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OBJECTIVE: Fibrin sealants are routinely used for intra-articular surgical fixation of cartilage fragments and implants. However, the mechanical properties of fibrin sealants in the context of cartilage repair are unknown. The purpose of this study was to characterize the adhesive and frictional properties of fibrin sealants using an ex vivo model. DESIGN: Native bovine cartilage-bone composites were assembled with a single application of Tisseel or Vistaseal. Composites were tested in tension and lap shear. In addition, the coefficient of friction (COF) was measured in a native cartilage annulus model alone and with minced cartilage. Finally, the effect of a double application of fibrin sealant was evaluated. RESULTS: There were no significant differences in tensile modulus, ultimate tensile strength (UTS), shear modulus, or ultimate shear strength (USS) between the 2 fibrin sealants. Both fibrin sealants demonstrated a UTS and USS of

OBJECTIVE: The purpose of this study was to determine the in vitro effects of a single exposure of bupivacaine on the mechanical properties of bovine cartilage explants at 3 weeks. DESIGN: Femoral condyle articular cartilage explants were aseptically harvested from juvenile bovine stifle joints before being exposed to chondrogenic medium containing 0.50% (wt/vol) bupivacaine, 0.25% (wt/vol) bupivacaine, or no medication (control) for 1 hour. Explants were then washed and maintained in culture in vitro for 3 weeks before testing. Cell viability, tensile and compressive mechanical properties, histological properties, and biochemical properties were then assessed. RESULTS: Explants exhibited a dose-dependent decrease in mean tensile Youngs modulus with increasing bupivacaine concentration (9.86 MPa in the controls, 6.48 MPa in the 0.25% bupivacaine group [P = 0.048], and 4.72 MPa in the 0.50% bupivacaine group [P = 0.005]). Consistent with these results, collagen content and collagen crosslinking decreased with bupivacaine exposure as measured by mass spectrometry. Compressive properties of the explants were unaffected by bupivacaine exposure. Explants also exhibited a trend toward dose-dependent decreases in viability (51.2% for the controls, 47.3% for the 0.25% bupivacaine-exposed group, and 37.0% for the 0.50% bupivacaine-exposed group [P = 0.072]). CONCLUSIONS: Three weeks after 1-hour bupivacaine exposure, the tensile properties of bovine cartilage explants were significantly decreased, while the compressive properties remained unaffected. These decreases in tensile properties corresponded with reductions in collagen content and crosslinking of collagen fibers. Physicians should be judicious regarding the intra-articular administration of bupivacaine in native joints.

Geologic features (e.g., fractures and alluvial fans) can play an important role in the locations and volumes of groundwater discharge and degree of groundwater-surface water (GW-SW) interactions. However, the role of these features in controlling GW-SW dynamics and streamflow generation processes are not well constrained. GW-SW interactions and streamflow generation processes are further complicated by variability in precipitation inputs from summer and fall monsoon rains, as well as declines in snowpack and changing melt dynamics driven by warming temperatures. Using high spatial and temporal resolution radon and water stable isotope sampling and a 1D groundwater flux model, we evaluated how groundwater contributions and GW-SW interactions varied along a stream reach impacted by fractures (fractured-zone) and downstream of the fractured hillslope (non-fractured zone) in Coal Creek, a Colorado River headwater stream affected by summer monsoons. During early summer, groundwater contributions from the fractured zone were high, but declined throughout the summer. Groundwater contributions from the non-fractured zone were constant throughout the summer and became proportionally more important later in the summer. We hypothesize that groundwater in the non-fractured zone is dominantly sourced from a high-storage alluvial fan at the base of a tributary that is connected to Coal Creek throughout the summer and provides consistent groundwater influx. Water isotope data revealed that Coal Creek responds quickly to incoming precipitation early in the summer, and summer precipitation becomes more important for streamflow generation later in the summer. We quantified the change in catchment dynamic storage and found it negatively related to stream water isotope values, and positively related to modeled groundwater discharge and the ratio of fractured zone to non-fractured zone groundwater. We interpret these relationships as declining hydrologic connectivity throughout the summer leading to late summer streamflow supported predominantly by shallow flow paths, with variable response to drying from geologic features based on their storage. As groundwater becomes more important for sustaining summer flows, quantifying local geologic controls on groundwater inputs and their response to variable moisture conditions may become critical for accurate predictions of streamflow.

About 80 % of the precipitation at the Colorado River s headwaters is snow, and the resulting snowmeltdriven hydrograph is a crucial water source for about 40 million people. Snowmelt from alpine and subalpine snowpack contributes substantially to groundwater recharge and river flow. However, the dynamics of snowmelt progression are not well understood because observations of the highelevation snowpack are difficult due to challenging access in complex mountainous terrain as well as the cost and labor intensity of currently available methods. We present a novel approach to infer the processes and dynamics of highelevation snowmelt contributions predicated upon stable hydrogen and oxygen isotope ratios observed in streamflow. We show that deuterium-excess (d-excess) values of stream water could serve as a comparatively cost-effective proxy for a catchment-integrated signal of high-elevation snowmelt contributions to catchment runoff. We sampled stable hydrogen and oxygen isotope ratios of the precipitation, snowpack, and stream water in the East River, a headwater catchment of the Colorado River, and the stream water of larger catchments at sites on the Gunnison River and Colorado River. The d-excess of snowpack increased with elevation; the upper subalpine and alpine snowpack (> 3200 m) had substantially higher d-excess compared to lower elevations (< 3200 m) in the study area. The d-excess values of stream water reflected this because d-excess values increased as the higher-elevation snowpack contributed more to stream water generation later in the snowmelt/runoff season. End-member mixing analyses based on the d-excess data showed that the share of high-elevation snowmelt contributions within the snowmelt hydrograph was on average 44 % and generally increased during melt period progression, up to 70 %. The observed pattern was consistent during 6 years for the East River, and a similar relation was found for the larger catchments on the Gunnison and Colorado rivers. High-elevation snowpack contributions were found to be higher for years with lower snowpack and warmer spring temperatures. Thus, we conclude that the d-excess of stream water is a viable proxy to observe changes in high-elevation snowmelt contributions in catchments at various scales. Inter-catchment comparisons and temporal trends of the d-excess of stream water could therefore serve as a catchment-integrated measure to monitor if mountain systems rely on high-elevation water inputs more during snow drought compared to years of average snowpack depths.

Quantifying flow and transport from hillslopes is vital for understanding water quantity and quality in rivers, but remains obscure because of limited subsurface measurements. Using measured hydraulic conductivity K profiles and water balance over a single year to calibrate a transmissivity feedback model for a hillslope in the East River watershed (Colorado) proved unsatisfactory for predicting flow over the subsequent years. Well-constrained field-scale K were obtained by optimizing subsurface flux predictions over years having large differences in recharge, and by including estimates of interannual transfer of excess snowmelt recharge. Water and solute exports during high snowmelt recharge occur predominantly via shallow groundwater flow through weathered rock and soil because of their enlarged transmissivities under saturated conditions. Conversely, these shallow pathways are less active in snow drought years when the water table remains deeper within the weathering zone. Hillslope soil water monitoring showed that rainfall does not infiltrate deeply during summer and fall months, and revealed water losses consistent with model ET predictions. By combining water table-dependent fluxes with pore water chemistry in different zones, time-dependent rates of solute exports become predictable. As an example, calibrated K were combined with dissolved nitrogen concentrations in pore waters to show the snowmelt-dependence of reactive nitrogen exported from the hillslope, further supporting the recent finding that the weathering zone is the dominant source of reactive nitrogen at this site. Subsurface export predictions can now be obtained for wide ranges of recharge based on measurements of water table elevation and profiles of pore water chemistry.

BackgroundPosterolateral corner (PLC) reconstruction of the knee involves precise drilling of a single tunnel from anterolateral to posteromedial in the fibular head (FH) to ensure adequate graft fixation. Misplacement of the tunnel in a too lateral or too superior trajectory can lead to cortical breach and inadequate graft fixation.PurposeTo (1) determine the mechanical consequence of a lateralized FH tunnel in PLC reconstruction and (2) compare the mechanical strength of 3 salvage fixation techniques for a lateralized FH tunnel.Study designControlled laboratory study.MethodsSawbones models of a uniform density were utilized. FH tunnels (7-mm diameter) were drilled from anterolateral to posteromedial in positive controls (lateral cortex thickness, 7.6 ± 0.7 mm) to represent an improperly placed FH tunnel at risk of lateral cortical breach. For negative controls and salvage experimental groups, FH tunnels were drilled from anterolateral to posterolateral (lateral cortex thickness, 2.7 ± 0.9 mm). Three salvage fixation techniques were compared: suture anchor fixation, tunnel redrilling, and nitinol staple fixation. Samples (n = 5 per group) underwent uniaxial tension testing, and the ultimate tensile strength (UTS) and mode of failure were recorded. Data were analyzed using the 1-sample t test and nonparametric 1-sample Wilcoxon signed-rank test.ResultsThe negative control group had a 4-fold lower mean UTS relative to the positive control group (1.49 ± 0.17 vs 6.25 ± 1.98 MPa; P < .01) and exhibited failure through the lateral cortex and tunnel. Nitinol staple fixation improved the mean UTS by >16 times compared with the negative control group (24.06 ± 6.49 vs 1.49 ± 0.17 MPa; P < .01). Suture anchors and tunnel redrilling exhibited similar UTS and mode of failure to those of negative controls.ConclusionReinforcement of a thinned lateral FH cortex with a single nitinol staple improved graft fixation strength in a sawbones model.Clinical relevanceA lateralized FH tunnel can be a common intraoperative pitfall during PLC reconstruction. Salvage of a thinned lateral FH cortex with a single nitinol staple may reduce the risk of cortical breach and graft failure.

A coupled hydrologic and snowpack stable water isotope model assesses controls on isotopic inputs across a mountainous basin. Annually, the most depleted isotope conditions occur in the upper subalpine where snow accumulation is high, and rainfall is low. Snowmelt isotopic evolution over time indicates fractionation processes account for

Isotopic information from 81 snowpits was collected over a 5-year period in a large, Colorado watershed. Data spans gradients in elevation, aspect, vegetation, and seasonal climate. They are combined with overlapping campaigns for water isotopes in precipitation and snowmelt, and a land-surface model for detailed estimates of snowfall and climate at sample locations. Snowfall isotopic inputs, describe the majority of δ18O snowpack variability. Aspect is a secondary control, with slightly more enriched conditions on east and north facing slopes. This is attributed to preservation of seasonally enriched snowfall and vapour loss in the early winter. Sublimation, expressed by decreases in snowpack d-excess in comparison to snowfall contributions, increases at low elevation and when seasonal temperature and solar radiation are high. At peak snow accumulation, post-depositional fractionation appears to occur in the top 25 ± 14% of the snowpack due to melt-freeze redistribution of lighter isotopes deeper into the snowpack and vapour loss to the atmosphere during intermittent periods of low relative humidity and high windspeed. Relative depth of fractionation increases when winter daytime temperatures are high and winter precipitation is low. Once isothermal, snowpack isotopic homogenization and enrichment was observed with initial snowmelt isotopically depleted in comparison to snowpack and enriching over time. The rate of δ18O increase (d-excess decrease) in snowmelt was 0.02‰ per day per 100-m elevation loss. Isotopic data suggests elevation dictates snowpack and snowmelt evolution by controlling early snow persistence (or absence), isotopic lapse rates in precipitation and the ratio of energy to snow availability. Hydrologic tracer studies using stable water isotopes in basins of large topographic relief will require adjustment for these elevational controls to properly constrain stream water sourcing from snowmelt.

Understanding the partitioning of snow and rain contributing to either catchment streamflow or evapotranspiration (ET) is of critical relevance for water management in response to climate change. To investigate this partitioning, we use endmember splitting and mixing analyses based on stable isotope (18O) data from nine headwater catchments in the East River, Colorado. Our results show that one third of the snow partitions to ET and 13% of the snowmelt sustains summer streamflow. Only 8% of the rainfall contributes to the summer streamflow, because most of the rain (67%) partitions to ET. The spatial variability of precipitation partitioning is mainly driven by aspect and tree cover across the sub-catchments. Catchments with higher tree cover have a higher share of snow becoming ET, resulting in less snow in summer streamflow. Summer streamflow did not contain more rain with higher rainfall sums, but more rain was taken up in ET.

Sulfur (S) is an essential macronutrient and important component of the earth’s crust, and its cycling has critical impacts on trace metal mobility, water quality, and human health. Pyrite weathering is the primary pathway by which sulfur enters surface waters. However, biogeochemical cycling of sulfur in soils and the river corridor mediates sulfate exports. In this study, we identified the major forms of sulfur across multiple compartments and scales in a pristine mountainous watershed, including shale bedrock weathering profiles, hillslope soils, and alluvial floodplain sediments, in order to provide insight into biogeochemical sulfur cycling in a hydrologically variable alpine system. X-ray absorption near-edge spectroscopy (XANES) analysis of shale weathering profiles showed clear evidence of pyrite oxidation to sulfate, with large accumulations of intermediate S(0) (20%–53%). Micro-scale XANES showed evidence of reprecipitation of pyrite at fracture surfaces within the permanently saturated zone. Organic sulfur dominated S speciation in shallow hillslope soil and floodplain sediment, with little evidence of reduced inorganic S. However, mackinawite formation, representing active sulfate reduction, was observed in saturated oxbow sediments and saturated weathered shale underlying floodplain sediments. Further evidence of sulfate reduction from aqueous sulfur isotopic analysis was observed in shallow groundwater transects across an Fe-reducing meander, whereas increases in pore water sulfate concentrations implied sulfur oxidation at other locations. The data present an integrated picture of sulfur cycling in a shale-dominated watershed, where riverine sulfate exports are mediated by biological cycling, particularly in redox-stratified and temporally dynamic hyporheic zone sediments.

Background There is little long-term causal evidence on the effect of physical activity on health-related quality of life. This study aimed to examine the associations between longitudinal patterns of physical activity over 15 years and health-related quality of life in both the physical and mental health domains, in a cohort of middle-aged Australian women. Methods and findings We used data collected at 3-year intervals (1998 to 2019) from 11,336 participants in the Australian Longitudinal Study on Women's Health (ALSWH) (1946 to 1951 birth cohort). Primary outcomes were the physical (PCS) and mental health component summary (MCS) scores (range from 0 to 100; higher scores indicate higher perceived physical/mental health) from the SF-36 in 2019 (when women aged 68 to 73 years). Using target trial emulation to imitate a randomized controlled trial (RCT), we tested 2 interventions: (1) meeting the World Health Organization (WHO) physical activity guidelines consistently throughout the 15-year 'exposure period' (2001 to 2016; when women aged 50-55 to 65-70 years; physical activity assessed every 3 years); and (2) not meeting the guidelines at the beginning of the exposure period but starting to first meet the guidelines at age 55, 60, or 65; against the control of not meeting the guidelines throughout the exposure period. Analysis controlled for confounding using marginal structural models which were adjusted for sociodemographic and health variables and conditions. Consistent adherence to guidelines during the exposure period (PCS: 46.93 [99.5% confidence interval [CI]: 46.32, 47.54]) and first starting to meet the guidelines at age 55 (PCS: 46.96 [99.5% CI: 45.53, 48.40]) were associated with three-point higher PCS (mean score difference: 3.0 [99.5% CI: 1.8, 4.1] and 3.0 [99.5% CI:1.2, 4.8]) than consistent non-adherence (PCS: 43.90 [99.5% CI: 42.79, 45.01]). We found a similar pattern for most SF-36 subscales but no significant effects of the interventions on MCS. The main limitations of the study were that it may not account for all underlying health conditions and/or other unmeasured or insufficiently measured confounders, the use of self-reported physical activity and that findings may not be generalizable to all mid-age women. Conclusions Results from the emulated RCT suggest women should be active throughout mid-age, ideally increasing activity levels to meet the guidelines by age 55, to gain the most benefits for physical health in later life., Author(s): Binh Nguyen 1,2,*, Philip Clare 1,2,3, Gregore I. Mielke 4, Wendy J. Brown 5,6, Ding Ding 1,2 Introduction The health benefits of physical activity are well established [1-4]. The [...]

Despite the prevalence of large (>5 cm2) articular cartilage defects involving underlying bone, current tissue-engineered therapies only address small defects. Tissue-engineered, anatomically shaped, native-like implants may address the need for off-the-shelf, tissue-repairing therapies for large cartilage lesions. This study fabricated an osteochondral construct of translationally relevant geometry with robust functional properties. Scaffold-free, self-assembled neocartilage served as the chondral phase, and porous hydroxyapatite served as the osseous phase of the osteochondral constructs. Constructs in the shape and size of an ovine femoral condyle (31 × 14 mm) were assembled at day 4 (early) or day 10 (late) of neocartilage maturation. Early osteochondral assembly increased the interfacial interdigitation depth by 244%, interdigitation frequency by 438%, interfacial shear modulus by 243-fold, and ultimate interfacial shear strength by 4.9-fold, compared to late assembly. Toward the development of a bioprosthesis for the repair of cartilage lesions encompassing up to an entire condylar surface, this study generated a large, anatomically shaped osteochondral construct with robust interfacial mechanical properties and native-like neocartilage interdigitation.

Human articular chondrocytes (hACs) are scarce and lose their chondrogenic potential during monolayer passaging, impeding their therapeutic use. This study investigated (a) the translatability of conservative chondrogenic passaging and aggregate rejuvenation on restoring chondrogenic properties of hACs passaged up to P9; and (b) the efficacy of a combined treatment of transforming growth factor-beta 1 (TGF-β1) (T), chondroitinase-ABC (C), and lysyl oxidase-like 2 (L), collectively termed TCL, on engineering functional human neocartilage via the self-assembling process, as a function of passage number up to P11. Here, we show that aggregate rejuvenation enhanced glycosaminoglycan (GAG) content and type II collagen staining at all passages and yielded human neocartilage with chondrogenic phenotype present up to P7. Addition of TCL extended the chondrogenic phenotype to P11 and significantly enhanced GAG content and type II collagen staining at all passages. Human neocartilage derived from high passages, treated with TCL, displayed mechanical properties that were on par with or greater than those derived from low passages. Conservative chondrogenic passaging and aggregate rejuvenation may be a viable new strategy (a) to address the perennial problem of chondrocyte scarcity and (b) to successfully rejuvenate the chondrogenic phenotype of extensively passaged cells (up to P11). Furthermore, tissue engineering human neocartilage via self-assembly in conjunction with TCL treatment advances the clinical use of extensively passaged human chondrocytes for cartilage repair.

BackgroundAlthough the toxic effects of bupivacaine on chondrocyte monolayer culture have been well described, its cellular and mechanical effects on native and engineered articular cartilage remain unclear. For the repair of articular cartilage defects, fresh autologous and allogenic cartilage grafts are commonly used, and engineered cell-based therapies are emerging. The outcome of grafting therapies aimed at repairing damaged cartilage relies largely on maintaining proper viability and mechanical suitability of the donor tissues.PurposeTo investigate the in vitro effects of single bupivacaine exposure on the viability and mechanics of 2 cartilage graft types: native articular cartilage and engineered neocartilage.Study designControlled laboratory study.MethodsArticular cartilage explants were harvested from the bovine stifle femoral condyles, and neocartilage constructs were engineered from bovine stifle chondrocytes using the self-assembling process, a scaffold-free approach to engineer cartilage tissue. Both explants and neocartilage were exposed to chondrogenic medium containing a clinically applicable bolus of 0.5%, 0.25%, or 0% (control) bupivacaine for 1 hour, followed by fresh medium wash and exchange. Cell viability and matrix content (collagen and glycosaminoglycan) were assessed at t = 24 hours after treatment, and compressive mechanical properties were assessed with creep indentation testing at t = 5 to 6 days after treatment.ResultsSingle bupivacaine exposure was chondrotoxic in both explants and neocartilage, with 0.5% bupivacaine causing a significant decrease in chondrocyte viability compared with the control condition (55.0% ± 13.4% vs 71.9% ± 13.5%; P < .001). Bupivacaine had no significant effect on matrix content for either tissue type. There was significant weakening of the mechanical properties in the neocartilage when treated with 0.5% bupivacaine compared with control, with decreased aggregate modulus (415.8 ± 155.1 vs 660.3 ± 145.8 kPa; P = .003), decreased shear modulus (143.2 ± 14.0 vs 266.5 ± 89.2 kPa; P = .002), and increased permeability (14.7 ± 8.1 vs 6.6 ± 1.7 × 10-15 m4/Ns; P = .009). Bupivacaine exposure did not have a significant effect on the mechanical properties of native cartilage explants.ConclusionSingle bupivacaine exposure resulted in significant chondrotoxicity in native explants and neocartilage and significant weakening of mechanical properties of neocartilage. The presence of abundant extracellular matrix does not appear to confer any additional resistance to the toxic effects of bupivacaine.Clinical relevanceClinicians should be judicious regarding the use of intra-articular bupivacaine in the setting of articular cartilage repair.

Atmospheric nitrous oxide contributes directly to global warming, yet models of the nitrogen cycle do not account for bedrock, the largest pool of terrestrial nitrogen, as a source of nitrous oxide. Although it is known that release rates of nitrogen from bedrock are large, there is an incomplete understanding of the connection between bedrock-hosted nitrogen and atmospheric nitrous oxide. Here, we quantify nitrogen fluxes and mass balances at a hillslope underlain by marine shale. We found that, at this site, bedrock weathering contributes 78% of the subsurface reactive nitrogen, while atmospheric sources (commonly regarded as the sole sources of reactive nitrogen in pristine environments) account for only the remaining 22%. About 56% of the total subsurface reactive nitrogen denitrifies, including 14% emitted as nitrous oxide. The remaining reactive nitrogen discharges in porewaters to a floodplain where additional denitrification probably occurs. We also found that the release of bedrock nitrogen occurs primarily within the zone of the seasonally fluctuating water table and suggest that the accumulation of nitrate in the vadose zone, often attributed to fertilization and soil leaching, may also include contributions from weathered nitrogen-rich bedrock. Our hillslope study suggests that, under oxygenated and moisture-rich conditions, weathering of deep, nitrogen-rich bedrock makes an important contribution to the nitrogen cycle.