Elucidating the roles of electrolytes and hydrogen bonding in the dewetting dynamics of the tear film.

This study explores the impact of electrostatic interactions and hydrogen bonding on tear film stability, a crucial factor for ocular surface health. While mucosal and meibomian layers have been extensively studied, the role of electrolytes in the aqueous phase remains unclear. Dry eye syndrome, characterized by insufficient tear quantity or quality, is associated with hyperosmolality, making electrolyte composition an important factor that might impact tear stability. Using a model buffer solution on a silica glass dome, we simulated physiologically relevant tear film conditions. Sodium chloride alone induced premature dewetting through salt crystal nucleation. In contrast, trace amounts of solutes with hydroxyl groups (sodium phosphate dibasic, potassium phosphate monobasic, and glucose) exhibited intriguing phenomena: quasi-stable films, solutal Marangoni-driven fluid influx increasing film thickness, and viscous fingering due to Saffman-Taylor instability. These observations are rationalized by the association of salt solutions with increased surface tension and the propensity of hydroxyl-group-containing solutes to engage in significant hydrogen bonding, altering local viscosity. This creates a viscosity contrast between the bulk buffer solution and the film region. Moreover, these solutes shield the glass dome, counteracting sodium chloride crystallization. These insights not only advance our understanding of tear film mechanics but also pave the way for predictive diagnostics in dry eye syndrome, offering a robust platform for personalized medical interventions based on individual tear film composition.

Metformin mitigates adipogenesis of fibro-adipogenic progenitors after rotator cuff tears via activating mTOR/ULK1-mediated autophagy.

Muscular fatty infiltration is a common issue after rotator cuff tears (RCTs), which impair shoulder function. Females suffer a higher prevalence and a more severe degree of muscular fatty infiltration after RCT when compared with males, with the underlying mechanisms remaining unclear. Fibro-adipogenic progenitors (FAPs) are the primary source of muscular fatty infiltration following RCT. Our findings disclose that gender-specific disparities in muscular fatty infiltration are linked to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Furthermore, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Together, our study reveals that gender differences in muscular fatty infiltration arise from distinct autophagic activities. Metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.NEW & NOTEWORTHY The current study demonstrated that gender-specific disparities in muscular fatty infiltration are attributed to mTOR/ULK1-mediated autophagy of FAPs. Decreased autophagic activity contributes to adipogenic differentiation in female FAPs after RCT. Moreover, metformin could enhance mTOR/ULK1-mediated autophagic processes of FAPs, thereby alleviating fatty infiltration and improving shoulder functionality after RCT. Therefore, metformin could be a promising noninvasive intervention to ameliorate muscular fatty infiltration of RCT.

Effect of Acupuncture on Tear Proteomics in Patients with Video Display Terminal-Related Dry Eye.

Acupuncture is widely used to treat dry eye disease (DED), but its effect has not been reported in treating video display terminal (VDT)-related dry eye, and the mechanism of acupuncture on VDT-related dry eye is also unknown. In our study, the tear proteome was compared with identifying possible mechanisms and biomarkers for predicting acupuncture effectiveness in VDT-related dry eye. The results showed that the ocular surface disease index scores were significantly different between the acupuncture group (AC group) and artificial tears group (AT group) at the end of the study, whereas tear film breakup time (TFBUT) and Schirmer I test (SIT) were not significantly different between the groups. Proteome changes pre- and post-treatment in the AC group were associated with B cell-related immune processes, inflammation, glycolysis, and actin cytoskeleton. Furthermore, the proteins hexosaminidase A and mannose-binding lectin 1 could prospectively predict whether acupuncture treatment was effective. Therefore, we believe that acupuncture can provide greater improvement in the clinical symptoms of VDT-related dry eye than artificial tears. The mechanism of acupuncture in VDT-related dry eye treatment may be associated with glycolysis- and actin cytoskeleton remodeling-mediated inflammatory and immune processes. Additionally, hexosaminidase A and mannose-binding lectin 1 are biomarkers for predicting the efficacy of acupuncture for VDT-related dry eye.

Bisphenol A triggers activation of ocular immune system and aggravates allergic airway inflammation.

Bisphenol A (BPA) is widely used in manufacturing plastic products, and it has been reported that exposure through the airway or orally aggravates allergic airway inflammation. Because BPA is detected in the atmosphere and indoor environments, the eyes can also be exposed to BPA. After ocular exposure to BPA and antigen via eye drops, we observed enhanced antigen uptake of antigen-presenting cells (APCs) in tear duct-associated lymphoid tissue (TALT). Additionally, we observed the formation of germinal center (GC) B cells in TALT and induction of allergic airway inflammation in mice sensitized with BPA and antigen via eye drops, followed by airway antigen exposure. We also found that DNAX-activating protein of 12 kDa (DAP12)-deficient mice displayed impaired activation of APCs enhanced by ocular exposure to BPA. These results indicate that ocular sensitization to BPA and allergen triggers allergic inflammation via TALT activation, and that DAP12 might be a key molecule for modulating the ocular immune system.

Ocular tear fluid biomarkers collected by contact lenses.

PURPOSE: To collect tear fluid biomarkers from contact lenses (CLs) and determine the impact of CL wear duration. METHODS: Rabbits were fitted with commercial etafilcon A CLs, which were collected after 1 min, 4 and 8 h (n = 4/time point). Tear fluid proteins and cytokines were extracted from the CLs and quantified. An exploratory comparison was performed between CLs and Schirmer Strips (SS) for a 1 min duration. RESULTS: The concentration of MUC5AC was significantly higher after 4 h of CL wear. The expression of all investigated cytokines (IL-1α, IL-1ß, IL-8, IL-17A, IL-21, Leptin, MIP-1ß, MMP-9, NCAM-1, and TNF-α) was detectable after 1 min of CL wear, and over time, all showed significant variations throughout the 8-h CL wear period. Notably, IL-1α significantly increased by 8 h of CL wear, while MMP-9 decreased. Albumin and lysozyme did not show significant variations with CL wear. Differences between CLs and SS after 1 min were statistically significant for albumin, Leptin, TNF-α, IL-1α, IL-1ß, and IL-8. CONCLUSIONS: The duration of CL wear significantly affects the collection of some tear fluid biomarkers. Albumin, MUC5AC, and cytokines may have individual and synergistic diagnostic or prognostic potential. CLs and SS were similar for lysozyme and MUC5AC but differed in the collection of albumin and some cytokines. CLs are a viable tear fluid collection method for biomarker analyses and can be immediately added as a routine clinical test by being FDA-approved medical devices.

Eye infection risks from Pseudomonas aeruginosa via hand soap and eye drops.

Eye infections from bacterial contamination of bulk-refillable liquid soap dispensers and artificial tear eye drops continue to occur, resulting in adverse health outcomes that include impaired vision or eye enucleation. Pseudomonas aeruginosa (P. aeruginosa), a common cause of eye infections, can grow in eye drop containers and refillable soap dispensers to high numbers. To assess the risk of eye infection, a quantitative microbial risk assessment for P. aeruginosa was conducted to predict the probability of an eye infection for two potential exposure scenarios: (i) individuals using bacteria-contaminated eye drops and (ii) contact lens wearers washing their hands with bacteria-contaminated liquid soap prior to placing the lens. The median risk of an eye infection using contaminated eye drops and hand soap for both single and multiple exposure events (per day) ranged from 10-1 to 10-4, with contaminated eye drops having the greater risk. The concentration of P. aeruginosa was identified as the parameter contributing the greatest variance on eye infection risk; therefore, the prevalence and level of bacterial contamination of the product would have the greatest influence on health risk. Using eye drops in a single-use container or with preservatives can mitigate bacterial growth, and using non-refillable soap dispensers is recommended to reduce contamination of hand soap. Given the opportunistic nature of P. aeruginosa and its ability to thrive in unique environments, additional safeguards to mitigate bacterial growth and exposure are warranted.IMPORTANCEPseudomonas aeruginosa (P. aeruginosa) is a pathogen that can persist in a variety of unusual environments and continues to pose a significant risk for public health. This quantitative microbial risk assessment (QMRA) estimates the potential human health risks, specifically for eye infections, associated with exposure to P. aeruginosa in bacteria-contaminated artificial tear eye drops and hand soap. This study applies the risk assessment framework of QMRA to evaluate eye infection risks through both consumer products. The study examines the prevalence of this pathogen in eye drops and soap, as well as the critical need to implement measures that will mitigate bacterial exposure (e.g., single-use soap dispensers and eye drops with preservatives). Additionally, limitations and challenges are discussed, including the need to incorporate data regarding consumer practices, which may improve exposure assessments and health risk estimates.

Assessing the efficacy of the Stop OsteoARthritis (SOAR) program: A randomized delayed-controlled trial in persons at increased risk of early onset post-traumatic knee osteoarthritis.

OBJECTIVE: Assess the efficacy of an 8-week virtual, physiotherapist (PT)-guided knee health program (Stop OsteoARthritis (SOAR)) to improve knee extensor strength in individuals at risk of post-traumatic knee osteoarthritis (PTOA). METHOD: In this superiority, randomized delayed-control trial, persons aged 16-35 years, 1-4 years after a self-reported knee joint injury were randomly assigned (1:1) to receive the SOAR program immediately (experimental group) or after a 9-week delay (control group). SOAR includes 1) one-time Knee Camp (virtual PT-guided group education, knee assessment, 1:1 exercise and physical activity (PA) goal-setting); 2) Weekly personalized home-based exercise and PA program with tracking; 3) Weekly 1:1 PT counseling (virtual). The primary outcome was a change in isokinetic knee extensor strength (baseline to 9-weeks). Additional outcomes included change in self-reported knee-related quality-of-life (QOL), self-efficacy, self-management and kinesiophobia, and PA (accelerometer) at 9 and 18-weeks. Linear regression models estimated the effect of the 8-week intervention at the primary endpoint (9-week). RESULTS: 49 of 54 randomized participants completed the study (91%). Participants were a mean ± standard deviation age of 27 ± 5.0 years, and 2.4 ± 0.9 years post-injury. No mean between group differences for the primary (0.05; 95% confidence interval (CI): -0.10, 0.19) or other outcomes were seen at 9 weeks except for greater improvements in perceived self-management (Partner in Health Scale; 11.3/96, 95%CI: 5.5, 17.1) and kinesiophobia (Tampa Scale of Kinesiophobia; -4.4/33, 95%CI: -7.0, -1.8). CONCLUSION: For active persons with elevated risk of PTOA, an 8-week SOAR program did not change knee-related strength, QOL, self-efficacy, or PA, on average, but may benefit the ability to self-manage knee health and kinesiophobia.

Zoledronate alleviates subchondral bone collapse and articular cartilage degeneration in a rat model of rotator cuff tear arthropathy.

OBJECTIVE: To evaluate the humeral head bone volume of patients with cuff tear arthropathy (CTA) and examine the therapeutic effect of zoledronate in a rat modified model of CTA (mCTA). DESIGN: The bone mass in patients with CTA was measured using Hounsfield units from CT images. The mCTA was induced by transecting the rotator cuff, biceps brachii tendon, and superior half of the joint capsule in adult rat shoulders. A single subcutaneous injection of zoledronate was followed by bone histomorphometry and immunohistochemistry of the humeral head, as well as the Murine Shoulder Arthritis Score (MSAS) assessment. RESULTS: The humeral head bone volume was decreased in patients with CTA. In the mCTA model, M1 macrophages were increased in the synovium and were decreased by zoledronate treatment. The increased expressions of TNF-α, IL-1ß and IL-6 in mCTA synovium and articular cartilage were suppressed in the zoledronate-treated mCTA group. The expression of catabolic enzymes in the articular cartilage and MSAS showed similar results. The zoledronate-treated mCTA group showed a decreased subchondral bone collapse with a decreased RANKL/OPG expression ratio and a suppressed number of osteoclasts compared with the control mCTA group. The enhanced expressions of HMGB1 and S100A9 in the mCTA shoulders were eliminated in the zoledronate-treated mCTA group. CONCLUSIONS: The humeral head subchondral bone was decreased in patients with CTA. In the mCTA model, the collapse and osteoarthritic changes were prevented by zoledronate administration. Zoledronate seemed to suppress the number of M1 macrophages in the synovium and osteoclasts in the subchondral bone.

Causal relationships between pain, medical treatments, and knee osteoarthritis: A graphical causal model to guide analyses.

OBJECTIVE: Randomized controlled trials (RCTs) are a gold standard for estimating the benefits of clinical interventions, but their decision-making utility can be limited by relatively short follow-up time. Longer-term follow-up of RCT participants is essential to support treatment decisions. However, as time from randomization accrues, loss to follow-up and competing events can introduce biases and require covariate adjustment even for intention-to-treat effects. We describe a process for synthesizing expert knowledge and apply this to long-term follow-up of an RCT of treatments for meniscal tears in patients with knee osteoarthritis (OA). METHODS: We identified 2 post-randomization events likely to impact accurate assessment of pain outcomes beyond 5 years in trial participants: loss to follow-up and total knee replacement (TKR). We conducted literature searches for covariates related to pain and TKR in individuals with knee OA and combined these with expert input. We synthesized the evidence into graphical models. RESULTS: We identified 94 potential covariates potentially related to pain and/or TKR among individuals with knee OA. Of these, 46 were identified in the literature review and 48 by expert panelists. We determined that adjustment for 50 covariates may be required to estimate the long-term effects of knee OA treatments on pain. CONCLUSION: We present a process for combining literature reviews with expert input to synthesize existing knowledge and improve covariate selection. We apply this process to the long-term follow-up of a randomized trial and show that expert input provides additional information not obtainable from literature reviews alone.

Retinal Tear and Retinal Detachment after Cataract Surgery in Eyes with a Previous History of Treated Phakic Retinal Tears.

PURPOSE: To investigate the incidence and outcomes of retinal tear (RT) and retinal detachment (RD) after cataract extraction in patients with a history of previous phakic RT. DESIGN: Retrospective case series. PARTICIPANTS: Patients with phakic eyes with RT that were treated successfully with laser photocoagulation or cryotherapy and subsequently underwent cataract surgery. METHODS: A retrospective review of data between April 1, 2012, and May 31, 2023, was performed. Exclusions included prior vitreoretinal surgery before cataract removal and follow-up of less than 6 months after cataract surgery. MAIN OUTCOME MEASURES: The incidence of RTs and RDs after cataract surgery, along with visual and anatomic outcomes. RESULTS: Of 12 109 phakic eyes treated for RTs, 1039 eyes (8.6%) underwent cataract surgery. After exclusions, 713 eyes of 660 patients were studied. The mean ± standard deviation follow-up period after cataract surgery was 34.8 ± 24.6 months, with a median of 239 and 246 days to a new RT or RD development, respectively. The overall incidence of RT and RD diagnosis after cataract surgery was 7.3% (52/713; 2.9% and 4.3%, respectively), with a 1-year incidence of 5.6% (2.2% and 3.4%, respectively). Multivariable regression analysis identified a higher risk of RT and RD among younger individuals (odds ratio [OR], 1.034; P = 0.028), male patients (OR, 2.058; P = 0.022), and those with a shorter interval between laser treatment and cataract surgery (OR, 1.001; P = 0.011). Single-surgery anatomic success for the RD repair was achieved in 25 eyes (80.6%) at 3 months, with a 100% final reattachment rate. The median final visual acuity was 0.10 logarithm of the minimum angle of resolution (logMAR; Snellen equivalent, 20/25) for RT, showing no significant change from after cataract surgery, and 0.18 logMAR (Snellen equivalent, 20/30) for RD, a significant worsening from after cataract surgery. CONCLUSIONS: One year after cataract surgery, the rate of diagnosed RT and RD in patients with previously treated RTs was relatively high, occurring in nearly 1 in 18 eyes. Higher risk was noted among younger individuals, male patients, and patients with a shorter interval between initial treatment for RT and cataract surgery. Retinal detachment repair achieved good anatomic results, but vision declined. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Comparison of early changes in tear film protein profiles after small incision lenticule extraction (SMILE) and femtosecond LASIK (FS-LASIK) surgery.

BACKGROUND: Small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (LASIK) are widely used surgical methods to correct myopia with comparable efficacy, predictability, and safety. We examined and compared the early changes of tear protein profiles after SMILE and FS-LASIK surgery in order to find possible differences in the initial corneal healing process. METHODS: SMILE operations for 26 eyes were made with Visumax femtosecond laser. In FS-LASIK surgery for 30 eyes, the flaps were made with Ziemer FEMTO LDV Z6 femtosecond laser and stromal ablation with Wavelight EX500 excimer laser. Tear samples were collected preoperatively, and 1.5 h and 1 month postoperatively using glass microcapillary tubes. Tear protein identification and quantification were performed with sequential window acquisition of all theoretical fragment ion spectra mass spectrometry (SWATH-MS). RESULTS: Immediately (1.5 h) after we found differences in 89 proteins after SMILE and in 123 after FS-LASIK operation compared to preoperative protein levels. Of these differentially expressed proteins, 48 proteins were common for both surgery types. There were, however, quantitative differences between SMILE and FS-LASIK. Upregulated proteins were mostly connected to inflammatory response and migration of the cells connected to immune system. One month after the operation protein expressions levels were returned to baseline levels with both surgical methods. CONCLUSIONS: Our study showed that immediate changes in protein profiles after SMILE and FS-LASIK surgeries and differences between the methods are connected to inflammatory process, and the protein levels quickly return to the baseline within 1 month. The differences in protein profiles between the methods are probably associated with the different size of the epithelial wound induced.

Human tear film protein sampling using soft contact lenses.

BACKGROUND: Human tear protein biomarkers are useful for detecting ocular and systemic diseases. Unfortunately, existing tear film sampling methods (Schirmer strip; SS and microcapillary tube; MCT) have significant drawbacks, such as pain, risk of injury, sampling difficulty, and proteomic disparities between methods. Here, we present an alternative tear protein sampling method using soft contact lenses (SCLs). RESULTS: We optimized the SCL protein sampling in vitro and performed in vivo studies in 6 subjects. Using Etafilcon A SCLs and 4M guanidine-HCl for protein removal, we sampled an average of 60 ± 31 µg of protein per eye. We also performed objective and subjective assessments of all sampling methods. Signs of irritation post-sampling were observed with SS but not with MCT and SCLs. Proteomic analysis by mass spectrometry (MS) revealed that all sampling methods resulted in the detection of abundant tear proteins. However, smaller subsets of unique and shared proteins were identified, particularly for SS and MCT. Additionally, there was no significant intrasubject variation between MCT and SCL sampling. CONCLUSIONS: These experiments demonstrate that SCLs are an accessible tear-sampling method with the potential to surpass current methods in sampling basal tears.

Neutrophil-driven and interleukin-36γ-associated ocular surface inflammation in chronic Stevens-Johnson syndrome.

PURPOSE: This study aims to elucidate the tear proteome and understand the underlying molecular mechanisms involved in the ocular complications following Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). METHODS: Mass spectrometry (MS) was performed to quantify the tear fluid proteins from chronic SJS/TEN patients (n = 22 eyes) and age- and gender-matched controls (n = 22 eyes). The candidate proteins were validated using ELISA (n = 80 eyes) in tear samples and immunohistochemistry (IHC; n = 12) in eyelid margin specimens. These proteins were compared for significant differences based on age, gender, disease duration, and ocular severity. RESULTS: A total of 1692 tear fluid proteins were identified, of which 470 were significantly differentially regulated in chronic SJS/TEN. The top 10 significantly upregulated proteins were neutrophil secretions including neutrophil elastase (p < .0001), defensin (p < .0001), and matrix metalloproteinase 8 (p < .0001). The presence of neutrophils was confirmed by the upregulation of IL-8 (p < .001) in tears, a key cytokine known for recruiting neutrophils. Additionally, positive expression of myeloperoxidase was observed in the keratinized eyelid margins of SJS/TEN to validate the presence of neutrophils. Among 41 unique proteins identified by MS, IL-36γ (p < .01) was expressed in three SJS/TEN patients and was confirmed in SJS/TEN tears and eyelid margins by ELISA and IHC, respectively. IL-36γ was specifically expressed in the superficial layers of eyelid margin keratinized conjunctiva. The majority of the significantly downregulated proteins were lacrimal gland secretions such as lacritin (p < .0001) and opiorphin (p < .002). Neutrophil elastase (p < .02) was significantly elevated in patients with severe eyelid margin keratinization. CONCLUSION: Our observations indicate a clear correlation between eyelid margin keratinization and the expression of IL-36γ, potentially mediated by neutrophils recruited via IL-8. Future experimental studies are needed to test the role of therapies targeting IL-8 and/or IL-36γ in reducing eyelid margin keratinization and its associated ocular complications in SJS/TEN.

Atmospheric pollutant black carbon induces ocular surface damage in mice.

The threats of air pollution to human health have been gradually discovered, including its effects on eyes. The purpose of the study is to investigate the potential correlation between ocular surface exposure to black carbon and ocular surface structural damage as well as tear film dysfunction. To achieve this goal, 60 6-8-week-aged male BALB/C mice were randomly divided into 4 groups (n = 15). 0.5 mg/ml (group A), 1 mg/ml (group B), 5 mg/ml (group C) black carbon suspension droplets and PBS solution (group D) were used in the right eyes, 4 µl per time of three times per day. Tear break-up time, corneal fluorescein staining scores, and tear volume were assessed before treatment (day 0) and on days 4, 7, 10, and 14 after treatment. On day 14, the mice were sacrificed, and corneal and conjunctival tissues were collected for histological analysis. As the exposure time increased, there were no significant changes in the measured parameters from PBS-treated group of mice (P > 0.05). However, in the black carbon-treated group, there were significant decreases in tear film break-up time, significant increases in corneal fluorescein staining scores, and significant reductions in tear secretion (all P < 0.05). After 14 days, H&E staining of the corneal epithelium showed that in the PBS-treated group of mice, the corneal epithelial cells were neatly arranged, with no inflammatory cell infiltration, while in the black carbon-treated group, the corneal epithelium was significantly thickened, the basal cell arrangement was disrupted, the number of cell layers increased, and there was evidence of inflammatory cell infiltration. In the ultrastructure of the corneal epithelium, it could be observed that the black carbon-treated group had an increased amount of corneal epithelial cell detachment compared to the PBS-treated group, at the same time, the intercellular connections were looser, and there was a decrease in the number of microvilli and desmosomes in the black carbon-treated group. The results indicate that the ocular surface exposure to black carbon can result in a decrease in tear film stability and tear secretion in mice. Moreover, it can induce alterations in the corneal structure.

Raman spectroscopy assisted tear analysis: A label free, optical approach for noninvasive disease diagnostics.

In recent times, tear fluid analysis has garnered considerable attention in the field of biomarker-based diagnostics due to its noninvasive sample collection method. Tears encompass a reservoir of biomarkers that assist in diagnosing not only ocular disorders but also a diverse list of systemic diseases. This highlights the necessity for sensitive and dependable screening methods to employ tear fluid as a potential noninvasive diagnostic specimen in clinical environments. Considerable research has been conducted to investigate the potential of Raman spectroscopy-based investigations for tear analysis in various diagnostic applications. Raman Spectroscopy (RS) is a highly sensitive and label free spectroscopic technique which aids in investigating the molecular structure of samples by evaluating the vibrational frequencies of molecular bonds. Due to the distinct chemical compositions of different samples, it is possible to obtain a sample-specific spectral fingerprint. The distinctive spectral fingerprints obtained from Raman spectroscopy enable researchers to identify specific compounds or functional groups present in a sample, aiding in diverse biomedical applications. Its sensitivity to changes in molecular structure or environment provides invaluable insights into subtle alterations associated with various diseases. Thus, Raman Spectroscopy has the potential to assist in diagnosis and treatment as well as prognostic evaluation. Raman spectroscopy possesses several advantages, such as the non-destructive examination of samples, remarkable sensitivity to structural variations, minimal prerequisites for sample preparation, negligible interference from water, and the aptness for real-time investigation of tear samples. The purpose of this review is to highlight the potential of Raman spectroscopic technique in facilitating the clinical diagnosis of various ophthalmic and systemic disorders through non-invasive tear analysis. Additionally, the review delves into the advancements made in Raman spectroscopy with regards to paper-based sensing substrates and tear analysis methods integrated into contact lenses. Furthermore, the review also addresses the obstacles and future possibilities associated with implementing Raman spectroscopy as a routine diagnostic tool based on tear analysis in clinical settings.

Transcriptome sequencing reveals inflammation and macrophage heterogeneity in subacromial bursa from degenerative shoulder disorders.

PURPOSE: We aimed to investigate the transcriptomic alterations that occur in the subacromial bursa (SAB) following degenerative or traumatic shoulder diseases. MATERIALS AND METHODS: RNA sequencing was employed to evaluate the transcriptomic alterations of the SAB in individuals afflicted with degenerative rotator cuff tear (RCT), traumatic RCT and proximal humerus fracture (PHF). To gain insights into the biological significance of differentially expressed genes (DEGs), we conducted an enrichment analysis utilizing Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. We further utilized single-cell RNA sequencing datasets of SAB from a recently published study to explore the associated cellular dynamics and alterations. RESULTS: We detected 1,790 up-regulated and 1,964 down-regulated DEGs between degenerative RCT and PHF, 2,085 up-regulated and 1,919 down-regulated DEGs between degenerative RCT and traumatic RCT, and 20 up-regulated and 12 down-regulated DEGs between traumatic RCT and PHF. Given the similar expression pattern between traumatic RCT and PHF, they were integrated as the traumatic group. In comparison with the traumatic group, 1,983 up-regulated and 2,205 down-regulated DEGs were detected in degenerative SAB. Enrichment analysis of up-regulated DEGs uncovered an elevated inflammatory and immunologic responses in degenerative SAB. Single-cell transcriptomic analysis revealed macrophage represented the immune cell with the most DEGs between the degenerative and traumatic RCT. CONCLUSION: Our results revealed that the SAB in degenerative RCT exhibited a different transcriptional signature compared to that in traumatic RCT, and enrichment analysis showed immunologic and inflammatory activations. Macrophages may play a fundamental role in this process.

Diagnostic performance of long head of biceps tendon tears on MRI: systematic review and meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to determine the diagnostic performance of conventional MRI and MR arthrography for tendinosis, and partial and complete tears of the long head of the biceps tendon (LHBT) using arthroscopy as the reference standard. MATERIALS AND METHODS: A systematic review was performed using predefined data fields in PubMed, and all articles published from January 2000 up to April 2022 were retrospectively pooled and reviewed. Six MRI studies on complete tear (n = 555) and ten studies on partial tear/tendinosis (n = 2487) were included in the analysis. Two of the included studies in each group investigated the use of MR arthrography. The data sets were analyzed using a univariate approach with the DerSimonian and Laird random effects model and the proportional hazards model. RESULTS: MRI shows high specificities in diagnosing complete tears of the LHBT ranging from 93.0 to 99.0%. Diagnostic sensitivity was more heterogeneous ranging from 55.9 to 90.0%. The overall negative likelihood ratio was 0.29 (95% CI: 0.17-0.50) and the overall positive likelihood ratio was 37.3 (95% CI: 11.9-117.4). The mean sensitivity in diagnosing partial tear/tendinosis of the LHBT was 67.8% (95% CI: 54.3-78.9%) and the specificity was 75.9% (95% CI: 63.6-85.0%), resulting in a balanced accuracy of 71.9%. The overall negative likelihood ratio was 0.44 (95% CI: 0.32-0.59) and the overall positive likelihood ratio was 2.64 (95% CI: 1.91-3.65). CONCLUSION: MRI is highly specific for the diagnosis of complete tears of the LHBT, whereas diagnostic sensitivity was more heterogeneous. The diagnosis of partial tears and/or tendinosis of the LHBT remains challenging on MRI, which may warrant complementary clinical examination or other imaging modalities to increase diagnostic confidence in equivocal cases. CLINICAL RELEVANCE STATEMENT: Conventional MRI and MR arthrography have high diagnostic performance for complete tendon tear when compared to arthroscopy. The diagnosis of tendinosis/partial tears remains challenging and may require comparison with clinical tests and other imaging modalities. KEY POINTS: •There is no clear consensus regarding the primary imaging modality for the evaluation of LHBT disorders. •Conventional MRI and MR arthrography are highly specific in diagnosing complete tears of the LHBT. •Diagnosis of partial tears/tendinosis of the LHBT on conventional MRI and MR arthrography remains a diagnostic challenge.

Artificial intelligence applied to magnetic resonance imaging reliably detects the presence, but not the location, of meniscus tears: a systematic review and meta-analysis.

OBJECTIVES: To review and compare the accuracy of convolutional neural networks (CNN) for the diagnosis of meniscal tears in the current literature and analyze the decision-making processes utilized by these CNN algorithms. MATERIALS AND METHODS: PubMed, MEDLINE, EMBASE, and Cochrane databases up to December 2022 were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Risk of analysis was used for all identified articles. Predictive performance values, including sensitivity and specificity, were extracted for quantitative analysis. The meta-analysis was divided between AI prediction models identifying the presence of meniscus tears and the location of meniscus tears. RESULTS: Eleven articles were included in the final review, with a total of 13,467 patients and 57,551 images. Heterogeneity was statistically significantly large for the sensitivity of the tear identification analysis (I2 = 79%). A higher level of accuracy was observed in identifying the presence of a meniscal tear over locating tears in specific regions of the meniscus (AUC, 0.939 vs 0.905). Pooled sensitivity and specificity were 0.87 (95% confidence interval (CI) 0.80-0.91) and 0.89 (95% CI 0.83-0.93) for meniscus tear identification and 0.88 (95% CI 0.82-0.91) and 0.84 (95% CI 0.81-0.85) for locating the tears. CONCLUSIONS: AI prediction models achieved favorable performance in the diagnosis, but not location, of meniscus tears. Further studies on the clinical utilities of deep learning should include standardized reporting, external validation, and full reports of the predictive performances of these models, with a view to localizing tears more accurately. CLINICAL RELEVANCE STATEMENT: Meniscus tears are hard to diagnose in the knee magnetic resonance images. AI prediction models may play an important role in improving the diagnostic accuracy of clinicians and radiologists. KEY POINTS: • Artificial intelligence (AI) provides great potential in improving the diagnosis of meniscus tears. • The pooled diagnostic performance for artificial intelligence (AI) in identifying meniscus tears was better (sensitivity 87%, specificity 89%) than locating the tears (sensitivity 88%, specificity 84%). • AI is good at confirming the diagnosis of meniscus tears, but future work is required to guide the management of the disease.

Stereomicroscopic analysis of cut marks inflicted by a knife with blade damage.

Skeletal cut mark analysis provides relevant information on the general class characteristics of suspect knife. However, there is a lack of research on the influence of blade damage on cut mark analysis. This study aimed to thoroughly investigate the effects of damaged knife blades on cut marks' morphological and morphometrical characteristics. Fifteen undamaged, non-serrated knives were used to cut human ribs to make control cut marks. The knife blades were then damaged by a series of cuts on the bones. A comparison was made between the control cuts and 3 groups of cut marks inflicted by blades that had been damaged to different degrees. The results showed that the damaged blades created wider cut marks than undamaged one. Kerf morphology was likely to imitate the cuts made by the serrated blades such as an elliptical shape, a V-shaped cross-section and the presence of coarse striations. Wear-related features can affect cut mark analysis as the marks left behind by blades damaged to different degrees showed dissimilar dimensions and morphologies. The findings of this study can be applied to a forensic investigation when cut marks were caused by a knife with a damaged blade.

Reproductive history of parous women and urinary incontinence in midlife: A National Birth Cohort follow-up study.

OBJECTIVE: To investigate how reproductive history was associated with urinary incontinence in midlife. DESIGN: A follow-up study. SETTING: Denmark. POPULATION: A total of 39 977 mothers who participated in the Maternal Follow up (2013-2014) in the Danish National Birth Cohort. National registries provided their reproductive history. METHODS: How parity, mode of birth and obstetric tears associated with urinary incontinence were estimated with adjusted odds ratios (OR) and 95% CI using logistic regression. MAIN OUTCOME MEASURES: Self-reported urinary incontinence including subtypes stress, urge and mixed urinary incontinence. RESULTS: At an average age of 44 years, the prevalence of any urinary incontinence was 32% (21% stress, 2% urge, and 8% mixed urinary incontinence). Women with two births more often had urinary incontinence than women with one birth (OR 1.20, 95% CI 1.10-1.31). Compared with women with only spontaneous births, a history of only caesarean sections was associated with much lower odds of urinary incontinence (OR 0.39, 95% CI 0.35-0.42) and a history of instrumental births with slightly lower odds (OR 0.92, 95% CI 0.86-0.98). Compared with no tear/first-degree tear as the largest tear, episiotomy was associated with less urinary incontinence (OR 0.91, 95% CI 0.86-0.97) whereas third/fourth-degree tears were associated with more (OR 1.14, 95% CI 1.04-1.25). Findings were mainly explained by similar associations with stress and mixed urinary incontinence. CONCLUSIONS: Vaginal birth was associated with a higher risk of long-term urinary incontinence, but our results indicate that this risk may be reduced by shortening the second stage of birth.