Yeast cells actively tune their membranes to phase separate at temperatures that scale with growth temperatures.

Membranes of vacuoles, the lysosomal organelles of Saccharomyces cerevisiae (budding yeast), undergo extraordinary changes during the cell's normal growth cycle. The cycle begins with a stage of rapid cell growth. Then, as glucose becomes scarce, growth slows, and vacuole membranes phase separate into micrometer-scale domains of two liquid phases. Recent studies suggest that these domains promote yeast survival by organizing membrane proteins that play key roles in a central signaling pathway conserved among eukaryotes (TORC1). An outstanding question in the field has been whether cells regulate phase transitions in response to new physical conditions and how this occurs. Here, we measure transition temperatures and find that after an increase of roughly 15 °C, vacuole membranes appear uniform, independent of growth temperature. Moreover, populations of cells grown at a single temperature regulate this transition to occur over a surprisingly narrow temperature range. Remarkably, the transition temperature scales linearly with the growth temperature, demonstrating that the cells physiologically adapt to maintain proximity to the transition. Next, we ask how yeast adjust their membranes to achieve phase separation. We isolate vacuoles from yeast during the rapid stage of growth, when their membranes do not natively exhibit domains. Ergosterol is the major sterol in yeast. We find that domains appear when ergosterol is depleted, contradicting the prevalent assumption that increases in sterol concentration generally cause membrane phase separation in vivo, but in agreement with previous studies using artificial and cell-derived membranes.

Coupling liquid phases in 3D condensates and 2D membranes: Successes, challenges, and tools.

This review describes the major experimental challenges researchers meet when attempting to couple phase separation between membranes and condensates. Although it is well known that phase separation in a 2D membrane could affect molecules capable of forming a 3D condensate (and vice versa), few researchers have quantified the effects to date. The scarcity of these measurements is not due to a lack of intense interest or effort in the field. Rather, it reflects significant experimental challenges in manipulating coupled membranes and condensates to yield quantitative values. These challenges transcend many molecular details, which means they impact a wide range of systems. This review highlights recent exciting successes in the field, and it lays out a comprehensive list of tools that address potential pitfalls for researchers who are considering coupling membranes with condensates.

The value of non-enhanced MRI in the evaluation of patients with suspected idiopathic inflammatory myopathy.

INTRODUCTION/AIMS: The performance of magnetic resonance imaging (MRI) for diagnosing suspected idiopathic inflammatory myopathy (IIM) remains controversial. Furthermore, the role of contrast-enhanced magnetic resonance imaging (CE-MRI) sequences is unclear. The aim of this study was to evaluate the sensitivity and specificity of a non-enhanced magnetic resonance imaging (NE-MRI) protocol compared to a CE-MRI protocol in adult patients with confirmed IIM. METHODS: This study retrospectively enrolled patients with suspected IIM who underwent MRI of the upper thigh between 2008 and 2020. The protocol consisted of a T1-weighted (T1w) sequence, a turbo inversion recovery magnitude (TIRM) sequence and a contrast-enhanced T1-weighted sequence (CE-T1w). After randomly stratifying patients into a group with only the T1w and TIRM sequences available and another group with additional availability of CE-T1w, three blinded readers assessed the presence of IIM based on characteristic imaging features. Confirmation of the diagnosis was determined based on the 2017 ACR/EULAR criteria. RESULTS: Of the 80 patients (mean age 49.0 ± 21.1 years; 42 female, 38 male) included, 54 (67.5%) had a positive diagnosis of IIM. Cumulated sensitivity and specificity for MRI to detect IIM was 87.1% and 83.3% in the NE-MRI group versus 87.0% and 63.0% in the CE-MRI group. The group differences for sensitivity and specificity were non-significant for each of the three readers, respectively (p ≥ .081). DISCUSSION: NE-MRI detects suspected IIM with high diagnostic accuracy and performs equivalently to CE-MRI. Therefore, it may be appropriate to omit the use of contrast agents in MRI scans performed for suspected IIM.

Endocytic proteins with prion-like domains form viscoelastic condensates that enable membrane remodeling.

Membrane invagination and vesicle formation are key steps in endocytosis and cellular trafficking. Here, we show that endocytic coat proteins with prion-like domains (PLDs) form hemispherical puncta in the budding yeast, Saccharomyces cerevisiae These puncta have the hallmarks of biomolecular condensates and organize proteins at the membrane for actin-dependent endocytosis. They also enable membrane remodeling to drive actin-independent endocytosis. The puncta, which we refer to as endocytic condensates, form and dissolve reversibly in response to changes in temperature and solution conditions. We find that endocytic condensates are organized around dynamic protein-protein interaction networks, which involve interactions among PLDs with high glutamine contents. The endocytic coat protein Sla1 is at the hub of the protein-protein interaction network. Using active rheology, we inferred the material properties of endocytic condensates. These experiments show that endocytic condensates are akin to viscoelastic materials. We use these characterizations to estimate the interfacial tension between endocytic condensates and their surroundings. We then adapt the physics of contact mechanics, specifically modifications of Hertz theory, to develop a quantitative framework for describing how interfacial tensions among condensates, the membrane, and the cytosol can deform the plasma membrane to enable actin-independent endocytosis.

Remodeling of yeast vacuole membrane lipidomes from the log (one phase) to stationary stage (two phases).

Upon nutrient limitation, budding yeast of Saccharomyces cerevisiae shift from fast growth (the log stage) to quiescence (the stationary stage). This shift is accompanied by liquid-liquid phase separation in the membrane of the vacuole, an endosomal organelle. Recent work indicates that the resulting micrometer-scale domains in vacuole membranes enable yeast to survive periods of stress. An outstanding question is which molecular changes might cause this membrane phase separation. Here, we conduct lipidomics of vacuole membranes in both the log and stationary stages. Isolation of pure vacuole membranes is challenging in the stationary stage, when lipid droplets are in close contact with vacuoles. Immuno-isolation has previously been shown to successfully purify log-stage vacuole membranes with high organelle specificity, but it was not previously possible to immuno-isolate stationary-stage vacuole membranes. Here, we develop Mam3 as a bait protein for vacuole immuno-isolation, and demonstrate low contamination by non-vacuolar membranes. We find that stationary-stage vacuole membranes contain surprisingly high fractions of phosphatidylcholine lipids (∼40%), roughly twice as much as log-stage membranes. Moreover, in the stationary stage, these lipids have higher melting temperatures, due to longer and more saturated acyl chains. Another surprise is that no significant change in sterol content is observed. These lipidomic changes, which are largely reflected on the whole-cell level, fit within the predominant view that phase separation in membranes requires at least three types of molecules to be present: lipids with high melting temperatures, lipids with low melting temperatures, and sterols.

Work expectations, their fulfillment, and exhaustion among radiologists of all career levels: what can be learned from the example of Germany.

OBJECTIVES: To evaluate work expectations of radiologists at different career levels, their fulfillment, prevalence of exhaustion, and exhaustion-associated factors. METHODS: A standardized digital questionnaire was distributed internationally to radiologists of all career levels in the hospital and in ambulatory care via radiological societies and sent manually to 4500 radiologists of the largest German hospitals between December 2020 and April 2021. Statistics were based on age- and gender-adjusted regression analyses of respondents working in Germany (510 out of 594 total respondents). RESULTS: The most frequent expectations were "joy at work" (97%) and a "good working atmosphere" (97%), which were considered fulfilled by at least 78%. The expectation of a "structured residency within the regular time interval" (79%) was more frequently judged fulfilled by senior physicians (83%, odds ratio (OR) 4.31 [95% confidence interval (95% CI) 1.95-9.52]), chief physicians (85%, 6.81 [95% CI 1.91-24.29]), and radiologists outside the hospital (88%, 7.59 [95% CI 2.40-24.03]) than by residents (68%). Exhaustion was most common among residents (physical exhaustion: 38%; emotional exhaustion: 36%), in-hospital specialists (29%; 38%), and senior physicians (30%; 29%). In contrast to paid extra hours, unpaid extra hours were associated with physical exhaustion (5-10 extra hours: OR 2.54 [95% CI 1.54-4.19]). Fewer opportunities to shape the work environment were related to a higher probability of physical (2.03 [95% CI 1.32-3.13]) and emotional (2.15 [95% CI 1.39-3.33]) exhaustion. CONCLUSIONS: While most radiologists enjoy their work, residents wish for more training structure. Ensuring payment of extra hours and employee empowerment may help preventing burnout in high-risk groups. KEY POINTS: • Most important work expectations of radiologists who work in Germany are "joy at work," a "good working atmosphere," "support for further qualification," and a "structured residency within the regular time interval," with the latter containing potential for improvement according to residents. • Physical and emotional exhaustion are common at all career levels except for chief physicians and for radiologists who work outside the hospital in ambulatory care. • Exhaustion as a major burnout criterion is associated with unpaid extra hours and reduced opportunities to shape the work environment.

Direct imaging of liquid domains in membranes by cryo-electron tomography.

Images of micrometer-scale domains in lipid bilayers have provided the gold standard of model-free evidence to understand the domains' shapes, sizes, and distributions. Corresponding techniques to directly and quantitatively assess smaller (nanoscale and submicron) liquid domains have been limited. Researchers commonly seek to correlate activities of membrane proteins with attributes of the domains in which they reside; doing so hinges on identification and characterization of membrane domains. Although some features of membrane domains can be probed by indirect methods, these methods are often constrained by the limitation that data must be analyzed in the context of models that require multiple assumptions or parameters. Here, we address this challenge by developing and testing two methods of identifying submicron domains in biomimetic membranes. Both methods leverage cryo-electron tomograms of ternary membranes under vitrified, hydrated conditions. The first method is optimized for probe-free applications: Domains are directly distinguished from the surrounding membrane by their thickness. This technique quantitatively and accurately measures area fractions of domains, in excellent agreement with known phase diagrams. The second method is optimized for applications in which a single label is deployed for imaging membranes by both high-resolution cryo-electron tomography and diffraction-limited optical microscopy. For this method, we test a panel of probes, find that a trimeric mCherry label performs best, and specify criteria for developing future high-performance, dual-use probes. These developments have led to direct and quantitative imaging of submicron membrane domains in vitrified, hydrated vesicles.

Low back pain in adolescent rowers: Association to muscle changes detected by magnetic resonance imaging.

Adult elite rowers are at risk of developing low back pain (LBP). However, LBP data on adolescent elite rowers is currently insufficient. Therefore, the aim of this study was to assess LBP prevalence, LBP intensity and training characteristics in male adolescent elite rowers and a healthy control group. Twenty rowers (mean age 15.8 ± 1.2 years) and a non-athletic control group matched by age and gender (n = 13) were prospectively enrolled and underwent LBP assessment with a validated questionnaire and magnetic resonance imaging (MRI) of the lumbar spine muscles, which included a T2-mapping sequence. From the quantitative image data, T2 relaxation times were calculated. The prevalence of LBP in the last 24 hours and 3 months in the rowing group was 55.0% and 85.0%, respectively, compared to 23.1% and 30.8% in the control group (p < 0.001). Rowers had significantly longer T2 relaxation times of the paraspinal muscles compared to controls (p ≤ 0.041). LBP intensity was associated with longer T2 relaxation times (p < 0.001). Adolescent rowers had a higher prevalence of LBP compared to an age-matched control group. The observed increase in T2 relaxation might be explained by muscle soreness due to strenuous exercise, which is correlated with short-term pain intensity.

Gender differences and cooperation in medical authorships - an analysis of the recent ten years in five key medical disciplines.

BACKGROUND: Career prospects in academic medicine are strongly linked to scientific authorship and this marker has been widely used as an indicator of gender equity in academia. However, direct comparisons of medical disciplines regarding their proportion of female physicians (FP) in different countries are missing. This study examines the gender parity and gender cooperation using first authorships (FA) and senior authorships (SA) of scientific publications in five medical disciplines and six different OECD countries over a 10-year time-trend. METHODS: Articles from three high-impact journals in each of the medical discipline radiology, urology, surgery, gynecology, and pediatrics from the years 2007/8 and 2017/18 were retrospectively reviewed. The gender and affiliation location of the FA and SA of original research articles and reviews were assigned and compared with the proportion of in each discipline for the United States of America, Canada, United Kingdom, France, Germany, and Japan. Mantel-Haenszel test and multinomial logistic regression models were used to calculate differences in proportions of women authors and FP and to assess trends and proportions of FA and SA. RESULTS: 30,803 articles were evaluated. Equally, with rising proportions of FP in all disciplines, the number of women authors increased across years. The shares of women FAs were either significantly higher (urology/surgery/gynecology) or balanced (pediatrics/radiology) compared to the proportion of FP. In contrast, the shares of women SA were balanced only in disciplines with a low proportion of FP (urology and surgery) and otherwise reduced. Women same-gender cooperation was as common as men same-gender cooperation and preferred over a women-led mixed gender cooperation in disciplines where this seemed to be practicable due to the high proportions of FP. CONCLUSION: In contrast to FA, a significant disparity persists in SA, particularly in disciplines with a high proportion of FP. The discrepancy between FA and SA may reflect, among others, dropout from an academic career in early or mid-academic levels, for example, due to structural inequality; together with the findings on gender preference in authorship collaborations, this may inform future strategies for promoting equal career advancement for women physicians.

Ripples at edges of blooming lilies and torn plastic sheets.

Ripples arise at edges of petals of blooming Lilium casablanca flowers and at edges of torn plastic sheets. In both systems, ripples are a consequence of excess length along the edge of a sheet. Through the use of time-lapse videos of blooming lilies and published images of torn plastic sheets, we find that ripples in both systems are well described by the scaling relationship a∝w(L-w), where a is amplitude, w is wavelength, and L is arc length. A phenomenological relationship previously reported for self-similar ripple patterns, namely ⟨a⟩∝⟨w⟩, can be recovered by assuming that buckling stress is constant. Excess length along petal edges can also influence their overall Gaussian curvature, such that petals invert from a cup shape to a saddle shape upon blooming. Previous simulations of these shape changes have assumed that petal thickness decreases at least quadratically. Here, we evaluate tomograms of several varieties of lily buds and find that this assumption is valid along the short axis of the buds, but not the long axis. A challenge of employing traditional tomography methods to measure petal thickness is that the sample is destroyed; a single bud cannot be followed through the entire blooming process. To address this challenge, we provide proof of principle that the nondestructive, label-free method of x-ray tomography produces high-contrast three-dimensional scans on time scales short enough to follow lily blooming.

Prebiotic Membranes and Micelles Do Not Inhibit Peptide Formation During Dehydration.

Cycles of dehydration and rehydration could have enabled formation of peptides and RNA in otherwise unfavorable conditions on the early Earth. Development of the first protocells would have hinged upon colocalization of these biopolymers with fatty acid membranes. Using atomic force microscopy, we find that a prebiotic fatty acid (decanoic acid) forms stacks of membranes after dehydration. Using LC-MS-MS (liquid chromatography-tandem mass spectrometry) with isotope internal standards, we measure the rate of formation of serine dipeptides. We find that dipeptides form during dehydration at moderate temperatures (55 °C) at least as fast in the presence of decanoic acid membranes as in the absence of membranes. Our results are consistent with the hypothesis that protocells could have formed within evaporating environments on the early Earth.

Prebiotic Protocell Membranes Retain Encapsulated Contents during Flocculation, and Phospholipids Preserve Encapsulation during Dehydration.

The first cell membranes were likely composed of single-chain amphiphiles such as fatty acids. An open question is whether fatty acid membranes could have functioned within evaporative lakes on the early Earth, which have been hypothesized to concentrate prebiotic reactants. Evaporation also concentrates monovalent salts, which in turn cause fatty acid membrane vesicles to flocculate; significant loss of encapsulated contents during flocculation would have impeded early cell evolution. Here, we tested whether fatty acid vesicles retain encapsulated contents after flocculation and after drying. We found that vesicles composed of 2:1 decanoic acid:decanol encapsulate calcein dye throughout a process of flocculation in saturated salt solution and subsequent disaggregation of vesicles by dilution of the salt. However, 30 minutes of complete dehydration disrupted encapsulation by fatty acid vesicles. In contrast, phospholipid vesicles maintained encapsulation. Our results reveal a selective pressure for protocells to incorporate phospholipids: while fatty acid membranes can retain encapsulated contents during periods of dilute and saturating salt, phospholipids are necessary for encapsulation during dry periods. Our results are consistent with the hypothesis that evaporative lakes were productive sites for prebiotic chemistry and the origin of cells.

Prebiotic Vesicles Retain Solutes and Grow by Micelle Addition after Brief Cooling below the Membrane Melting Temperature.

Replication of RNA genomes within membrane vesicles may have been a critical step in the development of protocells on the early Earth. Cold temperatures near 0 °C improve the stability of RNA and allow efficient copying, while some climate models suggest a cold early Earth, so the first protocells may have arisen in cold-temperature environments. However, at cold temperatures, saturated fatty acids, which would have been available on the early Earth, form gel-phase membranes that are rigid and restrict mobility within the bilayer. Two primary roles of protocell membranes are to encapsulate solutes and to grow by incorporating additional fatty acids from the environment. We test here whether fatty acid membranes in the gel phase accomplish these roles. We find that gel-phase membranes of 10-carbon amphiphiles near 0 °C encapsulate aqueous dye molecules as efficiently as fluid-phase membranes do, but the contents are released if the aqueous solution is frozen at -20 °C. Gel-phase membranes do not grow measurably by micelle addition, but growth resumes when membranes are warmed above the gel-liquid transition temperature. We find that longer, 12-carbon amphiphiles do not retain encapsulated contents near 0 °C. Together, our results suggest that protocells could have developed within environments that experience temporary cooling below the membrane melting temperature, and that membranes composed of relatively short-chain fatty acids would encapsulate solutes more efficiently as temperatures approached 0 °C.

Growth of Prebiotically Plausible Fatty Acid Vesicles Proceeds in the Presence of Prebiotic Amino Acids, Dipeptides, Sugars, and Nucleic Acid Components.

Fatty acid vesicles may have played a role in the origin of life as a major structural component of protocells, with the potential for encapsulation of genetic materials. Vesicles that grew and divided more rapidly than other vesicles could have had a selective advantage. Fatty acid vesicles grow by incorporating additional fatty acids from micelles, and certain prebiotic molecules (e.g., sugars, nucleobases, and amino acids) can bind to fatty acid vesicles and stabilize them. Here, we investigated whether the presence of a variety of biomolecules affects the overall growth of vesicles composed of decanoic acid, a prebiotically plausible fatty acid, upon micelle addition. We tested 31 molecules, including 15 dipeptides, 7 amino acids, 6 nucleobases or nucleosides, and 3 sugars. We find that the initial radius and final radius of vesicles are largely unaffected by the presence of the additional compounds. However, three dipeptides enhanced the initial rates of growth compared to control vesicles with no small molecules added; another three dipeptides decreased the initial rates of growth. We conclude that vesicles can indeed grow in the presence of a wide range of molecules likely to have been involved in the origin of life. These results imply that vesicles would have been able to grow in complex and heterogeneous chemical environments. We find that the molecules that enhance the initial growth rate tend to have hydrophobic groups (e.g., leucine), which may interact with the lipid membrane to affect growth rate; furthermore, the molecules that cause the largest decrease in initial growth rate are dipeptides containing a serine residue, which contains a hydroxyl group that could potentially hydrogen-bond with the fatty acid carboxylate groups.

Prebiotic amino acids bind to and stabilize prebiotic fatty acid membranes.

The membranes of the first protocells on the early Earth were likely self-assembled from fatty acids. A major challenge in understanding how protocells could have arisen and withstood changes in their environment is that fatty acid membranes are unstable in solutions containing high concentrations of salt (such as would have been prevalent in early oceans) or divalent cations (which would have been required for RNA catalysis). To test whether the inclusion of amino acids addresses this problem, we coupled direct techniques of cryoelectron microscopy and fluorescence microscopy with techniques of NMR spectroscopy, centrifuge filtration assays, and turbidity measurements. We find that a set of unmodified, prebiotic amino acids binds to prebiotic fatty acid membranes and that a subset stabilizes membranes in the presence of salt and Mg2+ Furthermore, we find that final concentrations of the amino acids need not be high to cause these effects; membrane stabilization persists after dilution as would have occurred during the rehydration of dried or partially dried pools. In addition to providing a means to stabilize protocell membranes, our results address the challenge of explaining how proteins could have become colocalized with membranes. Amino acids are the building blocks of proteins, and our results are consistent with a positive feedback loop in which amino acids bound to self-assembled fatty acid membranes, resulting in membrane stabilization and leading to more binding in turn. High local concentrations of molecular building blocks at the surface of fatty acid membranes may have aided the eventual formation of proteins.

Deep learning for accurately recognizing common causes of shoulder pain on radiographs.

OBJECTIVE: Training a convolutional neural network (CNN) to detect the most common causes of shoulder pain on plain radiographs and to assess its potential value in serving as an assistive device to physicians. MATERIALS AND METHODS: We used a CNN of the ResNet-50 architecture which was trained on 2700 shoulder radiographs from clinical practice of multiple institutions. All radiographs were reviewed and labeled for six findings: proximal humeral fractures, joint dislocation, periarticular calcification, osteoarthritis, osteosynthesis, and joint endoprosthesis. The trained model was then evaluated on a separate test dataset, which was previously annotated by three independent expert radiologists. Both the training and the test datasets included radiographs of highly variable image quality to reflect the clinical situation and to foster robustness of the CNN. Performance of the model was evaluated using receiver operating characteristic (ROC) curves, the thereof derived AUC as well as sensitivity and specificity. RESULTS: The developed CNN demonstrated a high accuracy with an area under the curve (AUC) of 0.871 for detecting fractures, 0.896 for joint dislocation, 0.945 for osteoarthritis, and 0.800 for periarticular calcifications. It also detected osteosynthesis and endoprosthesis with near perfect accuracy (AUC 0.998 and 1.0, respectively). Sensitivity and specificity were 0.75 and 0.86 for fractures, 0.95 and 0.65 for joint dislocation, 0.90 and 0.86 for osteoarthrosis, and 0.60 and 0.89 for calcification. CONCLUSION: CNNs have the potential to serve as an assistive device by providing clinicians a means to prioritize worklists or providing additional safety in situations of increased workload.

Recent developments of metal-based compounds against fungal pathogens.

This review provides insight into the rapidly expanding field of metal-based antifungal agents. In recent decades, the antibacterial resistance crisis has caused reflection on many aspects of public health where weaknesses in our medicinal arsenal may potentially be present - including in the treatment of fungal infections, particularly in the immunocompromised and those with underlying health conditions where mortality rates can exceed 50%. Combination of organic moieties with known antifungal properties and metal ions can lead to increased bioavailability, uptake and efficacy. Development of such organometallic drugs may alleviate pressure on existing antifungal medications. Prodigious antimicrobial moieties such as azoles, Schiff bases, thiosemicarbazones and others reported herein lend themselves easily to the coordination of a host of metal ions, which can vastly improve the biocidal activity of the parent ligand, thereby extending the library of antifungal drugs available to medical professionals for treatment of an increasing incidence of fungal infections. Overall, this review shows the impressive but somewhat unexploited potential of metal-based compounds to treat fungal infections.

Gender trends in authorships and publication impact in Academic Radiology-a 10-year perspective.

OBJECTIVES: To analyze the development of publication numbers of female authors in high-, medium-, and low-impact radiological journals. METHODS: In this bibliometric analysis, gender of the first (FA) and senior author (SA) was assigned to all original research articles and reviews, published in 10 high-, medium-, and low-impact radiological journals in 2007/8 and 2017/18. The adjusted event rate (AER) and adjusted odds ratio (AOR) were calculated using mixed logistic and multinomial logistic regression models to assess and compare female publications according to impact factor, journal, author position, and combination. RESULTS: The proportion of female FA and female SA in N = 6979 (2007/2008) and N = 7383 (2017/2018) articles increased to 29.1% and 16.1% in 2017/2018, respectively. While most female authorships were continuously observed in medium-impact journals, the strongest increase occurred for both female FA (AOR 2.0; p < .0001) and SA (AOR 2.1; p < .0001) in low-impact journals. Female SA published significantly more often in a low- (AOR 1.5) or medium- (AOR 1.8) than in a high-ranking journal. Among the high-ranking journals, female FA published most frequently in European Radiology (32.4%; 95% CI [29.3-35.8]; p < .0001), female SA in Investigative Radiology (15.9%; 95% CI [13.7-18.4]; p < .0001). Male same-sex authorships decreased (AOR 0.9), but remained at least twice as common as all-female or mixed authorships. CONCLUSION: The increase in female authorship is reflected in all impact areas. Female FA and SA increased most in low-ranking journals but are most common in medium-ranking journals. Female SA remain rare, especially in high impact journals. KEY POINTS: • Compared to the proportion of female radiologists worldwide, female senior authors are underrepresented in all impact areas, in particular in high-impact journals. • Among the included high-ranking radiological journals, female first authors and senior authors were strongest represented in European Radiology and Investigative Radiology, while across all impact areas they mostly published in medium-ranking journals. • Female author combinations were more frequent in low- and medium- than in high-ranking journals, whereas male author combinations remained more common than female senior author collaborations in all impact areas.

A Clinical Practice Guideline for the Use of Ankle-Foot Orthoses and Functional Electrical Stimulation Post-Stroke.

BACKGROUND: Level of ambulation following stroke is a long-term predictor of participation and disability. Decreased lower extremity motor control can impact ambulation and overall mobility. The purpose of this clinical practice guideline (CPG) is to provide evidence to guide clinical decision-making for the use of either ankle-foot orthosis (AFO) or functional electrical stimulation (FES) as an intervention to improve body function and structure, activity, and participation as defined by the International Classification of Functioning, Disability and Health (ICF) for individuals with poststroke hemiplegia with decreased lower extremity motor control. METHODS: A review of literature published through November 2019 was performed across 7 databases for all studies involving stroke and AFO or FES. Data extracted included time post-stroke, participant characteristics, device types, outcomes assessed, and intervention parameters. Outcomes were examined upon initial application and after training. Recommendations were determined on the basis of the strength of the evidence and the potential benefits, harm, risks, or costs of providing AFO or FES. RESULTS/DISCUSSION: One-hundred twenty-two meta-analyses, systematic reviews, randomized controlled trials, and cohort studies were included. Strong evidence exists that AFO and FES can each increase gait speed, mobility, and dynamic balance. Moderate evidence exists that AFO and FES increase quality of life, walking endurance, and muscle activation, and weak evidence exists for improving gait kinematics. AFO or FES should not be used to decrease plantarflexor spasticity. Studies that directly compare AFO and FES do not indicate overall superiority of one over the other. But evidence suggests that AFO may lead to more compensatory effects while FES may lead to more therapeutic effects. Due to the potential for gains at any phase post-stroke, the most appropriate device for an individual may change, and reassessments should be completed to ensure the device is meeting the individual's needs. LIMITATIONS: This CPG cannot address the effects of one type of AFO over another for the majority of outcomes, as studies used a variety of AFO types and rarely differentiated effects. The recommendations also do not address the severity of hemiparesis, and most studies included participants with varied baseline ambulation ability. SUMMARY: This CPG suggests that AFO and FES both lead to improvements post-stroke. Future studies should examine timing of provision, device types, intervention duration and delivery, longer term follow-up, responders versus nonresponders, and individuals with greater impairments. DISCLAIMER: These recommendations are intended as a guide for clinicians to optimize rehabilitation outcomes for people with poststroke hemiplegia who have decreased lower extremity motor control that impacts ambulation and overall mobility.A Video Abstract is available as supplemental digital content from the authors (available at: http://links.lww.com/JNPT/A335).

Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights.

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.