Neuronal activation in the geomagnetic responsive region Cluster N covaries with nocturnal migratory restlessness in white-throated sparrows (Zonotrichia albicollis).

Cluster N is a region of the visual forebrain of nocturnally migrating songbirds that supports the geomagnetic compass of nocturnal migrants. Cluster N expresses immediate-early genes (ZENK), indicating neuronal activation. This neuronal activity has only been recorded at night during the migratory season. Night-to-night variation in Cluster N activity in relation to migratory behaviour has not been previously examined. We tested whether Cluster N is activated only when birds are motivated to migrate and presumably engage their magnetic compass. We measured immediate-early gene activation in Cluster N of white-throated sparrows (Zonotrichia albicollis) in three conditions: daytime, nighttime migratory restless and nighttime resting. Birds in the nighttime migratory restlessness group had significantly greater numbers of ZENK-labelled cells in Cluster N compared to both the daytime and the nighttime resting groups. Additionally, the degree of migratory restlessness was positively correlated with the number of ZENK-labelled cells in the nighttime migratory restless group. Our study adds to the number of species observed to have neural activation in Cluster N and demonstrates for the first time that immediate early gene activation in Cluster N is correlated with the amount of active migratory behaviour displayed across sampled individuals. We conclude that Cluster N is facultatively regulated by the motivation to migrate, together with nocturnal activity, rather than obligatorily active during the migration season.

The role of insight, social rank, mindfulness and self-compassion in depression following first episode psychosis.

Gaining awareness of psychosis (i.e., insight) is linked to depression, particularly in the post-acute phase of psychosis. Informed by social rank theory, we examined whether the insight-depression relationship is explained by reduced social rank related to psychosis and whether self-compassion (including uncompassionate self-responding [UCS] and compassionate self-responding [CSR]) and mindfulness buffered the relationship between social rank and depression in individuals with first episode psychosis during the post-acute phase. Participants were 145 young people (Mage  = 20.81; female = 66) with first episode psychosis approaching discharge from an early psychosis intervention centre. Questionnaires and interviews assessed insight, depressive symptoms, perceived social rank, self-compassion, mindfulness and illness severity. Results showed that insight was not significantly associated to depression and thus no mediation analysis was conducted. However, lower perceived social rank was related to higher depression, and this relationship was moderated by self-compassion and, more specifically, UCS. Mindfulness was related to depression but had no moderating effect on social rank and depression. Results supported previous findings that depressive symptoms are common during the post-acute phase. The role of insight in depression for this sample is unclear and may be less important during the post-acute phase than previously considered. Supporting social rank theory, the results suggest that low perceived social rank contributes to depression, and reducing UCS may ameliorate this effect. UCS, social rank and possibly mindfulness may be valuable intervention targets for depression intervention and prevention efforts in the recovery of psychosis.

In vivo dissection of Rhoa function in vascular development using zebrafish.

The small monomeric GTPase RHOA acts as a master regulator of signal transduction cascades by activating effectors of cellular signaling, including the Rho-associated protein kinases ROCK1/2. Previous in vitro cell culture studies suggest that RHOA can regulate many critical aspects of vascular endothelial cell (EC) biology, including focal adhesion, stress fiber formation, and angiogenesis. However, the specific in vivo roles of RHOA during vascular development and homeostasis are still not well understood. In this study, we examine the in vivo functions of RHOA in regulating vascular development and integrity in zebrafish. We use zebrafish RHOA-ortholog (rhoaa) mutants, transgenic embryos expressing wild type, dominant negative, or constitutively active forms of rhoaa in ECs, pharmacological inhibitors of RHOA and ROCK1/2, and Rock1 and Rock2a/b dgRNP-injected zebrafish embryos to study the in vivo consequences of RHOA gain- and loss-of-function in the vascular endothelium. Our findings document roles for RHOA in vascular integrity, developmental angiogenesis, and vascular morphogenesis in vivo, showing that either too much or too little RHOA activity leads to vascular dysfunction.

Neighborhood Composition and Air Pollution in Chicago: Monitoring Inequities With a Dense, Low-Cost Sensing Network, 2021.

Objectives. To evaluate the efficacy of a novel, real-time sensor network for routine monitoring of racial and economic disparities in fine particulate matter (PM2.5; particulate matter ≤ 2.5 µm in diameter) exposures at the neighborhood level. Methods. We deployed a dense network of low-cost PM2.5 sensors in Chicago, Illinois, to evaluate associations between neighborhood-level composition variables (percentage of Black residents, percentage of Hispanic/Latinx residents, and percentage of households below poverty) and interpolated PM2.5. Relationships were assessed in spatial lag models after adjustment for all composition variables. Models were fit with data both from the overall period and during high-pollution episodes associated with social events (July 4, 2021) and wildfires (July 23, 2021). Results. The spatial lag models showed that racial/ethnic composition variables were associated with higher PM2.5 levels. Levels were notably higher in neighborhoods with larger compositions of Hispanic/Latinx residents across the entire study period and notably higher in neighborhoods with larger Black populations during the July 4 episode. Conclusions. As a complement to sparse regulatory networks, dense, low-cost sensor networks can capture spatial variations during short-term air pollution episodes and enable monitoring of neighborhood-level inequities in air pollution exposures in real time. (Am J Public Health. 2022;112(12):1765-1773. https://doi.org/10.2105/AJPH.2022.307068).

IgG and IgM glycosylation patterns in patients undergoing image-guided tumor ablation.

BACKGROUND: Image-guided tumor ablation is a technique whereby needle-like applicators are placed directly into solid tumors under guidance typically with computed tomography or ultrasound. Changes in IgG and IgM antibody glycosylation were studied during ablation-induced immune response to cancer, and the use of glycosylation as a biomarker for diagnosis, prognosis and disease treatment was examined. METHODS: Plasma from 27 tumor patients was collected immediately before, after and for 6 months following ablation. IgG and IgM antibodies were isolated by use high-throughput chromatography, and analyzed by hydrophilic liquid chromatography. Thorough identification of glycan structures in each chromatography peak was performed by nano-liquid chromatography electrospray ionization mass spectrometry. RESULTS: Although antibody glycosylation was found to vary with cancer type, discernable patterns of change based on the successful treatment of tumors by ablation were not identified. One patient with renal clear cell carcinoma and poor disease outcome had unexpectedly high amount of oligomannose IgG glycans during the whole period of monitoring. In contrast, IgM antibodies did not follow the same pattern. CONCLUSIONS: These findings suggest that glycosylation patterns are indicative of an immune system that is unable to prevent different types of cancer, rather than products of the immunostimulatory response to the ablation of tumor itself. Analyses of the outcome effect suggested that IgG glycosylation and IgM glycosylation are not associated with tumor ablation. GENERAL SIGNIFICANCE: Present work opens a new way for parallel determination of glycosylation changes of both IgG and IgM antibodies by use of high-throughput methods, and their future use as biomarkers for disease diagnosis and prognosis. This article is part of a Special Issue entitled "Glycans in personalised medicine" Guest Editor: Professor Gordan Lauc.

Postdischarge Falls and Readmissions: Associations with Insufficient Vision and Low Health Literacy among Hospitalized Seniors.

The role of patient-level risk factors such as insufficient vision has been understudied. Because insufficient vision may interfere with health literacy assessments, the full impact of low health literacy among older patients with impaired vision is unknown. We sought to determine whether senior inpatients' insufficient vision and low health literacy are associated with adverse outcomes postdischarge, specifically falls and readmissions. We conducted an observational study of adult medicine inpatients at an urban hospital. Visual acuity and health literacy were screened at bedside. Outcomes data were collected by telephone 30 days postdischarge. Among 1,900 participants, 1,244 (65%) were reached postdischarge; 44% had insufficient vision and 43% had low health literacy. Insufficient vision was associated with postdischarge falls among participants ≥65 years (adjusted odds ratio [AOR] 3.38, 95% confidence interval [CI] 1.42-8.05), but not among participants <65 years (AOR 1.44, 95% CI 0.89-2.32). Low health literacy was associated with readmissions among participants ≥65 years (AOR 3.15, 95% CI 1.77-5.61), but not among participants <65 years (AOR 0.78, 95% CI 0.56-1.09). The results suggest the need to implement screening for older inpatients' vision and health literacy. Developing effective interventions to reduce these risks is critical given national priorities to reduce falls and readmissions.

Diet-related chronic disease in the northeastern United States: a model-based clustering approach.

BACKGROUND: Obesity and diabetes are global public health concerns. Studies indicate a relationship between socioeconomic, demographic and environmental variables and the spatial patterns of diet-related chronic disease. In this paper, we propose a methodology using model-based clustering and variable selection to predict rates of obesity and diabetes. We test this method through an application in the northeastern United States. METHODS: We use model-based clustering, an unsupervised learning approach, to find latent clusters of similar US counties based on a set of socioeconomic, demographic, and environmental variables chosen through the process of variable selection. We then use Analysis of Variance and Post-hoc Tukey comparisons to examine differences in rates of obesity and diabetes for the clusters from the resulting clustering solution. RESULTS: We find access to supermarkets, median household income, population density and socioeconomic status to be important in clustering the counties of two northeastern states. The results of the cluster analysis can be used to identify two sets of counties with significantly lower rates of diet-related chronic disease than those observed in the other identified clusters. These relatively healthy clusters are distinguished by the large central and large fringe metropolitan areas contained in their component counties. However, the relationship of socio-demographic factors and diet-related chronic disease is more complicated than previous research would suggest. Additionally, we find evidence of low food access in two clusters of counties adjacent to large central and fringe metropolitan areas. While food access has previously been seen as a problem of inner-city or remote rural areas, this study offers preliminary evidence of declining food access in suburban areas. CONCLUSIONS: Model-based clustering with variable selection offers a new approach to the analysis of socioeconomic, demographic, and environmental data for diet-related chronic disease prediction. In a test application to two northeastern states, this method allows us to identify two sets of metropolitan counties with significantly lower diet-related chronic disease rates than those observed in most rural and suburban areas. Our method could be applied to larger geographic areas or other countries with comparable data sets, offering a promising method for researchers interested in the global increase in diet-related chronic disease.

Sleep disturbance mediates the link between both self-compassion and self-criticism and psychological distress during prolonged periods of stress.

Poor sleep and subsequent decline in mental health often occur during times of prolonged stress, such as a pandemic. Self-compassion is linked with improved sleep and better mental health, while self-criticism is linked with poorer sleep and psychological distress. Given there is little evidence of the interrelationships of these constructs, we examined whether higher self-compassion or lower levels of self-criticism can reduce psychological distress directly and indirectly via sleep during times of prolonged stress. Structural equation modelling was used to analyse two samples (N = 722, Study 1, and N = 622, Replication Study) of university students during different stages of the pandemic. An aggregate psychological distress construct was calculated using depression, anxiety and stress measures. We created models that showed insomnia symptoms mediated the relationship between self-compassion/self-criticism and psychological distress. Sleep partially mediated both relationships, and this was the strongest effect in both samples. This suggests that improving self-compassion and reducing self-criticism will improve sleep, leading to reduced psychological distress. As our findings are robust and held at two time points, future research should investigate broader demographics and differing stress responses.

The efficacy of personalized psychological interventions in adolescents: a scoping review and meta-analysis.

This review compared the efficacy of personalized psychological interventions to standardized interventions for adolescents. We conducted a scoping review and meta-analysis of randomized controlled trials that compared personalized interventions with standardized interventions in adolescents. Data was analyzed using Bayesian multilevel random effects meta-analysis. Eligible studies were identified through five databases: Scopus, PsycINFO, MEDLINE, Web of Science, and EMBASE. Moderation analysis was conducted to explain potential sources of effect size heterogeneity. Eight studies across 13 articles (participant N = 2,490) met inclusion criteria for the review with seven studies across 10 articles (N = 1,347) providing sufficient data for inclusion in the meta-analysis. A small but significant effect size favoring personalized interventions was found (d = 0.21, 95% CrI [0.02, 0.39]), indicating that personalized interventions are associated with superior treatment outcomes compared to standardized interventions. Moderate between-study heterogeneity was found (I2 = 53.3%). There was no evidence of publication bias. The review also found significant variation in methods of treatment personalization. This review provides evidence that personalization of adolescent psychological interventions is an effective way to improve treatment outcomes. Given the large number of adolescents worldwide who will experience some sort of mental health problem, personalization could have a significantly large impact on global mental health outcomes. Systematic review registration: https://doi.org/10.17605/OSF.IO/XRNCG.

The axillary lymphoid organ - an external, experimentally accessible immune organ in the zebrafish.

Lymph nodes and other secondary lymphoid organs play critical roles in immune surveillance and immune activation in mammals, but the deep internal locations of these organs make it challenging to image and study them in living animals. Here, we describe a previously uncharacterized external immune organ in the zebrafish ideally suited for studying immune cell dynamics in vivo, the axillary lymphoid organ (ALO). This small, translucent organ has an outer cortex teeming with immune cells, an inner medulla with a mesh-like network of fibroblastic reticular cells along which immune cells migrate, and a network of lymphatic vessels draining to a large adjacent lymph sac. Noninvasive high-resolution imaging of transgenically marked immune cells can be carried out in the lobes of living animals, and the ALO is readily accessible to external treatment. This newly discovered tissue provides a superb model for dynamic live imaging of immune cells and their interaction with pathogens and surrounding tissues, including blood and lymphatic vessels.

More than meets the eye: relationship between low health literacy and poor vision in hospitalized patients.

Patient-centered care includes involving patients and their families in self-management of chronic diseases. Identifying and addressing barriers to self-management, including those related to health literacy and vision limitations, may enhance one's ability to self-manage. A set of brief verbal screening questions (BVSQ) that does not rely on sufficient vision to assess health literacy was developed by Chew and colleagues in the outpatient setting. The authors aimed to evaluate the usefulness of this tool for hospitalized patients and to determine the prevalence of poor vision among inpatients. In a prospective study, the BVSQ and the Rapid Estimate of Adult Learning in Medicine-Revised (REALM-R; among participants with sufficient vision, ≥ 20/50 Snellen) were administered to general medicine inpatients. Of 893 participants, 79% were African American, and 57% were female; the mean age was 53 years. Among 668 participants who completed both tools, the proportion with low health literacy was 38% with the BVSQ versus 47% with the REALM-R (p = .0001). Almost one fourth of participants had insufficient vision; participants with insufficient vision were more likely to be identified as having low health literacy by the BVSQ, compared with those with sufficient vision (59% vs. 38%, p < .001).

The bifactor structure of the Self-Compassion Scale: Bayesian approaches to overcome exploratory structural equation modeling (ESEM) limitations.

The rapidly expanding self-compassion research is driven mainly by Neff's (2003a, 2003b, 2023) six-factor Self-Compassion Scale (SCS). Despite broad agreement on its six-first-order factor structure, there is much debate on SCS's global structure (one- vs. two-global factors). Neff et al. (2019) argue for an exploratory structural equation model (ESEM) with six specific and one global bifactor (6ESEM + 1GlbBF) rather than two global factors (6ESEM + 2GlbBF). However, ESEM's methodological limitations precluded testing the appropriate 6ESEM + 2GlbBF, relying instead on a model combining ESEM and traditional confirmatory factor analysis (6ESEM + 2CFA). Although intuitively reasonable, this alternative model results in internally inconsistent, illogical interpretations. Instead, we apply recent advances in Bayesian SEM frameworks and Bayes structural equation models fit indices to test a more appropriate bifactor model with two global factors. This model (as does 6CFA + 2GlbBF) fits the data well, and correlations between compassionate self-responding (CS) and reverse-scored uncompassionate self-responding (RUS) factors (∼.6) are much less than the 1.0 correlation implied by a single bipolar factor. We discuss the critical implications for theory, scoring, and clinical application for the SCS that previously were inappropriately based on this now-discredited 6ESEM + 2GlbCFA. In applied practice, we endorse using scores representing the six SCS factors, total SCS, and CS and RUS components rather than relying solely on one global factor. Our approach to these issues (dimensionality, factor structure, first-order and higher order models, positive vs. negatively oriented constructs, item-wording effects, and alternative estimation procedures) has wide applicability to clinical measurement (see our annotated bibliography of 20 instruments that might benefit from our approach). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Characterizing the effects of structural fires on fine particulate matter with a dense sensing network.

Short-term increases in air pollution levels are linked to large adverse effects on health and productivity. However, existing regulatory monitoring systems lack the spatial or temporal resolution needed to capture localized events. This study uses a dense network of over 100 sensors, deployed across the city of Chicago, Illinois, to capture the spread of smoke from short-term structural fire events. Examining all large structural fires that occurred in the city over a year (N = 21), we characterize differences in PM[Formula: see text] concentrations downwind versus upwind of the fires. On average, we observed increases of up to 10.7 [Formula: see text]g/m[Formula: see text] (95% CI 5.7-15.7) for sensors within 2 km and up to 7.7 [Formula: see text]g/m[Formula: see text] (95% CI 3.4-12.0) for sensors 2-5 km downwind of fires. Statistically significant elevated concentrations were evident as far as 5 km downwind of the location of the fire and persisted over approximately 2 h on average. This work shows how low-cost sensors can provide insight on local and short-term pollution events, enabling regulators to provide timely warnings to vulnerable populations.

DARE Training: Teaching Educators How to Revise Internal Medicine Residency Lectures by Using an Anti-racism Framework.

Introduction: Systemic inequities and provider-held biases reinforce racism and further disparities in graduate medical education. We developed the Department of Medicine Anti-Racism and Equity Educational Initiative (DARE) to improve internal medicine residency conferences. We trained faculty and residents to serve as coaches to support other faculty in delivering lectures. The training leveraged a best-practices checklist to revise existing lectures. Methods: We recruited internal medicine faculty and residents to serve as DARE coaches, who supported educators in improving lectures' anti-racism content. During the training, coaches watched a videotaped didactic presentation that we created about health equity and anti-racism frameworks. DARE coaches then participated in a workshop where they engaged in case-based learning and small-group discussion to apply the DARE best-practices checklist to sample lecture slides. To assess training effectiveness, coaches completed pre- and posttraining assessments in which they edited different sample lecture slides. Our training took 1 hour to complete. Results: Thirty-four individuals completed DARE training. Following the training, the sample slides were significantly improved with respect to diversity of graphics (p < .001), discussion of research participant demographics (p < .001), and discussion of the impact of racism/bias on health disparities (p = .03). After DARE training, 23 of 24 participants (96%) endorsed feeling more prepared to bring an anti-racist framework to lectures and to support colleagues in doing the same. Discussion: Training residents and faculty to use DARE principles in delivering internal medicine lectures is an innovative and effective way to integrate anti-racism into internal medicine residency conferences.

An Anti-Racism and Equity Initiative Improves Residency Educational Conferences.

Background: Graduate medical education curricula may reinforce systemic inequities and bias, thus contributing to health disparities. Curricular interventions and evaluation measures are needed to increase trainee awareness of bias and known inequities in health care. Objective: This study sought to improve the content of core noontime internal medicine residency educational conferences by implementing the Department of Medicine Anti-Racism and Equity (DARE) educational initiative. Methods: DARE best practices were developed from available anti-racism and equity educational materials. Volunteer trainees and faculty in the department of medicine of a large urban academic medical center were recruited and underwent an hourlong training to utilize DARE best practices to coach faculty on improving the anti-racist and equity content of educational conferences. DARE coaches then met with faculty to review the planned 2021-2022 academic year (AY) lectures and facilitate alignment with DARE best practices. A rubric was created from DARE practices and utilized to compare pre-intervention (AY21) and post-intervention (AY22) conferences. Results: Using the DARE best practices while coaching increased the anti-racism and equity content from AY21 to AY22 (total rubric score mean [SD] 0.16 [1.19] to 1.38 [1.39]; P=.001; possible scores -4 to +5), with 75% (21 of 28) of AY22 conferences showing improvement. This included increased diversity of photographs, discussion of the racial or ethnic makeup of research study participants, appropriate use of race in case vignettes, and discussion of the impact of racism or bias on health disparities. Conclusions: Training coaches to implement DARE best practices improved the anti-racism and equity content of existing noontime internal medicine residency educational conferences.

Multimodality Imaging of Progressive Aortic Valve Endocarditis: From Endophthalmitis to Aorto-Atrial Fistula.

Our case highlights an atypical presentation of aortic valve endocarditis after initial presentation with endophthalmitis. This case demonstrates the rapidity of evolution of aortic valve endocarditis through sequential, multimodal imaging, and features the importance of a multidisciplinary approach required for the management of complicated aortic valve endocarditis. A male in his mid-thirties was admitted to the hospital with left endophthalmitis and diabetic ketoacidosis. He was found to have aortic valve endocarditis and severe aortic insufficiency, which progressed to aortic root pseudoaneurysm and subsequently to aorto-atrial fistula in less than 72 hours, as demonstrated by consecutive multimodality imaging studies. After extensive surgical repair, post-operative recovery, and rehabilitation, he was discharged home with a good functional outcome. Sequential and multimodal imaging can be beneficial in diagnosing paravalvular infection early in its evolution, which is crucial for decision-making regarding medical and surgical treatment strategies.

Going Virtual: Objective Structured Teaching Exercises as an Innovative Method for Formative Resident Education.

BACKGROUND: The coronavirus disease 2019 pandemic forced residency programs to adapt teaching to the virtual arena. Objective Structured Teaching Exercises (OSTEs) are a simulation-based session we previously implemented in our in-person pediatric curriculum. We aimed to assess feasibility of and resident satisfaction with the transition to virtual learning for simulation-based OSTEs. METHODS: The pediatrics residency program at our hospital has a weekly academic half-day for residents where the OSTEs were held annually in person 2018 to 2019 and virtually in 2020. Surveys were collected from participating residents and faculty to compare teaching experience, feedback quality, and satisfaction with the session. RESULTS: Over 3 academic years, there were 159 total teaching sessions, 3 of which were OSTEs. The OSTE session was highly rated each year and was the second highest rated virtual session. Residents felt the OSTEs improved their teaching regardless of the virtual versus in-person platform (P = .77), and the quality of feedback as rated by the resident teacher was higher for virtual sessions (P < .001). CONCLUSIONS: Transitioning the OSTE to a virtual platform was both feasible and effective when compared to the in-person OSTE. In the transition to virtual learning, educators should consider opportunities for simulation-based teaching such as OSTEs.

Chemoinformatic Design and Profiling of Derivatives of Dasabuvir, Efavirenz, and Tipranavir as Potential Inhibitors of Zika Virus RNA-Dependent RNA Polymerase and Methyltransferase.

Zika virus (ZIKV) infection is one of the mosquito-borne flaviviruses of human importance with more than 2 million suspected cases and more than 1 million people infected in about 30 countries. There are reported inhibitors of the zika virus replication machinery, but no approved effective antiviral therapy including vaccines directed against the virus for treatment or prevention is currently available. The study investigated the chemoinformatic design and profiling of derivatives of dasabuvir, efavirenz, and tipranavir as potential inhibitors of the zika virus RNA-dependent RNA polymerase (RdRP) and/or methyltransferase (MTase). The three-dimensional (3D) coordinates of dasabuvir, efavirenz, and tipranavir were obtained from the PubChem database, and their respective derivatives were designed with DataWarrior-5.2.1 using an evolutionary algorithm. Derivatives that were not mutagenic, tumorigenic, or irritant were selected; docked into RdRP and MTase; and further subjected to absorption, distribution, metabolism, excretion, and toxicity (ADMET) evaluation with Swiss-ADME and pkCSM web tools. Some of the designed compounds are Lipinski's rule-of-five compliant, with good synthetic accessibilities. Compounds 20d, 21d, 22d, and 1e are nontoxic with the only limitation of CYP1A2, CYP2C19, and/or CYP2C9 inhibition. Replacements of -CH3 and -NH- in the methanesulfonamide moiety of dasabuvir with -OH and -CH2- or -CH2CH2-, respectively, improved the safety/toxicity profile. Hepatotoxicity in 5d, 4d, and 18d is likely due to -NH- in their methanesulfonamide/sulfamic acid moieties. These compounds are potent inhibitors of N-7 and 2'-methylation activities of ZIKV methyltransferase and/or RNA synthesis through interactions with amino acid residues in the priming loop/"N-pocket" in the virus RdRP. Synthesis of these compounds and wet laboratory validation against ZIKV are recommended.

An engineered dual function peptide to repair fractured bones.

Targeted drug delivery, often referred to as "smart" drug delivery, is a process whereby a therapeutic drug is delivered to specific parts of the body in a manner that increases its concentration at the desired sites relative to others. This approach is poised to revolutionize medicine as exemplified by the recent FDA approval of Cytalux (FDA approves pioneering drug for ovarian cancer surgery - Purdue University News) which is a folate-receptor targeted intraoperative near infrared (NIR) imaging agent that was developed in our laboratories. Fracture-associated morbidities and mortality affect a significant portion of world population. United states, Canada and Europe alone spent $48 billion in treating osteoporosis related fractures although this number doesn't count the economic burden due to loss in productivity. It is estimated that by 2050 ca 21 million hip fractures would occur globally which will be leading cause of premature death and disability. Despite the need for improvement in the treatment for fracture repair, methods for treating fractures have changed little in recent decades. Systemic delivery of fracture-homing bone anabolics holds great promise as a therapeutic strategy in this regard. Here we report the design of a fracture-targeted peptide comprised of a payload that binds and activates the parathyroid hormone receptor (PTHR1) and is linked to a targeting ligand comprised of 20 D-glutamic acids (D-Glu20) that directs accumulation of the payload specifically at fracture sites. This targeted delivery results in reduction of fracture healing times to <1/2 while creating repaired bones that are >2-fold stronger than saline-treated controls in mice. Moreover, this hydroxyapatite-targeted peptide can be administered without detectable toxicity to healthy tissues or modification of healthy bones in dogs. Additionally, since similar results are obtained upon treatment of osteoporotic and diabetic fractures in mice, and pain resolution is simultaneously accelerated by this approach, we conclude that this fracture-targeted anabolic peptide displays significant potential to revolutionize the treatment of bone fractures.