Recognition and coacervation of G-quadruplexes by a multifunctional disordered region in RECQ4 helicase

Biomolecular polyelectrolyte complexes can be formed between oppositely charged intrinsically disordered regions (IDRs) of proteins or between IDRs and nucleic acids. Highly charged IDRs are abundant in the nucleus, yet few have been functionally characterized. Here, we show that a positively charged IDR within the human ATP-dependent DNA helicase Q4 (RECQ4) forms coacervates with G-quadruplexes (G4s). We describe a three-step model of charge-driven coacervation by integrating equilibrium and kinetic binding data in a global numerical model. The oppositely charged IDR and G4 molecules form a complex in the solution that follows a rapid nucleation-growth mechanism leading to a dynamic equilibrium between dilute and condensed phases. We also discover a physical interaction with Replication Protein A (RPA) and demonstrate that the IDR can switch between the two extremes of the structural continuum of complexes. The structural, kinetic, and thermodynamic profile of its interactions revealed a dynamic disordered complex with nucleic acids and a static ordered complex with RPA protein. The two mutually exclusive binding modes suggest a regulatory role for the IDR in RECQ4 function by enabling molecular handoffs. Our study extends the functional repertoire of IDRs and demonstrates a role of polyelectrolyte complexes involved in G4 binding

Assessing collaborative efforts of making care fit for each patient – A systematic review

Introduction: For too many people, their care plans are designed without fully accounting for who they are, the lives they live, what matters to them or what they aspire to achieve. We aimed to summarize instruments capable of measuring dimensions of patient–clinician collaboration to make care fit. Methods: We systematically searched several databases (Medline, Embase, Cochrane, Scopus and Web of Science) from inception to September 2021 for studies using quantitative measures to assess, evaluate or rate the work of making care fit by any participant in real-life clinical encounters. Eligibility was assessed in duplicate. After extracting all items from relevant instruments, we coded them deductively on dimensions relevant to making care fit (as presented in a recent Making Care Fit Manifesto), and inductively on the main action described. Results: We included 189 papers, mostly from North America (N = 83, 44%) and in the context of primary care (N = 54, 29%). Half of the papers (N = 88, 47%) were published in the last 5 years. We found 1243 relevant items to assess efforts of making care fit, included within 151 instruments. Most items related to the dimensions ‘Patient-clinician collaboration: content’ (N = 396, 32%) and ‘Patient-clinician collaboration: manner’ (N = 382, 31%) and the least related to ‘Ongoing and iterative process’ (N = 22, 2%) and in ‘Minimally disruptive of patient lives’ (N = 29, 2%). The items referred to 27 specific actions. Most items referred to ‘Informing’ (N = 308, 25%) and ‘Exploring’ (N = 93, 8%), the fewest items referred to ‘Following up’, ‘Comforting’ and ‘Praising’ (each N = 3, 0.2%). Discussion: Measures of the work that patients and clinicians do together to make care fit focus heavily on the content of their collaborations, particularly on exchanging information. Other dimensions and actions previously identified as crucial to making care fit are assessed infrequently or not at all. The breadth of extant measures of making care fit and the lack of appropriate measures of this key construct limit both the assessment and the successful implementation of efforts to improve patient care. Patient Contribution: Patients and caregivers from the ‘Making care fit Collaborative’ were involved in drafting the dimensions relevant to patient–clinician collaboration

RADIOLUCENT COMPOSITES PROVIDING HIGH RESISTANCE AGAINST STERILIZATION DECOMPOSITION

We present a study of radiolucent composite materials for use in medicine, providing suitable mechanical properties and high resistance against sterilization decomposition. The composites are composed of carbon (C), aramid or glass (R-glass) fabrics embedded in polydimethylsiloxane (PDMS), polyetheretherketone (PEEK) or polyphenylene sulfide (PPS) matrix. The effect of multiple steam sterilization processes on degrading the mechanical properties, structural integrity and hydrolytic decomposition of the composites was verified. The radiolucency of the composites was also investigated. The mechanical performance of ARAMID/PDMS composite is strongly influenced by the sterilization technique that is applied. The mechanical behavior of R-glass/PDMS composite during steam sterilization is negatively influenced by its porosity. The relatively high porosity of C/PDMS composite may lead to lower ultimate bending strength values, but in general its mechanical behavior is influenced only at a low rate by steam sterilization. On the basis of our analyses, we can state that both C/PEEK and C/PPS composites are good candidates for application as radiolucent materials providing resistance against sterilization decomposition

Recent growth coherence in long-term oak (Quercus spp.) ring width chronologies in the Czech Republic

Oak ring width measurements compiled from 44 sampling sites throughout the territory of the Czech Republic are analysed for the 1655-2013 period. Measurements taken at all these sites are sorted into 10 sub-chronologies on the basis of 5 environmental factors: soil moisture (dry/wet), elevation (low/high), age (young/old), species (Quercus robur or Q. petraea), and geographical position (east/west). Several statistical tests are applied to investigate existing significant differences between chronologies during 1920-2013. Further, the sensitivities of individual sub-chronologies to precipitation are compared. Three tests indicate 5 pairs of very similar sub-chronologies. Moreover, the growth-response to May-July precipitation totals is very much the same in these sub-chronologies. This analysis demonstrates that, even in the absence of certainty about age structure, species composition and some environmental factors in the earlier parts of oak ring width chronologies, the internal homogeneity of the chronology remains essentially unaffected, and the lack of such information does not preclude their use in dendroclimatology

Grading of carotid artery stenosis with multidetector-row CT angiography: visual estimation or caliper measurements?

To assess the optimal method for grading carotid artery stenosis with computed tomographic angiography (CTA), we compared visual estimation to caliper measurements, and determined inter-observer variability and agreement relative to digital subtraction angiography (DSA). We included 46 patients with symptomatic carotid stenosis for whom CTA and DSA of 55 carotids was available. Stenosis quantification by CTA using visual estimation (CTAVE) (method 1) was compared with caliper measurements using subjectively optimized wide window settings (method 2) or predefined contrast-dependent narrow window settings (method 3). Measurements were independently performed by two radiologists and two residents. To determine accuracy and inter-observer variability, we calculated linear weighted kappa, performed a Bland-Altman analysis and calculated mean difference (bias) and standard deviation of differences (SDD). For inter-observer variability, kappa analysis was “very good” (0.85) for expert observers using CTAVE compared with “good” (0.61) for experts using DSA. Compared with DSA, method 1 led to overestimation (bias 5.8–8.0%, SDD 10.6–14.4), method 3 led to underestimation (bias −6.3 to −3.0%, SDD 13.0–18.1). Measurement variability between DSA and visual estimation on CTA (SDD 11.5) is close to the inter-observer variability of repeated measurements on DSA that we found in this study (SDD 11.6). For CTA of carotids, stenosis grading based on visual estimation provides better agreement to grading by DSA compared with stenosis grading based on caliper measurements

Autosomal recessive LRP1-related syndrome featuring cardiopulmonary dysfunction, bone dysmorphology, and corneal clouding.

We provide the first study of two siblings with a novel autosomal recessive LRP1-related syndrome identified by rapid genome sequencing and overlapping multiple genetic models. The patients presented with respiratory distress, congenital heart defects, hypotonia, dysmorphology, and unique findings, including corneal clouding and ascites. Both siblings had compound heterozygous damaging variants, c.11420G \u3e C (p.Cys3807Ser) and c.12407T \u3e G (p.Val4136Gly) i

The Impact of Warmed Intravenous Contrast Material on the Bolus Geometry of Coronary CT Angiography Applications

Objective This study was designed to investigate the effect of administration of warmed contrast material (CM) on the bolus geometry and enhancement as depicted on coronary CT angiography. Materials and Methods A total of 64 patients (42 men, 22 women; mean age, 56 years) were randomly divided into two groups. Group 1 included 32 patients administered CM (Omnipaque [Iohexol] 350 mg I/ mL; Nycomed, Princeton, NJ) saline solutions kept in an incubator at a constant temperature (37℃). Group 2 included 32 patients administered the CM saline solutions kept at constant room temperature (24℃). Cardiac CT scans were performed with a dual source computed tomography (DSCT) scanner. For each group, region of interest curves were plotted inside the ascending aorta, main pulmonary artery and descending aorta on test bolus images. Using enhancement values, time/enhancement diagrams were produced for each vessel. On diagrams, basal Hounsfield unit (HU) values were subtracted from sequentially obtained values. A value of 100 HU was accepted as a cut-off value for the beginning of opacification. The time to peak, the time required to reach 100 HU opacification, maximum enhancement and duration of enhancement above 100 HU were noted. DSCT angiography studies were evaluated for coronary vessel enhancement. Results Maximum enhancement values in the ascending aorta, descending aorta and main pulmonary artery were significantly higher in group 1 subjects. In the ascending aorta, the median time required to reach 100 HU opacification during the test bolus analysis was significantly shorter for group 2 subjects than for group 1 subjects. In the ascending aorta, the descending aorta and main pulmonary artery, for group 1 subjects, the bolus geometry curve shifted to the left and upwards as compared with the bolus geometry curve for group 2 subjects. Conclusion The use of warmed CM yields higher enhancement values and a shorter time to reach maximum enhancement duration, resulting in a shift of the bolus geometry curve to the left that may provide optimized image quality.PubMedWoSScopu