor axis of 2.68 +/- 0.02 au, a period of 1221 +/- 15 days, and an eccentricity of 0.32 +/- 0.02, the orbital parameters of β Pictoris c are now constrained as precisely as those of β Pictoris b. The orbital configuration is compatible with a high-order mean-motion resonance (7:1). The impact of the resonance on the planets' dynamics would then be negligible with respect to the secular perturbations, which might have played an important role in the eccentricity excitation of the outer planet.
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| 7. |
- Schoch, CL, et al.
(författare)
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Nuclear ribosomal internal transcribed spacer (ITS) region as a universal DNA barcode marker for Fungi
- 2012
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 1091-6490. ; 109:16, s. 6241-6246
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Tidskriftsartikel (refereegranskat)abstract
- Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter- and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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| 8. |
- Björling, Alexander, 1983, et al.
(författare)
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Ubiquitous Structural Signaling in Bacterial Phytochromes
- 2015
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Ingår i: Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 6:17, s. 3379-3383
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Tidskriftsartikel (refereegranskat)abstract
- The phytochrome family of light-switchable proteins has long been studied by biochemical, spectroscopic and crystallographic means, while a direct probe for global conformational signal propagation has been lacking. Using solution X-ray scattering, we find that the photosensory cores of several bacterial phytochromes undergo similar large-scale structural changes upon red-light excitation. The data establish that phytochromes with ordinary and inverted photocycles share a structural signaling mechanism and that a particular conserved histidine, previously proposed to be involved in signal propagation, in fact tunes photoresponse.
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| 9. |
- Duong, M., et al.
(författare)
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Global differences in lung function by region (PURE): An international, community-based prospective study
- 2013
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Ingår i: The Lancet Respiratory Medicine. - 2213-2600. ; 1:8, s. 599-609
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Tidskriftsartikel (refereegranskat)abstract
- Background: Despite the rising burden of chronic respiratory diseases, global data for lung function are not available. We investigated global variation in lung function in healthy populations by region to establish whether regional factors contribute to lung function. Methods: In an international, community-based prospective study, we enrolled individuals from communities in 17 countries between Jan 1, 2005, and Dec 31, 2009 (except for in Karnataka, India, where enrolment began on Jan 1, 2003). Trained local staff obtained data from participants with interview-based questionnaires, measured weight and height, and recorded forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC). We analysed data from participants 130-190 cm tall and aged 34-80 years who had a 5 pack-year smoking history or less, who were not affected by specified disorders and were not pregnant, and for whom we had at least two FEV1 and FVC measurements that did not vary by more than 200 mL. We divided the countries into seven socioeconomic and geographical regions: south Asia (India, Bangladesh, and Pakistan), east Asia (China), southeast Asia (Malaysia), sub-Saharan Africa (South Africa and Zimbabwe), South America (Argentina, Brazil, Colombia, and Chile), the Middle East (Iran, United Arab Emirates, and Turkey), and North America or Europe (Canada, Sweden, and Poland). Data were analysed with non-linear regression to model height, age, sex, and region. Findings: 153 996 individuals were enrolled from 628 communities. Data from 38 517 asymptomatic, healthy non-smokers (25 614 women; 12 903 men) were analysed. For all regions, lung function increased with height non-linearly, decreased with age, and was proportionately higher in men than women. The quantitative effect of height, age, and sex on lung function differed by region. Compared with North America or Europe, FEV1 adjusted for height, age, and sex was 31·3% (95% CI 30·8-31·8%) lower in south Asia, 24·2% (23·5-24·9%) lower in southeast Asia, 12·8% (12·4-13·4%) lower in east Asia, 20·9% (19·9-22·0%) lower in sub-Saharan Africa, 5·7% (5·1-6·4%) lower in South America, and 11·2% (10·6-11·8%) lower in the Middle East. We recorded similar but larger differences in FVC. The differences were not accounted for by variation in weight, urban versus rural location, and education level between regions. Interpretation: Lung function differs substantially between regions of the world. These large differences are not explained by factors investigated in this study; the contribution of socioeconomic, genetic, and environmental factors and their interactions with lung function and lung health need further clarification. Funding: Full funding sources listed at end of the paper (see Acknowledgments). © 2013 Elsevier Ltd.
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| 10. |
- Garpvall, K., et al.
(författare)
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Admission screening and cohort care decrease carbapenem resistant enterobacteriaceae in Vietnamese pediatric ICUs
- 2021
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Ingår i: Antimicrobial Resistance and Infection Control. - : BMC. - 2047-2994. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To assess if admission screening for Carbapenem Resistant Enterobacteriaceae (CRE) and cohort care can reduce CRE acquisition (CRE colonization during hospital stay), Hospital Acquired Infections (HAI), hospital-stay, mortality, and costs in three Intensive Care Units (ICUs) at the Vietnamese National Childrens Hospital. Method CRE screening using rectal swabs and ChromIDCarbas elective culture at admission and if CRE negative, once weekly. Patients were treated in cohorts based on CRE colonization status. Results CRE colonization at baseline point-prevalence screening was 76.9% (103/134). Of 941 CRE screened at admission, 337 (35.8%) were CREpos. 694 patients met inclusion criteria. The 244 patients CRE negative at admission and screened > 2 times were stratified in 8 similar size groups (periods), based on time of admission. CRE acquisition decreased significant (OR - 3.2, p < 0.005) from 90% in period 2 (highest) to 48% in period 8 (last period). Patients with CRE acquisition compared to no CRE acquisition had a significantly higher rate of culture confirmed HAI, n = 20 (14%) vs. n = 2 (2%), longer hospital stays, 3.26 vs. 2.37 weeks, and higher total treatment costs, 2852 vs. 2295 USD. Conclusion Admission CRE screening and cohort care in pediatric ICUs significantly decreased CRE acquisition, cases of HAI and duration of hospital-stay.
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