Outcomes After Extent I Thoracoabdominal Aortic Repair: Focus on Heritable Aortic Disease.

BACKGROUND: Crawford extent I thoracoabdominal aortic aneurysm (TAAA) repairs are increasingly performed by an endovascular approach, including in patients with heritable thoracic aortic disease (HTAD). We evaluated outcomes after open extent I TAAA repair in patients with and without HTAD. METHODS: This retrospective study included 992 patients (median age, 67 years; quartile 1-quartile 3, 57-73 years) who underwent extent I TAAA (1990-2022), stratified by the presence of HTAD (n = 177 [17.8%]). Patients with HTAD had genetic aortopathies or presented at age ≤50 years, and 35% (62 of 177) had Marfan syndrome. Logistic regression was used to identify predictors of operative death and adverse event, a composite of operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Long-term outcomes were analyzed with competing risks analysis. RESULTS: Patients with HTAD had lower rates of operative mortality (1.7% vs 7.0%, P = .01) and composite adverse event (2.8% vs 12.3%, P < .001) than non-HTAD patients. Most HTAD patients were discharged home (92.6% vs 76.9%, P < .001). Predictors of operative death were increasing age, aortic dissection, tobacco use, chronic symptoms, and rupture. Predictors for adverse event were increasing age, acute symptoms, chronic dissection, and rupture. Patients with HTAD had substantially better repair-failure-free survival (P < .001). CONCLUSIONS: Open extent I TAAA repair was effective in patients with HTAD, with low operative mortality and adverse event rates, better late survival, and excellent long-term durability, making a compelling argument for preferring open repair in these patients.

The severity of chronic obstructive pulmonary disease is associated with adverse outcomes after open thoracoabdominal aortic aneurysm repair.

OBJECTIVE: We assessed associations between outcomes after open thoracoabdominal aortic aneurysm (TAAA) repair and preoperative airflow limitation stratified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric classification of chronic obstructive pulmonary disease (COPD) severity. METHODS: Among 2368 open elective TAAA repairs in patients with spirometric data, 1735 patients had COPD and 633 did not. Those with COPD were stratified by preoperative respiratory dysfunction as GOLD 1 (forced expiratory volume in the first second of expiration [FEV1] ≥80% of predicted; n = 228), GOLD 2 (50% ≤ FEV1 < 80% of predicted; n = 1215), GOLD 3 (30% ≤ FEV1 < 50% of predicted; n = 260), or GOLD 4 (FEV1 < 30% of predicted; n = 32). Early outcomes included operative mortality and adverse events (operative death or persistent stroke, spinal cord deficit, or renal failure requiring dialysis); associations of outcomes were determined using logistic regression models. Kaplan-Meier analysis compared late survival by the log-rank test. RESULTS: Pulmonary complications occurred in 38.4% of patients with COPD versus 30.0% without COPD (P < .001). Operative mortality and adverse events were more frequent in patients with COPD than without COPD (7.9% vs 3.8% [P < .001] and 14.9% vs 9.8% [P = .001], respectively). Worsening GOLD severity was independently associated with operative death and adverse event. Survival was poorer in patients with COPD than in those without (61.9% ± 1.2% vs 73.6% ± 1.8% at 5 years; P < .001), particularly in patients with increasing GOLD severity (68.7% ± 3.2% vs 63.7% ± 1.4% vs 51.4% ± 3.2% vs 31.3% ± 8.2% at 5 years; P < .001). CONCLUSIONS: Patients with COPD are at elevated risk for operative death and adverse events. Staging by GOLD severity aids preoperative risk stratification. Patients with airflow limitations may benefit from optimization before TAAA repair.

Can a quality improvement intervention improve person-centred maternity care in Kenya?

Few evidence-based interventions exist to improve person-centred maternity care in low-resource settings. This study aimed to understand whether a quality improvement (QI) intervention could improve person-centred maternity care (PCMC) experiences for women delivering in public health facilities in Kenya. A pre-post design was used to examine changes in PCMC scores across three intervention and matched control facilities at baseline (n = 491) and endline (n = 677). A QI intervention, using the Model for Improvement, was implemented in three public health facilities in Nairobi and Kiambu Counties in Kenya. Difference-in-difference analyses using models that included main effects of both treatment group and survey round was conducted to understand the impact of the intervention on PCMC scores. Findings suggest that intervention facilities' average total PCMC score decreased by 5.3 points post-intervention compared to baseline (95% CI: -8.8, -1.9) and relative to control facilities, holding socio-demographic and facility variables constant. Additionally, the intervention was significantly associated with a 1.8-point decrease in clinical quality index pre-post-intervention (95% CI: -2.9, -0.7), decreased odds of provider visits, and less likelihood to plan to use postpartum family planning. While improving the quality of women's experiences during childbirth is a critical component to ensure comprehensive, high-quality maternity care experiences and outcomes, further research is required to understand which intervention methods may be most appropriate to improve PCMC in resource-constrained settings.

Trauma Team High-Fidelity Simulation Training in a Rural Level III Trauma Center: An Interprofessional Experience.

BACKGROUND: Emergency department trauma resuscitation requires teamwork and high-stakes clinical decision-making. Rural trauma centers with low trauma activation volumes must ensure that resuscitations are efficient and safe. OBJECTIVE: The purpose of this article is to describe the implementation of high-fidelity, interprofessional simulation training to foster trauma teamwork and role identification for trauma team members responding to trauma activations in the emergency department. METHODS: High-fidelity, interprofessional simulation training was developed for members of a rural Level III trauma center. Subject matter experts created trauma scenarios. An embedded participant led the simulations using a guidebook that outlined the scenario and learner objectives. The simulations were implemented from May 2021 through September 2021. RESULTS: Postsimulation survey results identified that participants found training with other professions valuable and that knowledge was gained. CONCLUSION: Interprofessional simulations enhance team communication and skills. Combining interprofessional education with high-fidelity simulation creates a learning environment that optimizes trauma team function.

How to treat type 1b endoleakage-extension, fEVAR, bEVAR, or open repair.

Thoracic endovascular aneurysm repair has been well described in the literature as a treatment for a wide range of thoracic aortic pathologies. As with any intervention, there remains a risk of an unfavorable outcome, including endoleak, a term used to describe unexpected blood flow between the stent-graft and the wall of the excluded aneurysm. Endoleaks cause pressurized enlargement of the aneurysmal sac and may lead to catastrophic outcomes such as rupture and death. Type 1b endoleak represents a distal landing zone that is compromised by retrograde blood flow. Moreover, there is a lack of data on type 1b endoleaks and its management options. With the increase in emerging endovascular techniques and technologies, endoleaks are more frequent. However, the management of endoleaks is not standardized among different centers. The purpose of this article is to provide an overview of type 1b endoleaks after thoracic endovascular aneurysm repair, current management options, and our experience.

Aortic arch repair: lessons learned over three decades at Baylor College of Medicine.

The treatment of complex aortic arch disease continues to be among the most demanding cardiovascular operations, with a considerable risk of death and stroke. Since January 1990, our single-practice service has performed over 3000 repairs of the aortic arch. Our aim was to describe the progression of our technical approach to open aortic arch repair. Our center's surgical technique has evolved considerably over the last three decades. When it comes to initial arterial cannulation, we have shifted away from femoral artery cannulation to innominate and axillary artery cannulation. During difficult repairs, this transition has made it easier to use antegrade cerebral perfusion rather than retrograde cerebral perfusion, which was commonly used in the early days. Brain protection tactics during open aortic arch procedures have evolved from profound (≤14 °C) hypothermia during circulatory arrest to moderate (22-24 °C) hypothermia. Aortic arch repair is performed through a median sternotomy and may treat acute aortic dissection, chronic aortic dissection, or degenerative aneurysm. Reoperative repair - that necessitating redo sternotomy - is common in patients undergoing aortic arch repair. The majority of repairs will include varying portions of the ascending aorta and may involve the aortic valve or the aortic root. In some patients, repair may extend into the proximal descending thoracic aorta; this includes elephant trunk, frozen elephant trunk, and antegrade hybrid approaches.

HIV RGB: Automated Single-Cell Analysis of HIV-1 Rev-Dependent RNA Nuclear Export and Translation Using Image Processing in KNIME.

Single-cell imaging has emerged as a powerful means to study viral replication dynamics and identify sites of virus−host interactions. Multivariate aspects of viral replication cycles yield challenges inherent to handling large, complex imaging datasets. Herein, we describe the design and implementation of an automated, imaging-based strategy, "Human Immunodeficiency Virus Red-Green-Blue" (HIV RGB), for deriving comprehensive single-cell measurements of HIV-1 unspliced (US) RNA nuclear export, translation, and bulk changes to viral RNA and protein (HIV-1 Rev and Gag) subcellular distribution over time. Differentially tagged fluorescent viral RNA and protein species are recorded using multicolor long-term (>24 h) time-lapse video microscopy, followed by image processing using a new open-source computational imaging workflow dubbed "Nuclear Ring Segmentation Analysis and Tracking" (NR-SAT) based on ImageJ plugins that have been integrated into the Konstanz Information Miner (KNIME) analytics platform. We describe a typical HIV RGB experimental setup, detail the image acquisition and NR-SAT workflow accompanied by a step-by-step tutorial, and demonstrate a use case wherein we test the effects of perturbing subcellular localization of the Rev protein, which is essential for viral US RNA nuclear export, on the kinetics of HIV-1 late-stage gene regulation. Collectively, HIV RGB represents a powerful platform for single-cell studies of HIV-1 post-transcriptional RNA regulation. Moreover, we discuss how similar NR-SAT-based design principles and open-source tools might be readily adapted to study a broad range of dynamic viral or cellular processes.

Person-centered maternity care and postnatal health: associations with maternal and newborn health outcomes.

BACKGROUND: Limited evidence exists on how women's experiences of care, specifically person-centered maternity care during childbirth, influence maternal and newborn health outcomes. OBJECTIVE: This study aimed to examine the associations between person-centered maternity care and maternal and newborn health outcomes. STUDY DESIGN: Longitudinal data were collected with 1014 women who completed baseline at a health facility and followed up at 2 weeks and 10 weeks after birth. A validated 30-item person-centered maternity care scale was administered to postpartum women within 48 hours after childbirth. The person-centered maternity care scale has 3 subscales: dignity and respect, communication and autonomy, and supportive care. Bivariate and multivariable log Poisson regressions were used to examine the relationship between person-centered maternity care and reported maternal complications, newborn complications, postpartum depression, postpartum family planning uptake, exclusive breastfeeding, and newborn immunizations. RESULTS: Controlling for demographic characteristics, women with high total person-centered maternity care score at baseline had significantly lower risk of reporting maternal complications (adjusted relative risk, 0.63; 95% confidence interval, 0.42-0.95), screening positive for depression (adjusted relative risk, 0.55; 95% confidence interval, 0.38-0.81), and reporting newborn complications (adjusted relative risk, 0.74; 95% confidence interval, 0.56-0.97), respectively, than women with low total person-centered maternity care scores. Women with high scores on the supportive care subscale had significantly lower risk of reporting maternal and newborn complications than women with low scores on these subscales (adjusted relative risk, 0.52 [95% confidence interval, 0.42-0.65] and 0.74 [95% confidence interval, 0.60-0.91], respectively). Significant associations were found between all 3 subscale scores and screening positive for depression. Women with high total person-centered maternity care scores were also more likely to adopt a family planning method than those with low scores (adjusted relative risk, 1.25; 95% confidence interval, 1.02-1.52). In particular, women with high scores on the communication and autonomy subscale had significantly higher odds of adopting a family planning method than women with low scores (risk ratio, 1.15; 95% confidence interval, 1.08-1.23). CONCLUSION: Improving person-centered maternity care may improve maternal and newborn health outcomes. Specifically, improving supportive care may decrease the risk of maternal and newborn complications, whereas improving communication and autonomy may increase postpartum family planning uptake.

Blueprint for cancer research: Critical gaps and opportunities.

We are experiencing a revolution in cancer. Advances in screening, targeted and immune therapies, big data, computational methodologies, and significant new knowledge of cancer biology are transforming the ways in which we prevent, detect, diagnose, treat, and survive cancer. These advances are enabling durable progress in the goal to achieve personalized cancer care. Despite these gains, more work is needed to develop better tools and strategies to limit cancer as a major health concern. One persistent gap is the inconsistent coordination among researchers and caregivers to implement evidence-based programs that rely on a fuller understanding of the molecular, cellular, and systems biology mechanisms underpinning different types of cancer. Here, the authors integrate conversations with over 90 leading cancer experts to highlight current challenges, encourage a robust and diverse national research portfolio, and capture timely opportunities to advance evidence-based approaches for all patients with cancer and for all communities.

Heart Watch Study: protocol for a pragmatic randomised controlled trial.

INTRODUCTION: Personal digital devices that provide health information, such as the Apple Watch, have developed an increasing array of cardiopulmonary tracking features which have received regulatory clearance and are directly marketed to consumers. Despite their widespread and increasing use, data about the impact of personal digital device use on patient-reported outcomes and healthcare utilisation are sparse. Among a population of patients with atrial fibrillation and/or atrial flutter undergoing cardioversion, our primary aim is to determine the impact of the heart rate measurement, irregular rhythm notification, and ECG features of the Apple Watch on quality of life and healthcare utilisation. METHODS AND ANALYSIS: We are conducting a prospective, open-label multicentre pragmatic randomised clinical trial, leveraging a unique patient-centred health data sharing platform for enrolment and follow-up. A total of 150 patients undergoing cardioversion for atrial fibrillation or atrial flutter will be randomised 1:1 to receive the Apple Watch Series 6 or Withings Move at the time of cardioversion. The primary outcome is the difference in the Atrial Fibrillation Effect on QualiTy-of-life global score at 6 months postcardioversion. Secondary outcomes include inpatient and outpatient healthcare utilisation. Additional secondary outcomes include a comparison of the Apple Watch ECG and pulse oximeter features with gold-standard data obtained in routine clinical care settings. ETHICS AND DISSEMINATION: The Institutional Review Boards at Yale University, Mayo Clinic, and Duke University Health System have approved the trial protocol. This trial will provide important data to policymakers, clinicians and patients about the impact of the heart rate, irregular rhythm notification, and ECG features of widely used personal digital devices on patient quality of life and healthcare utilisation. Findings will be disseminated to study participants, at professional society meetings and in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04468321.

Attribution of Adverse Events Following Coronary Stent Placement Identified Using Administrative Claims Data.

Background More than 600 000 coronary stents are implanted during percutaneous coronary interventions (PCIs) annually in the United States. Because no real-world surveillance system exists to monitor their long-term safety, claims data are often used for this purpose. The extent to which adverse events identified with claims data can be reasonably attributed to a specific medical device is uncertain. Methods and Results We used deterministic matching to link the NCDR (National Cardiovascular Data Registry) CathPCI Registry to Medicare fee-for-service claims for patients aged ≥65 years who underwent PCI with drug-eluting stents (DESs) between July 1, 2009 and December 31, 2013. We identified subsequent PCIs within 1 year of the index procedure in Medicare claims as potential safety events. We linked these subsequent PCIs back to the NCDR CathPCI Registry to ascertain how often the revascularization could be reasonably attributed to the same coronary artery as the index PCI (ie, target vessel revascularization). Of 415 306 DES placements in 368 194 patients, 33 174 repeat PCIs were identified in Medicare claims within 1 year. Of these, 28 632 (86.3%) could be linked back to the NCDR CathPCI Registry; 16 942 (51.1% of repeat PCIs) were target vessel revascularizations. Of these, 8544 (50.4%) were within a previously placed DES: 7652 for in-stent restenosis and 1341 for stent thrombosis. Of 16 176 patients with a claim for acute myocardial infarction in the follow-up period, 4446 (27.5%) were attributed to the same coronary artery in which the DES was implanted during the index PCI (ie, target vessel myocardial infarction). Of 24 288 patients whose death was identified in claims data, 278 (1.1%) were attributed to the same coronary artery in which the DES was implanted during the index PCI. Conclusions Most repeat PCIs following DES stent implantation identified in longitudinal claims data could be linked to real-world registry data, but only half could be reasonably attributed to the same coronary artery as the index procedure. Attribution among those with acute myocardial infarction or who died was even less frequent. Safety signals identified using claims data alone will require more in-depth examination to accurately assess stent safety.

Measurement of Retinal Microvascular Blood Velocity Using Erythrocyte Mediated Velocimetry.

Changes in retinal blood flow may be involved in the pathogenesis of glaucoma and other ocular diseases. Erythrocyte mediated velocimetry (EMV) is a novel technique where indocyanine green (ICG) dye is sequestered in erythrocyte ghosts and autologously re-injected to allow direct visualization of erythrocytes for in vivo measurement of speed. The purpose of this study is to determine the mean erythrocyte speed in the retinal microvasculature, as well as the intravisit and intervisit variability of EMV. Data from 23 EMV sessions from control, glaucoma suspect, and glaucoma patients were included in this study. In arteries with an average diameter of 43.11 µm ± 6.62 µm, the mean speed was 7.17 mm/s ± 2.35 mm/s. In veins with an average diameter of 45.87 µm ± 12.04 µm, the mean speed was 6.05 mm/s ± 1.96 mm/s. Intravisit variability, as measured by the mean coefficient of variation, was 3.57% (range 0.44-9.68%). Intervisit variability was 4.85% (range 0.15-8.43%). EMV may represent reliable method for determination of retinal blood speed, potentially allowing insights into the effects of pharmacologic agents or pathogenesis of ocular diseases.

Can machine learning complement traditional medical device surveillance? A case study of dual-chamber implantable cardioverter-defibrillators.

BACKGROUND: Machine learning methods may complement traditional analytic methods for medical device surveillance. METHODS AND RESULTS: Using data from the National Cardiovascular Data Registry for implantable cardioverter-defibrillators (ICDs) linked to Medicare administrative claims for longitudinal follow-up, we applied three statistical approaches to safety-signal detection for commonly used dual-chamber ICDs that used two propensity score (PS) models: one specified by subject-matter experts (PS-SME), and the other one by machine learning-based selection (PS-ML). The first approach used PS-SME and cumulative incidence (time-to-event), the second approach used PS-SME and cumulative risk (Data Extraction and Longitudinal Trend Analysis [DELTA]), and the third approach used PS-ML and cumulative risk (embedded feature selection). Safety-signal surveillance was conducted for eleven dual-chamber ICD models implanted at least 2,000 times over 3 years. Between 2006 and 2010, there were 71,948 Medicare fee-for-service beneficiaries who received dual-chamber ICDs. Cumulative device-specific unadjusted 3-year event rates varied for three surveyed safety signals: death from any cause, 12.8%-20.9%; nonfatal ICD-related adverse events, 19.3%-26.3%; and death from any cause or nonfatal ICD-related adverse event, 27.1%-37.6%. Agreement among safety signals detected/not detected between the time-to-event and DELTA approaches was 90.9% (360 of 396, k=0.068), between the time-to-event and embedded feature-selection approaches was 91.7% (363 of 396, k=-0.028), and between the DELTA and embedded feature selection approaches was 88.1% (349 of 396, k=-0.042). CONCLUSION: Three statistical approaches, including one machine learning method, identified important safety signals, but without exact agreement. Ensemble methods may be needed to detect all safety signals for further evaluation during medical device surveillance.

Physician and Staff Acceptance of Care Managers in Primary Care Offices.

INTRODUCTION: Embedded care managers are increasingly implemented as part of the care team within primary care practices, yet previous studies have indicated variability in acceptance by physicians and staff. This study assesses the acceptability of care managers among staff and physicians within the Michigan Primary Care Transformation (MiPCT) demonstration. METHODS: Care manager acceptance was measured using a web-based survey distributed to practices participating in the MiPCT demonstration. RESULTS: Both physicians and staff reported high levels of care manager acceptance. Longer length of care manager employment at the practice, higher care manager FTE dedicated to care management, and care manager employed by practice were all significantly associated with care manager acceptance. DISCUSSION: The MiPCT demonstration found high care manager acceptance across all care team members. The high level of acceptance may be due to the structures and processes developed by MiPCT to support implementation of care managers and the length of the intervention period. CONCLUSION: The MiPCT demonstration confirms that following three years of implementation, embedded care managers are acceptable to both physicians and staff within primary care practices. Importantly, embeddedness, or the amount of time care managers are located within practices, is associated with increased acceptance.

Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. IMPORTANCE: HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide, thereby biasing its trafficking to and retention within the nucleus. Targeted pharmacological disruption of Rev-Rev interactions should perturb multiple Rev activities, both Rev-RNA binding and Rev's trafficking to the nucleus in the first place.

Diverse activities of viral cis-acting RNA regulatory elements revealed using multicolor, long-term, single-cell imaging.

Cis-acting RNA structural elements govern crucial aspects of viral gene expression. How these structures and other posttranscriptional signals affect RNA trafficking and translation in the context of single cells is poorly understood. Herein we describe a multicolor, long-term (>24 h) imaging strategy for measuring integrated aspects of viral RNA regulatory control in individual cells. We apply this strategy to demonstrate differential mRNA trafficking behaviors governed by RNA elements derived from three retroviruses (HIV-1, murine leukemia virus, and Mason-Pfizer monkey virus), two hepadnaviruses (hepatitis B virus and woodchuck hepatitis virus), and an intron-retaining transcript encoded by the cellular NXF1 gene. Striking behaviors include "burst" RNA nuclear export dynamics regulated by HIV-1's Rev response element and the viral Rev protein; transient aggregations of RNAs into discrete foci at or near the nuclear membrane triggered by multiple elements; and a novel, pulsiform RNA export activity regulated by the hepadnaviral posttranscriptional regulatory element. We incorporate single-cell tracking and a data-mining algorithm into our approach to obtain RNA element-specific, high-resolution gene expression signatures. Together these imaging assays constitute a tractable, systems-based platform for studying otherwise difficult to access spatiotemporal features of viral and cellular gene regulation.

Human iNKT Cells Promote Protective Inflammation by Inducing Oscillating Purinergic Signaling in Monocyte-Derived DCs.

Invariant natural killer T (iNKT) cells are innate T lymphocytes that promote host defense against a variety of microbial pathogens. Whether microbial ligands are required for their protective effects remains unclear. Here, we show that iNKT cells stimulate human-monocyte-derived dendritic cells (DCs) to produce inflammatory mediators in a manner that does not require the presence of microbial compounds. Interleukin 2 (IL-2)-exposed iNKT cells selectively induced repeated cytoplasmic Ca(2+) fluxes in DCs that were dependent on signaling by the P2X7 purinergic receptor and mediated by ATP released during iNKT-DC interactions. Exposure to iNKT cells led to DC cyclooxygenase 2 (PTGS2) gene transcription, and release of PGE2 that was associated with vascular permeabilization in vivo. Additionally, soluble factors were released that induced neutrophil recruitment and activation and enhanced control of Candida albicans. These results suggest that sterile interactions between iNKT cells and monocyte-derived DCs lead to the production of non-redundant inflammatory mediators that promote neutrophil responses.

Effect of acceleration and deceleration distance on the walking speed of people with chronic stroke.

OBJECTIVE: To examine the effect of acceleration and deceleration distance (0, 1, 2 and 3 m) on the comfortable and maximum walking speeds in: (i) the 5-m walk test (5mWT); and (ii) the 10-m walk test (10mWT) in people with chronic stroke. DESIGN: Cross-sectional study. SETTING: University-based rehabilitation centre. SUBJECTS: Thirty individuals with chronic stroke. METHODS: Timed walking at comfortable and maximum walking speeds in the 5mWT and 10mWT with different acceleration and deceleration distances (0, 1, 2 and 3 m). RESULTS: The comfortable walking speed in the 5mWT with 0 m acceleration and deceleration distance was significantly slower than that with 1, 2 or 3 m acceleration and deceleration distances (p < 0.0083), but there was no significant difference among 1, 2 and 3 m acceleration and deceleration distances. No significant difference was found in the maximum walking speed in the 5mWT, or in the comfortable and maximum walking speeds of the 10mWT. CONCLUSION: Adoption of 1 m acceleration and deceleration distance is recommended when measuring the comfortable walking speed in the 5mWT in people with stroke. Neither acceleration nor deceleration distance is needed when measuring the maximum walking speed in the 5mWT, the comfortable walking speed or the maximum walking speed in the 10mWT.

HIV-1 and M-PMV RNA Nuclear Export Elements Program Viral Genomes for Distinct Cytoplasmic Trafficking Behaviors.

Retroviruses encode cis-acting RNA nuclear export elements that override nuclear retention of intron-containing viral mRNAs including the full-length, unspliced genomic RNAs (gRNAs) packaged into assembling virions. The HIV-1 Rev-response element (RRE) recruits the cellular nuclear export receptor CRM1 (also known as exportin-1/XPO1) using the viral protein Rev, while simple retroviruses encode constitutive transport elements (CTEs) that directly recruit components of the NXF1(Tap)/NXT1(p15) mRNA nuclear export machinery. How gRNA nuclear export is linked to trafficking machineries in the cytoplasm upstream of virus particle assembly is unknown. Here we used long-term (>24 h), multicolor live cell imaging to directly visualize HIV-1 gRNA nuclear export, translation, cytoplasmic trafficking, and virus particle production in single cells. We show that the HIV-1 RRE regulates unique, en masse, Rev- and CRM1-dependent "burst-like" transitions of mRNAs from the nucleus to flood the cytoplasm in a non-localized fashion. By contrast, the CTE derived from Mason-Pfizer monkey virus (M-PMV) links gRNAs to microtubules in the cytoplasm, driving them to cluster markedly to the centrosome that forms the pericentriolar core of the microtubule-organizing center (MTOC). Adding each export element to selected heterologous mRNAs was sufficient to confer each distinct export behavior, as was directing Rev/CRM1 or NXF1/NXT1 transport modules to mRNAs using a site-specific RNA tethering strategy. Moreover, multiple CTEs per transcript enhanced MTOC targeting, suggesting that a cooperative mechanism links NXF1/NXT1 to microtubules. Combined, these results reveal striking, unexpected features of retroviral gRNA nucleocytoplasmic transport and demonstrate roles for mRNA export elements that extend beyond nuclear pores to impact gRNA distribution in the cytoplasm.