The subacromial bursa modulates tendon healing after rotator cuff injury in rats.

Rotator cuff injuries result in more than 500,000 surgeries annually in the United States, many of which fail. These surgeries typically involve repair of the injured tendon and removal of the subacromial bursa, a synovial-like tissue that sits between the rotator cuff and the acromion. The subacromial bursa has been implicated in rotator cuff pathogenesis and healing. Using proteomic profiling of bursa samples from nine patients with rotator cuff injury, we show that the bursa responds to injury in the underlying tendon. In a rat model of supraspinatus tenotomy, we evaluated the bursa's effect on the injured supraspinatus tendon, the uninjured infraspinatus tendon, and the underlying humeral head. The bursa protected the intact infraspinatus tendon adjacent to the injured supraspinatus tendon by maintaining its mechanical properties and protected the underlying humeral head by maintaining bone morphometry. The bursa promoted an inflammatory response in injured rat tendon, initiating expression of genes associated with wound healing, including Cox2 and Il6. These results were confirmed in rat bursa organ cultures. To evaluate the potential of the bursa as a therapeutic target, polymer microspheres loaded with dexamethasone were delivered to the intact bursae of rats after tenotomy. Dexamethasone released from the bursa reduced Il1b expression in injured rat supraspinatus tendon, suggesting that the bursa could be used for drug delivery to reduce inflammation in the healing tendon. Our findings indicate that the subacromial bursa contributes to healing in underlying tissues of the shoulder joint, suggesting that its removal during rotator cuff surgery should be reconsidered.

A qualitative assessment of cleaning and hand hygiene practices at shelters serving people experiencing homelessness during the COVID-19 pandemic, Atlanta, GA - May-June, 2020.

BACKGROUND: Cleaning practices and hand hygiene are important behaviors to prevent and control the spread of infectious disease, especially in congregate settings. This project explored hygiene- and cleaning-related experiences in shelters serving people experiencing homelessness (PEH) during May-June 2020 of the COVID-19 pandemic. METHODS: We conducted qualitative, in-depth interviews by phone with 22 staff from six shelters in Atlanta, Georgia. The interview guide included questions about cleaning routines, cleaning barriers and facilitators, cleaning promotion, hand hygiene promotion, and hand hygiene barriers and facilitators. We analyzed interview transcripts using thematic analysis. RESULTS: Multiple individuals, such as shelter individuals (clients), volunteers, and staff, played a role in shelter cleaning. Staff reported engaging in frequent hand hygiene and cleaning practices. Barriers to cleaning included staffing shortages and access to cleaning supplies. Staff reported barriers (e.g., differing perceptions of cleanliness) for clients who were often involved in cleaning activities. Barriers to hand hygiene included limited time to wash hands, forgetting, and inconvenient handwashing facilities. Specific guidance about when and how to clean, and what supplies to use, were requested. CONCLUSION: During the early months of the COVID-19 pandemic, shelters serving PEH in the Atlanta-metro area needed resources and support to ensure sufficient staffing and supplies for cleaning activities. As part of future pandemic planning and outbreak prevention efforts, shelters serving PEH could benefit from specific guidance and training materials on cleaning and hand hygiene practices.

Specimen-specific finite element representations of implanted hip capsules.

The hip capsule is a ligamentous structure that contributes to hip stability. This article developed specimen-specific finite element models that replicated internal-external (I-E) laxity for ten implanted hip capsules. Capsule properties were calibrated to minimize root mean square error (RMSE) between model and experimental torques. RMSE across specimens was 1.02 ± 0.21 Nm for I-E laxity and 0.78 ± 0.33 Nm and 1.10 ± 0.48 Nm during anterior and posterior dislocation, respectively. RMSE for the same models with average capsule properties was 2.39 ± 0.68 Nm. Specimen-specific models demonstrated the importance of capsule tensioning in hip stability and have relevance for surgical planning and evaluation of implant designs.

Hedgehog Activation for Enhanced Rotator Cuff Tendon-to-Bone Healing.

BACKGROUND: Rotator cuff repair is a common orthopaedic procedure, yet the rate of failure to heal after surgery is high. Repair site rupture is due to poor tendon-to-bone healing and lack of regeneration of the native fibrocartilaginous enthesis. During development, the enthesis is formed and mineralized by a pool of progenitors activated by hedgehog signaling. Furthermore, hedgehog signaling drives regenerative enthesis healing in young animals, in contrast to older animals, in which enthesis injuries heal via fibrovascular scar and without participation of hedgehog signaling. HYPOTHESIS: Hedgehog activation improves tendon-to-bone healing in an animal model of rotator cuff repair. STUDY DESIGN: Controlled laboratory study. METHODS: A total of 78 adult Sprague-Dawley rats were used. Supraspinatus tendon injury and repair were completed bilaterally, with microsphere-encapsulated hedgehog agonist administered to right shoulders and control microspheres administered to left shoulders. Animals were sacrificed after 3, 14, 28, or 56 days. Gene expression and histological, biomechanical, and bone morphometric analyses were conducted. RESULTS: At 3 days, hedgehog signaling pathway genes Gli1 (1.70; P = .029) and Smo (2.06; P = .0173), as well as Runx2 (1.69; P = .0386), a transcription factor of osteogenesis, were upregulated in treated relative to control repairs. At 14 days, transcription factors of tenogenesis, Scx (4.00; P = .041), and chondrogenesis, Sox9 (2.95; P = .010), and mineralized fibrocartilage genes Col2 (3.18; P = .031) and Colx (1.85; P = .006), were upregulated in treated relative to control repairs. Treatment promoted fibrocartilage formation at the healing interface by 28 days, with improvements in tendon-bone maturity, organization, and continuity. Treatment led to improved biomechanical properties. The material property strength (2.43 vs 1.89 N/m2; P = .046) and the structural property work to failure (29.01 vs 18.09 mJ; P = .030) were increased in treated relative to control repairs at 28 days and 56 days, respectively. Treatment had a marginal effect on bone morphometry underlying the repair. Trabecular thickness (0.08 vs 0.07 mm; P = .035) was increased at 28 days. CONCLUSION: Hedgehog agonist treatment activated hedgehog signaling at the tendon-to-bone repair site and prompted increased mineralized fibrocartilage production. This extracellular matrix production and mineralization resulted in improved biomechanical properties, demonstrating the therapeutic potential of hedgehog agonism for improving tendon-to-bone healing after rotator cuff repair. CLINICAL RELEVANCE: This study demonstrates the therapeutic potential of hedgehog agonist treatment for improving tendon-to-bone healing after rotator cuff injury and repair.

The subacromial bursa is a key regulator of the rotator cuff and a new therapeutic target for improving repair.

Rotator cuff injuries result in over 500,000 surgeries performed annually, an alarmingly high number of which fail. These procedures typically involve repair of the injured tendon and removal of the subacromial bursa. However, recent identification of a resident population of mesenchymal stem cells and inflammatory responsiveness of the bursa to tendinopathy indicate an unexplored biological role of the bursa in the context of rotator cuff disease. Therefore, we aimed to understand the clinical relevance of bursa-tendon crosstalk, characterize the biologic role of the bursa within the shoulder, and test the therapeutic potential for targeting the bursa. Proteomic profiling of patient bursa and tendon samples demonstrated that the bursa is activated by tendon injury. Using a rat to model rotator cuff injury and repair, tenotomy-activated bursa protected the intact tendon adjacent to the injured tendon and maintained the morphology of the underlying bone. The bursa also promoted an early inflammatory response in the injured tendon, initiating key players in wound healing. In vivo results were supported by targeted organ culture studies of the bursa. To examine the potential to therapeutically target the bursa, dexamethasone was delivered to the bursa, prompting a shift in cellular signaling towards resolution of inflammation in the healing tendon. In conclusion, contrary to current clinical practice, the bursa should be retained to the greatest extent possible and provides a new therapeutically target for improving tendon healing outcomes. One Sentence Summary: The subacromial bursa is activated by rotator cuff injury and regulates the paracrine environment of the shoulder to maintain the properties of the underlying tendon and bone.

The utility of evaluation in optimizing implementation and improvement of HIV prevention programming.

The objective of this article is to describe Project PrIDE (PrEP Implementation, Data to Care, and Evaluation) through the lens of Evaluation Utilization and provide examples of how twelve funded health departments (HD) utilized evaluation findings to make decisions related to improving PrEP awareness and uptake, and/or enhancing capacity for data to care (D2C) activities. Each HD conducted a local evaluation (LE) and reported ongoing and planned utilization of evaluation findings in the final LE reports. Information from all reports was abstracted for qualitative analysis to identify main evaluation utilization themes. Findings showed that program evaluation was incorporated as early as the project development phase and designed with the goal of improving, and not just demonstrating the efficacy of the programs. Evaluation data were effectively utilized to improve PrEP and D2C activities, for example, by increasing community engagement throughout LEs, enhancing social media implementation, prioritizing the most effective referral sources at re-linking clients into HIV care, reducing client wait time between receiving PrEP referral and obtaining appointment with provider, and incorporating evaluation findings into program planning and development. Project PrIDE highlights the importance of a planned evaluation in providing ongoing improvements to HIV prevention services to better serve priority populations.

Reaching racial/ethnic and sexual and gender minorities with HIV prevention information via social marketing.

The Pre-exposure Prophylaxis, Data to Care, Implementation, and Evaluation (PrIDE) multi-site demonstration project utilized a cluster evaluation approach and identified six funding recipients that evaluated similar media evaluation questions (Baltimore, Los Angeles County, Lousiana, Michigan, New York City, and Virginia). All of the evaluated social marketing campaigns were developed in collaboration with health department staff, external marketing firms, and community advisory boards (CAB) aiming to produce changes in PrEP outcomes by reaching racial/ethnic and sexual and gender minorities. Jurisdictions demonstrated changes in PrEP awareness, knowledge, willingness to take PrEP, and/or PrEP literacy following initiation of the campaigns. In data from four sites, PrEP awareness significantly increased from 72 % at baseline to 86 % at mid-project, and to 90 % post-campaigns. The campaigns illustrate the importance of partnerships and stakeholder engagement, audience segmentation, and intentional evaluation planning. As PrEP services mature, evaluating PrEP demand and PrEP use resulting from campaigns, will be necessary. Also, future campaigns for racial/ethnic and sexual and gender minorities should identify the best channels to reach each group based on their input, disaggregate data by priority group, and determine campaign effectiveness.

Toughening mechanisms for the attachment of architectured materials: The mechanics of the tendon enthesis.

Architectured materials offer tailored mechanical properties but are limited in engineering applications due to challenges in maintaining toughness across their attachments. The enthesis connects tendon and bone, two vastly different architectured materials, and exhibits toughness across a wide range of loadings. Understanding the mechanisms by which this is achieved could inform the development of engineered attachments. Integrating experiments, simulations, and previously unexplored imaging that enabled simultaneous observation of mineralized and unmineralized tissues, we identified putative mechanisms of enthesis toughening in a mouse model and then manipulated these mechanisms via in vivo control of mineralization and architecture. Imaging uncovered a fibrous architecture within the enthesis that controls trade-offs between strength and toughness. In vivo models of pathology revealed architectural adaptations that optimize these trade-offs through cross-scale mechanisms including nanoscale protein denaturation, milliscale load-sharing, and macroscale energy absorption. Results suggest strategies for optimizing architecture for tough bimaterial attachments in medicine and engineering.

Cyclic strain enhances the early stage mineral nucleation and the modulus of demineralized bone matrix.

The adaptive response of bones to mechanical loading is essential for musculoskeletal development. Despite the importance of collagen in bone mineralization, little is known about how cyclic strain influences physicochemical responses of collagen, especially at the early stage of mineralization when the levels of strain are higher than those in mature bones. The findings in this study show that, without any cell-mediated activity, cyclic strain increases nucleation rates of calcium phosphate (CaP) nanocrystals in highly-organized collagen matrices. The cyclic strain enhances the transport of mineralization fluids with nucleation precursors into the matrix, thus forming more CaP nanocrystals and increasing the elastic modulus of the collagen matrix. The results also suggest that the multiscale spatial distribution of nanocrystals in the fibrous collagen network determines tissue-level mechanical properties more critically than the total mineral content. By linking nano- and micro-scale observations with tissue-level mechanical properties, we provide new insights into designing better biomaterials.

Hand hygiene during the COVID-19 pandemic among people experiencing homelessness-Atlanta, Georgia, 2020.

People experiencing homelessness are at risk for coronavirus disease 2019 (COVID-19) and may experience barriers to hand hygiene, a primary recommendation for COVID-19 prevention. We conducted in-depth interviews with 51 people experiencing sheltered and unsheltered homelessness in Atlanta, Georgia during May 2020 to August 2020 to (1) describe challenges and opportunities related to hand hygiene and (2) assess hand hygiene communication preferences. The primary hand hygiene barrier reported was limited access to facilities and supplies, which has disproportionately impacted people experiencing unsheltered homelessness. This lack of access has reportedly been exacerbated during COVID-19 by the closure of public facilities and businesses. Increased access to housing and employment were identified as long-term solutions to improving hand hygiene. Overall, participants expressed a preference for access to facilities and supplies over hand hygiene communication materials.

Does Embedding Restricted Interests of Students with Autism in Text Improve Reading Comprehension?

Reading comprehension deficits are common for students with Autism Spectrum Disorder (ASD) but there are few studies that have examined specific strategies for teaching reading comprehension to this population. The current study investigated the effect of embedding the restricted interests (RI) of two high school students with ASD in text on reading comprehension performance using a single-subject, multi-element research design. Neither participant showed an increase in the number of relevant words shared during oral retell and only one participant showed an increase in the percent of correctly answered reading comprehension questions. Embedding the RI in text more frequently did not impact reading comprehension performance. The results indicate there are potential variables that may limit the effect of embedding the RI of students with ASD in text on reading comprehension.

The Benefits of Expert Instruction in Microsurgery Courses.

BACKGROUND: Microsurgery requires repeated practice and training to achieve proficiency, and there are a variety of curriculums available. This study aims to determine the importance of an expert instructor to guide students through procedures. We compared student proficiency across two microsurgery courses: one with (Columbia University, United States [CU] cohort) and one without a dedicated microsurgery instructor (University of Thessaloniki, Greece [UT] cohort). METHODS: Students were divided into two cohorts of 22 students (UT cohort) and 25 students (CU cohort). Student progress was evaluated by examining patency (lift-up and milking tests), anastomotic timing, and quality (Anastomosis Lapse Index [ALI]) of end-to-end arterial and venous anastomoses on day 1 and again on day 5. Chi-squared tests evaluated patency immediately and 30 minutes postoperation. t-Tests evaluated anastomotic timing and ALI scores. p-Values < 0.05 were considered significant. RESULTS: We evaluated progress within and between each cohort. Within the CU cohort, the quality of the arterial and venous anastomosis improved, respectively (by 54%, p = 0.0059 and by 43%, p = 0.0027), the patency of both the arterial and venous anastomosis improved, respectively (by 44%, p = 0.0002 and by 40%, p = 0.0019), and timing of arterial and venous anastomosis reduced respectively (by 36%, p = 0.0002 and by 33%, p = 0.0010). The UT cohort improved the quality of their arterial anastomoses (by 29%, p = 0.0312). The UT cohort did not demonstrate significant improvement in the other above-mentioned parameters. The CU cohort improved materially over the UT cohort across categories of quality, patency, and timing. CONCLUSION: There are clear benefits of an expert instructor when examining the rate of progress and proficiency level attained at the conclusion of the course. We suggest students who are seeking to maximize proficiency in microsurgical procedures enroll in courses with an expert instructor.

Developing a STEM+M Identity in Underrepresented Minority Youth Through Biomechanics and Sports-Based Education.

A Science, Technology, Engineering, Math, and Medicine (STEM+M) identity, a form of social identity, is the extent to which an individual feels accepted in the STEM+M career fields. The development of a strong STEM+M identity hinges largely on one's perceived self-efficacy in STEM+M and can be bolstered by associating STEM+M with other areas in which an individual already exhibits self-efficacy. In this study, a basketball camp served as a platform for STEM+M education in an effort to link participants' self-efficacy in basketball to STEM+M concepts where they may feel less self-efficacious. Over the first 2 years of the program, known as the Youth Sports Lab (YSL), two cohorts of underrepresented minority (URM) middle school students attended a 4-day long basketball camp hosted at Columbia University in partnership with Harlem- and Albany-based afterschool programs. The camp consisted of basketball training, jump plate fabrication, data collection, invited speakers, and group-based research projects. Our hypotheses were that participation in the program would lead to improved (1) familiarity, (2) perceived importance, and (3) interest in STEM+M. Participant responses, gathered from a 17-question Likert-scale survey administered before and after the camp, demonstrated 10 questions with significantly increased responses due to the program. The results support the conclusion that the sports-based engineering program increased STEM+M identity in the URM cohort. Future improvements to the program will include midyear student engagement and long-term follow-up.

Characteristics Associated with Adults Remembering to Wash Hands in Multiple Situations Before and During the COVID-19 Pandemic - United States, October 2019 and June 2020.

Washing hands often, especially during times when one is likely to acquire and spread pathogens,* is one important measure to help prevent the spread of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), as well as other pathogens spread by respiratory or fecal-oral transmission (1,2). Studies have reported moderate to high levels of self-reported handwashing among adults worldwide during the COVID-19 pandemic (3-5)†; however, little is known about how handwashing behavior among U.S. adults has changed since the start of the pandemic. For this study, survey data from October 2019 (prepandemic) and June 2020 (during pandemic) were compared to assess changes in adults' remembering to wash their hands in six situations.§ Statistically significant increases in reported handwashing were seen in June 2020 compared with October 2019 in four of the six situations; the odds of remembering to wash hands was 2.3 times higher among respondents after coughing, sneezing, or blowing their nose, 2.0 times higher before eating at a restaurant, and 1.7 times higher before eating at home. Men, young adults aged 18-24 years, and non-Hispanic White (White) adults were less likely to remember to wash hands in multiple situations. Strategies to help persons remember to wash their hands frequently and at important times should be identified and implemented, especially among groups reporting low prevalence of remembering to wash their hands.

Pulsed Electrical Stimulation Enhances Body Fluid Transport for Collagen Biomineralization.

Mechanical loads from physiologic activities such as walking and running generate bioelectricity in bones. By mimicking bioelectricity, external electrical stimulations have also been used therapeutically to stimulate bone-forming cells and, thus, to promote bone regeneration. However, little is known about the physicochemical mechanism(s) by which electrical stimulations drives calcium phosphate mineralization of collagen. Here, we showed that, during in vitro collagen mineralization in the absence of cells, application of pulsed electrical stimulation significantly enhanced the transport of ionic body fluid components through a micrometer-scale channel (∼100-200 µm gap space between the inner surfaces of tube-like collagen scaffolds and a cathode placed inside the collagen scaffolds). The enhanced transport of ionic precursors increased diffusion of the charged precursors from the channel to the inner collagen surface, where bone mineralization was otherwise restricted. The results indicate that pulsed electrical signals can locally accelerate the nucleation of calcium phosphate nanocrystals in or on collagen, allowing us to better control the spatial distribution of the nanocrystals at the microscale. The findings from this study provide insights into the utilization of electrical stimulation for applications such as facilitating bone-fracture healing and designing better bone-specific biomaterials.

Unique Structural/Stereo-Isomer and Isobar Analysis of Novel Fentanyl Analogues in Postmortem and DUID Whole Blood by UHPLC-MS-MS.

The presented analytical method enabled the Toxicology Department at the Cuyahoga County Medical Examiner's Office to identify 26 and quantitatively report 24 compounds in 500 µL of whole blood, including fentanyl analogues (fentalogues) such as methoxyacetyl fentanyl (MeOAF) and cyclopropyl fentanyl (CPF). This second-generation method (FG2) was developed with the objective to improve the existing analysis (FG1) by decreasing sample size, lowering limits of detection (LOD) and lower limit of quantitation, minimizing ion suppression and resolving chromatographic interferences. Interferences may occur in the analysis of fentanyl, MeOAF, CPF, 3-methylfentanyl (3MF), butyryl fentanyl and isobutyryl fentanyl due to isobars and structural or geometric isomerism with another analogue or metabolite. The isomeric and isobaric fentalogues were grouped into three sets. The LOD established for Set 1 [MeOAF, para-methoxyacetyl fentanyl, para-fluoro acryl fentanyl (isobar), fentanyl carbamate], 2-furanyl fentanyl, Set 2 [CPF, (E)-crotonyl fentanyl] and carfentanil was 0.0125 ng/mL. The LOD established for N-methyl norfentanyl, norfentanyl, norcarfentanil, despropionyl fentanyl (4-ANPP), acetyl fentanyl, ß-hydroxy fentanyl, benzyl fentanyl, acryl fentanyl, alfentanil, fentanyl, para-fluoro fentanyl, Set 3 [(±)-trans-3MF, (±)-cis-3MF, isobutyryl and butyryl fentanyl], para-fluoroisobutyryl fentanyl, sufentanil, phenyl fentanyl and cyclopentenyl fentanyl was 0.0625 ng/mL. Seven-point linear calibration curves were established between 0.025 and 4.0 ng/mL for the 8 analytes with the lower LOD and 0.125 and 20 ng/mL for the 18 analytes with the higher LOD. 4-ANPP and cyclopentenyl fentanyl met qualitative reporting criteria only. The results for five postmortem and two driving under the influence of drugs authentic case samples are presented. To the authors' knowledge, FG2 is the first published method that achieved baseline resolution of the nine structural/stereo isomers and one isobar by ultra-high performance liquid chromatography-MS-MS and provided quantitative validation data for nine compounds. FG2 may be used as the new baseline for future isomers that need to be chromatographically separated.

Eating disorders and substance use in adolescents: How substance users differ from nonsubstance users in an outpatient eating disorders treatment clinic.

OBJECTIVE: The relationship between eating disorders (EDs) and substance use (SU) has only been briefly described in literature using mainly adult populations. This study examined the prevalence and characteristics of SU among patients of an adolescent ED outpatient treatment program. METHOD: A retrospective chart analysis was conducted to determine and subsequently compare medical status, psychosocial factors, treatment course and outcome between patients with and without SU. RESULTS: Over 60% of patients with SU status (n = 203) reported regularly consuming substances. 33.4% of substance users received a diagnosis involving purging behaviors compared to 5.9% of nonusers. Females composed 96.4% and 81.7% of users and nonusers, respectively. Users reported significantly more self-harm (57.7% of users vs. 38.6% of nonusers) but did not differ significantly in terms of trauma (abuse or victimization; 48.3% of users vs. 44.9% of nonusers). The percentage of ideal body weight significantly improved throughout treatment and did not differ by SU with a mean increase of 5.29% (SD = 13.6) among nonusers compared to 5.45% (SD = 7.5) of users. While users and nonusers did not differ before and after treatment in ED severity, users were more likely than nonusers to drop-out of treatment (41.5% of users vs. 25.2% of nonusers). DISCUSSION: Adolescents with SU benefit from ED outpatient treatment as much as those without SU, however, users are more likely to drop-out. Therefore, treatment should target these adolescents' emotional dysregulation to improve treatment compliance. Further research is necessary to determine the efficacy of such an approach.

Physiological determinants of walking effort in older adults: should they be targets for physical activity intervention?

Older adults do not get enough physical activity increasing risk for chronic disease and loss of physical function. The purpose of this study was to determine whether neuromuscular, metabolic, and cardiorespiratory indicators of walking effort explain daily activity in community-dwelling older adults. Sixteen women and fourteen men, 78 ± 8 years, performed a steady-state walk on a treadmill at 1.25 m s-1 while muscle activation, heart rate, lactate, respiratory exchange ratio, oxygen consumption (VO2), ventilation, and rating of perceived exertion (RPE) were recorded as markers of Walking Effort. Daily walking time, sitting/lying time, energy expenditure, and up-down transitions were recorded by accelerometers as markers of Daily Activity. Structural equation modeling was used to explore the relationship between the latent variables Walking Effort and Daily Activity controlling for age and BMI. Participants spent 9.4 ± 1.9 h of the waking day sedentary and 1.9 ± 0.6 h walking. In the structural equation model, the latent variable Walking Effort explained 64% of the variance in the Daily Activity latent variable (ß = 0.80, p = 0.004). Walking Effort was identified by heart rate (ß = 0.64), ventilation (ß = 0.88), vastus lateralis activation (ß = 0.49), and lactate (ß = 0.58), all p < 0.05, but not RPE or VO2. Daily Activity was identified by stepping time (ß = 0.75) and up-down transitions (ß = 0.52), all p < 0.05. Walking effort mediated the effects of age and BMI on older adults' daily activity making physiological determinants of walking effort potential points of intervention.