What are participant beliefs regarding physical therapy led treatment? A qualitative study of people living with femoroacetabular impingement syndrome.

BACKGROUND: Physical therapist-led treatment programs are recommended for patients with femoroacetabular impingement (FAI) syndrome. Views of people with FAI syndrome regarding such interventions are currently unknown, including perceptions of potential barriers and facilitators to participation and adherence to exercise programs. OBJECTIVES: To explore participant perceptions of physical therapist-led programs for FAI syndrome, including barriers and facilitators for accessing physical therapy, and adhering to a rehabilitation program. METHODS: Our qualitative study used semi-structured interviews to explore the perceptions of patients with FAI syndrome undertaking physical therapy-led treatment, where treatment was ceased due to Coronavirus Disease 2019 (COVID-19). The interview topic guide was informed by the Theoretical Domain Framework. Interviews were transcribed verbatim and data categories were developed using inductive thematic analysis. Themes were discussed between researchers until consensus was reached. RESULTS: Fourteen participants (mean age: 30 years) with a range of physical activity backgrounds undertook interviews. We identified four key themes, 1) Patients believed their hip pain was caused by structural damage worsened through exercise; 2) Barriers and facilitators on the feasibility of physical therapist-led programs; 3) Participants held beliefs regarding the importance of adjunct treatments to exercise; and 4) Impact of FAI syndrome on physical activity participation. CONCLUSION: People with FAI syndrome believe they have structural damage which leads to their hip pain and are often afraid to exercise due to fear of causing more damage to their hip. Our findings suggest that people with FAI syndrome want clear education about exercise, imaging, and expectations of cost and duration of treatment.

Facilitation of motor evoked potentials after tetanic peripheral nerve stimulation.

OBJECTIVE: Tetanic stimulation of a peripheral nerve prior to transcranial electrical stimulation (TES) may enhance motor evoked potential (MEP) amplitudes. The purpose of this study was to investigate the post-tetanic MEP (p-MEP) technique in improving MEP amplitudes. METHODS: Conventional TES MEPs (c-MEP) and p-MEPs with left upper limb stimulation (p-MEPUL) or left lower limb stimulation (p-MEPLL) were performed in 26 patients. Bilateral hand and foot MEP amplitudes obtained with each protocol were compared. Subgroup comparisons were performed for myelopathy and peripheral neuropathy patients. Within-subject amplitude differences between c-MEP and each p-MEP technique were compared using a Wilcoxon test. RESULTS: The mean age of the patients was 52.7 years (range, 12-79 years). Overall, p-MEPUL resulted in MEP improvement in 25 of 26 (96%) patients, and p-MEPLL improved MEPs in 19 of 26 (73%) patients. The increase in MEP amplitudes were statistically significant in all muscle groups except left foot. Similar improvements were seen in the myelopathy group; in the neuropathy group, p-MEPUL produced similar results, but p-MEPLL did not. CONCLUSIONS: The p-MEP technique can improve MEP amplitudes, including in patients with myelopathy. In patients with peripheral neuropathy, the results were mixed. SIGNIFICANCE: Tetanic stimulation can enhance intraoperative MEP amplitudes.

Metabolomic Biomarker Signatures for Bipolar and Unipolar Depression.

Importance: Bipolar disorder (BD) is frequently misdiagnosed as major depressive disorder (MDD) because of overlapping symptoms and the lack of objective diagnostic tools. Objective: To identify a reproducible metabolomic biomarker signature in patient dried blood spots (DBSs) that differentiates BD from MDD during depressive episodes and assess its added value when combined with self-reported patient information. Design, Setting, and Participants: This diagnostic analysis used samples and data from the Delta study, conducted in the UK between April 27, 2018, and February 6, 2020. The primary objective was to identify BD in patients with a recent (within the past 5 years) diagnosis of MDD and current depressive symptoms (Patient Health Questionnaire-9 score of 5 or more). Participants were recruited online through voluntary response sampling. The analysis was carried out between February 2022 and July 2023. Main Outcomes and Measures: Patient data were collected using a purpose-built online questionnaire (n = 635 questions). DBS metabolites (n = 630) were analyzed using a targeted mass spectrometry-based platform. Mood disorder diagnoses were established using the Composite International Diagnostic Interview. Results: Of 241 patients in the discovery cohort, 170 (70.5%) were female; 67 (27.8%) were subsequently diagnosed with BD and 174 (72.2%) were confirmed as having MDD; and the mean (SD) age was 28.1 (7.1) years. Of 30 participants in the validation cohort, 16 (53%) were female; 9 (30%) were diagnosed with BD and 21 (70%) with MDD; and the mean (SD) age was 25.4 (6.3) years. DBS metabolite levels were assessed in 241 patients with depressive symptoms with a recent diagnosis of MDD, of whom 67 were subsequently diagnosed with BD by the Composite International Diagnostic Interview and 174 were confirmed as having MDD. The identified 17-biomarker panel provided a mean (SD) cross-validated area under the receiver operating characteristic curve (AUROC) of 0.71 (SD, 0.12; P < .001), with ceramide d18:0/24:1 emerging as the strongest biomarker. Combining biomarker data with patient-reported information significantly enhanced diagnostic performance of models based on extensive demographic data, PHQ-9 scores, and the outcomes from the Mood Disorder Questionnaire. The identified biomarkers were correlated primarily with lifetime manic symptoms and were validated in a separate group of patients who received a new clinical diagnosis of MDD (n = 21) or BD (n = 9) during the study's 1-year follow-up period, with a mean (SD) AUROC of 0.73 (0.06; P < .001). Conclusions and Relevance: This study provides a proof of concept for developing an accessible biomarker test to facilitate the differential diagnosis of BD and MDD and highlights the potential involvement of ceramides in the pathophysiological mechanisms of mood disorders.

Using SUpported Motivational InTerviewing (SUMIT) to increase physical activity for people with knee osteoarthritis: a pilot, feasibility randomised controlled trial.

OBJECTIVE: The objective of this study was to determine the feasibility and effectiveness of using SUpported Motivational InTerviewing (SUMIT) to increase physical activity in people with knee osteoarthritis (KOA). DESIGN: Randomised controlled trial. SETTING: We recruited people who had completed Good Life with osteoArthritis Denmark (GLA:D) from private, public and community settings in Victoria, Australia. INTERVENTIONS: Participants were randomised participants to receive SUMIT or usual care. SUMIT comprised five motivational interviewing sessions targeting physical activity over 10 weeks, and access to a multimedia web-based platform. PARTICIPANTS: Thirty-two participants were recruited (17 SUMIT, 15 control) including 22 females (69%). OUTCOME MEASURES: Feasibility outcomes included recruitment rate, adherence to motivational interviewing, ActivPAL wear and drop-out rate. Effect sizes (ESs) were calculated for daily steps, stepping time, time with cadence >100 steps per minute, time in bouts >1 min; 6 min walk distance, Knee Osteoarthritis Outcome Score (KOOS) subscales (pain, symptoms, function, sport and recreation, and quality of life (QoL)), Euroqual, systolic blood pressure, body mass index, waist circumference, 30 s chair stand test and walking speed during 40 m walk test. RESULTS: All feasibility criteria were achieved, with 32/63 eligible participants recruited over seven months; with all participants adhering to all motivational interviewing calls and achieving sufficient ActivPAL wear time, and only two drop-outs (6%).12/15 outcome measures showed at least a small effect (ES>0.2) favouring the SUMIT group, including daily time with cadence >100 steps per minute (ES=0.43). Two outcomes, walking speed (ES= 0.97) and KOOS QoL (ES=0.81), showed a large effect (ES>0.8). CONCLUSION: SUMIT is feasible in people with knee osteoarthritis. Potential benefits included more time spent walking at moderate intensity, faster walking speeds and better QoL. TRIAL REGISTRATION NUMBER: ACTRN12621000267853.

Association of baseline physical activity participation with participant characteristics and outcomes following education and exercise-therapy in people with knee osteoarthritis: A GLA:D® Australia prospective cohort study.

OBJECTIVES: To investigate whether participants with knee osteoarthritis classified as 'more' or 'less' physically active at baseline differ in characteristics and/or outcomes at baseline and at 3 and 12 months following the commencement of an education and exercise-therapy program. METHODS: Prospective cohort study using the GLA:D® Australia registry. The University of California, Los Angeles Physical Activity Scale (UCLA) participant data dichotomised as 'more' (≥7) or 'less' active (≤6). Groups were compared using chi-square (obesity [baseline only], comorbidity prevalence, medication consumption, fear of damage from physical activity); and linear mixed model regression (12-item Injury Osteoarthritis Outcome Score [KOOS-12], pain [visual analogue scale], health-related quality of life [QoL] [EQ-5D-5L]) statistics, adjusted for age, sex and baseline physical activity at 3 and 12 months. RESULTS: We included 1059 participants (70% female). At baseline, 267 (25%) were classified as 'more' active, increasing to 29% and 30% at 3 and 12 months, respectively. At baseline, compared to the 'less' active group, the 'more' active group had a lower proportion of participants who were obese ('more' = 21% vs. 'less' = 44%), had comorbidities (58% vs. 74%) and consumed medications (71% vs. 85%); lower pain intensity (37 vs. 47); and higher KOOS-12 (59 vs. 50), and health-related QoL (0.738 vs. 0.665) scores. When accounting for age, sex and baseline physical activity, improvements seen in knee-related burden and health-related QoL were not different between groups at 3 or 12 months. Compared to the 'less' active group, the proportion of participants not consuming medication remained higher in the 'more' active group at 3 ('more' 45% vs. 'less' 28%) and 12 months (43% vs. 32%). CONCLUSION: 'More' active people with knee osteoarthritis were less likely to be obese, had fewer comorbidities, lower medication consumption, knee-related burden and pain intensity, and higher health-related QoL than 'less' active participants at all timepoints.

Use of a mixed-methods approach to develop a guidebook with messaging to encourage colorectal cancer screening among Black individuals 45 and older.

INTRODUCTION: Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States and disproportionately impacts Black individuals. Here, we describe the mixed-methods approach used to develop a tailored message guidebook to promote CRC screening among Black individuals in the setting of recently updated screening guidelines. METHODS: This mixed-methods study included 10 in-depth qualitative interviews and 490 surveys in a nationally representative sample of unscreened Black individuals age ≥ 45. Messages were developed based on American Cancer Society (ACS) and National Colorectal Cancer Roundtable (NCCRT) research findings, tested among Black individuals using MaxDiff analytic methods, and reviewed by a multi-sector expert advisory committee of NCCRT members. RESULTS: The most frequently reported screening barrier in all age groups was self-reported procrastination (40.0% in age 45-49, 42.8% for age 50-54, 34.2% for age ≥ 55). Reasons for procrastination varied by age and included financial concerns, COVID-19 concerns, and fear of the test and bowel preparation. Additional screening barriers included lack of symptoms, provider recommendation, and family history of CRC. Most individuals age 45-49 preferred to receive screening information from a healthcare provider (57.5%); however, only 20% reported that a provider had initiated a screening conversation. CONCLUSIONS: We identified age-specific barriers to CRC screening and tailored messaging to motivate participation among unscreened Black people age ≥ 45. Findings informed the development of the NCCRT and ACS guidebook for organizations and institutions aiming to increase CRC screening participation in Black individuals.

Nonpoint source pollution measures in the Clean Water Act have no detectable impact on decadal trends in nutrient concentrations in U.S. inland waters.

The Clean Water Act (CWA) of 1972 regulates water quality in U.S. inland waters under a system of cooperative federalism in which states are delegated implementation and enforcement authority of CWA provisions by the U.S. Environmental Protection Agency. We leveraged heterogeneity in state implementation of the CWA to evaluate the efficacy of its nonpoint source provisions in reducing nutrient pollution, the leading cause of water quality impairment in U.S. inland waters. We used national survey data to estimate changes in nutrient concentrations over a decade and evaluated the effect of state-level policy implementation. We found no evidence to support an effect of (i) grant spending on nonpoint source pollution remediation, (ii) nutrient criteria development, or (iii) water quality monitoring intensity on 10-year trends in nutrient concentrations. These results suggest that the current federal policy paradigm for improving water quality is not creating desired outcomes.

Social complexity, life-history and lineage influence the molecular basis of castes in vespid wasps.

A key mechanistic hypothesis for the evolution of division of labour in social insects is that a shared set of genes co-opted from a common solitary ancestral ground plan (a genetic toolkit for sociality) regulates caste differentiation across levels of social complexity. Using brain transcriptome data from nine species of vespid wasps, we test for overlap in differentially expressed caste genes and use machine learning models to predict castes using different gene sets. We find evidence of a shared genetic toolkit across species representing different levels of social complexity. We also find evidence of additional fine-scale differences in predictive gene sets, functional enrichment and rates of gene evolution that are related to level of social complexity, lineage and of colony founding. These results suggest that the concept of a shared genetic toolkit for sociality may be too simplistic to fully describe the process of the major transition to sociality.

Race, geography, and risk of breast cancer treatment delays: A population-based study 2004-2015.

BACKGROUND: Treatment delays affect breast cancer survival and constitute poor-quality care. Black patients experience more treatment delay, but the relationship of geography to these disparities is poorly understood. METHODS: We studied a population-based, retrospective, observational cohort of patients with breast cancer in North Carolina between 2004 and 2017 from the Cancer Information and Population Health Resource, which links cancer registry and sociodemographic data to multipayer insurance claims. We included patients >18 years with Stage I-III breast cancer who received surgery or chemotherapy as their first treatment. Delay was defined as >60 days from diagnosis to first treatment. Counties were aggregated into nine Area Health Education Center regions. Race was dichotomized as Black versus non-Black. RESULTS: Among 32,626 patients, 6190 (19.0%) were Black. Black patients were more likely to experience treatment delay >60 days (15.0% of Black vs. 8.0% of non-Black). Using race-stratified modified Poisson regression, age-adjusted relative risk of delay in the highest risk region was approximately twice that in the lowest risk region among Black (relative risk, 2.1; 95% CI, 1.6-2.6) and non-Black patients (relative risk, 1.9; 95% CI, 1.5-2.3). Adjustment for clinical and sociodemographic features only slightly attenuated interregion differences. The magnitude of the racial gap in treatment delay varied by region, from 0.0% to 9.4%. CONCLUSIONS: Geographic region was significantly associated with risk of treatment delays for both Black and non-Black patients. The magnitude of racial disparities in treatment delay varied markedly between regions. Future studies should consider both high-risk geographic regions and high-risk patient groups for intervention to prevent delays.

The relative importance of platelet integrins in hemostasis, thrombosis and beyond.

Integrins are heterodimeric transmembrane receptors composed of α and ß chains, with an N-terminal extracellular domain forming a globular head corresponding to the ligand binding site. Integrins regulate various cellular functions including adhesion, migration, proliferation, spreading and apoptosis. On platelets, integrins play a central role in adhesion and aggregation on subendothelial matrix proteins of the vascular wall, thereby ensuring hemostasis. Platelet integrins belong either to the ß1 family (α2ß1, α5ß1 and α6ß1) or to the ß3 family (αIIbß3 and αvß3). On resting platelets, integrins can engage their ligands when the latter are immobilized but not in their soluble form. The effects of various agonists promote an inside-out signal in platelets, increasing the affinity of integrins for their ligands and conveying a modest signal reinforcing platelet activation, called outside-in signaling. This outside-in signal ensures platelet adhesion, shape change, granule secretion and aggregation. In this review, we examine the role of each platelet integrin in hemostatic plug formation, hemostasis and arterial thrombosis and also beyond these classical functions, notably in tumor metastasis and sepsis.

Consumer research priorities for pediatric anesthesia and perioperative medicine.

BACKGROUND: Consumer-driven research is increasingly being prioritized. AIM: Our aim was to partner with consumers to identify the top 10 research priorities for pediatric anesthesia and perioperative medicine. The ACORN (Anesthesia Consumer Research Network) was formed to collaborate with children and families across Australia. METHODS: A prospective online survey was developed to generate research ideas from consumers. The survey was developed in Qualtrics, a survey research platform. Consumers were invited to participate through poster advertising, social media posts, via consumer networks at participating hospitals and in addition 35 national consumer/patient representative organizations were approached. We also conducted a similar idea generating survey for clinicians through email invitation and via Twitter. A second round of surveys was conducted to prioritize the long list of research questions and a shortlist of priorities developed. A single consensus meeting was held, and a final consensus list of top 10 priorities emerged. RESULTS: A total of 281 research ideas were submitted between 356 consumers in the idea generating survey and from four consumer/patient representative groups. Seventy-five clinicians responded to the clinician idea generation survey. This was consolidated into 20 research ideas/themes for the second survey for each group. 566 responses were received to the consumer prioritization top 10 survey and 525 responses to the clinician survey. The consensus meeting produced the final 10 consumer research priorities. CONCLUSION: This study has given Australian consumers the opportunity to shape the anesthesia and perioperative medicine research agenda for pediatric patients both nationally and internationally.

Airborne Lidar Measurements of XCO2 in Synoptically Active Environment and Associated Comparisons With Numerical Simulations.

Frontal boundaries have been shown to cause large changes in CO2 mole-fractions, but clouds and the complex vertical structure of fronts make these gradients difficult to observe. It remains unclear how the column average CO2 dry air mole-fraction (XCO2) changes spatially across fronts, and how well airborne lidar observations, data assimilation systems, and numerical models without assimilation capture XCO2 frontal contrasts (ΔXCO2, i.e., warm minus cold sector average of XCO2). We demonstrated the potential of airborne Multifunctional Fiber Laser Lidar (MFLL) measurements in heterogeneous weather conditions (i.e., frontal environment) to investigate the ΔXCO2 during four seasonal field campaigns of the Atmospheric Carbon and Transport-America (ACT-America) mission. Most frontal cases in summer (winter) reveal higher (lower) XCO2 in the warm (cold) sector than in the cold (warm) sector. During the transitional seasons (spring and fall), no clear signal in ΔXCO2 was observed. Intercomparison among the MFLL, assimilated fields from NASA's Global Modeling and Assimilation Office (GMAO), and simulations from the Weather Research and Forecasting--Chemistry (WRF-Chem) showed that (a) all products had a similar sign of ΔXCO2 though with different levels of agreement in ΔXCO2 magnitudes among seasons; (b) ΔXCO2 in summer decreases with altitude; and (c) significant challenges remain in observing and simulating XCO2 frontal contrasts. A linear regression analyses between ΔXCO2 for MFLL versus GMAO, and MFLL versus WRF-Chem for summer-2016 cases yielded a correlation coefficient of 0.95 and 0.88, respectively. The reported ΔXCO2 variability among four seasons provide guidance to the spatial structures of XCO2 transport errors in models and satellite measurements of XCO2 in synoptically-active weather systems.

Evaluation of Cisplatin-Induced Pathology in the Larval Zebrafish Lateral Line.

Cisplatin is an effective anticancer agent, but also causes permanent hearing loss by damaging hair cells-the sensory receptors essential for hearing. There is an urgent clinical need to protect cochlear hair cells in patients undergoing cisplatin chemotherapy. The zebrafish lateral line organ contains hair cells and has been frequently used in studies to screen for otoprotective compounds. However, these studies have employed a wide range of cisplatin dosages and exposure times. We therefore performed a comprehensive evaluation of cisplatin ototoxicity in the zebrafish lateral line with the goal of producing a standardized, clinically relevant protocol for future studies. To define the dose- and time-response patterns of cisplatin-induced hair-cell death, we treated 6-day-old larvae for 2 h in 50 µM-1 mM cisplatin and allowed them to recover. We observed delayed hair cell death, which peaked at 4-8 h post-exposure. Cisplatin also activated a robust inflammatory response, as determined by macrophage recruitment and phagocytosis of hair cells. However, selective depletion of macrophages did not affect hair cell loss. We also examined the effect of cisplatin treatment on fish behavior and found that cisplatin-induced lateral line injury measurably impaired rheotaxis. Finally, we examined the function of remaining hair cells that appeared resistant to cisplatin treatment. We observed significantly reduced uptake of the cationic dye FM1-43 in these cells relative to untreated controls, indicating that surviving hair cells may be functionally impaired. Cumulatively, these results indicate that relatively brief exposures to cisplatin can produce hair cell damage and delayed hair cell death. Our observations provide guidance on standardizing methods for the use of the zebrafish model in studies of cisplatin ototoxicity.

Low lamin A levels enhance confined cell migration and metastatic capacity in breast cancer.

Aberrations in nuclear size and shape are commonly used to identify cancerous tissue. However, it remains unclear whether the disturbed nuclear structure directly contributes to the cancer pathology or is merely a consequence of other events occurring during tumorigenesis. Here, we show that highly invasive and proliferative breast cancer cells frequently exhibit Akt-driven lower expression of the nuclear envelope proteins lamin A/C, leading to increased nuclear deformability that permits enhanced cell migration through confined environments that mimic interstitial spaces encountered during metastasis. Importantly, increasing lamin A/C expression in highly invasive breast cancer cells reflected gene expression changes characteristic of human breast tumors with higher LMNA expression, and specifically affected pathways related to cell-ECM interactions, cell metabolism, and PI3K/Akt signaling. Further supporting an important role of lamins in breast cancer metastasis, analysis of lamin levels in human breast tumors revealed a significant association between lower lamin A levels, Akt signaling, and decreased disease-free survival. These findings suggest that downregulation of lamin A/C in breast cancer cells may influence both cellular physical properties and biochemical signaling to promote metastatic progression.

Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation.

Autophagy selectively targets cargo for degradation, yet mechanistic understanding remains incomplete. The ATG8-family plays key roles in autophagic cargo recruitment. Here by mapping the proximal interactome of ATG8-paralogs, LC3B and LC3C, we uncover a LC3C-Endocytic-Associated-Pathway (LEAP) that selectively recruits plasma-membrane (PM) cargo to autophagosomes. We show that LC3C localizes to peripheral endosomes and engages proteins that traffic between PM, endosomes and autophagosomes, including the SNARE-VAMP3 and ATG9, a transmembrane protein essential for autophagy. We establish that endocytic LC3C binds cargo internalized from the PM, including the Met receptor tyrosine kinase and transferrin receptor, and is necessary for their recruitment into ATG9 vesicles targeted to sites of autophagosome initiation. Structure-function analysis identified that LC3C-endocytic localization and engagement with PM-cargo requires the extended carboxy-tail unique to LC3C, the TBK1 kinase, and TBK1-phosphosites on LC3C. These findings identify LEAP as an unexpected LC3C-dependent pathway, providing new understanding of selective coupling of PM signalling with autophagic degradation.

Knowledge, confidence and learning needs of physiotherapists treating persistent knee pain in Australia and Canada: a mixed-methods study.

AIM: To determine the knowledge and confidence of physiotherapists in managing knee osteoarthritis (OA) and patellofemoral pain (PFP); and explore their learning behaviors and preferences related to the management of these knee conditions. METHODS: One hundred and sixteen Australian and Canadian Physiotherapists were recruited via social media, e-mail, and an online course. Part 1: Quantitative involved an online survey evaluating knowledge of evidence and confidence in providing treatments for knee OA and PFP. Part 2: Qualitative involved semi-structured interviews with 13 participants exploring current practice and learning needs, that were analyzed using an initial framework structured on interview questions, followed by inductive approach to identify additional themes. RESULTS: Awareness regarding evidence supporting exercise for knee OA and PFP was good (89-96%), and qualitative themes indicated physiotherapists emphasized exercise-therapy and education. Perceived value of passive treatments and surgery varied. Preference for face-to-face workshops to address learning needs, alongside describing time and cost barriers to access them, emerged from qualitative findings. Online learning formats were viewed as convenient, but not as effective as face-to-face learning. CONCLUSION: Knowledge and confidence related to interventions for knee OA and PFP of Australian and Canadian physiotherapist participants broadly aligns with guidelines. Knowledge translation strategies focused on face-to-face workshops, supported by online education may help to bridge evidence-to-practice gaps.

Intervention Strategies and Lessons Learned From a Student-Led Initiative to Support Lactating Women in the University Setting.

The benefits of breastfeeding for mother and baby are strongly supported by research. However, lactating parents who return to school or work soon after delivery face many barriers to continued breastfeeding. This article presents a student-led initiative to support lactation at a large public university that emerged from advocacy efforts of student mothers of color. The socioecological model was used as a framework to understand and address the multifaceted influences on breastfeeding practices. Project activities included providing breastfeeding education to lactating parents and their partners, measuring availability and accessibility of lactation spaces, improving lactation spaces, connecting university stakeholders, and strengthening university lactation policies. The project achieved the following outcomes: formation of a stakeholder group with members across campus departments, improvement in accessibility and appropriateness of lactation spaces, provision of breastfeeding services through workshops and one-on-one appointments with lactation educators, and creation and dissemination of an online toolkit outlining parents' lactation rights and support available on campus. Comprehensive lactation support at universities is essential to enhance educational and professional equity for women and to promote postpartum and infant health. Throughout the project implementation, the team learned many lessons that can help guide similar university initiatives.

Characterization of the Role of Integrin α5ß1 in Platelet Function, Hemostasis, and Experimental Thrombosis.

OBJECTIVE: Integrins are key regulators of various platelet functions. The pathophysiological importance of most platelet integrins has been investigated, with the exception of α5ß1, a receptor for fibronectin. The aim of this study was to characterize the role of α5ß1 in megakaryopoiesis, platelet function, and to determine its importance in hemostasis and arterial thrombosis. APPROACH AND RESULTS: We generated a mouse strain deficient for integrin α5ß1 on megakaryocytes and platelets (PF4Cre-α5-/-). PF4Cre-α5-/- mice were viable, fertile, and presented no apparent signs of abnormality. Megakaryopoiesis appears unaltered as evidence by a normal megakaryocyte morphology and development, which is in agreement with a normal platelet count. Expression of the main platelet receptors and the response of PF4Cre-α5-/- platelets to a series of agonists were all completely normal. Adhesion and aggregation of PF4Cre-α5-/- platelets under shear flow on fibrinogen, laminin, or von Willebrand factor were unimpaired. In contrast, PF4Cre-α5-/- platelets displayed a marked decrease in adhesion, activation, and aggregation on fibrillar cellular fibronectin and collagen. PF4Cre-α5-/- mice presented no defect in a tail-bleeding time assay and no increase in inflammatory bleeding in a reverse passive Arthus model and a lipopolysaccharide pulmonary inflammation model. Finally, no defects were observed in three distinct experimental models of arterial thrombosis based on ferric chloride-induced injury of the carotid artery, mechanical injury of the abdominal aorta, or laser-induced injury of mesenteric vessels. CONCLUSION: In summary, this study shows that platelet integrin α5ß1 is a key receptor for fibrillar cellular fibronectin but is dispensable in hemostasis and arterial thrombosis.

Knee Osteoarthritis Education Interventions in Published Trials Are Typically Unclear, Not Comprehensive Enough, and Lack Robust Development: Ancillary Analysis of a Systematic Review.

OBJECTIVE: To summarize the content, development, and delivery of education interventions in clinical trials for people with knee osteoarthritis (OA). DESIGN: Ancillary analysis of a systematic review. LITERATURE SEARCH: MEDLINE, EMBASE, SPORTDiscus, CINAHL, and Web of Science were searched from inception to April 2020. STUDY SELECTION CRITERIA: Randomized controlled trials involving patient education for people with knee OA. DATA SYNTHESIS: Content of education interventions was matched against a predefined topic list (n = 14) and categorized as accurate and clear, partially accurate/lacks clarity, or not reported. We examined whether education interventions included skill development or stated learning objectives and if they were developed based on theory, previous research, or codesign principles. Delivery methods and mode(s) were also identified. Data were summarized descriptively. RESULTS: Thirty-eight education interventions (30 trials) were included. Interventions lacked comprehensiveness (median topics per intervention = 3/14, range = 0-11). Few topics were accurately and clearly described (10%, 13/136). Sixty-one percent (n = 23/38) of interventions targeted skill development, and 34% (n = 13/38) identified learning objectives. Forty-two percent (n = 16/38) were based on theory; 45% (n = 17/38) were based on research for chronic conditions, including 32% (n = 12/38) based on OA. Eleven percent of interventions (n = 4/38) were codesigned. Education was typically facilitated through face-to-face sessions (median = 9, range = 0-55), supplemented with telephone calls and/or written materials. CONCLUSION: Education interventions for people with knee OA lacked comprehensiveness plus accurate and clear descriptions of topics covered. Most interventions failed to identify learning objectives and were not based on theory, previous research, or codesign principles. J Orthop Sports Phys Ther 2022;52(5):276-286. Epub 14 Dec 2021. doi:10.2519/jospt.2022.10771.

Substantial Intra-Individual Variability in Post-Prandial Time to Peak in Controlled and Free-Living Conditions in Children with Type 1 Diabetes.

The optimal time to bolus insulin for meals is challenging for children and adolescents with type 1 diabetes (T1D). Current guidelines to control glucose excursions do not account for individual differences in glycaemic responses to meals. This study aimed to examine the within- and between-person variability in time to peak (TTP) glycaemic responses after consuming meals under controlled and free-living conditions. Participants aged 8-15 years with T1D ≥ 1 year and using a continuous glucose monitor (CGM) were recruited. Participants consumed a standardised breakfast for six controlled days and maintained their usual daily routine for 14 free-living days. CGM traces were collected after eating. Linear mixed models were used to identify within- and between-person variability in the TTP after each of the controlled breakfasts, free-living breakfasts (FLB), and free-living dinners (FLD) conditions. Thirty participants completed the study (16 females; mean age and standard deviation (SD) 10.5 (1.9)). The TTP variability was greater within a person than the variability between people for all three meal types (between-person vs. within-person SD; controlled breakfast 18.5 vs. 38.9 min; FLB 14.1 vs. 49.6 min; FLD 5.7 vs. 64.5 min). For the first time, the study showed that within-person variability in TTP glycaemic responses is even greater than between-person variability.