Effective Use of Twitter by Orthopaedic Sports Medicine Journals Can Result in Increased Impact Factor.

Purpose: To determine whether activity on Twitter was correlated with increasing impact factor (IF) among 6 orthopaedic sports medicine journals. Methods: Twitonomy software was used to collect account activity for the American Journal of Sports Medicine; Arthroscopy: The Journal of Arthroscopic and Related Surgery; Knee Surgery, Sports Traumatology, Arthroscopy; Journal of Shoulder and Elbow Surgery; Orthopaedic Journal of Sports Medicine; and Sports Health. Data from 2000 to 2020 were collected. Each journal's annual IF score was collected via scijournal.org. A multivariate regression model was used to predict the influence of different Twitter metrics on IF from 2012 to 2019. The journal name, number of tweets, and interaction of the two were used to predict IF. Additionally, Pearson correlation was used to assess correlations between Twitter account metrics and IF. Results: Over the study period, all IFs increased, with the exception of that for American Journal of Sports Medicine. The effect size between number of tweets and IF was not the same for each journal. For every additional tweet, American Journal of Sports Medicine increased its IF by 0.001 (P = .18). Sports Health and Orthopaedic Journal of Sports Medicine increased their IF by 0.01 (P = .002) and 0.022 (P < .001), respectively. Knee Surgery, Sports Traumatology, Arthroscopy would expect a decrease in its IF by 0.004 (P = .55) and Journal of Shoulder and Elbow Surgery and Arthroscopy would increase its IF by 0.002 (P = .71) and 0.001 (P = .99), but this was not significant. There was a statistically significant positive correlation between annual tweets and IF across all journals. Conclusions: Markers of Twitter account activity, specifically the number of annual tweets, were predictive of an increase in IF among the orthopedic sports medicine journals included in this study. Clinical Relevance: The findings of this study may allow orthopaedic sports medicine journals to make more effective, targeted, and productive use of their social media accounts to reach a broader audience, increase their influence, and increase the IF of their journal.

Effect of Surgery Setting for Outpatient Shoulder Procedures on Early Postoperative Complications in a Military Population.

BACKGROUND: There has been a recent push to transition procedures previously performed at hospital-based outpatient surgical departments (HOPDs) to ambulatory surgery centers (ASCs). However, limited data regarding differences in early postoperative complications and care utilization (e.g., emergency department visits and unplanned admissions) may drive increased overall costs or worse outcomes. PURPOSE: /Hypothesis: The purpose of this study was to examine differences in early 90-day adverse outcomes and postoperative emergency department visits associated with shoulder surgeries excluding arthroplasties that were performed in HOPDs and ASCs in a closed military health care system. We hypothesized that there would be no difference in outcomes between treatment settings. METHODS: We retrospectively evaluated the records for 1,748 elective shoulder surgeries from 2015 to 2020. Patients were considered as one of two cohorts depending on whether they underwent surgery in an ASC or HOPD setting. We evaluated groups for differences incomplexity, surgical time, and medical risk. Outcome measures were emergency department visits, unplanned hospital admissions, and complications within the first 90 days after surgery. RESULTS: There was no difference in 90-day postoperative emergency department visits between procedures performed at HOPDs (n = 606) and ASCs (n = 1142). There was a slight increase in rate of unplanned hospital admission within 90 days after surgery in the HOPD cohort, most commonly for pain or overnight observation. The surgical time was significantly shorter (105 vs 119 minutes, p <0.01) at the ASC, but there was no difference in case complexity between the cohorts (p = 0.28). DISCUSSION/CONCLUSION: Our results suggest that in appropriate patients, surgery in ASCs can be safely leveraged for its costs savings, efficiency, patient satisfaction, decreases in operative time, and potentially decreased resource utilization both during surgery and in the early postoperative period.

A fecal egg count reduction test in grazing beef steers using topical pioneer and generic eprinomectin and fenbendazole oral suspension.

Many generic anthelmintics are commercially available; however, little information exists regarding product effectiveness compared to pioneer brands. The objective of this study was to compare the effectiveness of a generic eprinomectin to the pioneer eprinomectin, as well as to fenbendazole and fenbendazole in combination with the pioneer eprinomectin in grazing beef steers via a fecal egg count reduction test. Forty naturally infected steers were allocated into five treatment groups based on ranked fecal egg counts: 1. pioneer eprinomectin (Eprinex®, topical), 2. generic eprinomectin (Eprizero®, topical), 3. fenbendazole (Safeguard® 0.5% oral suspension), 4. combination of pioneer eprinomectin topical and fenbendazole oral suspension, 5. negative control. Fecal samples were collected on days -14, 0, 14, and 29. Data were analyzed using the MIXED procedure of SAS 9.4. Neither the pioneer nor the generic eprinomectin groups reached a 90% fecal egg count reduction (FECR) throughout the study with reductions of 50% and 11% for pioneer eprinomectin and 79% and - 5% for generic eprinomectin at days 14 and 29 post-treatment, respectively. Both the fenbendazole and combination groups showed 98% and 99% FECR, respectively, at 14 days post-treatment; these reductions dropped slightly at day 29 post-treatment to 94% and 89%, respectively. Primarily Cooperia punctata, Cooperia oncophora and Ostertagia ostertagi larvae were recovered from the coprocultures across all treatment groups. Interestingly, the proportions of C. punctata and C. oncophora essentially demonstrated a post-treatment reversal in the both the fenbendazole and combination treatment groups when comparing days 0 and 29, demonstrating prepatency period differences or a fenbendazole treatment effect.

All-Suture Suspensory Button Has Similar Biomechanical Performance to Metal Suspensory Button for Onlay Subpectoral Biceps Tenodesis.

Purpose: To evaluate the maximal load at failure, cyclic displacement, and stiffness of onlay subpectoral biceps tenodesis (BT) with an intramedullary unicortical metal button (MB) versus a unicortical all-suture button (ASB). Methods: Eighteen matched paired human cadaveric proximal humeri were randomly allocated for subpectoral BT with either ASB or MB using a high-strength suture. Specimens were tested on a servohydraulic mechanical testing apparatus under cyclic load for 1,000 cycles and then loaded to failure. The clamp was then adjusted to isolate the suture-anchor point interface and loaded to failure. Maximal load to failure, displacement, and stiffness were compared. Results: There was no significant difference between groups in stiffness, displacement, or yield load. The maximal load to failure for the MB was greater than the ASB (347.6 ± 74.1N vs 266.5 ± 69.3N, P = .047). Eight specimens in each group failed by suture pull-through on the tendon. When the suture-anchor point interface was isolated, there was no significant difference in maximal load at failure (MB 586.5 ± 215.8N vs ASB 579.6 ± 255.9N, P = .957). Conclusions: This study demonstrates that the MB and ASB have similar biomechanical performance when used in subpectoral BT. Although the MB showed statistically significant greater maximal load to failure, there was no difference between the MB and ASB when the suture-tendon interface was eliminated. Suture pull-through was the most common mode of failure for both implants, underscoring the importance of the suture-tendon interface. Clinical Relevance: Fixation techniques for the treatment of long head of the biceps brachii tenodesis continue to evolve. The use of an all-suture suspensory button has advantages, but it is important to understand if this implant is a biomechanically suitable alternative to a metal suspensory button.

Differences in Outcomes between Patellar Dislocations Managed in Emergent versus Non-Emergent Care Settings.

Patellar dislocations occur at a much higher rate in military than civilian populations. Past population-level studies have shown that surgical management is as good as or superior to conservative care and may reduce future reoccurrences. Although in acute cases and in civilian clinics, patellar dislocations are usually managed first in an emergent care setting, previous work suggests this can lead to increased costs. This study compared differences in downstream care type and intensity of services based on whether initial care occurred in emergent or non-emergent care settings. In our sample of 1,523 Military Health System (MHS) beneficiaries with patellar dislocation and 2-year follow-up, we found non-significant differences in costs, intensity of services, and rates of surgical repair regardless of whether the patient was initially seen in an emergent versus non-emergent care setting. Although we found significant increases in the use of imaging, patellar dislocation-related medical visits, and frequency of closed treatment approaches in emergent care settings, these values were very small and likely not clinically significant. These findings, which included all the patellar dislocations reported across the entire MHS in a 24-month period, suggest that neither emergent nor non-emergent care settings are likely to influence the long-term care received by the individual.

Molecular Interactions between Amino Silane Adhesion Promoter and Acrylic Polymer Adhesive at Buried Silica Interfaces.

In this study, the influence of an amino silane (3-(2-aminoethylamino)-propyldimethoxymethylsilane, AEAPS) on the interfacial structure and adhesion of butyl acrylate/methyl methacrylate copolymers (BAMMAs) to silica was investigated by sum frequency generation vibrational spectroscopy (SFG). Small amounts of methacrylic acid, MAA, were included in the BAMMA polymerizations to assess the impact of carboxylic acid functionality on the glass interface. SFG was used to probe the O-H and C═O groups of incorporated MAA, ester C═O groups of BAMMA, and CH groups from all species at the silica interfaces. The addition of AEAPS resulted in a significant change in the molecular structure of the polymer at the buried interface with silica due to specific interactions between the BAMMA polymers and silane. SFG results were consistent with the formation of ionic bonds between the primary and secondary amines of the AEAPS tail group and the MAA component of the polymer, as evidenced by the loss of the MAA O-H and C═O signals at the interface. It is extensively reported in the literature that methoxy head groups of an amino silane chemically bind to the silanols of glass, leaving the amine groups available to react with various chemical functionalities. Our results are consistent with this scenario and support an adhesion promotion mechanism of amino silane with various aspects: (1) the ionic bond formation between the tail amine group and acid functionality on BAMMA, (2) the chemical coupling between the silane head group and glass, (3) migration of more ester C═O groups to the interface with order, and (4) disordering or reduced levels of CH groups at the interface. These results are important for better understanding of the mechanisms and effect of amino silanes on the adhesion between acrylate polymers and glass substrates in a variety of applications.

Use of Novel Strategies to Develop Guidelines for Management of Pyogenic Osteomyelitis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Traditional approaches to practice guidelines frequently result in dissociation between strength of recommendation and quality of evidence. Objective: To construct a clinical guideline for pyogenic osteomyelitis management, with a new standard of evidence to resolve the gap between strength of recommendation and quality of evidence, through the use of a novel open access approach utilizing social media tools. Evidence Review: This consensus statement and systematic review study used a novel approach from the WikiGuidelines Group, an open access collaborative research project, to construct clinical guidelines for pyogenic osteomyelitis. In June 2021 and February 2022, authors recruited via social media conducted multiple PubMed literature searches, including all years and languages, regarding osteomyelitis management; criteria for article quality and inclusion were specified in the group's charter. The GRADE system for evaluating evidence was not used based on previously published concerns regarding the potential dissociation between strength of recommendation and quality of evidence. Instead, the charter required that clear recommendations be made only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were drafted to discuss pros and cons of care choices. Both clear recommendations and clinical reviews were planned with the intention to be regularly updated as new data become available. Findings: Sixty-three participants with diverse expertise from 8 countries developed the group's charter and its first guideline on pyogenic osteomyelitis. These participants included both nonacademic and academic physicians and pharmacists specializing in general internal medicine or hospital medicine, infectious diseases, orthopedic surgery, pharmacology, and medical microbiology. Of the 7 questions addressed in the guideline, 2 clear recommendations were offered for the use of oral antibiotic therapy and the duration of therapy. In addition, 5 clinical reviews were authored addressing diagnosis, approaches to osteomyelitis underlying a pressure ulcer, timing for the administration of empirical therapy, specific antimicrobial options (including empirical regimens, use of antimicrobials targeting resistant pathogens, the role of bone penetration, and the use of rifampin as adjunctive therapy), and the role of biomarkers and imaging to assess responses to therapy. Conclusions and Relevance: The WikiGuidelines approach offers a novel methodology for clinical guideline development that precludes recommendations based on low-quality data or opinion. The primary limitation is the need for more rigorous clinical investigations, enabling additional clear recommendations for clinical questions currently unresolved by high-quality data.

Epidemiology of Meniscus Injuries in the Military Health System and Predictive Factors for Arthroscopic Surgery.

Meniscus injuries occur at a higher rate in the military than the general population. Appropriate management and rehabilitation of meniscus injuries is important for maintaining readiness. The purpose of this study was to describe the health burden of meniscus injuries in the Military Health System (MHS) to identify the surgical intervention rate for meniscus injuries, and to determine which injury characteristics and demographic variables were associated with the likelihood of surgery after injury. The U.S. Department of Defense Management Analysis and Reporting Tool, a database of health care encounters by military personnel and dependents, was queried for encounters associated with a meniscal injury diagnosis between January 1, 2010, and December 31, 2011. Meniscus injuries were categorized into (1) isolated medial, (2) isolated lateral, (3) combined medial and lateral, and (4) unspecified cohorts. Patients under 18 and over 51 years were excluded, as well as patients without records at least 1 year prior to diagnosis or 2 years after. Relevant surgical procedures were identified with the Current Procedural Terminology (CPT) codes for arthroscopic surgery of the knee, meniscus repair, meniscectomy, and anterior cruciate ligament (ACL) reconstruction. There were 2,969 meniscus injuries meeting inclusion criteria during the study period. There were 1,547 (52.1%) isolated medial meniscus injuries, 530 (17.9%) isolated lateral meniscus injuries, 452 (15.3%) involved both menisci, and 435 (14.7%) were unspecified. The mean age was 35.5 years (standard deviation [SD] = 9.3). An adjacent ligamentous injury occurred in 901 patients (30.3%). The treatment course led to arthroscopic surgery in 52.8% (n = 1,568) of all meniscus injuries. Eighty-five percent (n = 385) of combined medial and lateral tears, 54.9% of medial tears, and 51.6% of lateral tears underwent surgery. Partial meniscectomy was the most common procedure performed while 47.2% (n = 1,401) of tears were not treated surgically. Bilateral meniscus injuries had 4.57 greater odds of undergoing knee arthroscopy (95% confidence interval [CI]: 3.46, 6.04), 2.42 times odds of undergoing a meniscus repair, and 4.59 times odds for undergoing a meniscus debridement (95% CI: 3.62, 5.82). The closed nature of the MHS allows reliable capture of surgical rates for meniscus injuries within the military population. Meniscus injuries are common in the military and impose a significant burden on the MHS. Appropriate management and rehabilitation of this injury is important for maintaining readiness.

Patellar Stress Fracture After Suture Anchor Patellar Tendon Repair in an Active Duty Military Member: A Case Report.

CASE: A 31-year-old US service member presented with a patellar tendon tear that was repaired acutely with 2 biocomposite suture anchors. He presented more than 2 years later with a stress fracture through a suture anchor drill hole and was treated with partially threaded screw fixation. CONCLUSION: Stress fracture through a suture anchor drill hole after patellar tendon repair is a previously unreported complication. Surgeons should have a high index of suspicion and low threshold to obtain advanced imaging in cases of unexplained pain after patellar tendon repair.

Nonoperative Care Including Rehabilitation Should Be Considered and Clearly Defined Prior to Elective Orthopaedic Surgery to Maximize Optimal Outcomes.

Orthopaedic surgery has revolutionized the expectations for restoration of physical function after musculoskeletal injury and, along with physical therapy, has transformed the limits of recovery. Many orthopaedic procedures have a high success rate for improving quality of life and patient-reported outcomes, yet these procedures carry some level of risk, including postoperative complications. The stepped-care model of health care delivery, when applied to musculoskeletal care, recommends implementing less-intense and lower-risk treatments with known efficacy, such as promotion and education of self-management strategies and physical therapy, before more-invasive and higher-risk treatments such as surgery. This model of managing musculoskeletal disability can improve efficiency of care delivery and reduce medical costs at the health system level. Unfortunately, there is a documented lack of implementing an appropriate course of conservative care, especially physical therapy, prior to surgery across multiple orthopaedic disciplines including sports, spine, and trauma medicine and joint arthroplasty. Failure to respond to nonsurgical treatment has been suggested as a requisite component of the surgical appropriateness criteria, yet practical application can be elusive. Multiple barriers to adequate utilization of conservative treatment exist, including U.S. payment models that increase out-of-pocket expense for patients, negative patient perception of therapy, unreasonable patient expectations from therapy versus surgery, and communication barriers between patient, surgeon, and therapist. Surgeons should ensure that high-quality guideline-appropriate care is delivered early and adequately to their patients. Rehabilitation professionals have a responsibility to deliver high-value care, properly documenting the type and extent of treatment to improve surgical decision-making between surgeons and patients. Criteria to determine appropriateness for surgery should include a standardized and extensive assessment of failed therapies prior to certain elective surgeries. Improved collaboration between surgeons and rehabilitation professionals can result in improved outcomes for patients with musculoskeletal disorders. LEVEL OF EVIDENCE: V, expert opinion.

World scientists' warnings into action, local to global.

'We have kicked the can down the road once again - but we are running out of road.' - Rachel Kyte, Dean of Fletcher School at Tufts University.We, in our capacities as scientists, economists, governance and policy specialists, are shifting from warnings to guidance for action before there is no more 'road.' The science is clear and irrefutable; humanity is in advanced ecological overshoot. Our overexploitation of resources exceeds ecosystems' capacity to provide them or to absorb our waste. Society has failed to meet clearly stated goals of the UN Framework Convention on Climate Change. Civilization faces an epochal crossroads, but with potentially much better, wiser outcomes if we act now.What are the concrete and transformative actions by which we can turn away from the abyss? In this paper we forcefully recommend priority actions and resource allocation to avert the worst of the climate and nature emergencies, two of the most pressing symptoms of overshoot, and lead society into a future of greater wellbeing and wisdom. Humanity has begun the social, economic, political and technological initiatives needed for this transformation. Now, massive upscaling and acceleration of these actions and collaborations are essential before irreversible tipping points are crossed in the coming decade. We still can overcome significant societal, political and economic barriers of our own making.Previously, we identified six core areas for urgent global action - energy, pollutants, nature, food systems, population stabilization and economic goals. Here we identify an indicative, systemic and time-limited framework for priority actions for policy, planning and management at multiple scales from household to global. We broadly follow the 'Reduce-Remove-Repair' approach to rapid action. To guide decision makers, planners, managers, and budgeters, we cite some of the many experiments, mechanisms and resources in order to facilitate rapid global adoption of effective solutions.Our biggest challenges are not technical, but social, economic, political and behavioral. To have hope of success, we must accelerate collaborative actions across scales, in different cultures and governance systems, while maintaining adequate social, economic and political stability. Effective and timely actions are still achievable on many, though not all fronts. Such change will mean the difference for billions of children and adults, hundreds of thousands of species, health of many ecosystems, and will determine our common future.

A High-Sensitivity International Knee Documentation Committee Survey Index From the PROMIS System: The Next-Generation Patient-Reported Outcome for a Knee Injury Population.

BACKGROUND: Patient-reported outcomes (PROs) measure progression and quality of care. While legacy PROs such as the International Knee Documentation Committee (IKDC) survey are well-validated, a lengthy PRO creates a time burden on patients, decreasing adherence. In recent years, PROs such as the Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function and Pain Interference surveys were developed as computer adaptive tests, reducing time to completion. Previous studies have examined correlation between legacy PROs and PROMIS; however, no studies have developed effective prediction models utilizing PROMIS to create an IKDC index. While the IKDC is the standard knee PRO, computer adaptive PROs offer numerous practical advantages. PURPOSE: To develop a nonlinear predictive model utilizing PROMIS Physical Function and Pain Interference to estimate IKDC survey scores and examine algorithm sensitivity and validity. STUDY DESIGN: Cohort study (diagnosis); Level of evidence, 3. METHODS: The MOTION (Military Orthopaedics Tracking Injuries and Outcomes Network) database is a prospectively collected repository of PROs and intraoperative variables. Patients undergoing knee surgery completed the IKDC and PROMIS surveys at varying time points. Nonlinear multivariable predictive models using Gaussian and beta distributions were created to establish an IKDC index score, which was then validated using leave-one-out techniques and minimal clinically important difference analysis. RESULTS: A total of 1011 patients completed the IKDC and PROMIS Physical Function and Pain Interference, providing 1618 complete observations. The algorithms for the Gaussian and beta distribution were validated to predict the IKDC (Pearson = 0.84-0.86; R2 = 0.71-0.74; root mean square error = 9.3-10.0). CONCLUSION: The publicly available predictive models can approximate the IKDC score. The results can be used to compare PROMIS Physical Function and Pain Interference against historical IKDC scores by creating an IKDC index score. Serial use of the IKDC index allows for a lower minimal clinically important difference than the conventional IKDC. PROMIS can be substituted to reduce patient burden, increase completion rates, and produce orthopaedic-specific survey analogs.

Effect of Surfactant Concentration and Hydrophobicity on the Ordering of Water at a Silica Surface.

The performance of nonionic surfactants is mediated by the interfacial interactions at the solid-liquid interface. Here we applied sum frequency generation (SFG) vibrational spectroscopy to probe the molecular structure of the silica-nonionic surfactant solution interface in situ, supplemented by quartz crystal microbalance with dissipation monitoring (QCM-D) and molecular dynamics (MD) simulations. The combined studies elucidated the effects of nonionic surfactant solution concentration, surfactant composition, and rinsing on the silica-surfactant solution interfacial structure. The nonionic surfactants studied include ethylene-oxide (EO) and butylene oxide (BO) components with different ratios. It was found that the CH groups of the surfactants at the silica-surfactant solution interfaces are disordered, but the interfacial water molecules are ordered, generating strong SFG OH signals. Solutions with higher concentrations of surfactant lead to a slightly higher amount of adsorbed surfactant at the silica interface, resulting in more water molecules being ordered at the interface, or a higher ordering of water molecules at the interface, or both. MD simulation results indicated that the nonionic surface molecules preferentially adsorb onto silanol sites on silica. A surfactant with a higher EO/BO ratio leads to more water molecules being ordered and a higher degree of ordering of water molecules at the silica-surfactant solution interface, exhibiting stronger SFG OH signal, although less material is adsorbed according to the QCM-D data. A thin layer of surfactants remained on the silica surface after multiple water rinses. To the best of our knowledge, this is the first time the combined approaches of SFG, QCM-D and MD simulation techniques have been applied to study nonionic surfactants at the silica-solution interface, which enhances our understanding on the interfacial interactions between nonionic surfactants, water and silica. The knowledge obtained from this study can be helpful to design the optimal surfactant concentration and composition for future applications.

The Pericapsular Nerve Group Block for Perioperative Pain Management for Hip Arthroscopy.

Perioperative pain control for hip arthroscopy procedures represents a significant challenge for both surgeons and anesthetists. In light of the opioid crisis, greater emphasis has been placed on multimodal pain control techniques. There is considerable debate regarding regional nerve blockade for hip arthroscopy. Although regional anesthesia has a significant role in perioperative pain management strategies, many of the most common techniques present their own risks and limitations. In particular, the less desirable effects of postoperative weakness in the lower extremity and difficulty with ambulation are commonly produced with standard regional blockades. We present a technique for performing a targeted, sensory nerve block that can be done efficiently and safely in the immediate preoperative period. This block can potentially lower the intraoperative and postoperative opioid requirements without the risks of muscle blockade and falls from other regional anesthesia modalities.

Enhanced CD4+ and CD8+ T cell infiltrate within convex hull defined pancreatic islet borders as autoimmune diabetes progresses.

The notion that T cell insulitis increases as type 1 diabetes (T1D) develops is unsurprising, however, the quantitative analysis of CD4+ and CD8+ T cells within the islet mass is complex and limited with standard approaches. Optical microscopy is an important and widely used method to evaluate immune cell infiltration into pancreatic islets of Langerhans for the study of disease progression or therapeutic efficacy in murine T1D. However, the accuracy of this approach is often limited by subjective and potentially biased qualitative assessment of immune cell subsets. In addition, attempts at quantitative measurements require significant time for manual analysis and often involve sophisticated and expensive imaging software. In this study, we developed and illustrate here a streamlined analytical strategy for the rapid, automated and unbiased investigation of islet area and immune cell infiltration within (insulitis) and around (peri-insulitis) pancreatic islets. To this end, we demonstrate swift and accurate detection of islet borders by modeling cross-sectional islet areas with convex polygons (convex hulls) surrounding islet-associated insulin-producing ß cell and glucagon-producing α cell fluorescent signals. To accomplish this, we used a macro produced with the freeware software ImageJ equipped with the Fiji Is Just ImageJ (FIJI) image processing package. Our image analysis procedure allows for direct quantification and statistical determination of islet area and infiltration in a reproducible manner, with location-specific data that more accurately reflect islet areas as insulitis proceeds throughout T1D. Using this approach, we quantified the islet area infiltrated with CD4+ and CD8+ T cells allowing statistical comparison between different age groups of non-obese diabetic (NOD) mice progressing towards T1D. We found significantly more CD4+ and CD8+ T cells infiltrating the convex hull-defined islet mass of 13-week-old non-diabetic and 17-week-old diabetic NOD mice compared to 4-week-old NOD mice. We also determined a significant and measurable loss of islet mass in mice that developed T1D. This approach will be helpful for the location-dependent quantitative calculation of islet mass and cellular infiltration during T1D pathogenesis and can be combined with other markers of inflammation or activation in future studies.

The Role of Programmed Death-1 in Type 1 Diabetes.

PURPOSE OF REVIEW: Programmed death-1 (PD-1) is an inhibitory receptor that controls T and B cell proliferation and function through interacting with its ligand PD-L1 or PD-L2. PD-1/PD-L1 blockade reboots anti-tumor immunity and is currently used to treat > 15 different types of cancer. However, the response rate is not at 100% and some patients relapse. Importantly, up to 37% of patients treated with PD-1/PD-L1 blocking antibodies develop immune-related adverse events, including overt autoimmunity, such as type 1 diabetes (T1D). Herein, we discuss the role of PD-1, PD-L1, and PD-L2 signaling in pre-clinical models of T1D, including recent work from our laboratory. RECENT FINDINGS: We highlight ongoing efforts to harness PD-1/PD-L1 signaling and treat autoimmunity. We also evaluate studies aimed at defining biomarkers that could reliably predict the development of immune-related adverse events after clinical PD-1/PD-L1 blockade. With increasing use of PD-1 blockade in the clinic, onset of autoimmunity is a growing health concern. In this review, we discuss what is known about the role of PD-1 pathway signaling in T1D and comment on ongoing efforts to identify patients at risk of T1D development after PD-1 pathway blockade.

Probing Molecular Behavior of Carbonyl Groups at Buried Nylon/Polyolefin Interfaces in Situ.

Nylon and maleic anhydride (MAH)-grafted polyolefin-based thin co-extruded multilayer films are widely used in packaging applications encountered in daily life. The molecular structure of the nylon/MAH-grafted polyolefin buried interface and molecular bonding between these two chemically dissimilar layers are thought to play an important role in achieving packaging structures with good adhesion. Here, the molecular bonds present at a nylon/maleic anhydride (MAH)-grafted polyethylene buried interface were systematically examined in situ for the first time using sum frequency generation (SFG) vibrational spectroscopy. The carbonyl stretching frequency region of the SFG spectra of a nylon/MAH-grafted polyethylene buried interface showed the presence of hydrolyzed MAH groups grafted to the polyethylene chain and very low levels of unreacted MAH enriched at the buried interface. The ability of SFG to detect these molecular species at the buried interface yields important understanding of the interfacial molecular structure and provides the basis for subsequent in situ studies of the bonding reaction between the grafted MAH and nylon directly at the interface. This understanding may guide the design of multilayer films with improved properties such as enhanced adhesion between polymer layers. The approach used in this study is general and is applicable to study the molecular characteristics of other buried interfaces of significance, such as buried interfaces involving polymers in solar cells, polymer semiconductors, and batteries. Nylon impact modification is another area of interest where the interaction between the MAH-grafted elastomer and the continuous phase of nylon is important.

Limited proliferation capacity of aortic intima resident macrophages requires monocyte recruitment for atherosclerotic plaque progression.

Early atherosclerosis depends upon responses by immune cells resident in the intimal aortic wall. Specifically, the healthy intima is thought to be populated by vascular dendritic cells (DCs) that, during hypercholesterolemia, initiate atherosclerosis by being the first to accumulate cholesterol. Whether these cells remain key players in later stages of disease is unknown. Using murine lineage-tracing models and gene expression profiling, we reveal that myeloid cells present in the intima of the aortic arch are not DCs but instead specialized aortic intima resident macrophages (MacAIR) that depend upon colony-stimulating factor 1 and are sustained by local proliferation. Although MacAIR comprise the earliest foam cells in plaques, their proliferation during plaque progression is limited. After months of hypercholesterolemia, their presence in plaques is overtaken by recruited monocytes, which induce MacAIR-defining genes. These data redefine the lineage of intimal phagocytes and suggest that proliferation is insufficient to sustain generations of macrophages during plaque progression.

Observing a Chemical Reaction at a Buried Solid/Solid Interface in Situ.

Chemical reactions are the most important phenomena in chemistry. However, chemical reactions at buried solid/solid interfaces are very difficult to study in situ. In this research, the chemical reaction between two solid polymer materials, a nylon film and a maleic anhydride (MAH) grafted poly(ethylene-octene) (MAHgEO) sample, was directly analyzed at the buried nylon/MAHgEO interface at the molecular level in real time and in situ, using surface and interface sensitive sum-frequency generation (SFG) vibrational spectroscopy. Disappearance of nylon signals indicated a chemical reaction between amine and hydrolyzed amide groups of nylon and MAH groups on the MAHgEO at the buried interface. The appearance of SFG signals from reaction products was also observed at the buried nylon/MAHgEO interface. The mechanism of the observed interfacial reaction was further analyzed. Temperature-dependent SFG experiments were performed to measure the activation energy of the interfacial reaction, enabling a comparison with that reported for the bulk materials. The interfacial chemical reaction between nylon and MAHgEO greatly improved the adhesion of these dissimilar materials. The detailed analysis of a chemical reaction between two polymers at the polymer/polymer buried interface underscores the utility of SFG as a powerful analytical tool to build understanding of buried interfaces and to accelerate the design of interfacial structures with desired properties.

Nonionic Surfactant Properties of Amphiphilic Hyperbranched Polyglycerols.

The surfactant properties of amphiphilic hyperbranched polyglycerols (HPGs) were investigated. The HPGs were prepared by ring-opening multibranching polymerization of glycidol using hydrophobic initiators of varying size and structure. The cloud points for all HPG surfactants were found to be >80 °C in deionized water with >1 wt % NaCl. The HPG surfactants with hydrophilic-lipophilic balance values between 16 and 18 were found to form stable octanol/water (o/w) emulsions within a 24 h period. Several surface properties, including critical micelle concentration (CMC), efficiency of surface tension reduction (pC20), effectiveness of surface tension reduction (γCMC), surface excess concentration at the CMC (Γmax), minimum area/molecule at the interface (Amin), and the CMC/C20 ratio of the HPG surfactants were measured in deionized water at 22.6 °C. In general, increasing HPG size was marked by an increase in minimum surface area per molecule (Amin) at the aqueous liquid/air interface. This increase in size also led to lower CMC and greater pC20 values of HPG surfactants prepared with Tergitol 15-S-7 initiator (HPG 5a-5d), a commercially available ethylene glycol oligomer with a branched hydrophobic tail.