Single-Cell Profiling Reveals Immune Aberrations in Progressive Idiopathic Pulmonary Fibrosis.

RATIONALE: Changes in peripheral blood cell populations have been observed but not detailed at single-cell resolution in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To provide an atlas of the changes in the peripheral immune system in stable and progressive IPF. METHODS: Peripheral blood mononuclear cells (PBMCs) from IPF patients and controls were profiled using 10x Chromium 5' single-cell RNA sequencing (scRNA-seq). Flow cytometry was used for validation. Protein concentrations of Regulatory T-cells (Tregs) and Monocytes chemoattractants were measured in plasma and lung homogenates from patients and controls. MEASUREMENTS AND MAIN RESULTS: Thirty-eight PBMC samples from 25 patients with IPF and 13 matched controls yielded 149,564 cells that segregated into 23 subpopulations. Classical monocytes were increased in progressive and stable IPF compared to controls (32.1%, 25.2%, 17.9%, respectively, p<0.05). Total lymphocytes were decreased in IPF vs controls, and in progressive vs stable IPF (52.6% vs 62.6%, p=0.035). Tregs were increased in progressive vs stable IPF (1.8% vs 1.1% of all PBMC, p=0.007), although not different than controls, and may be associated with decreased survival (P=0.009 in Kaplan-Meier analysis; P=0.069 after adjusting for age, sex, and baseline FVC). Flow cytometry analysis confirmed this finding in an independent cohort of IPF patients. Fraction of Tregs out of all T cells was also increased in two cohorts of lung scRNA-seq. CCL22 and CCL18, ligands for CCR4 and CCR8 Treg chemotaxis receptors, were increased in IPF. CONCLUSIONS: The single-cell atlas of the peripheral immune system in IPF, reveals an outcome-predictive increase in classical monocytes and Tregs, as well as evidence for a lung-blood immune recruitment axis involving CCL7 (for classical monocytes) and CCL18/CCL22 (for Tregs).

Single Cell Analysis Reveals Novel Immune Perturbations in Fibrotic Hypersensitivity Pneumonitis.

Rationale: Fibrotic hypersensitivity pneumonitis is a debilitating interstitial lung disease driven by incompletely understood immune mechanisms. Objectives: To elucidate immune aberrations in fibrotic hypersensitivity pneumonitis in single-cell resolution. Methods: Single-cell 5' RNA sequencing was conducted on peripheral blood mononuclear cells and bronchoalveolar lavage cells obtained from 45 patients with fibrotic hypersensitivity pneumonitis, 63 idiopathic pulmonary fibrosis, 4 non-fibrotic hypersensitivity pneumonitis, and 36 healthy controls in the United States and Mexico. Analyses included differential gene expression (Seurat), transcription factor activity imputation (DoRothEA-VIPER), and trajectory analyses (Monocle3/Velocyto-scVelo-CellRank). Measurements and Main Results: Overall, 501,534 peripheral blood mononuclear cells from 110 patients and controls and 88,336 bronchoalveolar lavage cells from 19 patients were profiled. Compared to controls, fibrotic hypersensitivity pneumonitis has elevated classical monocytes (adjusted-p=2.5e-3) and are enriched in CCL3hi/CCL4hi and S100Ahi classical monocytes (adjusted-p<2.2e-16). Trajectory analyses demonstrate that S100Ahi classical monocytes differentiate into SPP1hi lung macrophages associated with fibrosis. Compared to both controls and idiopathic pulmonary fibrosis, fibrotic hypersensitivity pneumonitis patient cells are significantly enriched in GZMhi cytotoxic T cells. These cells exhibit transcription factor activities indicative of TGFß and TNFα/NFκB pathways. These results are publicly available at https://ildimmunecellatlas.org. Conclusions: Single-cell transcriptomics of fibrotic hypersensitivity pneumonitis patients uncovered novel immune perturbations, including previously undescribed increases in GZMhi cytotoxic CD4+ and CD8+ T cells - reflecting this disease's unique inflammatory T-cell driven nature - as well as increased S100Ahi and CCL3hi/CCL4hi classical monocytes also observed in idiopathic pulmonary fibrosis. Both cell populations may guide the development of new biomarkers and therapeutic interventions.

Mast-cell expressed membrane protein-1 is expressed in classical monocytes and alveolar macrophages in idiopathic pulmonary fibrosis and regulates cell chemotaxis, adhesion, and migration in a TGFß-dependent manner.

Mast-cell expressed membrane protein-1 (MCEMP1) is higher in patients with idiopathic pulmonary fibrosis (IPF) with an increased risk of death. Here we aimed to establish the mechanistic role of MCEMP1 in pulmonary fibrosis. We identified increased MCEMP1 expression in classical monocytes and alveolar macrophages in IPF compared with controls. MCEMP1 is upregulated by transforming growth factor beta (TGFß) at the mRNA and protein levels in monocytic leukemia THP-1 cells. TGFß-mediated MCEMP1 upregulation results from the cooperation of SMAD3 and SP1 via concomitant binding to SMAD3/SP1 cis-regulatory elements within the MCEMP1 promoter. We also found that MCEMP1 regulates TGFß-mediated monocyte chemotaxis, adhesion, and migration. Our results suggest that MCEMP1 may regulate the migration and transition of monocytes to monocyte-derived alveolar macrophages during pulmonary fibrosis development and progression.NEW & NOTEWORTHY MCEMP1 is highly expressed in circulating classical monocytes and alveolar macrophages in IPF, is regulated by TGFß, and participates in the chemotaxis, adhesion, and migration of circulating monocytes by modulating the effect of TGFß in RHO activity.

Prior fragility fractures are associated with a higher risk of 8-year complications following total shoulder arthroplasty.

Patients who sustain fragility fractures prior to total shoulder arthroplasty have significantly higher risk for bone health-related complications within 8 years of procedure. Identification of these high-risk patients with an emphasis on preoperative, intraoperative, and postoperative bone health optimization may help minimize these preventable complications. PURPOSE: As the population ages, more patients with osteoporosis are undergoing total shoulder arthroplasty (TSA), including those who have sustained a prior fragility fracture. Sustaining a fragility fracture before TSA has been associated with increased risk of short-term revision rates, periprosthetic fracture (PPF), and secondary fragility fractures but long-term implant survivorship in this patient population is unknown. Therefore, the purpose of this study was to characterize the association of prior fragility fractures with 8-year risks of revision TSA, periprosthetic fracture, and secondary fragility fracture. METHODS: Patients aged 50 years and older who underwent TSA were identified in a large national database. Patients were stratified based on whether they sustained a fragility fracture within 3 years prior to TSA. Patients who had a prior fragility fracture (7631) were matched 1:1 to patients who did not based on age, gender, Charlson Comorbidity Index (CCI), smoking, obesity, diabetes mellitus, and alcohol use. Kaplan-Meier and Cox Proportional Hazards analyses were used to observe the cumulative incidences of all-cause revision, periprosthetic fracture, and secondary fragility fracture within 8 years of index surgery. RESULTS: The 8-year cumulative incidence of revision TSA (5.7% vs. 4.1%), periprosthetic fracture (3.8% vs. 1.4%), and secondary fragility fracture (46.5% vs. 10.1%) were significantly higher for those who had a prior fragility fracture when compared to those who did not. On multivariable analysis, a prior fragility fracture was associated with higher risks of revision (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.24-1.74; p < 0.001), periprosthetic fracture (HR, 2.98; 95% CI, 2.18-4.07; p < 0.001) and secondary fragility fracture (HR, 8.39; 95% CI, 7.62-9.24; p < 0.001). CONCLUSIONS: Prior fragility fracture was a significant risk factor for revision, periprosthetic fracture, and secondary fragility fracture within 8 years of primary TSA. Identification of these high-risk patients with an emphasis on preoperative and postoperative bone health optimization may help minimize these complications. LEVEL OF EVIDENCE: III.

The cost-effectiveness of osteoporosis medications for preventing periprosthetic fractures following femoral neck fracture indicated hip arthroplasty: a break-even analysis.

Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Our study evaluated the economic viability of treatment in patients following arthroplasty and demonstrates that treatment with oral bisphosphonates can be cost-effective in preventing PPF. INTRODUCTION: Osteoporosis treatment following arthroplasty for femoral neck fracture (FNF) is associated with lower rates of periprosthetic fracture (PPF). Although cost-effective in reducing the rate of secondary fragility fracture, the economic viability of osteoporosis treatment in preventing PPF has not been evaluated. Therefore, the purpose of this study is to use a break-even analysis to determine whether and which current osteoporosis medications are cost-effective in preventing PPF following arthroplasty for FNFs. METHODS: Three-year average cost of osteoporosis medication (oral bisphosphonates, estrogen hormonal therapy, intravenous (IV) bisphosphonates, denosumab, teriparatide, and abaloparatide), costs of PPF care, and PPF rates in patients who underwent hip arthroplasty for FNFs without osteoporosis treatment were used to perform a break-even analysis. The absolute risk reduction (ARR) related to osteoporosis treatment and sensitivity analyses were used to evaluate the cost-effectiveness of this intervention and break-even PPF rates. RESULTS: Oral bisphosphonate therapy following arthroplasty for hip fractures would be economically justified if it prevents one out of 56 PPFs (ARR, 1.8%). Given the current cost and incidence of PPF, overall treatment can only be economically viable for PPF prophylaxis if the 3-year costs of these agents are less than $1500. CONCLUSION: The utilization of lower cost osteoporosis medications such as oral bisphosphonates and estrogen hormonal therapy as PPF prophylaxis in this patient population would be economically viable if they reduce the PPF rate by 1.8% and 1.5%, respectively. For IV bisphosphonates and newer agents to be economically viable as PPF prophylaxis in the USA, their costs need to be significantly reduced.

Increased Coronary Contraction to Thromboxane A2 in Cardiac Surgery Patients With Poorly Controlled Hypertension.

INTRODUCTION: Cardioplegia and cardiopulmonary bypass (CP/CPB) alters coronary arteriolar response to thromboxane A2 (TXA2) in patients undergoing cardiac surgery. Comorbidities, including hypertension (HTN), can further alter coronary vasomotor tone. This study investigates the effects of HTN on coronary arteriolar response to TXA2 pre and post-CP/CPB and cardiac surgery. MATERIALS AND METHODS: Coronary arterioles pre and post-CP/CPB were dissected from atrial tissue samples in patients with no HTN (NH, n = 9), well-controlled HTN (WC, n = 12), or uncontrolled HTN (UC, n = 12). In-vitro coronary microvascular reactivity was examined in the presence of TXA2 analog U46619 (10-9-10-4M). Protein expression of TXA2 receptor in the harvested right atrial tissue samples were measured by immunoblotting. RESULTS: TXA2 analog U46619 induced dose-dependent contractile responses of coronary arterioles in all groups. Pre-CPB contractile responses to U46619 were significantly increased in microvessels in the UC group compared to the NH group (P < 0.05). The pre-CP/CPB contractile responses of coronary arterioles were significantly diminished post-CP/CPB among the three groups (P < 0.05), but there remained an increased contractile response in the microvessels of the UC group compared to the WC and NH groups (P < 0.05). There were no significant differences in U46619-induced vasomotor tone between patients in the NH and WC groups (P > 0.05). There were no differences in expression of TXA2R among groups. CONCLUSIONS: Poorly controlled HTN is associated with increased contractile response of coronary arterioles to TXA2. This alteration may contribute to worsened recovery of coronary microvascular function in patients with poorly controlled HTN after CP/CPB and cardiac surgery.

The Definition of Anemia Matters When Using Preoperative Hemoglobin as a Screening Tool Prior to Total Hip and Knee Arthroplasty.

BACKGROUND: Preoperative anemia is common in patients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA). Several definitions of anemia have been described, with no clear consensus on the optimal one for preoperative screening. We hypothesized that depending on the definition used preoperatively, the proportion of anemic patients identified who would require a postoperative allogeneic blood transfusion would vary significantly. METHODS: A total of 681,141 patients were identified in a national database who underwent either THA or TKA. Preoperative anemia was classified according to the World Health Organization (WHO) definition, Cleveland Clinic (CC) definition, or race, age, and sex-specific definition described by Beutler et al in 2006. The optimal preoperative (OP) hemoglobin thresholds to predict perioperative transfusions were also calculated using receiver operating characteristic curves. RESULTS: When using the WHO definition, 18% of anemic patients required a transfusion versus 14% (OP definition), 12% (CC definition), and 16% (Beutler definition). Similarly, 0.69% of anemic patients sustained a periprosthetic joint infection within 30 days using the WHO definition versus 0.59% (OP definition), 0.60% (CC definition), or 0.66% (Beutler definition). Using the WHO definition, 5.3% of patients would have sustained a major complication versus 4.5% (OP definition), 4.4% (CC definition), and 5.0% (Beutler definition). CONCLUSIONS: Variation in the definition of anemia for preoperative screening in THA and TKA results in substantial differences in discriminative ability to predict perioperative transfusions. The WHO definition identified the largest proportion of patients who ultimately received a perioperative transfusion.

The Creation of Data-Driven Preoperative Hemoglobin A1c and Same-Day Glucose Strata to Stratify Complication Risk Following Total Hip Arthroplasty.

BACKGROUND: This study identifies data-driven strata for preoperative Hemoglobin A1c (HbA1c) and same-day glucose levels that maximize differences in the likelihood of complications following total hip arthroplasty (THA). METHODS: Patients who underwent THA from 2013 to 2022 were identified using a national database. In total, 18,728 patients were identified with a mean age of 67 years (range, 18 to 80). Stratum specific likelihood ratio (SSLR) analysis determined separate strata for HbA1c and same-day glucose levels that minimized the likelihood of 90-day complications following THA. Each stratum was propensity-score matched based on age, sex, hypertension, heart failure, chronic obstructive pulmonary disease, and obesity to the lowest respective stratum. The risk ratio (RR) with respect to the lowest matched stratum was observed. RESULTS: Our SSLR analysis identified 3 data-driven HbA1c strata (4.5 to 5.9, 6.0 to 6.9, and 7.0+) and two same-day glucose strata (60 to 189 and 190+) that predicted 90-day major complications. For HbA1c, when compared to the lowest strata (4.5 to 5.9), the risk of 90-day major complications sequentially increased as the HbA1c strata increased: 6.0 to 6.9 (RR: 1.21; P = .041), 7+ (RR: 1.82; P < .001). For same-day glucose, when compared to the matched lowest strata (60 to 189), the risk of 90-day major complications was higher for the 190+ strata (RR: 1.5; P < .001). CONCLUSIONS: Our results support the use of multiple HbA1c strata that can be incorporated into preoperative risk-stratification models. Additionally, we identified a single cut-off level of 190 as a maximum target blood glucose level perioperatively.

Trends in Extended Oral Antibiotic Prophylaxis Utilization Following Primary and Revision Total Hip Arthroplasty From 2010 to 2022.

BACKGROUND: In patients considered high-risk for infection, extended oral antibiotic (EOA) prophylaxis has been demonstrated to reduce rates of prosthetic joint infection following total hip arthroplasty (THA). Although national guidelines regarding their use have not yet been created, the increase in literature surrounding EOA prophylaxis suggests a potential change in practice patterns. The purpose of this study was to investigate the trends in utilization of EOA prophylaxis following THA from 2010 to 2022 and identify prescription patterns. METHODS: A total of 646,059 primary THA and 51,879 aseptic revision THA patients were included in this study. Patients who underwent primary or aseptic revision THA between 2010 and 2022 were identified in a national administrative claims database. Rates and duration of EOA prescriptions were calculated. A secondary analysis examined rates of utilization across demographics, including patients considered high risk for infection. RESULTS: From 2010 to 2022, utilization of EOA increased by 366% and 298% following primary and revision THA, respectively. Of patients prescribed postoperative antibiotics, 30% and 59% were prescribed antibiotics for more than 7 days following primary and revision THA, respectively. Rates of utilization were similar between high-risk individuals and the general population. CONCLUSIONS: Rates of utilization of EOA prophylaxis after THA have increased significantly since 2010. As current trends demonstrate a wide variation in prescription patterns, including in length of antibiotic duration and in patient population prescribed, guidelines surrounding the use of EOA prophylaxis after THA are necessary to promote antibiotic stewardship while preventing rates of periprosthetic joint infection.

Patients Who Have Prior Solid Organ Transplants Have Increased Risk of 10-Year Periprosthetic Joint Infection Revision Following Primary Total Knee Arthroplasty: A Propensity-Matched Analysis.

BACKGROUND: Total knee arthroplasty (TKA) for solid organ transplant (SOT) patients is becoming more prominent as life expectancy in this population increases. However, data on long-term (10 year) implant survivorship in this cohort are sparse. The purpose of this study was to compare 90-day, 2-year, 5-year, and 10-year implant survivability following primary TKA in patients who did and did not have prior SOT. METHODS: The PearlDiver database was utilized to query patients who underwent unilateral elective TKA with at least 2 years of active follow-up. These patients were stratified into those who had a SOT before TKA and those who did not. The SOT cohort was propensity-matched to control patients based on age, sex, Charlson Comorbidity Index, and obesity in a 1:2 ratio. Cumulative incidence rates and hazard ratios (HRs) were compared between the SOT, matched, and unmatched cohorts. RESULTS: No difference was observed in 10-year cumulative incidence and risk of all-cause revision surgery in TKA patients with prior SOT when compared to matched and unmatched controls. Compared to the matched control, the SOT cohort had no difference in the risk of revision when stratified by indication and timing. However, when compared to the unmatched control, patients who had prior SOT had a higher risk for revision due to periprosthetic joint infection at 10 years (HR: 1.80; 95% confidence interval: 1.17 to 2.76) as well as all-cause revision within 90 days after TKA (HR: 1.93; 95% confidence interval: 1.10 to 3.36). CONCLUSIONS: Prior SOT patients have higher rates of all-cause revision within 90 days and periprosthetic joint infection within 10 years when compared to the general population, likely associated with the elevated number of comorbidities in SOT patients and not the transplant itself. Therefore, these patients should be monitored in the preoperative and early postoperative settings to optimize their known comorbidities.

Longitudinal Associations Between Neighborhood Child Opportunity and Physical Fitness for New York City Public School Youth.

Neighborhood environments can support fitness-promoting behavior, yet little is known about their influence on youth physical fitness outcomes over time. We examined longitudinal associations between neighborhood opportunity and youth physical fitness among New York City (NYC) public school youth. The Child Opportunity Index (COI), a composite index of 29 indicators measuring neighborhood opportunity at the census-tract level, along with scores on 4 selected COI indicators were linked to NYC FITNESSGRAM youth data at baseline. Fitness outcomes (measured annually, 2011-2018) included body mass index, curl-ups, push-ups, and Progressive Aerobic Cardiovascular Endurance Run (PACER) laps. Unstratified and age-stratified, adjusted, 3-level generalized linear mixed models, nested by census tract and time, estimated the association between COI and fitness outcomes. The analytical sample (n = 204,939) lived in very low (41%) or low (30%) opportunity neighborhoods. Unstratified models indicated that overall COI is modestly associated with improved youth physical fitness outcomes. The strongest opportunity-fitness associations were observed for PACER. Stratified models show differences in associations across younger vs. older youth. We find that neighborhood factors are associated with youth fitness outcomes over time, with the strength of the associations dependent on age. Future implications include better informed place-based interventions tailored to specific life stages to promote youth health.

From COVID to fibrosis: lessons from single-cell analyses of the human lung.

The increased resolution of single-cell RNA-sequencing technologies has led to major breakthroughs and improved our understanding of the normal and pathologic conditions of multiple tissues and organs. In the study of parenchymal lung disease, single-cell RNA-sequencing has better delineated known cell populations and identified novel cells and changes in cellular phenotypes and gene expression patterns associated with disease. In this review, we aim to highlight the advances and insights that have been made possible by applying these technologies to two seemingly very different lung diseases: fibrotic interstitial lung diseases, a group of relentlessly progressive lung diseases leading to pulmonary fibrosis, and COVID-19 pneumonia, an acute viral disease with life-threatening complications, including pulmonary fibrosis. We discuss changes in cell populations and gene expression, highlighting potential common features, such as alveolar cell epithelial injury and aberrant repair and monocyte-derived macrophage populations, as well as relevance and implications to mechanisms of disease and future directions.

The Association of Prior Fragility Fractures on 8-Year Periprosthetic Fracture Risk Following Total Hip Arthroplasty.

BACKGROUND: Fragility fractures are often the initial clinical presentation of osteoporosis. Patients who have a history of fragility fractures undergoing total hip arthroplasty (THA) have an increased risk of 2-year postoperative complications. However, the association of recent fragility fractures with complications beyond 2 years following THA remains unknown. The purpose of this study was to characterize the association of prior fragility fractures with 8-year risks of revision THA, periprosthetic fracture (PPF), and secondary fragility fracture. METHODS: Patients aged 50 years and more who underwent THA for osteoarthritis were identified in a large national database. Patients were stratified based on whether they sustained a fragility fracture within 3 years prior to THA. There were 18,529 patients who had a prior fragility fracture and 408,753 who did not have a prior fragility fracture. Demographics and comorbidities were collected. Kaplan-Meier and Cox Proportional Hazards analyses were used to observe the cumulative incidences of all-cause revision, PPF, and secondary fragility fracture within 8 years of index surgery. RESULTS: Patients who had recent fragility fracture had significantly higher risks of revision THA (Hazard Ratio [HR] 1.7; P < .001), PPF (HR 2.2; P < .001), and secondary fragility fracture (HR 4.9; P < .001). CONCLUSION: Prior fragility fracture was shown to be a significant risk factor for revision THA, PPF, and secondary fragility fracture within 8 years of THA. Identification of these high-risk patients with an emphasis on preoperative and postoperative bone health optimization may help minimize these complications.

Diagnostic and Invasive Colonoscopy Are Not Risk Factors for Revision Surgery Due to Periprosthetic Joint Infection.

BACKGROUND: Colonoscopy is routinely performed for colorectal cancer screening in patients who have a preexisting unicompartmental knee arthroplasty (UKA), total knee arthroplasty (TKA), or total hip arthroplasty (THA) prostheses. However, colonoscopy is theorized to provoke transient bacteremia, providing a potential nidus for periprosthetic joint infection. This study aimed to investigate the risk of aseptic and septic revision surgery in patients who underwent diagnostic colonoscopy or invasive colonoscopy within one year following UKA, TKA, or THA. METHODS: A retrospective cohort analysis was performed using a national database. Patients were identified using Current Procedural Terminology. In total, 52,891 patients underwent UKA, 1,049,218 underwent TKA, and 526,296 underwent THA. Data were analyzed with univariate analysis preceding multivariable logistic regressions to investigate outcomes of interest at 2 and 3 years from the index procedure. RESULTS: Diagnostic colonoscopy resulted in no increase in odds of all-cause or septic revision surgery for any prostheses. At both time points, invasive colonoscopy resulted in lower odds of all-cause revision (P < .05) for patients with UKA, decreased odds of septic revision (P < .001) for patients with TKA, and decreased odds of both all-cause and septic revision (P < .05) for patients with THA. CONCLUSION: Our results show that diagnostic colonoscopy was not a significant risk factor for revision following UKA, TKA, or THA. Paradoxically, invasive colonoscopy was protective against revision, even with very minimal use of antibiotic prophylaxis observed. This study addresses the theory that colonoscopy procedures may threaten an existing joint prosthesis via transient bacteremia and shows no increase in revision outcomes following colonoscopy. LEVEL OF EVIDENCE: Level III.

Latent Profile/Class Analysis Identifying Differentiated Intervention Effects.

BACKGROUND: The randomized clinical trial is generally considered the most rigorous study design for evaluating overall intervention effects. Because of patient heterogeneity, subgroup analysis is often used to identify differential intervention effects. In research of behavioral interventions, such subgroups often depend on a latent construct measured by multiple correlated observed variables. OBJECTIVES: The purpose of this article was to illustrate latent class analysis/latent profile analysis as a helpful tool to characterize latent subgroups, conduct exploratory subgroup analysis, and identify potential differential intervention effects using clinical trial data. METHODS: After reviewing different approaches for subgroup analysis, latent class analysis/latent profile analysis was chosen to identify heterogeneous patient groups based on multiple correlated variables. This approach is superior in this specific scenario because of its ability to control Type I error, assess intersection of multiple moderators, and improve interpretability. We used a case study example to illustrate the process of identifying latent classes as potential moderators based on both clinical and perceived risk scores and then tested the differential effects of health coaching in improving health behavior for patients with elevated risk of developing coronary heart disease. RESULTS: We identified three classes based on one clinical risk score and four perceived risk measures for individuals with high risk of developing coronary heart disease. Compared to other classes we assessed, individuals in the class with low clinical risk and low perceived risk benefit most from health coaching to improve their physical activity levels. DISCUSSION: Latent class analysis/latent profile analysis offers a person-centered approach to identifying distinct patient profiles that can be used as moderators for subgroup analysis. This offers tremendous opportunity to identify differential intervention effects in behavioral research.

Surgical strategies for older patients with glioblastoma.

OBJECTIVE: While adjuvant treatment regimens have been modified for older patients with glioblastoma (GBM), surgical strategies have not been tailored. METHODS: Clinical data of 48 consecutive patients aged 70 years or older, who underwent surgical resection for GBM with intraoperative ultrasonography (IoUS) alone or combination with intraoperative MRI (IoMRI) at Yale New Haven Hospital were retrospectively reviewed. Variables were analyzed, and comparative analyses were performed. RESULTS: The addition of IoMRI was not superior to IoUS alone in terms of overall survival (OS) (P = 0.306), Karnofsky Performance Score (KPS) at postoperative 6 weeks (P = 0.704) or extent of resection (P = 0.263). Length of surgery (LOSx), however, was significantly longer (P = 0.0002) in the IoMRI group. LOSx (P = 0.015) and hospital stay (P = 0.025) were predictors of postoperative complications. Increased EOR (GTR or NTR) (P = 0.030), postoperative adjuvant treatment (P < 0.0001) and postoperative complications (P = 0.006) were predictive for OS. Patients with relatively lower preoperative KPS scores (<70) showed significant improvement at postoperative 6 weeks (P<0.0001). Patients with complications (P = 0.038) were more likely to have lower KPS at postoperative 6 weeks. CONCLUSIONS: Aggressive management with surgical resection should be considered in older patients with GBM, even those with relatively poor KPS. The use of ioMRI in this population does not appear to confer any measurable benefit over ioUS in experienced hands, but prolongs the length of surgery significantly, which is a preventable prognostic factor for impeding care.

Inpatient rehabilitation facility discharge destination among younger adults with traumatic brain injury: differences by race and ethnicity.

OBJECTIVE: : To determine the association of race and ethnicity with discharge destination among patients with traumatic brain injury (TBI) receiving inpatient rehabilitation facility (IRF) care. DESIGN: Secondary analysis using Uniform Data System for Medical Rehabilitation data. METHODS: : Patients (N = 99,614) diagnosed with TBI, age 18-64, admitted for IRF care between 2002 and 2018. Logistic regression was used to analyze data. OUTCOME: : Discharge destination (home/community vs. subacute settings). RESULTS: : Most younger adults (age 18-64) with TBI were discharged home (89.24%) after IRF care vs. subacute (10.76%). Of those discharged home, 63.16% were white, 10.42% Black, 8.94% Hispanic/Latino, and 6.72% other races/ethnicities. After adjusting for covariates, patients who were Hispanic/Latino [OR = 1.26; 95% CI: 1.15, 1.37] and other race/ethnicities [OR = 1.10; 95% CI: 1.00, 1.21] (vs. White) had higher odds of discharge home vs. subacute. There was no difference in discharge destination for Black patients (vs. white). Predictors of discharge destination for groups stratified by race/ethnicity varied. CONCLUSIONS: : Younger patients with TBI who were Hispanic/Latino or other races/ethnicities (vs. white) were more likely to go home vs. subacute. Findings can be used to inform IRF planning, resource allocation, and transitional care planning.

Bee pathogen transmission dynamics: deposition, persistence and acquisition on flowers.

Infectious diseases are a primary driver of bee decline worldwide, but limited understanding of how pathogens are transmitted hampers effective management. Flowers have been implicated as hubs of bee disease transmission, but we know little about how interspecific floral variation affects transmission dynamics. Using bumblebees ( Bombus impatiens), a trypanosomatid pathogen ( Crithidia bombi) and three plant species varying in floral morphology, we assessed how host infection and plant species affect pathogen deposition on flowers, and plant species and flower parts impact pathogen survival and acquisition at flowers. We found that host infection with Crithidia increased defaecation rates on flowers, and that bees deposited faeces onto bracts of Lobelia siphilitica and Lythrum salicaria more frequently than onto Monarda didyma bracts . Among flower parts, bracts were associated with the lowest pathogen survival but highest resulting infection intensity in bee hosts. Additionally, we found that Crithidia survival across flower parts was reduced with sun exposure. These results suggest that efficiency of pathogen transmission depends on where deposition occurs and the timing and place of acquisition, which varies among plant species and environmental conditions. This information could be used for development of wildflower mixes that maximize forage while minimizing disease spread.

Environmental aging and degradation of multiwalled carbon nanotube reinforced polypropylene.

The degradation of polypropylene (PP) and PP-multiwalled carbon nanotube (PP-MWCNT) panels during environmental weathering resulted in an increased degree of crystallinity, making them brittle, and creating surface cracks. The degradation led to a breakdown of the panels and increased the potential for nanorelease. Thermal analysis revealed that the thickness of the test panels and reinforcement with MWCNTs had a significant influence on the stability of PP-MWCNT composites. Differential scanning calorimetry indicated that the MWCNTs acted as nucleation points, increasing the crystallization temperatures of PP-MWCNT, which reduced the extent of aging. Weathering decreased both the melting and crystallization temperatures of PP by as much as 20 o C. The reduction in the temperatures was inversely proportional to the thickness of the panels. The activation energy (E a ) obtained using isoconversional kinetics of the TGA analysis showed that the effective thermo-oxidative degradations of PP changed during aging. The E a for the initial stages of thermal degradation decreased from ~330 kJ/mol to ~100 kJ/mol for aged PP. During the late degradation stages, the E a values increased to ~300 kJ/mol. These results suggest that early degradation were altered because of the changes in the molecular structure of the aged P and a shift in the degradation rate-limiting steps.

Mitochondrial Translocator Protein (TSPO) Function Is Not Essential for Heme Biosynthesis.

Function of the mammalian translocator protein (TSPO; previously known as the peripheral benzodiazepine receptor) remains unclear because its presumed role in steroidogenesis and mitochondrial permeability transition established using pharmacological methods has been refuted in recent genetic studies. Protoporphyrin IX (PPIX) is considered a conserved endogenous ligand for TSPO. In bacteria, TSPO was identified to regulate tetrapyrrole metabolism and chemical catalysis of PPIX in the presence of light, and in vertebrates, TSPO function has been linked to porphyrin transport and heme biosynthesis. Positive correlation between high TSPO expression in cancer cells and susceptibility to photodynamic therapy based on their increased ability to convert the precursor 5-aminolevulinic acid (ALA) to PPIX appeared to reinforce this mechanism. In this study, we used TSPO knock-out (Tspo(-/-)) mice, primary cells, and different tumor cell lines to examine the role of TSPO in erythropoiesis, heme levels, PPIX biosynthesis, phototoxic cell death, and mitochondrial bioenergetic homeostasis. In contrast to expectations, our results demonstrate that TSPO deficiency does not adversely affect erythropoiesis, heme biosynthesis, bioconversion of ALA to PPIX, and porphyrin-mediated phototoxic cell death. TSPO expression levels in cancer cells do not correlate with their ability to convert ALA to PPIX. In fibroblasts, we observed that TSPO deficiency decreased the oxygen consumption rate and mitochondrial membrane potential (ΔΨm) indicative of a cellular metabolic shift, without a negative impact on porphyrin biosynthetic capability. Based on these findings, we conclude that mammalian TSPO does not have a critical physiological function related to PPIX and heme biosynthesis.