Nanopore Blockade Sensors for Quantitative Analysis Using an Optical Nanopore Assay.

Nanopore sensing is a popular biosensing strategy that is being explored for the quantitative analysis of biomarkers. With low concentrations of analytes, nanopore sensors face challenges related to slow response times and selectivity. Here, we demonstrate an approach to rapidly detect species at ultralow concentrations using an optical nanopore blockade sensor for quantitative detection of the protein vascular endothelial growth factor (VEGF). This sensor relies on monitoring fluorescent polystyrene nanoparticles blocking nanopores in a nanopore array of 676 nanopores. The fluorescent signal is read out using a wide-field fluorescence microscope. Nonspecific blockade events are then distinguished from specific blockade events based on the ability to pull the particles out of the pore using an applied electric field. This allows the detection of VEGF at sub-picomolar concentration in less than 15 min.

Prevalence of Presbyphonia in Older Adults With Dysphonia: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to investigate the prevalence of presbyphonia among older adults who report voice complaints. METHOD: We conducted a systematic search of five medical databases to identify studies that reported on presbyphonia as the cause of voice disorders in older adults. The pooled prevalence was calculated using random-effects models and presented as percentages with 95% confidence intervals (CI). The degree of heterogeneity among studies was assessed using I2 statistics. Subgroup analyses were performed to identify the sources of heterogeneity. RESULTS: Out of 764 abstracts from five libraries, 11 studies were included in this systematic review. The pooled prevalence of presbyphonia among older adults with voice disorders is 17.78% (95% CI [12.69, 23.51]). We conducted a subgroup analysis on studies that used laryngeal visualization to confirm the diagnosis for all patients and found that the prevalence of presbyphonia was lower in studies with unrestrictive inclusion criteria (12.84%, 95% CI [8.38, 18.08]) compared to studies with restricted inclusion criteria (22.59%, 95% CI [14.49, 31.88]). CONCLUSIONS: This study suggests that voice disorders in older adults have multiple causes, not predominantly presbyphonia. Overestimation of presbyphonia prevalence occurs if certain diagnoses are excluded at recruitment. This study emphasizes the importance of recognizing the diverse underlying etiologies of dysphonia in older adults; therefore, comprehensive examination and accurate diagnosis are crucial. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.24263029.

Improved Cartilage Protection with Low Molecular Weight Hyaluronic Acid Hydrogel.

Traumatic joint injuries are common, leading to progressive tissue degeneration and the development of osteoarthritis. The post-traumatic joint experiences a pro-inflammatory milieu, initiating a subtle but deteriorative process in cartilage tissue. To prevent or even reverse this process, our group previously developed a tissue-penetrating methacrylated hyaluronic acid (MeHA) hydrogel system, crosslinked within cartilage to restore and/or protect the tissue. In the current study, we further optimized this approach by investigating the impact of biomaterial molecular weight (MW; 20, 75, 100 kDa) on its integration within and reinforcement of cartilage, as well as its ability to protect tissue degradation in a catabolic state. Indeed, the low MW MeHA integrated and reinforced cartilage tissue better than the high MW counterparts. Furthermore, in a 2 week IL-1ß explant culture model, the 20 kDa MeHA demonstrated the most protection from biphasic mechanical loss, best retention of proteoglycans (Safranin O staining), and least aggrecan breakdown (NITEGE). Thus, the lower MW MeHA gels integrated better into the tissue and provided the greatest protection of the cartilage matrix. Future work will test this formulation in a preclinical model, with the goal of translating this therapeutic approach for cartilage preservation.

Evaluation of the Retinal Vessel Density and Subfoveal Choroidal Thickness in Central Cerous Chorioretinopathy Using Optical Coherence Tomography.

PURPOSE: The purpose of this study was to quantitatively assess changes in the subfoveal choroidal thickness (SFCT) and superficial retinal vessel density (SRVD) in acute and chronic central serous chorioretinopathy (CSCR) patients, and estimate the correlation of SFCT and SRVD with best-corrected visual acuity (BCVA), respectively, using spectral domain optical coherence tomography (SD-OCT) and optical coherence tomography angiography (OCTA). METHODS: This was a cross-sectional, case-control study. The study included CSCR patients treated at the Ho Chi Minh City Eye Hospital from May 2022 to October 2022. RESULTS: A total of 91 subjects (182 eyes) were included in this study, with 74 eyes in the unilateral acute CSCR group and 17 eyes in the unilateral chronic CSCR group; 91 eyes in the control group were patients' unaffected other eyes. The mean age was 40.78 ± 1.26 years (ranging from 31 to 45 years). The proportions of male and female patients were 78.0% and 22.0%, respectively. The major symptom was reduced vision, and the mean BCVA was 0.36 ± 0.05 logMAR. The mean SFCT of CSCR eyes was 357.2 ± 11.8 µm, which was 290.4 ± 8.5 µm in the control group (p < 0.05). The mean SRVD of chronic CSCR (24.2 ± 4.94%) and acute CSCR (28 ± 2.33%) eyes was lower compared with the control group (21.7 ± 1.87%). SFCT had a correlation with BCVA (r = -0.490, p < 0.05) in chronic CSCR; the center region of SRVD was likewise correlated with BCVA (r = -0.384, p < 0.05) and the parafoveal region of SRVD was also correlated with BCVA (r = -0.271, p < 0.05). CONCLUSION: Both altered SFCT and SRVD were identified in CSCR patients by SD-OCT and 6 x 6 mm OCT angiography scans, and both were found to be correlated with BCVA. SD-OCT along with OCTA could be a good technique for quantitatively evaluating different CSCR courses.

Prevalence of Voice Disorders in Older Adults: A Systematic Review and Meta-Analysis.

PURPOSE: Voice disorders significantly impair the ability to communicate effectively and reduce the quality of life in older adults; however, its prevalence has not been well established. The aim of our research was to investigate the prevalence and associated factors of voice disorders among the older population. METHOD: Five medical databases were systematically searched for studies that reported the prevalence of voice disorders in older adults. The overall prevalence was exhibited in proportions and 95% confidence intervals (CIs) utilizing random-effects models. Heterogeneity was measured using I 2 statistics. RESULTS: Of 930 articles screened, 13 fulfilled the eligibility criteria, including 10 studies in community-based settings and three in institutionalized settings. An overall prevalence of voice disorders in older adults was estimated to be 18.79% (95% CI [16.34, 21.37], I 2 = 96%). Subgroup analysis showed a prevalence of 33.03% (95% CI [26.85, 39.51], I 2 = 35%) in institutionalized older adults, which was significantly higher than that in the community-based older adults with 15.2% (95% CI [12.65, 17.92], I 2 = 92%). Some factors that influenced the reported prevalence were identified, including types of survey, the definition of voice disorders, sampling methods, and the mean age of the population among included studies. CONCLUSIONS: The prevalence of voice disorders in the older population depends on various factors but is relatively common in older adults. The findings of this study accentuate the necessity for researchers to standardize the protocol for reporting geriatric dysphonia as well as for older adults to express their voice-related problems so that they will receive appropriate diagnosis and treatment.

High production of poly(3-hydroxybutyrate) in Escherichia coli using crude glycerol.

Poly(3-hydroxybutyrate) (PHB) is a prominent bio-plastic and recognized as the potential replacement of petroleum-derived plastics. To make PHB cost-effective, the production scheme based on crude glycerol was developed using Escherichia coli. The heterogeneous synthesis pathway of PHB was introduced into the E. coli strain capable of efficiently utilizing glycerol. The central metabolism that links to the synthesis of acetyl-CoA and NADPH was further reprogrammed to improve the PHB production. Key genes were targeted for manipulation, involving those in glycolysis, the pentose phosphate pathway, and the tricarboxylic cycle. As a result, the engineered strain gained a 22-fold increase in the PHB titer. Finally, the fed-batch fermentation was conducted with the producer strain to give the PHB titer, content, and productivity reaching 36.3 ± 3.0 g/L, 66.5 ± 2.8%, and 1.2 ± 0.1 g/L/h, respectively. The PHB yield on crude glycerol accounts for 0.3 g/g. The result indicates that the technology platform as developed is promising for the production of bio-plastics.

High electrochemical performance of ink solution based on manganese cobalt sulfide/reduced graphene oxide nano-composites for supercapacitor electrode materials.

Large scale supercapacitor electrodes were prepared by 3D-printing directly on a graphite paper substrate from ink solution containing manganese cobalt sulfide/reduced graphene oxide (MCS/rGO) nanocomposites. The MCS/rGO composite solution was synthesized through the dispersion of MCS NPs and rGO in dimethylformamide (DMF) solvent at room temperature. Their morphology and composition were investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray diffraction (EDS). The role of rGO on decreasing charge transfer resistance and enhancing ion exchange was discussed. The MCS/rGO electrode exhibits an excellent specific capacitance of 3812.5 F g-1 at 2 A g-1 and it maintains 1780.8 F g-1 at a high current density of 50 A g-1. The cycling stability of the electrodes reveals capacitance retention of over 92% after 22 000 cycles at 50 A g-1.

Therapeutic Effect and Optimal Electrode Placement of Transcutaneous Neuromuscular Electrical Stimulation in Patients with Post-Stroke Dysphagia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: To date, there is no conclusive evidence that transcutaneous neuromuscular electrical stimulation (TNMES) benefits patients with post-stroke dysphagia (PSD). In addition, the optimal TNMES electrode placement has not been well-established. This systematic review and meta-analysis were conducted to investigate these two research gaps. Methods: Five major databases were systematically searched for randomized controlled trials (RCTs) through January 2022. Effect sizes were computed using Hedges' g statistic, which were then entered into the random-effects model to obtain pooled effect estimates. Results: Twenty-four RCTs met the eligibility criteria. On the improvement of swallowing function, TNMES alone was not superior to conventional swallowing therapies (CSTs); combined therapy of TNMES and CSTs significantly surpassed CSTs alone (standardized mean difference (SMD) = 0.91, 95% confidence interval (95% CI): 0.68 to 1.14, p < 0.0001; I2 = 63%). Moreover, significant pooled effect sizes were observed in subgroups with horizontal electrode placement above the hyoid bone (SMD = 0.94, 95% CI: 0.72 to 1.16; I2 = 0%) and horizontal electrode placement just above and below the hyoid bone (SMD = 0.87, 95% CI: 0.59 to 1.14; I2 = 0%). The largest pooled effect size was observed in the subgroup that individualized electrode placement according to dysphagia evaluation (SMD = 1.65, 95% CI: 0.38 to 2.91; I2 = 90%). Conclusion: TNMES should be used in combination with CSTs for PSD. Horizontal electrode placement should target suprahyoid muscles or both suprahyoid and thyrohyoid muscles.

Association between Exposure to Ambient Air Pollution and the Risk of Rheumatoid Arthritis in Taiwan: A Population-Based Retrospective Cohort Study.

Background: The association between ambient air pollution (AAP) and the risk of Rheumatoid arthritis (RA) remains debatable. We conducted a population-based cohort study to investigate the association between exposure to AAP and the risk of RA in Taiwan. Methods: We analyzed and combined the longitudinal Health Insurance Database (LHID) and the Taiwan Air Quality-Monitoring Database (TAQMD), which were in line with the residential areas. We calculated the RA incidence rates per 10,000 person-years exposed to each quartile of PM2.5 or PM10 concentrations or RH. Hazards regression was conducted to analyze the associations between exposure to each quartile of PM2.5 and PM10 concentrations and the risk of developing RA. The hazard ratios of RA were analyzed between participants exposed to annual average concentrations of PM2.5 and PM10. All the hazard ratios of RA were stratified by gender and adjusted for age and relative humidity (RH). A p-value < 0.05 was considered statistically significant. Results: Among 722,885 subjects, 9338 RA cases were observed. The analyses adjusted for age, gender, and humidity suggested an increased risk of developing RA in the exposure to PM2.5 in the last quartile (Q4) with the adjusted hazard ratio (aHR) was 1.053 (95%CI: 1.043 to 1.063). Conclusion: Our study suggests that exposure to PM2.5 is associated with an increased risk of RA. The finding has implications for policymaking to develop coping strategies to confront AAP as a risk factor for RA.

Postnatal development of projections of the postrhinal cortex to the entorhinal cortex in the rat.

The ability to encode and retrieve contextual information is an inherent feature of episodic memory that starts to develop during childhood. The postrhinal cortex, an area of the parahippocampal region, has a crucial role in encoding object-space information and translating egocentric to allocentric representation of local space. The strong connectivity of POR with the adjacent entorhinal cortex, and consequently the hippocampus, suggests that the development of these connections could support the postnatal development of contextual memory. Here, we report that postrhinal cortex projections of the rat develop progressively from the first to the third postnatal week starting in the medial entorhinal cortex before spreading to the lateral entorhinal cortex. The increased spread and complexity of postrhinal axonal distributions is accompanied by an increased complexity of entorhinal dendritic trees and an increase of postrhinal - entorhinal synapses, which supports a gradual maturation in functional activity.SIGNIFICANCE STATEMENTPostrhinal-entorhinal cortical interplay mediates important aspects of encoding and retrieval of contextual information that is important for episodic memory. To better understand the function of the postrhinal interactions with the entorhinal cortex we studied the postnatal development of the connection between the two cortical areas. Our study describes the postnatal development of the postrhinal-to-entorhinal projections as established with neuroanatomical and electrophysiological methods. The projections gradually reach functionally different areas of the entorhinal cortex, reaching the area involved in spatial functions first, followed by the part involved in representing information about objects and sequences of events.

Transient global amnesia: 7 Tesla MRI reveals more hippocampal lesions with diffusion restriction compared to 1.5 and 3 Tesla MRI.

PURPOSE: To assess the ability of 7 T MRI to detect hippocampal DWI lesions in the acute phase of TGA compared to 1.5 T/3 T MRI. METHODS: Patients with a clinical diagnosis consistent with TGA and a 1.5/3 T MRI underwent an additional 7 T MRI when the 7 T system was available for clinical use, thus serving as their own controls. RESULTS: Thirteen TGA patients with a median age of 68.5 years (range 46-77 years) were included and imaged at 1.5/3 T (median 17 h after onset of symptoms, range 3-23 h) and 7 T (median 23 h after onset, range 15-46 h). The 7 T MRIs were performed a median of 15 h after the 1.5/3 T MRIs (range 1-28 h). At 1.5/3 T, six patients (46%) were found to have at least one hippocampal DWI-lesions supporting the TGA diagnosis, which increased to 11 patients (85%) when examined at 7 T (p = 0.03). At 1.5/3 T, nine hippocampal DWI lesions were detected, which increased to 19 at 7 T, giving an increased detection rate of 111% (p = 0.002). Both neuroradiologists found the hippocampal DWI lesions at 7 T to have higher conspicuity and be easier to categorize as true findings compared to 1.5/3 T. CONCLUSION: Seven-Tesla MRI showed both a statistically significant increase in the total number of detected hippocampal DWI lesions and the proportion of patients with at least one hippocampal DWI lesion supporting the TGA diagnosis compared to 1.5/3 T. Clinical use of 7 T will increase the number of patients having their TGA diagnosis supported by MRI, which can be especially useful in patients with negative 1.5/3 T MRI and low clinical certainty.

Prevalence and Methods for Assessment of Oropharyngeal Dysphagia in Older Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: This systematic review and meta-analysis aimed to estimate the pooled prevalence of dysphagia in older adults, subgrouping by recruitment settings and varying dysphagia assessment methods. METHODS: Five major databases were systematically searched through January 2022. A random-effects model for meta-analysis was conducted to obtain the pooled prevalence. RESULTS: Prevalence of dysphagia in the community-dwelling elderly screened by water swallow test was 12.14% (95% CI: 6.48% to 19.25%, I2 = 0%), which was significantly lower than the combined prevalence of 30.52% (95% CI: 21.75% to 40.07%, I2 = 68%) assessed by Standardized Swallowing Assessment (SSA) and volume-viscosity swallow test (V-VST). The dysphagia prevalence among elderly nursing home residents evaluated by SSA was 58.69% (95% CI: 47.71% to 69.25%, I2 = 0%) and by the Gugging Swallowing Screen test (GUSS) test was 53.60% (95% CI: 41.20% to 65.79%, I2 = 0%). The prevalence of dysphagia in hospitalized older adults screened by the 10-item Eating Assessment Tool was 24.10% (95% CI: 16.64% to 32.44%, I2 = 0%), which was significantly lower than those assessed by V-VST or GUSS tests of 47.18% (95% CI: 38.30% to 56.14%, I2 = 0%). CONCLUSIONS: Dysphagia is prevalent in the elderly, affecting approximately one in three community-dwelling elderly, almost half of the geriatric patients, and even more than half of elderly nursing home residents. The use of non-validated screening tools to report dysphagia underestimates its actual prevalence.

Prevalence of Frailty among Community-Dwelling Older Adults in Asian Countries: A Systematic Review and Meta-Analysis.

This study aimed to synthesize frailty prevalence among community-dwelling older adults in Asia and identify factors influencing prevalence estimates. Five electronic databases were searched by 29 April 2022, including representative samples of community-dwelling adults who were aged 60 years and older and lived in Asia. Cross-sectional or national longitudinal population-based cohort studies completed with validated instruments were selected. Twenty-one studies with 52,283 participants were included. The pooled prevalence rate of frailty was 20.5% (95% CI = 15.5% to 26.0%). The estimated frailty prevalence was 14.6% (95% CI = 10.9% to 18.8%) while assessed by the Fried frailty phenotype, 28.0% (95% CI = 21.3% to 35.3%) by the Cumulative Frailty Index, 36.4% (95% CI = 33.6% to 39.3%) by the Study of Osteoporotic Fractures (SOF) index, and 46.3% (95% CI = 40.1% to 52.4%) by the Clinical Frailty Scale (p < 0.01). Subgroup analysis in studies using the Fried's phenotype tool found that frailty prevalence was increased with older age (p = 0.01) and was higher in those who were single (21.5%) than in married participants (9.0%) (p = 0.02). The study results supported a better understanding of frailty prevalence in different geographical distributions and provide references for health policy decision-making regarding preventing frailty progression in older adults.

Effect of Human Synovial Fluid From Osteoarthritis Patients and Healthy Individuals on Lymphatic Contractile Activity.

The lymphatic system has been proposed to play a crucial role in preventing the development and progression of osteoarthritis (OA). As OA develops and progresses, inflammatory cytokines and degradation by-products of joint tissues build up in the synovial fluid (SF) providing a feedback system to exacerbate disease. The lymphatic system plays a critical role in resolving inflammation and maintaining overall joint homeostasis; however, there is some evidence that the lymphatics can become dysfunctional during OA. We hypothesized that the functional mechanics of lymphatic vessels (LVs) draining the joint could be directly compromised due to factors within SF derived from osteoarthritis patients (OASF). Here, we utilized OASF and SF derived from healthy (non-OA) individuals (healthy SF (HSF)) to investigate potential effects of SF entering the draining lymph on migration of lymphatic endothelial cells (LECs) in vitro, and lymphatic contractile activity of rat femoral LVs (RFLVs) ex vivo. Dilutions of both OASF and HSF containing serum resulted in a similar LEC migratory response to the physiologically endothelial basal medium-treated LECs (endothelial basal medium containing serum) in vitro. Ex vivo, OASF and HSF treatments were administered within the lumen of isolated LVs under controlled pressures. OASF treatment transiently enhanced the RFLVs tonic contractions while phasic contractions were significantly reduced after 1 h of treatment and complete ceased after overnight treatment. HSF treatment on the other hand displayed a gradual decrease in lymphatic contractile activity (both tonic and phasic contractions). The observed variations after SF treatments suggest that the pump function of lymphatic vessel draining the joint could be directly compromised in OA and thus might present a new therapeutic target.

Sodium alginate microencapsulation of human mesenchymal stromal cells modulates paracrine signaling response and enhances efficacy for treatment of established osteoarthritis.

Mesenchymal stromal cells (MSCs) have shown promise as osteoarthritis (OA) treatments; however, effective translation has been limited by high variability and heterogeneity of MSCs, suboptimal delivery strategies, and poor understanding of critical quality and potency attributes. Furthermore, most pre-clinical studies of MSC therapeutics for OA have focused on delaying OA development and not on treating established OA, which brings added clinical relevance. Thus, the objective of the current study was to assess the effects of sodium alginate microencapsulation on human MSC (hMSC) secretion of immunomodulatory cytokines in an OA microenvironment and therapeutic efficacy in treating established OA. A Medial Meniscal Transection (MMT) pre-clinical model of OA was implemented. Three weeks post-surgery, after OA was established, intra-articular injections of encapsulated hMSCs or nonencapsulated hMSCs were administered. Six weeks post-surgery, microstructural changes in the knee joint were quantified using microCT. Encapsulated hMSCs reduced articular cartilage degeneration and subchondral bone remodeling. A multiplexed immunoassay panel was used to profile the in vitro secretome of hMSCs in response to IL-1ß. Nonencapsulated hMSCs showed an indiscriminate increase in all cytokines in response to IL-1ß while encapsulated hMSCs showed a targeted secretory response with increased expression of pro-inflammatory (IL-1ß, IL-6, IL-7, IL-8), anti-inflammatory (IL-1RA), and chemotactic (G-CSF, MDC, IP10) cytokines. These data show that sodium alginate microencapsulation can modulate hMSC paracrine signaling and enhance the therapeutic efficacy of the hMSCs in treating established OA. This cytokine profile provides a foundation for the identification of key factors affecting the overall potency of hMSC therapeutics for OA. STATEMENT OF SIGNIFICANCE: While there has been considerable interest in material based MSC encapsulation for treatment of OA, there are critical gaps in our translational understanding of these biomaterial-based technologies for OA. More specifically, previous studies have several important limitations: (1) they have been largely focused on preventing OA development, which limits their translational utility and (2) little prior work has been done to delineate potential routes/mechanisms by which material encapsulation alters MSC therapeutic action. In our manuscript, we aimed to fill these gaps in knowledge by testing the hypotheses that: (1) hMSC encapsulation can attenuate established disease progression, which is a more clinically relevant scenario and (2) hMSC encapsulation significantly changes the secreted paracrine factors from hMSCs.

Sustainable additives for the regulation of NH3 concentration and emissions during the production of biomethane and biohydrogen: A review.

This study reviews the recent advances and innovations in the application of additives to improve biomethane and biohydrogen production. Biochar, nanostructured materials, novel biopolymers, zeolites, and clays are described in terms of chemical composition, properties and impact on anaerobic digestion, dark fermentation, and photofermentation. These additives can have both a simple physical effect of microbial adhesion and growth, and a more complex biochemical impact on the regulation of key parameters for CH4 and H2 production: in this study, these effects in different experimental conditions are reviewed and described. The considered parameters include pH, volatile fatty acids (VFA), C:N ratio, and NH3; additionally, the global impact on the total production yield of biogas and bioH2 is reviewed. A special focus is given to NH3, due to its strong inhibition effect towards methanogens, and its contribution to digestate quality, leaching, and emissions into the atmosphere.

Poison With a Purpose: A Case Report on Arsenic Cardiotoxicity and Obesity.

Acute promyelocytic leukemia (APL) is a form of leukemia in which there is an arrest of the maturation of the myeloid lineage at the promyelocyte stage. Although there is high early mortality due to coagulopathy, APL is now a curable disease with the use of arsenic trioxide (ATO) and all-trans-retinoic acid (ATRA). Arsenic is weight-based for the treatment of APL, and many toxicities are dose-dependent, although there are no guidelines regarding dosing adjustments for obese patients. We present a case of a 34-year-old male with obesity and APL who developed arsenic-induced QTc prolongation and symptomatic sinus tachycardia while receiving treatment. Further research is needed to guide appropriate dosing for obese patients to determine if ideal body weight dosing is able to provide similar cure rates with fewer adverse events.

Multichromatic near-infrared imaging to assess interstitial lymphatic and venous uptake in vivo.

SIGNIFICANCE: Changes in interstitial fluid clearance are implicated in many diseases. Using near-infrared (NIR) imaging with properly sized tracers could enhance our understanding of how venous and lymphatic drainage are involved in disease progression or enhance drug delivery strategies. AIM: We investigated multichromatic NIR imaging with multiple tracers to assess in vivo microvascular clearance kinetics and pathways in different tissue spaces. APPROACH: We used a chemically inert IR Dye 800CW (D800) to target venous capillaries and a purified conjugate of IR dye 680RD with 40 kDa PEG (P40D680) to target lymphatic capillaries in vivo. Optical imaging settings were validated and tuned in vitro using tissue phantoms. We investigated multichromatic NIR imaging's utility in two in vivo tissue beds: the mouse tail and rat knee joint. We then tested the ability of the approach to detect interstitial fluid perturbations due to exercise. RESULTS: In an in vitro simulated tissue environment, free dye and PEG mixture allowed for simultaneous detection without interference. In the mouse tail, co-injected NIR tracers cleared from the interstitial space via distinct routes, suggestive of lymphatic and venous uptake mechanisms. In the rat knee, we determined that exercise after injection transiently increased lymphatic drainage as measured by lower normalized intensity immediately after exercise, whereas exercise pre-injection exhibited a transient delay in clearance from the joint. CONCLUSIONS: NIR imaging enables simultaneous imaging of lymphatic and venous-mediated fluid clearance with great sensitivity and can be used to measure temporal changes in clearance rates and pathways.