Collagen organization and structure in FLBN5-/- mice using label-free microscopy: implications for pelvic organ prolapse.

Pelvic organ prolapse (POP) is a gynecological disorder described by the descent of superior pelvic organs into or out of the vagina as a consequence of disrupted muscles and tissue. A thorough understanding of the etiology of POP is limited by the availability of clinically relevant samples, restricting longitudinal POP studies on soft-tissue biomechanics and structure to POP-induced models such as fibulin-5 knockout (FBLN5-/-) mice. Despite being a principal constituent in the extracellular matrix, little is known about structural perturbations to collagen networks in the FBLN5-/- mouse cervix. We identify significantly different collagen network populations in normal and prolapsed cervical cross-sections using two label-free, nonlinear microscopy techniques. Collagen in the prolapsed mouse cervix tends to be more isotropic, and displays reduced alignment persistence via 2-D Fourier Transform analysis of images acquired using second harmonic generation microscopy. Furthermore, coherent Raman hyperspectral imaging revealed elevated disorder in the secondary structure of collagen in prolapsed tissues. Our results underscore the need for in situ multimodal monitoring of collagen organization to improve POP predictive capabilities.

Pregnancy-induced remodeling of the murine reproductive tract: a longitudinal in vivo magnetic resonance imaging study.

Mammalian pregnancy requires gradual yet extreme remodeling of the reproductive organs to support the growth of the embryos and their birth. After delivery, the reproductive organs return to their non-pregnant state. As pregnancy has traditionally been understudied, there are many unknowns pertaining to the mechanisms behind this remarkable remodeling and repair process which, when not successful, can lead to pregnancy-related complications such as maternal trauma, pre-term birth, and pelvic floor disorders. This study presents the first longitudinal imaging data that focuses on revealing anatomical alterations of the vagina, cervix, and uterine horns during pregnancy and postpartum using the mouse model. By utilizing advanced magnetic resonance imaging (MRI) technology, T1-weighted and T2-weighted images of the reproductive organs of three mice in their in vivo environment were collected at five time points: non-pregnant, mid-pregnant (gestation day: 9-10), late pregnant (gestation day: 16-17), postpartum (24-72 h after delivery) and three weeks postpartum. Measurements of the vagina, cervix, and uterine horns were taken by analyzing MRI segmentations of these organs. The cross-sectional diameter, length, and volume of the vagina increased in late pregnancy and then returned to non-pregnant values three weeks after delivery. The cross-sectional diameter of the cervix decreased at mid-pregnancy before increasing in late pregnancy. The volume of the cervix peaked at late pregnancy before shortening by 24-72 h postpartum. As expected, the uterus increased in cross-sectional diameter, length, and volume during pregnancy. The uterine horns decreased in size postpartum, ultimately returning to their average non-pregnant size three weeks postpartum. The newly developed methods for acquiring longitudinal in vivo MRI scans of the murine reproductive system can be extended to future studies that evaluate functional and morphological alterations of this system due to pathologies, interventions, and treatments.

Remodeling of murine vaginal smooth muscle function with reproductive age and elastic fiber disruption.

Advanced maternal age during pregnancy is associated with increased risk of vaginal tearing during delivery and maladaptive postpartum healing. Although the underlying mechanisms of age-related vaginal injuries are not fully elucidated, changes in vaginal microstructure may contribute. Smooth muscle cells promote the contractile nature of the vagina and contribute to pelvic floor stability. While menopause is associated with decreased vaginal smooth muscle content, whether contractile changes occur before the onset of menopause remains unknown. Therefore, the first objective of this study was to quantify the active mechanical behavior of the murine vagina with age. Further, aging is associated with decreased vaginal elastin content. As such, the second objective was to determine if elastic fiber disruption alters vaginal contractility. Vaginal samples from mice aged 2-14 months were used in maximum contractility experiments and biaxial extension-inflation protocols. To evaluate the role of elastic fibers with age, half of the vaginal samples were randomly allocated to enzymatic elastic fiber disruption. Contractile potential decreased and vaginal material stiffness increased with age. These age-related changes in smooth muscle function may be due, in part, to changes in microstructural composition or contractile gene expression. Furthermore, elastic fiber disruption had a diminished effect on smooth muscle contractility in older mice. This suggests a decreased functional role of elastic fibers with age. Quantifying the age-dependent mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties provides a first step towards better understanding how age-related changes in vaginal structure may contribute to tissue integrity and healing. STATEMENT OF SIGNIFICANCE: Advanced maternal age at the time of pregnancy is linked to increased risks of vaginal tearing during delivery, postpartum hemorrhaging, and the development of pelvic floor disorders. While the underlying causes of increased vaginal injuries with age and associated pathologies remain unclear, changes in vaginal microstructure, such as elastic fibers and smooth muscle cells, may contribute. Menopause is associated with fragmented elastic fibers and decreased smooth muscle content; however, how reproductive aging affects changes in the vaginal composition and the mechanical properties remains unknown. Quantifying the mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties with age will advance understanding of the potential structural causes of age-related changes to tissue integrity and healing.

Characteristics and Outcomes of Patients Requiring Repeat Intensive Care Unit Consults.

Objective: To better understand the mortality and notable characteristics of patients initially denied intensive care unit (ICU) admission that are later admitted on reconsultation. Patients and Methods: We collected data regarding all adult inpatients (n=3725) who received one or more ICU consults at an academic tertiary care hospital medical center between January 1, 2018 and October 1, 2021. We compared patients who were initially denied ICU admission and later admitted on reconsultation (C2A1, n=144) with those who were admitted after the first consultation (C1A1, n=2286) and those denied at first consult and never later admitted (C1A0, n=1295). Results: Ten percent of patients initially rejected by the ICU were later admitted on reconsultation. There was no significant difference in the adjusted hospital death odds ratios between C1A1 and C2A1 (0.67; 95% CI 0.43-1.01; P=.11). Assessing subgroups of the C2A1 population, we found that 8.2% (n=100) of full code patients were later admitted to the ICU on reconsultation vs 23.2% (n=40) of do not attempt resuscitation patients (P<.001); 7.6% (n=77) of patients initially consulted from the emergency department were later admitted to the ICU on reconsultation vs 15.1% (n=52) of patients initially consulted from an inpatient setting (P<.001). Conclusion: In this cohort, we demonstrated that patients admitted on repeat ICU consultation have no significant difference in mortality compared with equivalent patients admitted after the first consultation. Understanding and further exploring the consequences of these ICU reconsultations is vital to developing optimal critical care triaging practices.

"It's not time for us to sit down yet": how group exercise programs can motivate physical activity and overcome barriers in inactive older adults.

PURPOSE: Physical activity and exercise are critical for older adults' physical and mental health. The purpose of this qualitative study was to richly capture the motivators of and barriers to engaging in physical activity in previously inactive older adults who participated in a three-arm randomized controlled trial (RCT) of eight-week group exercise interventions. METHODS: We conducted a qualitative content analysis of individual interviews with fifteen participants-five from each study arm: strength training, walking, and inactive control. Participants included nine females and six males ranging from 60 to 86 years of age. RESULTS: Key motivators of physical activity included perceived improvements in physical and mental health, positive social influences, observed health deterioration in others, and the desire to spend time with and take care of family members. Barriers to physical activity included existing health conditions, fear of getting hurt, negative social influences, perceived lack of time and motivation, inconvenient times and locations, and monetary cost. CONCLUSIONS: Our findings add to the body of literature identifying factors that motivate and stand in the way of older adults' engagement in physical activity. These factors influence older adults' self-efficacy and should be incorporated into the design of new and existing programs to encourage initiation and maintenance of physical activity.

Smooth muscle contribution to vaginal viscoelastic response.

Smooth muscle cells contribute to the mechanical function of various soft tissues, however, their contribution to the viscoelastic response when subjected to multiaxial loading remains unknown. The vagina is a fibromuscular viscoelastic organ that is exposed to prolonged and increased pressures with daily activities and physiologic processes such as vaginal birth. The vagina changes in geometry over time under prolonged pressure, known as creep. Vaginal smooth muscle cells may contribute to creep. This may be critical for the function of vaginal and other soft tissues that experience fluctuations in their biomechanical environment. Therefore, the objective of this study was to develop methods to evaluate the contribution of smooth muscle to vaginal creep under multiaxial loading using extension - inflation tests. The vaginas from wildtype mice (C57BL/6 × 129SvEv; 3-6 months; n = 10) were stimulated with various concentrations of potassium chloride then subjected to the measured in vivo pressure (7 mmHg) for 100 s. In a different cohort of mice (n = 5), the vagina was stimulated with a single concentration of potassium chloride then subjected to 5 and 15 mmHg. A laser micrometer measured vaginal outer diameter in real-time. Immunofluorescence evaluated the expression of alpha-smooth muscle actin and myosin heavy chain in the vaginal muscularis (n = 6). When smooth muscle contraction was activated, vaginal creep behavior increased compared to the relaxed state. However, increased pressure decreased the active creep response. This study demonstrated that extension - inflation protocols can be used to evaluate smooth muscle contribution to the viscoelastic response of tubular soft tissues.

Results from a type two hybrid-effectiveness study to implement a preoperative anemia and iron deficiency screening, evaluation, and management pathway.

BACKGROUND: Implementation of pathways to screen surgical patients for preoperative anemia and iron deficiency remains limited. This study sought to measure the impact of a theoretically informed, bespoke change package on improving the uptake of a Preoperative Anemia and Iron Deficiency Screening, Evaluation, and Management Pathway. STUDY DESIGN AND METHODS: Pre-post interventional study using a type two hybrid-effectiveness design evaluated implementation. Four hundred (400) patient medical record reviews provided the dataset (200 pre- and 200-post implementation). The primary outcome measure was compliance with the pathway. Secondary outcome measures (clinical outcomes) were anemia on day of surgery, exposure to a red blood cell (RBC) transfusion, and hospital length of stay. Validated surveys facilitated data collection of implementation measures. Propensity score-adjusted analyses determined the effect of the intervention on clinical outcomes, and a cost analysis determined the economic impact. RESULTS: For the primary outcome, compliance improved significantly post-implementation (Odds Ratio 10.6 [95% CI 4.4-25.5] p < .000). In secondary outcomes, adjusted analyses point estimates showed clinical outcomes were slightly improved for anemia on day of surgery (Odds Ratio 0.792 [95% CI 0.5-1.3] p = .32), RBC transfusion (Odds Ratio 0.86 [95% CI 0.41-1.78] p = .69) and hospital length of stay (Hazard Ratio 0.96 [95% CI 0.77-1.18] p = .67), although these were not statistically significant. Cost savings of $13,340 per patient were realized. Implementation outcomes were favorable for acceptability, appropriateness, and feasibility. CONCLUSION: The change package significantly improved compliance. The absence of a statistically significant change in clinical outcomes may be because the study was powered to detect an improvement in compliance only. Further prospective studies with larger samples are needed. Cost savings of $13,340 per patient were achieved and the change package was viewed favorably.

Considerations and complexities of accurate PTSD assessment among transgender and gender diverse adults.

Posttraumatic stress disorder (PTSD) assessment among transgender and gender diverse (TGD) adults is complex because the literature offers little guidance on affirming assessment that accurately captures both trauma- and discrimination-related distress. This study aimed to characterize threats to precise PTSD assessment that arose during the Clinician-Administered PTSD Scale for the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (CAPS-5). Our sample (N = 44) included trans women (38%), trans men (25%), nonbinary people (23%), and other TGD identities (14%). Participants were mostly White (75%), non-Latinx (82%), educated (91% at least some college), with a mean age of 37 years (SD = 15.5). Demographic and CAPS-5 scoring data as well as content analysis of audio-recorded CAPS-5 interviews are reported. All participants reported trauma exposure, and nearly half met PTSD diagnostic criteria (49%). Interpersonal assault was a common trauma type linked to posttraumatic symptoms (77%); 41% were sexual assaults; and 41% were discrimination-based (e.g., linked to gender identity) physical or sexual assaults. Qualitative findings suggest how and when discrimination-related experiences may threaten PTSD assessment accuracy, leading to overpathologizing or underdetection of symptoms, for example, (a) initial selection of a noncriterion A discrimination event as "worst event," (b) linking symptoms to internalized transphobia (rather than trauma), and (c) linking victimization to gender identity/expression. Threats to PTSD assessment were more common when symptoms were linked to discrimination-based traumatic events, suggesting the importance of understanding contextual factors of index events. We offer a framework for understanding unique challenges to the assessment of PTSD among TGD people and provide recommendations for improving assessment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Older adults who resistance train improve physical function and adopt long-term exercise habits despite COVID-19 restrictions.

Exercise interventions targeting older adults often focus on acute changes, but lasting improvements require the adoption of long-term, independent exercise habits. This study aimed to assess the influence of eight-weeks of resistance training (SSSH) on clinically relevant fall-risk indicators in older adults and to evaluate if SSSH participation altered independent exercise engagement 12 months later. Sixty adults aged 50 yrs+ were randomised into SSSH, Walk, or Control groups and completed questionnaires and muscle strength and flexibility tests pre/post 8 weeks. SSSH and Walk met 2x/wk for 60 min. Twelve months later 24 participants also completed a follow-up survey amid COVID-19 restrictions. Eight-week group changes were analysed using one-way ANOVA with Bonferroni post hoc analyses, and survey responses were compared using paired t-tests with a Bonferroni correction. SSSH demonstrated greater absolute changes over 8 weeks in sleep quality, activity engagement, 30-second-sit-to-stand and upper-body flexibility than Walk or Controls (p < 0.05). Twelve months later, SSSH participants reported significantly increasing independent resistance (+68), aerobic (+125) and flexibility (+26) training minutes per week (all p < 0.01). In conclusion, SSSH reduced fall risk in 8 weeks and sparked older adults to begin and sustain positive exercise habits 12 months later, despite COVID-19 restrictions.

Trans-Stent FFR Gradient as a Modifiable Integrant in Predicting Long-Term Target Vessel Failure.

BACKGROUND: Fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) is associated with long-term outcomes. Data relating FFR-based trans-stent gradient (TSG) after PCI to long-term outcomes are sparse. OBJECTIVES: The aim of this study was to test whether TSG is associated with adverse events at follow-up after PCI. METHODS: Data were gathered from a prospective registry evaluating 501 vessels in 416 patients with median follow-up period of 596 days. Primary endpoints were: 1) target vessel failure (TVF), including target vessel revascularization, and target vessel myocardial infarction after discharge; and 2) major adverse cardiac events (MACE) including TVF, target vessel revascularization, nontarget vessel MI, cardiac death. RESULTS: After PCI, median post-PCI FFR was 0.86 and median TSG was 0.04. TSG >0.04 was associated with increased rates of TVF (8.7% vs 2.9%; P = 0.014) and MACE (17.8% vs 9.2%; P = 0.02). Post-PCI FFR < 0.86 was associated with increased rates of TVF (6.1% vs 2.2%; P = 0.03) and MACE (16.5% vs 10%; P = 0.036). The vessel subgroup with high TSG and low FFR had significantly higher rates of TVF (10.2%; P = 0.02) and MACE (20.1%; P = 0.049) than vessels with: 1) high TSG and high FFR (TVF, 2.9%; MACE, 9.7%); 2) low TSG and low FFR (TVF, 3.8%; MACE, 11.3%); and 3) low TSG high FFR (TVF, 2.2%; MACE, 7.5%). In multivariate analysis, TSG was independently predictive of TVF. CONCLUSIONS: Higher TSG was an independent predictor of adverse events, particularly TVF, and identified a subgroup of patients at higher risk for poor outcomes. The combination of high TSG and low FFR showed significantly worse outcomes compared with an "ideal result" (high FFR and low TSG). These data support a recommendation to use TSG during FFR evaluation to determine the functional success of PCI.

History-Dependent Deformations of Rat Vaginas under Inflation.

The vagina is a highly inhomogeneous, anisotropic, and viscoelastic organ that undergoes significant deformations in vivo. The mechanical attributes of this organ facilitate important physiological functions during menstruation, intercourse, and birthing. Despite the crucial mechanical role that the vagina plays within the female reproductive system, the deformations that the organ can sustain over time under constant pressure, in both the longitudinal direction (LD) and circumferential direction (CD), have not been fully characterized. This experimental study focuses on quantifying the creep properties of the vagina via ex vivo inflation testing using the rat as animal model. Toward this end, rat vaginas were subjected to three consecutively increasing constant luminal pressures (28 kPa, 55 kPa, and 83 kPa) using a custom-built experimental setup and the resulting inhomogeneous deformations were measured using the digital image correlation (DIC) method. The vagina was found to deform significantly more in the CD than the LD at any constant pressure, suggesting that the organ primarily adapts to constant pressures by significantly changing the diameter rather that the length. The change in deformation over time (i.e., creep) was significantly higher during the 1st inflation test at a constant pressure of 28 kPa than over the 2nd and 3rd inflation tests at constant pressures of 55 kPa and 83 kPa, respectively. The findings of this study on the mechanical behavior of the vagina could serve to advance our limited knowledge about the physiology and pathophysiology of this important reproductive organ.

Sex differences in vascular aging and impact of GPER deletion.

Aging is a nonmodifiable risk factor for cardiovascular disease associated with arterial stiffening and endothelial dysfunction. We hypothesized that sex differences exist in vascular aging processes and would be attenuated by global deletion of the G protein-coupled estrogen receptor. Blood pressure was measured by tail-cuff plethysmography, pulse wave velocity (PWV) and echocardiography were assessed with high-resolution ultrasound, and small vessel reactivity was measured using wire myography in adult (25 wk) and middle-aged (57 wk) male and female mice. Adult female mice displayed lower blood pressure and PWV, but this sex difference was absent in middle-aged mice. Aging significantly increased PWV but not blood pressure in both sexes. Adult female carotids were more distensible than males, but this sex difference was lost during aging. Acetylcholine-induced relaxation was greater in female than male mice at both ages, and only males showed aging-induced changes in cardiac hypertrophy and function. GPER deletion removed the sex difference in PWV and ex vivo stiffness in adult mice. The sex difference in blood pressure was absent in KO mice and was associated with endothelial dysfunction in females. These findings indicate that the impact of aging on arterial stiffening and endothelial function is not the same in male and female mice. Moreover, nongenomic estrogen signaling through GPER impacted vascular phenotype differently in male and female mice. Delineating sex differences in vascular changes during healthy aging is an important first step in improving early detection and sex-specific treatments in our aging population.NEW & NOTEWORTHY Indices of vascular aging were different in male and female mice. Sex differences in pulse wave velocity, blood pressure, and large artery stiffness were abrogated in middle-aged mice, but the female advantage in resistance artery vasodilator function was maintained. GPER deletion abrogated these sex differences and significantly reduced endothelial function in adult female mice. Additional studies are needed to characterize sex differences in vascular aging to personalize early detection and treatment for vascular diseases.

Smartphone-Guided Self-prone Positioning vs Usual Care in Nonintubated Hospital Ward Patients With COVID-19: A Pragmatic Randomized Clinical Trial.

BACKGROUND: Safe, effective, and easily implementable treatments that reduce the progression of respiratory failure in COVID-19 are urgently needed. Despite the increased adoption of prone positioning during the pandemic, the effectiveness of this technique on progression of respiratory failure among nonintubated patients is unclear. RESEARCH QUESTION: What is the effectiveness of smartphone-guided self-prone positioning recommendations and instructions compared with usual care in reducing progression of respiratory failure among nonintubated patients with COVID-19? STUDY DESIGN AND METHODS: Awake Prone Position for Early Hypoxemia in COVID-19 (APPEX-19) is a multicenter randomized clinical trial that randomized nonintubated adults with COVID-19 on < 6 L/min of supplemental oxygen to receive a smartphone-guided self-prone positioning intervention or usual care. The primary outcome was the composite of respiratory deterioration (an increase in supplemental oxygen requirement) or ICU transfer. Using a Bayesian statistical approach, the posterior probability of superiority within each treatment arm (superiority threshold 95%) was calculated. RESULTS: The trial was stopped early for slow enrollment. A total of 293 participants were included in the modified intention-to-treat analysis (159 self-prone positioning intervention and 134 usual care). Among participants who self-reported body positioning (n = 139 [70 intervention, 69 usual care]), 71.4% in the intervention arm and 59.4% in the usual care arm attempted prone positioning. Thirty-one participants (posterior mean, 24.7%; 95% credible interval, 18.6-31.4) receiving usual care and 32 participants (posterior mean, 22.1%; 95% credible interval, 16.6-28.1) receiving the self-prone positioning intervention experienced the primary outcome; the posterior probability of superiority for the self-prone positioning intervention was 72.1%, less than the 95% threshold for superiority. Adverse events occurred in 26.9% of participants in the usual care arm and in 11.9% of participants in the intervention arm. INTERPRETATION: Among nonintubated patients with COVID-19, smartphone-guided self-prone positioning recommendations and instructions did not promote strong adherence to prone positioning. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT04344587; URL: www. CLINICALTRIALS: gov.

Biaxial Murine Vaginal Remodeling With Reproductive Aging.

Higher reproductive age is associated with an increased risk of gestational diabetes, pre-eclampsia, and severe vaginal tearing during delivery. Further, menopause is associated with vaginal stiffening. However, the mechanical properties of the vagina during reproductive aging before the onset of menopause are unknown. Therefore, the first objective of this study was to quantify the biaxial mechanical properties of the nulliparous murine vagina with reproductive aging. Menopause is further associated with a decrease in elastic fiber content, which may contribute to vaginal stiffening. Hence, our second objective was to determine the effect of elastic fiber disruption on the biaxial vaginal mechanical properties. To accomplish this, vaginal samples from CD-1 mice aged 2-14 months underwent extension-inflation testing protocols (n = 64 total; n = 16/age group). Then, half of the samples were randomly allocated to undergo elastic fiber fragmentation via elastase digestion (n = 32 total; 8/age group) to evaluate the role of elastic fibers. The material stiffness increased with reproductive age in both the circumferential and axial directions within the control and elastase-treated vaginas. The vagina demonstrated anisotropic mechanical behavior, and anisotropy increased with age. In summary, vaginal remodeling with reproductive age included increased direction-dependent material stiffness, which further increased following elastic fiber disruption. Further work is needed to quantify vaginal remodeling during pregnancy and postpartum with reproductive aging to better understand how age-related vaginal remodeling may contribute to an increased risk of vaginal tearing.

Derivation and validation of Pd/Pa in the assessment of residual ischemia post-intervention: A prospective all-comer registry.

BACKGROUND: Measurement of post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) demonstrates residual ischemia in a large percentage of cases deemed angiographically successful which, in turn, has been associated with worse long-term outcomes. It has recently been shown that a resting pressure index, Pd/Pa, has prognostic value post stenting, however, its diagnostic value relative to FFR post-PCI has not been evaluated. METHODS: The diagnostic accuracy of Pd/Pa in identifying ischemia (FFR≤0.80) pre- and post-PCI was evaluated. Three patient subsets were analyzed. A reference pre-PCI cohort of 1,255 patients (1,560 vessels) was used to measure the accuracy of pre-PCI Pd/Pa vs. FFR. A derivation post-PCI group of 574 patient (664 vessels) was then used to calculate the diagnostic accuracy of post-PCI Pd/Pa vs. FFR. A final prospective validation cohort of 230 patients (255 vessels) was used to test and validate the diagnostic performance of post-PCI Pd/Pa. RESULTS: Median Pd/Pa and FFR were 0.90 (IQR 0.90-0.98) and 0.80 (IQR 0.71-0.88) in the reference pre-PCI model, 0.96 (IQR 0.93-1.00) and 0.87 (IQR 0.77-0.90) in the post-PCI derivation model, and 0.94 (IQR 0.89-0.97) and 0.84 (IQR 0.77-0.90) in the post-PCI validation model respectively. There was a strong linear correlation between Pd/Pa and FFR in all three models (p < 0.0001). Using ROC analysis, the optimal Pd/Pa cutoff value to predict a FFR ≤ 0.80 was ≤0.92 (AUC 0.87) in the pre-PCI model, ≤0.93 (AUC 0.85) in the post-PCI derivation model, and ≤ 0.90 (AUC 0.91) in the post-PCI validation model. Using a hybrid strategy of post-PCI Pd/Pa and post-PCI FFR when necessary (25% patients), overall diagnostic accuracy was improved to 95%. CONCLUSIONS: Pd/Pa has excellent diagnostic accuracy for identifying ischemia post-intervention. Using a hybrid strategy of post-PCI Pd/Pa first, and FFR afterwards, if required, adenosine administration can be avoided in over 75% of physiologic assessments post intervention.

Preparing and Leading Nurses to Complete an Organizational Assessment.

The ability to perform an organizational assessment is a valuable skill for nurses to have as we continue to equip nurses to lead in organizations. Organizational assessments are used to assess an organization before any change. This column discusses how to prepare and lead nurses to perform an organizational assessment. [J Contin Educ Nurs. 2021;52(12):550-553.].

Human adipose-derived stromal/stem cells expressing doublecortin improve cartilage repair in rabbits and monkeys.

Localized cartilage lesions in early osteoarthritis and acute joint injuries are usually treated surgically to restore function and relieve pain. However, a persistent clinical challenge remains in how to repair the cartilage lesions. We expressed doublecortin (DCX) in human adipose-derived stromal/stem cells (hASCs) and engineered hASCs into cartilage tissues using an in vitro 96-well pellet culture system. The cartilage tissue constructs with and without DCX expression were implanted in the knee cartilage defects of rabbits (n = 42) and monkeys (n = 12). Cohorts of animals were euthanized at 6, 12, and 24 months after surgery to evaluate the cartilage repair outcomes. We found that DCX expression in hASCs increased expression of growth differentiation factor 5 (GDF5) and matrilin 2 in the engineered cartilage tissues. The cartilage tissues with DCX expression significantly enhanced cartilage repair as assessed macroscopically and histologically at 6, 12, and 24 months after implantation in the rabbits and 24 months after implantation in the monkeys, compared to the cartilage tissues without DCX expression. These findings suggest that hASCs expressing DCX may be engineered into cartilage tissues that can be used to treat localized cartilage lesions.