Tissue signals imprint ILC2 identity with anticipatory function.

Group 2 innate lymphoid cells (ILC2s) are distributed systemically and produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP). Transcriptional profiling of ILC2s from different tissues, however, grouped ILC2s according to their tissue of origin, even in the setting of combined IL-25-, IL-33-receptor-, and TSLP-receptor-deficiency. Single-cell profiling confirmed a tissue-organizing transcriptome and identified ILC2 subsets expressing distinct activating receptors, including the major subset of skin ILC2s, which were activated preferentially by IL-18. Tissue ILC2 subsets were unaltered in number and expression in germ-free mice, suggesting that endogenous, tissue-derived signals drive the maturation of ILC2 subsets by controlling expression of distinct patterns of activating receptors, thus anticipating tissue-specific perturbations occurring later in life.

Metabolomics for dental caries diagnosis: Past, present, and future.

Dental caries, a prevalent global infectious condition affecting over 95% of adults, remains elusive in its precise etiology. Addressing the complex dynamics of caries demands a thorough exploration of taxonomic, potential, active, and encoded functions within the oral ecosystem. Metabolomic profiling emerges as a crucial tool, offering immediate insights into microecosystem physiology and linking directly to the phenotype. Identified metabolites, indicative of caries status, play a pivotal role in unraveling the metabolic processes underlying the disease. Despite challenges in metabolite variability, the use of metabolomics, particularly via mass spectrometry and nuclear magnetic resonance spectroscopy, holds promise in caries research. This review comprehensively examines metabolomics in caries prevention, diagnosis, and treatment, highlighting distinct metabolite expression patterns and their associations with disease-related bacterial communities. Pioneering in approach, it integrates singular and combinatory metabolomics methodologies, diverse biofluids, and study designs, critically evaluating prior limitations while offering expert insights for future investigations. By synthesizing existing knowledge, this review significantly advances our comprehension of caries, providing a foundation for improved prevention and treatment strategies.

Proteomic Analysis of Human Saliva via Solid-Phase Microextraction Coupled with Liquid Chromatography-Mass Spectrometry.

Proteomics of human saliva samples was achieved for the first time via biocompatible solid-phase microextraction (bio-SPME) devices. Upon introduction of a porogen to a conventional C18 coating, porous C18/polyacrylonitrile (PAN) SPME blades were able to extract peptides up to 3.0 kDa and more peptides than commercial SPME blades. Following Trypsin digestion, salivary proteomic analysis was achieved via SPME-LC-MS/MS. Seven endogenous proteins were consistently identified in all saliva samples via bio-SPME. Taking advantage of this strategy, untargeted peptidomics was applied for the comparison of saliva samples between healthy and SARS-CoV-2 positive individuals. The results showed clear peptidomic differences between the viral and healthy saliva samples. This proof-of-concept study demonstrates the potential of bio-SPME-LC-MS/MS for peptidomics and proteomics in biomedical applications.

Hemodynamic Characteristics of a Tortuous Microvessel Using High-Fidelity Red Blood Cell Resolved Simulations.

OBJECTIVE: Tortuous microvessels are characteristic of microvascular remodeling associated with numerous physiological and pathological scenarios. Three-dimensional (3D) hemodynamics in tortuous microvessels influenced by red blood cells (RBCs), however, are largely unknown, and important questions remain. Is blood viscosity influenced by vessel tortuosity? How do RBC dynamics affect wall shear stress (WSS) patterns and the near-wall cell-free layer (CFL) over a range of conditions? The objective of this work was to parameterize hemodynamic characteristics unique to a tortuous microvessel. METHODS: RBC-resolved simulations were performed using an immersed boundary method-based 3D fluid dynamics solver. A representative tortuous microvessel was selected from a stimulated angiogenic network obtained from imaging of the rat mesentery and digitally reconstructed for the simulations. The representative microvessel was a venule with a diameter of approximately 20 µm. The model assumes a constant diameter along the vessel length and does not consider variations due to endothelial cell shapes or the endothelial surface layer. RESULTS: Microvessel tortuosity was observed to increase blood apparent viscosity compared to a straight tube by up to 26%. WSS spatial variations in high curvature regions reached 23.6 dyne/cm2 over the vessel cross-section. The magnitudes of WSS and CFL thickness variations due to tortuosity were strongly influenced by shear rate and negligibly influenced by tube hematocrit levels. CONCLUSIONS: New findings from this work reveal unique tortuosity-dependent hemodynamic characteristics over a range of conditions. The results provide new thought-provoking information to better understand the contribution of tortuous vessels in physiological and pathological processes and help improve reduced-order models.

Contemporary burden and trends of opioid-overdose mortality in New York State.

BACKGROUND: Limited research exists on contemporary opioid overdose mortality burden and trends in New York State, with most studies focusing on New York City. This study aimed to assess opioid overdose burden and death trends in New York State by age, sex, race/ethnicity, geographic area, opioid type, and overdose intent from 1999 to 2020. METHODS: Mortality data were obtained from the Centers for Disease Control and Prevention's WONDER database. Opioid overdose decedents were identified using relevant International Classification of Diseases, 10th Revision codes. Joinpoint regression analyzed trends, estimating annual and average annual percentage changes in age-adjusted mortality rates (AAMR). 95% confidence intervals were derived using the Parametric Method. RESULTS: From 1999 to 2020, New York State recorded 34,109 opioid overdose deaths (AAMR = 7.9 per 100,000 persons; 95% CI: 7.8-7.9). The overall trend increased by 12.6% per year (95% CI: 10.8, 14.4) from 2004 to 2020. Subgroups exhibited varying trends, with an 11.1% yearly increase among Non-Hispanic White persons from 2007 to 2020 (95% CI: 9.0, 13.2), a 24.6% annual rise among Non-Hispanic Black persons from 2012 to 2020 (95% CI: 17.7, 31.8), and an 18.3% increase yearly among Hispanic individuals from 2011 to 2020 (95% CI: 14.0, 22.9). Recent trends have worsened in both males and females, across all age groups, in both New York City (NYC) and areas outside NYC, and for heroin, natural and semisynthetic opioids, and synthetic opioids. CONCLUSIONS: Opioid overdose mortality in New York State has worsened significantly in the last two decades. Further research is essential to identify driving factors for targeted public health interventions.

Progression from healthy periodontium to gingivitis and periodontitis: Insights from bioinformatics-driven proteomics - A systematic review with meta-analysis.

AIM: The current study aimed to: (1) systematically review the published literature regarding the proteomics analyses of saliva and gingival crevicular fluid (GCF) in healthy humans and gingivitis and/or periodontitis patients; and (2) to identify the differentially expressed proteins (DEPs) based on the systematic review, and comprehensively conduct meta-analyses and bioinformatics analyses. METHODS: An online search of Web of Science, Scopus, and PubMed was performed without any restriction on the year and language of publication. After the identification of the DEPs reported by the included human primary studies, gene ontology (GO), the Kyoto encyclopedia of genes and genomes pathway (KEGG), protein-protein interaction (PPI), and meta-analyses were conducted. The risk of bias among the included studies was evaluated using the modified Newcastle-Ottawa quality assessment scale. RESULTS: The review identified significant differences in protein expression between healthy individuals and those with gingivitis and periodontitis. In GCF, 247 proteins were upregulated and 128 downregulated in periodontal diseases. Saliva analysis revealed 79 upregulated and 70 downregulated proteins. There were distinct protein profiles between gingivitis and periodontitis, with 159 and 31 unique upregulated proteins in GCF, respectively. Meta-analyses confirmed significant upregulation of various proteins in periodontitis, including ALB and MMP9, while CSTB and GSTP1 were downregulated. AMY1A and SERPINA1 were upregulated in periodontitis saliva. HBD was upregulated in gingivitis GCF, while DEFA3 was downregulated. PPI analysis revealed complex networks of interactions among DEPs. GO and KEGG pathway analyses provided insights into biological processes and pathways associated with periodontal diseases. CONCLUSION: The ongoing MS-based proteomics studies emphasize the need for a highly sensitive and specific diagnostic tool for periodontal diseases. Clinician acceptance of the eventual diagnostic method relies on its ability to provide superior or complementary information to current clinical assessment procedures. Future research should prioritize the multiplex measurement of multiple biomarkers simultaneously to enhance diagnostic accuracy and large study cohorts are necessary to ensure the validity and reliability of research findings.

Does rapid sequence divergence preclude RNA structure conservation in vertebrates?

Accelerated evolution of any portion of the genome is of significant interest, potentially signaling positive selection of phenotypic traits and adaptation. Accelerated evolution remains understudied for structured RNAs, despite the fact that an RNA's structure is often key to its function. RNA structures are typically characterized by compensatory (structure-preserving) basepair changes that are unexpected given the underlying sequence variation, i.e., they have evolved through negative selection on structure. We address the question of how fast the primary sequence of an RNA can change through evolution while conserving its structure. Specifically, we consider predicted and known structures in vertebrate genomes. After careful control of false discovery rates, we obtain 13 de novo structures (and three known Rfam structures) that we predict to have rapidly evolving sequences-defined as structures where the primary sequences of human and mouse have diverged at least twice as fast (1.5 times for Rfam) as nearby neutrally evolving sequences. Two of the three known structures function in translation inhibition related to infection and immune response. We conclude that rapid sequence divergence does not preclude RNA structure conservation in vertebrates, although these events are relatively rare.

Comparisons of recycled manure solids and wood shavings/sawdust as bedding material-Implications for animal welfare, herd health, milk quality, and bedding costs in Swedish dairy herds.

Increasing shortages and costs of common bedding materials have led dairy farmers in Sweden to consider using recycled manure solids (RMS), which are readily available and low cost, as an alternative bedding material. The main risks are effects on udder health and milk quality, but RMS could also affect animal welfare and claw health. The advantages and disadvantages of using RMS bedding have not been fully investigated, and findings in other countries cannot be directly applied to Swedish conditions and climate. This observational cross-sectional study investigated the use of RMS as bedding, regarding associations with certain aspects of animal welfare, herd health, milk quality, and bedding costs in Swedish dairy herds. Thirty-four dairy farms using RMS or wood shavings/sawdust (each n = 17) were compared. Each farm was visited 2 times during the housing period from 2020 to 2021, once from October to December and once from March to May. Dairy barns were observed, animal welfare was assessed, and freestall dimensions were measured. Farm owners were interviewed about housing system characteristics, herd performance, and herd management. Data on milk production and herd health were obtained from the Swedish official milk recording scheme for the indoor period from October to March. The prevalence of claw disorders and abnormal claw conformation were collected from the national claw health database for the period from October to May. On each farm visit, composite samples of unused bedding outside the barn and used bedding material from the freestalls, respectively, were taken for total bacterial count and DM analysis. Samples of bulk tank milk for determination of total bacterial count were taken in connection to the visits. In addition, samples of unused and used bedding material and manure from alleys for analysis of 3 Treponema species associated with digital dermatitis (DD) were gathered and analyzed. Total bacterial count was significantly higher in unused (8.50 log10 cfu/g) and used RMS bedding (9.75 log10 cfu/g) than in wood shavings/sawdust (used 4.74; unused 8.63 log10 cfu/g), but there were no significant differences in bulk milk total bacterial count (median 4.07 vs. 3.89 log10 cfu/mL) or SCC (median 243,800 vs. 229,200 cells/mL). The aspects of animal welfare assessed did not differ significantly between the 2 bedding systems, whereas the prevalence of total claw disorders (25.9% vs. 38.0% of trimmed cows), dermatitis (6.9% vs. 16.2% of trimmed cows) and sole ulcers (2.0% vs. 4.0% of trimmed cows) were significantly lower in the RMS herds. Treponema spp. were not detected in unused RMS material, but all RMS herds had presence of DD recorded at foot trimming. An economic assessment based on the interview results and price level from winter 2021 revealed that the costs of RMS bedding varied with amount of RMS produced. Thus, RMS is a potential alternative bedding material for dairy cows in Sweden and can be a profitable option for large dairy herds. However, the high level of total bacteria in the material requires attention to bedding and milking routines as well as regular monitoring of herd health.

A Survey on the Management of Patients with Severe Traumatic Brain Injury During Pregnancy: The MAMA Study.

BACKGROUND: Trauma, including traumatic brain injury (TBI), is the leading cause of nonobstetric maternal mortality during pregnancy. Few data are available regarding the optimal management of pregnant patients with TBI, leading to a lack of dedicated guidelines. We performed an international survey to examine the management of severe TBI in pregnant patients, focusing on monitoring, therapy, and intensive care practices. METHODS: This survey, endorsed by the World Society of Emergency Surgery, was composed of a questionnaire with 79 items divided into four sections: (1) general information (items 1-7), (2) management of the maternal-fetal unit (items 8-43), (3) management of intracranial hypertension (items 44-76), and (4) specific considerations (items 77-79). RESULTS: One hundred and twenty-two physicians from 110 centers in 35 countries responded. The main findings related to TBI care in pregnant patients included the following: (1) a lack of availability of a specific TBI protocol in pregnancy; (2) an increase in the utilization of magnetic resonance imaging as the primary neuroimaging tool; (3) higher hemoglobin thresholds for transfusion; and (4) a lower utilization of therapeutic hypothermia, neuromuscular blocking agents, and barbiturate coma. We also report large variability in the timing of cesarean section in pregnant patients with TBI (≥ 23 weeks of gestation) needing an emergency craniotomy (simultaneously 23% vs. later cesarean section 50.8%). CONCLUSIONS: Great variability in the management of pregnant patients with severe TBI was identified worldwide from the results of our survey. These findings, highlighting the lack of robust evidence on this topic, will be helpful to stimulate future investigations and to promote educational efforts on this difficult scenario.

Robotic-assisted total knee arthroplasty is associated with the use of thinner polyethylene liners compared to navigation-guided and manual techniques.

PURPOSE: The purpose of this study was to examine the effects of intraoperative technology use on the rate of using polyethylene liners 15 mm or greater during primary total knee arthroplasty (TKA). METHODS: There were 103,295 implants from 16,386 primary unilateral TKAs performed on 14,253 patients at a single institution between 1 January 2018, and 30 June 2022, included in the current study. Robotic assistance and navigation guidance were used in 1274 (8%) and 8345 (51%) procedures, respectively. The remaining 6767 TKAs (41%) were performed manually. Polyethylene liners were manually identified and further subcategorised by implant thickness. Patients who underwent robotic-assisted TKA were younger (p < 0.001) and more likely to be male (p < 0.001) compared to patients who underwent navigation-guided or manual TKAs. RESULTS: Average polyethylene liner thickness was similar between groups (10.5 ± 1.5 mm for robotic-assisted TKAs, 10.9 ± 1.8 mm for navigation-guided TKAs and 10.8 ± 1.8 mm for manual TKAs). The proportions of polyethylene liners 15 mm or greater used were 4.9%, 3.8% and 1.9% for navigation-guided, manual and robotic-assisted procedures, respectively (p < 0.001). Multivariate regression analyses demonstrated that navigation-guided (odds ratio [OR]: 2.6, 95% confidence Interval [CI]: [1.75-4.07], p < 0.001) and manual (OR: 2.0, 95% CI: [1.34-3.20], p = 0.001) procedures were associated with an increased use of polyethylene liners 15 mm or greater. CONCLUSION: Robotic-assisted TKA was associated with a lower proportion of polyethylene liners 15 mm or greater used compared to navigation-guided and manual TKA. These findings suggest that robotic assistance can reduce human error via a more precise cutting system, limit over-resection of the tibia and flexion-extension gap mismatch and ultimately allow for more appropriately sized implants. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

An Artificial Intelligence Chatbot is an Accurate and Useful Online Patient Resource Prior to Total Knee Arthroplasty.

BACKGROUND: Online information is a useful resource for patients seeking advice on their orthopaedic care. While traditional websites provide responses to specific frequently asked questions (FAQs), sophisticated artificial intelligence tools may be able to provide the same information to patients in a more accessible manner. Chat Generative Pretrained Transformer (ChatGPT) is a powerful artificial intelligence chatbot that has been shown to effectively draw on its large reserves of information in a conversational context with a user. The purpose of this study was to assess the accuracy and reliability of ChatGPT-generated responses to FAQs regarding total knee arthroplasty. METHODS: We distributed a survey that challenged arthroplasty surgeons to identify which of the 2 responses to FAQs on our institution's website was human-written and which was generated by ChatGPT. All questions were total knee arthroplasty-related. The second portion of the survey investigated the potential to further leverage ChatGPT to assist with translation and accessibility as a means to better meet the needs of our diverse patient population. RESULTS: Surgeons correctly identified the ChatGPT-generated responses 4 out of 10 times on average (range: 0 to 7). No consensus was reached on any of the responses to the FAQs. Additionally, over 90% of our surgeons strongly encouraged the use of ChatGPT to more effectively accommodate the diverse patient populations that seek information from our hospital's online resources. CONCLUSIONS: ChatGPT provided accurate, reliable answers to our website's FAQs. Surgeons also agreed that ChatGPT's ability to provide targeted, language-specific responses to FAQs would be of benefit to our diverse patient population.

The Financial Burden of Aspirin versus Oral Factor Xa Inhibitors for Thromboprophylaxis Following Total Knee Arthroplasty.

BACKGROUND: Aspirin and oral factor Xa inhibitor thromboprophylaxis regimens are associated with similarly low rates of venous thromboembolism following total knee arthroplasty (TKA). However, the rate of prosthetic joint infection (PJI) is lower with aspirin use. This study aimed to compare the cost differential between aspirin and factor Xa inhibitor thromboprophylaxis with respect to PJI management. METHODS: We used previously published rates of PJI following aspirin and factor Xa inhibitor thromboprophylaxis in primary TKA patients at a single, large institution. Prices for individual drugs were obtained from our hospital's pharmacy service. The cost of PJI included that of 2-stage septic revision, with or without the cost of 1-year follow-up. National data were obtained to determine annual projected TKA volume. RESULTS: The per-patient costs associated with a 28-day course of aspirin versus factor Xa inhibitor thromboprophylaxis were $17.36 and $3,784.20, respectively. Including cost of follow-up, per-patient costs for a 28-day course of aspirin versus factor Xa inhibitors increased to $73,358.76 and $77,125.60, respectively. The weighted average per-patient costs for a 28-day course were $237.38 and $4,370.93, respectively. The annual cost difference could amount to over $14.1 billion in the United States by 2040. CONCLUSIONS: The per-patient cost associated with factor Xa inhibitor thromboprophylaxis is as much as 1,980.6% higher than that of an aspirin regimen due to increased costs of primary treatment, differential PJI rates, and high costs of management. In an era of value-based care, the use of aspirin is associated with major cost advantages.

Unreliable Continuous Treatment Indicators in Propensity Score Analysis.

Propensity score analyses (PSA) of continuous treatments often operationalize the treatment as a multi-indicator composite, and its composite reliability is unreported. Latent variables or factor scores accounting for this unreliability are seldom used as alternatives to composites. This study examines the effects of the unreliability of indicators of a latent treatment in PSA using the generalized propensity score (GPS). A Monte Carlo simulation study was conducted varying composite reliability, continuous treatment representation, variability of factor loadings, sample size, and number of treatment indicators to assess whether Average Treatment Effect (ATE) estimates differed in their relative bias, Root Mean Squared Error, and coverage rates. Results indicate that low composite reliability leads to underestimation of the ATE of latent continuous treatments, while the number of treatment indicators and variability of factor loadings show little effect on ATE estimates, after controlling for overall composite reliability. The results also show that, in correctly specified GPS models, the effects of low composite reliability can be somewhat ameliorated by using factor scores that were estimated including covariates. An illustrative example is provided using survey data to estimate the effect of teacher adoption of a workbook related to a virtual learning environment in the classroom.

Significant variation in computed tomography imaging of pregnant trauma patients: a retrospective multicenter study.

PURPOSE: Following motor vehicle collisions (MVCs), patients often undergo extensive computed tomography (CT) imaging. However, pregnant trauma patients (PTPs) represent a unique population where the risk of fetal radiation may supersede the benefits of liberal CT imaging. This study sought to evaluate imaging practices for PTPs, hypothesizing variability in CT imaging among trauma centers. If demonstrated, this might suggest the need to develop specific guidelines to standardize practice. METHODS: A multicenter retrospective study (2016-2021) was performed at 12 Level-I/II trauma centers. Adult (≥18 years old) PTPs involved in MVCs were included, with no patients excluded. The primary outcome was the frequency of CT. Chi-square tests were used to compare categorical variables, and ANOVA was used to compare the means of normally distributed continuous variables. RESULTS: A total of 729 PTPs sustained MVCs (73% at high speed of ≥ 25 miles per hour). Most patients were mildly injured but a small variation of injury severity score (range 1.1-4.6, p < 0.001) among centers was observed. There was a variation of imaging rates for CT head (range 11.8-62.5%, p < 0.001), cervical spine (11.8-75%, p < 0.001), chest (4.4-50.2%, p < 0.001), and abdomen/pelvis (0-57.3%, p < 0.001). In high-speed MVCs, there was variation for CT head (12.5-64.3%, p < 0.001), cervical spine (16.7-75%, p < 0.001), chest (5.9-83.3%, p < 0.001), and abdomen/pelvis (0-60%, p < 0.001). There was no difference in mortality (0-2.9%, p =0.19). CONCLUSION: Significant variability of CT imaging in PTPs after MVCs was demonstrated across 12 trauma centers, supporting the need for standardization of CT imaging for PTPs to reduce unnecessary radiation exposure while ensuring optimal injury identification is achieved.

Changes in Body Composition and Athletic Performance in National Collegiate Athletic Association Division I Female Field Hockey Athletes Throughout a Competitive Season.

ABSTRACT: Summer, LC, Cheng, R, Moran, JT, Lee, M, Belanger, AJ, TaylorIV, WL, and Gardner, EC. Changes in body composition and athletic performance in National Collegiate Athletic Association Division I female field hockey athletes throughout a competitive season. J Strength Cond Res 38(1): 146-152, 2024-The purposes of this study were (a) to analyze the changes in total and regional body composition measurements in a National Collegiate Athletic Association (NCAA) Division I female field hockey team throughout a 17-game competitive season using dual X-ray absorptiometry (DXA); (b) to examine improvements, if any, in athletic performance measures after a season; and (c) to report on the relationship between these body composition changes and changes in athletic performance. Preseason and postseason dual-energy DXA and performance data from the 2019-2020 season were retrospectively identified for 20 field players (forwards, midfielders, and defenders). Body composition data included total and regional fat mass, lean mass, and body fat percentage, whereas athletic performance measures included the vertical jump, 10-yard dash, and pro-agility (5-10-5) shuttle run. All variables were quantitative and analyzed using paired t -tests or its nonparametric equivalent and an alpha level of p < 0.05 was used to determine significance. After a competitive season, athletes had significant decreases in fat mass and increases in lean mass in their arms, legs, trunks, gynoids, and total body measurements. Android fat mass and body fat percentage also decreased. Athletes performed significantly better on the pro-agility shuttle run at the end of the season, but no significant differences were observed in other performance metrics. Moderate correlations were observed between changes in body composition (total fat mass and total lean mass) and changes in athletic performance. Our study provides a novel, longitudinal assessment of body composition and athletic performance for elite female field hockey athletes that will help trainers and coaches better understand how these variables change throughout a season and allow them to better prepare their players for competitive success.

Total knee arthroplasty survivorship and outcomes in young patients: a review of the literature and 40-year update to a longitudinal study.

INTRODUCTION: Growing numbers of younger patients are electing to undergo total knee arthroplasty (TKA) for end-stage osteoarthritis. The purpose of this study was to compare established literature regarding TKA outcomes in patients under age 55, to data from an ongoing longitudinal young patient cohort curated by our study group. Further, we aimed to provide a novel update on survivorship at 40 years post-TKA from our longitudinal cohort. METHODS: A literature search was conducted using the electronic databases PubMed, Embase, and Cochrane Library, using terms related to TKA, patients under age 55, and osteoarthritis. Demographic and outcome data were extracted from all studies that met the inclusion criteria. Data were divided into the "longitudinal study (LS) group," and the "literature review (LR) group" based on the patient population of the study from which it came. RESULTS: After screening, 10 studies met the inclusion criteria; 6 studies comprised the LR group, and 4 studies comprised the LS group. 2613 TKAs were performed among the LR group, and 114 TKAs were longitudinally followed in the LS group. The mean patient ages of the LR and LS groups were 46.1 and 51, respectively. Mean follow-up was 10.1 years for the LR group. Mean postoperative range of motion was 113.6° and 114.5° for the LR and LS groups, respectively. All-cause survivorship reported at 10 years or less ranged from 90.6% to 99.0%. The LS cohort studies reported survivorship ranges of 70.1-70.6% and 52.1-65.3% at 30 and 40 years, respectively. CONCLUSIONS: Young TKA patients demonstrated improved functionality at each follow-up time point assessed. Survivorship decreased with increasing lengths of follow-up, ultimately ranging from 52.1-65.3% at 40 years post-TKA. The paucity of literature on long-term TKA outcomes in this patient population reinforces the necessity of further research on this topic.

Mass spectrometry-based proteomics profiling of dogs with and without oral diseases: a systematic review.

BACKGROUND: Understanding the distinct proteomics profiles in dogs' oral biofluids enhances diagnostic and therapeutic insights for canine oral diseases, fostering cross-species translational research in dentistry and medicine. This study aimed to conduct a systematic review to investigate the similarities and differences between the oral biofluids' proteomics profile of dogs with and without oral diseases. METHODS: PubMed, Web of Science, and Scopus were searched with no restrictions on publication language or year to address the following focused question: "What is the proteome signature of healthy versus diseased (oral) dogs' biofluids?" Gene Ontology enrichment and the Kyoto Encyclopedia of Genes and Genomes pathway analyses of the most abundant proteins were performed. Moreover, protein-protein interaction analysis was conducted. The risk of bias (RoB) among the included studies was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklist for Studies Reporting Prevalence Data. RESULTS: In healthy dogs, the proteomic analysis identified 5,451 proteins, with 137 being the most abundant, predominantly associated with 'innate immune response'. Dogs with oral diseases displayed 6,470 proteins, with distinct associations: 'defense response to bacterium' (periodontal diseases), 'negative regulation of transcription' (dental calculus), and 'positive regulation of transcription' (oral tumors). Clustering revealed significant protein clusters in each case, emphasizing the diverse molecular profiles in health and oral diseases. Only six studies were provided to the JBI tool, as they encompassed case-control evaluations that compared healthy dogs to dogs with oral disease(s). All included studies were found to have low RoB (high quality). CONCLUSION: Significant differences in the proteomics profiles of oral biofluids between dogs with and without oral diseases were found. The synergy of animal proteomics and bioinformatics offers a promising avenue for cross-species research, despite persistent challenges in result validation.

Genomic characterization of the adolescent idiopathic scoliosis-associated transcriptome and regulome.

Adolescent idiopathic scoliosis (AIS), a sideways curvature of the spine, is the most common pediatric musculoskeletal disorder, affecting ~3% of the population worldwide. However, its genetic bases and tissues of origin remain largely unknown. Several genome-wide association studies (GWAS) have implicated nucleotide variants in non-coding sequences that control genes with important roles in cartilage, muscle, bone, connective tissue and intervertebral disks (IVDs) as drivers of AIS susceptibility. Here, we set out to define the expression of AIS-associated genes and active regulatory elements by performing RNA-seq and chromatin immunoprecipitation-sequencing against H3 lysine 27 acetylation in these tissues in mouse and human. Our study highlights genetic pathways involving AIS-associated loci that regulate chondrogenesis, IVD development and connective tissue maintenance and homeostasis. In addition, we identify thousands of putative AIS-associated regulatory elements which may orchestrate tissue-specific expression in musculoskeletal tissues of the spine. Quantification of enhancer activity of several candidate regulatory elements from our study identifies three functional enhancers carrying AIS-associated GWAS SNPs at the ADGRG6 and BNC2 loci. Our findings provide a novel genome-wide catalog of AIS-relevant genes and regulatory elements and aid in the identification of novel targets for AIS causality and treatment.

Lymphatic/blood vessel plasticity: motivation for a future research area based on present and past observations.

The lymphatic system plays a significant role in homeostasis and drainage of excess fluid back into venous circulation. Lymphatics are also associated with a number of diseases including lymphedema, tumor metastasis, and various lymphatic malformations. Emerging evidence suggests that lymphatics might have a bigger connection to the blood vascular system than originally presumed. As these two systems are often studied in isolation, several knowledge gaps exist surrounding what constitutes lymphatic vascular plasticity, under what conditions it arises, and where structures characteristic of plasticity can form. The objective of this review is to overview current structural, cell lineage-based, and cell identity-based evidence for lymphatic plasticity. These examples of plasticity will then be considered in the context of potential clinical and surgical implications of this evolving research area. This review details our current understanding of lymphatic plasticity, highlights key unanswered questions in the field, and motivates future research aimed at clarifying the role and therapeutic potential of lymphatic plasticity in disease.

Estimation of shear stress heterogeneity along capillary segments in angiogenic rat mesenteric microvascular networks.

OBJECTIVE: Fluid shear stress is thought to be a regulator of endothelial cell behavior during angiogenesis. The link, however, requires an understanding of stress values at the capillary level in angiogenic microvascular networks. Critical questions remain. What are the stresses? Do capillaries experience similar stress magnitudes? Can variations explain vessel-specific behavior? The objective of this study was to estimate segment-specific shear stresses in angiogenic networks. METHODS: Images of angiogenic networks characterized by increased vascular density were obtained from rat mesenteric tissues stimulated by compound 48/80-induced mast cell degranulation. Vessels were identified by perfusion of a 40 kDa fixable dextran prior to harvesting and immunolabeling for PECAM. Using a network flow-based segment model with physiologically relevant parameters, stresses were computed per vessel for regions across multiple networks. RESULTS: Stresses ranged from 0.003 to 2328.1 dyne/cm2 and varied dramatically at the capillary level. For all regions, the maximum segmental shear stresses were for capillary segments. Stresses along proximal capillaries branching from arteriole inlets were increased compared to stresses along capillaries in more distal regions. CONCLUSIONS: The results highlight the variability of shear stresses along angiogenic capillaries and motivate new discussions on how endothelial cells may respond in vivo to segment-specific microenvironment during angiogenesis.