Patellar Resurfacing Is Not a Risk Factor for Postoperative Patella Baja in Total Knee Arthroplasty.

Background: Patella baja is a known complication of total knee arthroplasty (TKA). There is a limited understanding of the association between patellar resurfacing and the incidence of patella baja. We aimed to compare rates of patella baja between unresurfaced and resurfaced patellas in patients undergoing TKA. Methods: A retrospective review of patients who underwent TKA between October 2009 and January 2020 was performed. Patients were included if they had at least one preoperative radiograph and a 1-year follow-up radiograph. Blackburne-Peel index (BPI) and Insall-Salvati ratios (ISRs) were measured on preoperative and 1-year postoperative radiographs and were used to define patella baja vs pseudopatella baja. Statistical analysis was performed using a linear model analysis of variance and the Fisher's exact test. Results: Three hundred eighteen TKAs were included, with 176 being resurfaced and 142 unresurfaced patellas. Of the resurfaced group, 4% (7/176) had true patella baja, compared to 5.6% (8/142) of the unresurfaced patellas. Of the resurfaced patellas, 8% (14/176) had pseudopatella baja, compared to 7% (10/142) in the unresurfaced group. Patellar resurfacing was not associated with a higher incidence of patella baja (P = .60) or pseudopatella baja (P = .83). Lower preoperative ISRs (P = .04) and BPIs (0.03) were highly predictive of a higher incidence of patella baja post-TKA. Conclusions: Patellar resurfacing in TKA is not associated with a higher incidence of patella baja in TKA when compared to unresurfaced patellas. Lower preoperative ISRs and BPIs are highly predictive of a higher incidence of postoperative patella baja.

Patient Interest in Quadriceps Autograft Anterior Cruciate Ligament Reconstruction Is Increasing Over Other Autograft Options: A 12-Year Google Trends Analysis.

Purpose: To use Google trends to explore differences in public interest among types of anterior cruciate ligament (ACL) autografts, specifically quadriceps tendon, patellar tendon, and hamstring tendon autografts, between 2008 and 2019. Methods: Data were obtained by querying Google Trends for key terms and phrases for online search data ranging from January 2008 to December 2019. Relative search volumes were created based on searches related to ACL reconstruction with comparative analysis generated for search terms related to quadriceps ACL, patellar tendon ACL, and hamstring ACL autografts. Statistical analysis included linear regression analysis, comparison of quarterly search volume trends over time, and comparison of cumulative annual search volumes for 2008 versus 2019. Results: Linear models for respective search terms were statistically significant for the quadriceps (P < .001) and patellar (P = .007) tendon autograft groups but not the hamstring group (P = .129). The quadriceps autograft group demonstrated a 12-year search volume trend change of 0.56, which was significantly greater than the hamstring (0.07; P < .001) and patellar tendon (0.168; P < .001) groups. There was no significant difference in the trend change between hamstring and patellar tendon groups (P = .20). Percent change in cumulative relative annual search volumes between 2008 and 2019 was 112% for the quadriceps tendon group, 12.9% for the hamstring group, and 18.6% for the patellar tendon group. Conclusions: This study indicates a consistently increasing public interest in quadriceps tendon autograft for ACL reconstruction. The quadriceps autograft group demonstrated a significantly greater 12-year online search volume, greater linear correlation, and larger percent change between 2008 and 2019 compared with patellar tendon or hamstring autograft groups. Clinical Relevance: Awareness of patient perceptions has value in informing shared decision-making, aligning patient expectations, and guiding areas of future research. Each of these has an impact on patient care. Being aware of patient interest and expectations is particularly important in areas with controversial or emerging research.

Neurovascular coupling, functional connectivity, and cerebrovascular endothelial extracellular vesicles as biomarkers of mild cognitive impairment.

INTRODUCTION: Mild cognitive impairment (MCI) is a prodromal stage of dementia. Understanding the mechanistic changes from healthy aging to MCI is critical for comprehending disease progression and enabling preventative intervention. METHODS: Patients with MCI and age-matched controls (CN) were administered cognitive tasks during functional near-infrared spectroscopy (fNIRS) recording, and changes in plasma levels of extracellular vesicles (EVs) were assessed using small-particle flow cytometry. RESULTS: Neurovascular coupling (NVC) and functional connectivity (FC) were decreased in MCI compared to CN, prominently in the left-dorsolateral prefrontal cortex (LDLPFC). We observed an increased ratio of cerebrovascular endothelial EVs (CEEVs) to total endothelial EVs in patients with MCI compared to CN, correlating with structural MRI small vessel ischemic damage in MCI. LDLPFC NVC, CEEV ratio, and LDLPFC FC had the highest feature importance in the random Forest group classification. DISCUSSION: NVC, CEEVs, and FC predict MCI diagnosis, indicating their potential as markers for MCI cerebrovascular pathology. HIGHLIGHTS: Neurovascular coupling (NVC) is impaired in mild cognitive impairment (MCI). Functional connectivity (FC) compensation mechanism is lost in MCI. Cerebrovascular endothelial extracellular vesicles (CEEVs) are increased in MCI. CEEV load strongly associates with cerebral small vessel ischemic lesions in MCI. NVC, CEEVs, and FC predict MCI diagnosis over demographic and comorbidity factors.

Atrioventricular Synchrony Delivered by a Dual-Chamber Leadless Pacemaker System.

BACKGROUND: A dual-chamber leadless pacemaker system has been designed for AV synchronous pacing using wireless, beat-to-beat, implant-to-implant (i2i) communication between distinct atrial and ventricular leadless pacemakers. The AV synchrony achieved across various ambulatory scenarios has yet to be systematically evaluated. METHODS: A prospective, single-arm, unblinded, multicenter, international clinical trial of the leadless pacemaker system was conducted in patients with a conventional dual-chamber pacing indication enrolled from February 2022 to March 2023. Leadless pacemaker systems were implanted, and 12-lead Holter electrocardiographic recordings were collected 3 months after implantation over various postures/activities: sitting, supine, left lateral recumbent, right lateral recumbent, standing, normal walk, and fast walk. An independent Holter core laboratory performed a manual adjudication of the percent of AV synchronous beats using the standard 300-millisecond PR interval limit. Atrium-to-ventricle and ventricle-to-atrium i2i communication success rates were also assessed. Post hoc summary statistics describing the relationships between AV synchrony and i2i success, posture/activity, implantation indication, AV event, and heart rate were calculated. RESULTS: In the evaluable population (n=384 of 464 enrolled [83%]; 61% male; age, 70 years; weight, 82 kg; 60% ejection fraction; 95% of beats evaluable), the mean AV synchrony of 98% of beats observed across all postures using the standard 300-millisecond limit was greater than both atrium-to-ventricle i2i (94%) and ventricle-to-atrium i2i (94%; P<0.001), exceeding both i2i values in 95% of patients. AV synchrony was achieved in >95% of evaluable beats across all postures/activities, implantation indications, AV paced/sensed event combinations, and heart rate ranges (including >100 bpm). CONCLUSIONS: This dual-chamber leadless pacemaker system demonstrated AV synchrony in 98% of evaluable beats at 3 months after implantation. AV synchrony was maintained across postures/activities and remained robust for heart rates >100 bpm.

Automatic Speech Recognition of Conversational Speech in Individuals With Disordered Speech.

PURPOSE: This study examines the effectiveness of automatic speech recognition (ASR) for individuals with speech disorders, addressing the gap in performance between read and conversational ASR. We analyze the factors influencing this disparity and the effect of speech mode-specific training on ASR accuracy. METHOD: Recordings of read and conversational speech from 27 individuals with various speech disorders were analyzed using both (a) one speaker-independent ASR system trained and optimized for typical speech and (b) multiple ASR models that were personalized to the speech of the participants with disordered speech. Word error rates were calculated for each speech model, read versus conversational, and subject. Linear mixed-effects models were used to assess the impact of speech mode and disorder severity on ASR accuracy. We investigated nine variables, classified as technical, linguistic, or speech impairment factors, for their potential influence on the performance gap. RESULTS: We found a significant performance gap between read and conversational speech in both personalized and unadapted ASR models. Speech impairment severity notably impacted recognition accuracy in unadapted models for both speech modes and in personalized models for read speech. Linguistic attributes of utterances were the most influential on accuracy, though atypical speech characteristics also played a role. Including conversational speech samples in model training notably improved recognition accuracy. CONCLUSIONS: We observed a significant performance gap in ASR accuracy between read and conversational speech for individuals with speech disorders. This gap was largely due to the linguistic complexity and unique characteristics of speech disorders in conversational speech. Training personalized ASR models using conversational speech significantly improved recognition accuracy, demonstrating the importance of domain-specific training and highlighting the need for further research into ASR systems capable of handling disordered conversational speech effectively.

Insect Flight: State of the Field and Future Directions.

The evolution of flight in an early winged insect ancestral lineage is recognized as a key adaptation explaining the unparalleled success and diversification of insects. Subsequent transitions and modifications to flight machinery, including secondary reductions and losses, also play a central role in shaping the impacts of insects on broadscale geographic and ecological processes and patterns in the present and future. Given the importance of insect flight, there has been a centuries-long history of research and debate on the evolutionary origins and biological mechanisms of flight. Here, we revisit this history from an interdisciplinary perspective, discussing recent discoveries regarding the developmental origins, physiology, biomechanics, and neurobiology and sensory control of flight in a diverse set of insect models. We also identify major outstanding questions yet to be addressed and provide recommendations for overcoming current methodological challenges faced when studying insect flight, which will allow the field to continue to move forward in new and exciting directions. By integrating mechanistic work into ecological and evolutionary contexts, we hope that this synthesis promotes and stimulates new interdisciplinary research efforts necessary to close the many existing gaps about the causes and consequences of insect flight evolution.

Central nervous system active medication use in Medicare enrollees receiving home health care: association with chronic pain and anxiety level.

ABSTRACT: No comparative effectiveness data exist on nonopioid analgesics and nonbenzodiazepine anxiolytics to treat pain with anxiety. We examined the relationship between drug class and central nervous system (CNS) active drug polypharmacy on pain and anxiety levels in Medicare enrollees receiving home health (HH) care. This retrospective cohort study included enrollees with diagnoses and 2+ assessments of pain and anxiety between HH admission and discharge. Three sets of linear regression difference-in-reduction analyses assessed the association of pain or anxiety reduction with number of drugs; drug type; and drug combinations in those with daily pain and daily anxiety. Logistic regression analysis assessed the effect of medication number and class on less-than-daily pain or anxiety at HH discharge. A sensitivity analysis using multinomial regression was conducted with a three-level improvement to further determine clinical significance. Of 85,403 HH patients, 43% received opioids, 27% benzodiazepines, 26% gabapentinoids, 32% selective serotonin reuptake inhibitors, and 8% serotonin and norepinephrine reuptake inhibitors (SNRI). Furthermore, 75% had depression, 40% had substance use disorder diagnoses, and 6.9% had PTSD diagnoses. At HH admission, 83%, 35%, and 30% of patients reported daily pain, daily anxiety, and both, respectively. Central nervous system polypharmacy was associated with worse pain control and had no significant effect on anxiety. For patients with daily pain plus anxiety, pain was best reduced with one medication or any drug combination without opioid/benzodiazepine; anxiety was best reduced with combinations other than opiate/benzodiazepine. Gabapentinoids or SNRI achieved clinically meaningful pain control. Selective serotonin reuptake inhibitors provided clinically meaningful anxiety relief.

Development of an improved blood-stage malaria vaccine targeting the essential RH5-CyRPA-RIPR invasion complex.

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called "R78C", combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial.

Listener effort quantifies clinically meaningful progression of dysarthria in people living with amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative motor neuron disease that causes progressive muscle weakness. Progressive bulbar dysfunction causes dysarthria and thus social isolation, reducing quality of life. The Everything ALS Speech Study obtained longitudinal clinical information and speech recordings from 292 participants. In a subset of 120 participants, we measured speaking rate (SR) and listener effort (LE), a measure of dysarthria severity rated by speech pathologists from recordings. LE intra- and inter-rater reliability was very high (ICC 0.88 to 0.92). LE correlated with other measures of dysarthria at baseline. LE changed over time in participants with ALS (slope 0.77 pts/month; p<0.001) but not controls (slope 0.005 pts/month; p=0.807). The slope of LE progression was similar in all participants with ALS who had bulbar dysfunction at baseline, regardless of ALS site of onset. LE could be a remotely collected clinically meaningful clinical outcome assessment for ALS clinical trials.

Neuroblastoma Predisposition and Surveillance-An Update from the 2023 AACR Childhood Cancer Predisposition Workshop.

Genetic predisposition to neuroblastoma (NB) is relatively rare. Only 1% to 2% of patients have a family history of NB, 3% to 4% of cases present with bilateral or multifocal primary tumors, and occasional patients have syndromes that are associated with increased NB risk. Previously, a germline pathogenic variant (GPV) in PHOX2B was associated with Hirschsprung disease and congenital central hypoventilation syndrome. Recently, certain GPVs were shown to be responsible for congenital central hypoventilation syndrome and NB predisposition. Also, several groups determined that activating GPVs in ALK accounted for a substantial number of familial NB. Finally, there are additional genes and cancer predisposition syndromes in which NB occurs with greater frequency or that have been associated with NB based on genome-wide association studies. We review the evidence for all these genes and whether there is sufficient evidence to warrant surveillance. We review recommended surveillance for hereditary patients with NB, including minor updates to surveillance recommendations that were published previously in 2017.

Clinical updates and surveillance recommendations for DNA replication-repair deficiency syndromes in children and young adults.

Replication repair deficiency (RRD) is a pan-cancer mechanism characterized by abnormalities in the DNA mismatch repair (MMR) system due to pathogenic variants in the PMS2, MSH6, MSH2 or MLH1 genes, and/ or in the polymerase-proofreading genes, POLE and POLD1. RRD predisposition syndromes [constitutional MMR deficiency (CMMRD), Lynch, polymerase-proofreading associated polyposis (PPAP)] share overlapping phenotypic and biological characteristics. Moreover, cancers stemming from germline defects of one mechanism can acquire somatic defects in another, leading to complete RRD. Here we describe the recent advances in the diagnostics, surveillance, and clinical management for children with RRD syndromes. For patients with CMMRD, new data combining clinical insights and cancer genomics have revealed genotype-phenotype associations, helped in the development of novel functional assays, diagnostic guidelines, and surveillance recommendations. Recognition of non-gastrointestinal/ genitourinary malignancies, particularly aggressive brain tumors, in select children with Lynch and PPAP syndromes harbouring an RRD biology have led to new management considerations. Additionally, universal hypermutation and microsatellite instability have allowed immunotherapy to be a paradigm shift in the treatment of RRD cancers independent of their germline etiology. These advances have also stimulated a need for expert recommendations regarding genetic counselling for these patients and their families. Future collaborative work will focus on newer technologies such as quantitative measurement of circulating tumor DNA and functional genomics to tailor surveillance and clinical care, improving immune surveillance, develop prevention strategies, and deliver these novel discoveries to resource-limited settings to maximize benefits for patients globally.

Autophagy suppression in DNA damaged cells occurs through a newly identified p53-proteasome-LC3 axis.

Macroautophagy is thought to have a critical role in shaping and refining cellular proteostasis in eukaryotic cells recovering from DNA damage. Here, we report a mechanism by which autophagy is suppressed in cells exposed to bacterial toxin-, chemical-, or radiation-mediated sources of genotoxicity. Autophagy suppression is directly linked to cellular responses to DNA damage, and specifically the stabilization of the tumor suppressor p53, which is both required and sufficient for regulating the ubiquitination and proteasome-dependent reduction in cellular pools of microtubule-associated protein 1 light chain 3 (LC3A/B), a key precursor of autophagosome biogenesis and maturation, in both epithelial cells and an ex vivo organoid model. Our data indicate that suppression of autophagy, through a newly identified p53-proteasome-LC3 axis, is a conserved cellular response to multiple sources of genotoxicity. Such a mechanism could potentially be important for realigning proteostasis in cells undergoing DNA damage repair.

Cystic fibrosis pathogens persist in the upper respiratory tract following initiation of elexacaftor/tezacaftor/ivacaftor therapy.

Elexacaftor/tezacaftor/ivacaftor (ETI) therapy has revolutionized the treatment of cystic fibrosis (CF) for most affected individuals but the effects of treatment on sinus microbiota are still unknown. Changes to the airway microbiota in CF are associated with disease state and alterations to the bacterial community after ETI initiation may require changes to clinical management regimens. We collected sinus swab samples from the middle meatus in an observational study of 38 adults with CF and chronic rhinosinusitis (CRS) from 2017 to 2021 and captured the initiation of ETI therapy. We performed 16S and custom amplicon sequencing to characterize the sinus microbiota pre- and post-ETI. Real-time quantitative PCR (RT-qPCR) was performed to estimate total bacterial abundance. Sinus samples from people with CF (pwCF) clustered into three community types, dependent on the dominant bacterial organism: a Pseudomonas-dominant, Staphylococcus-dominant, and mixed dominance cluster. Shannon's diversity index was low and not significantly altered post-ETI. Total bacterial load was not significantly lowered post-ETI. Pseudomonas spp. abundance was significantly reduced post-ETI, but eradication was not observed. Staphylococcus spp. became the dominant organism in most individuals post-ETI and we showed the presence of methicillin-resistant Staphylococcus aureus (MRSA) in the sinus both pre- and post-ETI. We also demonstrated that the sinus microbiome is predictive of the presence of Pseudomonas spp., Staphylococcus spp., and Serratia spp. in the sputum. Pseudomonas spp. and Staphylococcus spp., including MRSA, persist in the sinuses of pwCF after ETI therapy, indicating that these pathogens will continue to be important in CF airway disease management in the era of highly effective modulator therapies (HEMT).IMPORTANCEHighly effective modulator therapies (HEMT), such as elexacaftor/tezacaftor/ivacaftor (ETI), for cystic fibrosis (CF) have revolutionized patient care and quality of life for most affected individuals. The effects of these therapies on the microbiota of the airways are still unclear, though work has already been published on changes to microbiota in the sputum. Our study presents evidence for reduced relative abundance of Pseudomonas spp. in the sinuses following ETI therapy. We also show that Staphylococcus spp. becomes the dominant organism in the sinus communities of most individuals in this cohort after ETI therapy. We identified methicillin-resistant Staphylococcus aureus (MRSA) in the sinus microbiota both pre- and post-therapy. These findings demonstrate that pathogen monitoring and treatment will remain a vital part of airway disease management for people with cystic fibrosis (pwCF) in the era of HEMT.

An O-methylflavone from Artemisia afra kills non-replicating hypoxic Mycobacterium tuberculosis.

ETHNOPHARMACOLOGICAL RELEVANCE: African wormwood (Artemisia afra Jacq. ex Willd.) has been used traditionally in southern Africa to treat illnesses causing fever and was recently shown to possess anti-tuberculosis activity. As tuberculosis is an endemic cause of fever in southern Africa, this suggests that the anti-tubercular activity of A. afra may have contributed to its traditional medicinal use. AIM OF THE STUDY: Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a deadly and debilitating disease globally affecting millions annually. Emerging drug-resistant Mtb strains endanger the efficacy of the current therapies employed to treat tuberculosis; therefore, there is an urgent need to develop novel drugs to combat this disease. Given the reported activity of A. afra against Mtb, we sought to determine the mechanisms by which A. afra inhibits and kills this bacterium. MATERIALS AND METHODS: We used transcriptomics to investigate the impact of Artemisia spp. extracts on Mtb physiology. We then used chromatographic fractionation and biochemometric analyses to identify a bioactive fractions of A. afra extracts and identify an active compound. RESULTS: Transcriptomic analysis revealed that A. afra exerts different effects on Mtb compared to A. annua or artemisinin, suggesting that A. afra possesses other phytochemicals with unique modes of action. A biochemometric study of A. afra resulted in the isolation of an O-methylflavone (1), 5-hydroxy-7-methoxy-2-(4-methoxyphenyl)chromen-4-one, which displayed considerable activity against Mtb strain mc26230 in both log phase growth and metabolically downshifted hypoxic cultures. CONCLUSIONS: The present study demonstrated that an O-methylflavone constituent of Artemisia afra explains part of the activity of this plant against Mtb. This result contributes to a mechanistic understanding of the reported anti-tubercular activity of A. afra and highlights the need for further study of this traditional medicinal plant and its active compounds.

The relationship of rate and pause features to the communicative participation of people living with ALS.

INTRODUCTION/AIMS: Many people living with amyotrophic lateral sclerosis (PALS) report restrictions in their day-to-day communication (communicative participation). However, little is known about which speech features contribute to these restrictions. This study evaluated the effects of common speech symptoms in PALS (reduced overall speaking rate, slowed articulation rate, and increased pausing) on communicative participation restrictions. METHODS: Participants completed surveys (the Communicative Participation Item Bank-short form; the self-entry version of the ALS Functional Rating Scale-Revised) and recorded themselves reading the Bamboo Passage aloud using a smartphone app. Rate and pause measures were extracted from the recordings. The association of various demographic, clinical, self-reported, and acoustic speech features with communicative participation was evaluated with bivariate correlations. The contribution of salient rate and pause measures to communicative participation was assessed using multiple linear regression. RESULTS: Fifty seven people living with ALS participated in the study (mean age = 61.1 years). Acoustic and self-report measures of speech and bulbar function were moderately to highly associated with communicative participation (Spearman rho coefficients ranged from rs = 0.48 to rs = 0.77). A regression model including participant age, sex, articulation rate, and percent pause time accounted for 57% of the variance of communicative participation ratings. DISCUSSION: Even though PALS with slowed articulation rate and increased pausing may convey their message clearly, these speech features predict communicative participation restrictions. The identification of quantitative speech features, such as articulation rate and percent pause time, is critical to facilitating early and targeted intervention and for monitoring bulbar decline in ALS.

Improving structural damage tolerance and fracture energy via bamboo-inspired void patterns.

Bamboo has a functionally-graded microstructure that endows it with a combination of desirable properties, such as high failure strain, high toughness, and a low density. As a result, bamboo has been widely used in load-bearing structures. In this work, we study the use of bamboo-inspired void patterns to geometrically improve the failure properties of structures made from brittle polymers. We perform finite element analysis and experiments on 3D-printed structures to quantify the effect of the shape and spatial distribution of voids on the fracture behavior. The introduction of periodic, uniformly distributed voids in notched bend specimens leads to a 15-fold increase in the fracture energy relative to solid specimens. Adding a gradient to the pattern of voids leads to a cumulative 55-fold improvement in the fracture energy. Mechanistically, the individual voids result in crack blunting, which suppresses crack initiation, while neighboring voids redistribute stresses throughout the sample to enable large deformation before failure.

Skin repair and infection control in diabetic, obese mice using bioactive laser-activated sealants.

Conventional wound approximation devices, including sutures, staples, and glues, are widely used but risk of wound dehiscence, local infection, and scarring can be exacerbated in these approaches, including in diabetic and obese individuals. This study reports the efficacy and quality of tissue repair upon photothermal sealing of full-thickness incisional skin wounds using silk fibroin-based laser-activated sealants (LASEs) containing copper chloride salt (Cu-LASE) or silver nanoprisms (AgNPr-LASE), which absorb and convert near-infrared (NIR) laser energy to heat. LASE application results in rapid and effective skin sealing in healthy, immunodeficient, as well as diabetic and obese mice. Although lower recovery of epidermal structure and function was seen with AgNPr-LASE sealing, likely because of the hyperthermia induced by laser and presence of this material in the wound space, this approach resulted in higher enhancement in recovery of skin biomechanical strength compared to sutures and Cu-LASEs in diabetic, obese mice. Histological and immunohistochemical analyses revealed that AgNPr-LASEs resulted in significantly lower neutrophil migration to the wound compared to Cu-LASEs and sutures, indicating a more muted inflammatory response. Cu-LASEs resulted in local tissue toxicity likely because of effects of copper ions as manifested in the form of a significant epidermal gap and a 'depletion zone', which was a region devoid of viable cells proximal to the wound. Compared to sutures, LASE-mediated sealing, in later stages of healing, resulted in increased angiogenesis and diminished myofibroblast activation, which can be indicative of lower scarring. AgNPr-LASE loaded with vancomycin, an antibiotic drug, significantly lowered methicillin-resistant Staphylococcus aureus (MRSA) load in a pathogen challenge model in diabetic and obese mice and also reduced post-infection inflammation of tissue compared to antibacterial sutures. Taken together, these attributes indicate that AgNPr-LASE demonstrated a more balanced quality of tissue sealing and repair in diabetic and obese mice and can be used for combating local infections, that can result in poor healing in these individuals.

Assessing the Racial and Ethnic Diversity of Physician Assistant/Associate Program Graduates from 2010 to 2012 and 2019 to 2021.

INTRODUCTION: To assess the racial/ethnic diversity of graduates of US Physician Assistant/Associate (PA) programs compared with the diversity of the populations from which they draw students and to assess diversity changes over time among PA graduates. METHODS: We calculated proportion of Black or Hispanic PA graduates nationally and by school between 2010 to 2012 and 2019 to 2021 using the Integrated Postsecondary Education Data System (IPEDS) and compared it with the diversity of the 20 to 35-year-old population using the American Community Survey. We created benchmark populations for each school based on whether the school was public or private, with in-state/out-of-state proportions provided by the Physician Assistant Education Association. A diversity index (DI) was calculated for each program. A DI of 0.5 means that the representation of Black/Hispanic graduates is half their representation in the benchmark population. RESULTS: Although the numbers of Black/Hispanic graduates increased from 2010 to 2012 to 2019 to 2021, the percentage of Black graduates decreased. Nationally, the DI for Black graduates decreased from 0.28 to 0.23 and the Hispanic DI increased from 0.28 to 0.37 between 2010 to 2012 and 2019 to 2021. Among 213 PA programs included in the 2019 to 2021 dataset, 5 schools had a DI >1.0 for Black graduates and 7 schools had a DI >1.0 for Hispanic graduates. DISCUSSION: Using the IPEDS data, we found that Black and Hispanic graduates are underrepresented among PA program graduates. The PA education community needs to develop new strategies for diversifying the profession consistent with the new US Supreme Court decision banning race-conscious admissions.