Methodological considerations in assessing countermovement jumps with handheld accentuated eccentric loading.

This study aimed to compare the agreement between three-dimensional motion capture and vertical ground reaction force (vGRF) in identifying the point of dumbbell (DB) release during a countermovement jump with accentuated eccentric loading (CMJAEL), and to examine the influence of the vGRF analysis method on the reliability and magnitude of CMJAEL variables. Twenty participants (10 male, 10 female) completed five maximal effort CMJAEL at 20% and 30% of body mass (CMJAEL20 and CMJAEL30, respectively) using DBs. There was large variability between methods in both loading conditions, as indicated by the wide limits of agreement (CMJAEL20 = -0.22 to 0.07 s; CMJAEL30 = -0.29 to 0.14 s). Variables were calculated from the vGRF data, and compared between four methods (forward integration (FI), backward integration (BI), FI adjusted at bottom position (BP), FI adjusted at DB release point (DR)). Greater absolute reliability was observed for variables from DR (CV% ≤ 7.28) compared to BP (CV% ≤ 13.74), although relative reliability was superior following the BP method (ICC ≥ 0.781 vs ≥ 0.606, respectively). The vGRF method shows promise in pinpointing the DB release point when only force platforms are accessible, and a combination of FI and BI analyses is advised to understand CMJAEL dynamics.

Safety of outpatient commencement of sotalol.

Background: Inpatient monitoring is recommended for sotalol initiation. Objective: The purpose of this study was to assess the safety of outpatient sotalol commencement. Methods: This is a multicenter, retrospective, observational study of patients initiated on sotalol in an outpatient setting. Serial electrocardiogram monitoring at day 3, day 7, 1 month, and subsequently as clinically indicated was performed. Corrected QT (QTc) interval and clinical events were evaluated. Results: Between 2008 and 2023, 880 consecutive patients who were commenced on sotalol were evaluated. Indications were atrial fibrillation/flutter in 87.3% (n = 768), ventricular arrhythmias in 9.9% (n = 87), and other arrhythmias in 2.8% (n = 25). The daily dosage at initiation was 131.0 ± 53.2 mg/d. The QTc interval increased from baseline (431 ± 32 ms) to 444 ± 37 ms (day 3) and 440 ± 33 ms (day 7) after sotalol initiation (P < .001). Within the first week, QTc prolongation led to the discontinuation of sotalol in 4 and dose reduction in 1. No ventricular arrhythmia, syncope, or death was observed during the first week. Dose reduction due to asymptomatic bradycardia occurred in 3 and discontinuation due to dyspnea in 3 within the first week. Overall, 1.1% developed QTc prolongation (>500 ms/>25% from baseline); 4 within 3 days, 1 within 1 week, 4 within 60 days, and 1 after >3 years. Discontinuation of sotalol due to other adverse effects occurred in 41 patients within the first month of therapy. Conclusion: Sotalol initiation in an outpatient setting with protocolized follow-up is safe, with no recorded sotalol-related mortality, ventricular arrhythmias, or syncope. There was a low incidence of significant QTc prolongation necessitating discontinuation within the first month of treatment. Importantly, we observed a small incidence of late QT prolongation, highlighting the need for vigilant outpatient surveillance of individuals on sotalol.

The effect of impaired unilateral ankle propulsion on contralateral knee joint loading.

BACKGROUND: Impairments in unilateral ankle propulsion may result from restriction by an external device or pathology such as lower limb amputation. Models of gait suggest this reduction may lead to increased collisional force on the contralateral side, potentially increasing force through the knee and increasing the risk of knee pain or osteoarthritis. RESEARCH QUESTION: How do restrictions in unilateral ankle propulsive force affect contralateral knee joint loading in otherwise healthy individuals? METHODS: 18 individuals without impairment walked on a treadmill at 1.5 m/s for two conditions: one free of restrictions, and one where a randomized limb's ankle propulsive force was restricted using an off-the-shelf ankle-foot orthosis (AFO). Ankle propulsive power, lower extremity joint work, and ground reaction force variables were calculated for the final 3 gait cycles of each condition. Tibiofemoral joint contact force (TJCF) for the limb contralateral to the AFO was calculated through a standard OpenSim workflow utilizing the gait2392 model. Intra-limb pair-wise comparisons were made between conditions. RESULTS: Compared to walking unrestricted, the limb wearing the AFO demonstrated a significant reduction in peak ankle propulsive power and positive ankle work by approximately 50 % each (p<0.01). With ankle restriction, the ipsilateral knee significantly increased positive work (p<0.01). The overall propulsion produced by that limb did not change between conditions, demonstrated by a lack of change in anterior ground reaction force impulse (p=0.11). The knee of the limb contralateral to the AFO did not display differences in any TJCF variable between conditions (all p>0.07). SIGNIFICANCE: These results suggest a unilateral deficit in ankle propulsion will not increase contralateral knee joint forces in individuals who are able to use other joints of the limb to compensate for the loss of ankle function. However, further research should investigate this relationship in those who display pathologies that may prevent more proximal compensations.

Influence of test paradigm on loading dynamics during proximal femur fracture tests simulating sideways falls.

Fall-related hip fractures are a serious public health issue in older adults. As most mechanistic hip fracture risk prediction models incorporate tissue tolerance, test methods that can accurately characterize the fracture force of the femur (and factors that influence it) are imperative. While bone possesses viscoelastic properties, experimental characterization of rate-dependencies has been inconsistent in the whole-femur literature. The goal of this study was to investigate the influence of experimental paradigm on loading rate and fracture force (both means and variability) during mechanical tests simulating lateral fall loadings on the proximal femur. Six pairs of matched femurs were split randomly between two test paradigms: a 'lower rate' materials testing system (MTS) with a constant displacement rate of 60 mm/s, and a hip impact test system (HIT) comprised of a custom-built vertical drop tower utilizing an impact velocity of 4 m/s. The loading rate was 88-fold higher for the HIT (mean (SD) = 2465.49 (807.38) kN/s) compared to the MTS (27.78 (10.03) kN/s) paradigm. However, no difference in fracture force was observed between test paradigms (mean (SD) = 4096.4 (1272.6) N for HIT, and 3641.3 (1285.8) N for MTS). Within-paradigm variability was not significantly different across paradigms for either loading rate or fracture force (coefficients of variation ranging from 0.311 to 0.361). Within each test paradigm, significant positive relationships were observed between loading rate and fracture force (HIT adjusted R2 = 0.833, p = 0.007; MTS adjusted R2 = 0.983, p < 0.0001). Overall, this study provides evidence that energy-based impact simulators can be a valid method to measure femoral bone strength in the context of fall-related hip fractures. This study motivates future research to characterize potential non-linear relationships between loading rate and fracture threshold at both macro and microscales.

Do new lakes behave like natural lakes regarding sediment composition and phosphorus fluxes?

Numerous new lakes have been established during the last few decades. Lakes established on former agricultural soils often have high legacy phosphorus (P)-content, which constitutes a risk for potential internal P-loading after the lake is formed. In this study, we compared the P release and sediment P-pools from 31 new lakes and 31 natural lakes, to assess their similarities and differences. A suite of other sediment characteristics was identified and compared for both natural and new lakes; catchment characteristics of the new lakes also were analyzed. P release from the sediment of new lakes was significantly lower than from natural lakes (13.2 mg P m-2 d-1) compared to new lakes (6.9 mg P m-2 d-1). The P release was found to be low when molar Fe:P ratios were above 10. A significant correlation was found between the content of mobile-P (loosely adsorbed P, iron-bound P, and leachable organic P) and TP in the sediment, irrespective of lake type. The composition of the mobile P-pool also differed, with the new non-excavated lakes showing a higher proportion of RP-BD; both new lake types had significantly (p = 0.021) lower proportions of nrP, compared to natural lakes in the uppermost 10 cm sediment. In addition, variance in P release and mobile-P content of new lakes could be explained in terms of the land use of the catchments. Most sediment characteristics of new lakes established without topsoil excavation reached the average levels of natural Danish lakes with respect to density, organic content and P content within 20-30 years, while excavated lakes showed no such tendencies.

Primary Creep Characterization in Porcine Lumbar Spine Subject to Repeated Loading.

Low back pain (LBP) is a common medical condition worldwide, though the etiology of injuries causing most LBP is unknown. Flexion and repeated compression increase lumbar injury risk, yet the complex viscoelastic behavior of the lumbar spine has not been characterized under this loading scheme. Characterizing the non-injurious primary creep behavior in the lumbar spine is necessary for understanding the biomechanical response preceding injury. Fifteen porcine lumbar spinal units were loaded in repeated flexion-compression with peak compressive stresses ranging from 1.41 to 4.68 MPa. Applied loading simulated real loading exposures experienced by high-speed watercraft occupants. The strain response in the primary creep region was modeled for all tests using a generalized Kelvin-Voigt model. A quasilinear viscoelastic (QLV) approach was used to separate time-dependent (creep) and stress-dependent (elastic) responses. Optimizations between the models and experimental data determined creep time constants, creep coefficients, and elastic constants associated with this tissue under repeated flexion-compression loading. Average R2 for all fifteen models was 0.997. Creep time constants optimized across all fifteen models were 24 s and 580 s and contributed to 20 ± 3% and 30 ± 3% of the overall strain response, respectively. The non-transient behavior contributed to 50 ± 0% of the overall response. Elastic behavior for this porcine population had an average standard deviation of 24.5% strain across the applied stress range. The presented primary creep characterization provides the response precursor to injurious behavior in the lumbar spine. Results from this study can further inform lumbar injury prediction and kinematic models.

Water quality dynamics and underlying controls in the Halton Region, Ontario.

We assessed the hydrochemistry of 15 watersheds in the Halton Region, southern Ontario, in high resolution (n > 500 samples across n > 40 streams) to characterize water quality dynamics and governing controls on major and trace element concentrations in this rapidly urbanizing region. In 2022, major water quality parameters were generally in line with historic monitoring data yet significantly different across catchments, e.g., in specific conductance, turbidity, phosphate and chloride, and trace element concentrations. Distinct hydrochemical signatures were observed between urban and rural creeks, with urban stream sections and sites near the river mouths close to Lake Ontario having consistently higher chloride (up to 700 mg/L) and occasional enrichment in nutrients levels (up to 8 and 20 mg/L phosphate and nitrate, respectively). Particularly upper reaches exhibited hydrochemical signatures that were reflective of the catchment surface lithologies, for instance through higher dissolved Ca to Mg ratios. Unlike for chloride and phosphate, provincial water quality guidelines for trace elements and heavy metals were seldom surpassed (on < 10 occasions for copper, zinc, cadmium, and uranium). Concentrations of other trace elements (e.g., platinum group elements or rare earth elements) were expectedly low (< 0.3 µg/L) but showed spatiotemporal concentration patterns and concentration-discharge dynamics different from those of the major water quality parameters. Our results help improve the understanding of surface water conditions within Halton's regional Natural Heritage Systems and demonstrate how enhanced environmental monitoring can deliver actionable information for watershed decision-making.

Mechanical loading and orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA): a comprehensive review.

The importance of mechanical loading and its relationship to orthobiologic therapies in the treatment of post-traumatic osteoarthritis (PTOA) is beginning to receive attention. This review explores the current efficacy of orthobiologic interventions, notably platelet-rich plasma (PRP), bone marrow aspirate (BMA), and mesenchymal stem/stromal cells (MSCs), in combating PTOA drawing from a comprehensive review of both preclinical animal models and human clinical studies. This review suggests why mechanical joint loading, such as running, might improve outcomes in PTOA management in conjunction with orthiobiologic administration. Accumulating evidence underscores the influence of mechanical loading on chondrocyte behavior and its pivotal role in PTOA pathogenesis. Dynamic loading has been identified as a key factor for optimal articular cartilage (AC) health and function, offering the potential to slow down or even reverse PTOA progression. We hypothesize that integrating the activation of mechanotransduction pathways with orthobiologic treatment strategies may hold a key to mitigating or even preventing PTOA development. Specific loading patterns incorporating exercise and physical activity for optimal joint health remain to be defined, particularly in the clinical setting following joint trauma.

Rapid analysis of untreated food samples by gel loading tip spray ionization mass spectrometry.

Rapid, efficient, versatile, easy-to-use, and non-expensive analytical approaches are globally demanded for food analysis. Many ambient ionization approaches based on electrospray ionization (ESI) have been developed recently for the rapid molecular characterization of food products. However, those approaches mainly suffer from insufficient signal duration for comprehensive chemical characterization by tandem MS analysis. Here, a commercially available disposable gel loading tip is used as a low-cost emitter for the direct ionization of untreated food samples. The most important advantages of our approach include high stability, and durability of the signal (> 10 min), low cost (ca. 0.1 USD per run), low sample and solvent consumption, prevention of tip clogging and discharge, operational simplicity, and potential for automation. Quantitative analysis of sulfapyridine, HMF (hydroxymethylfurfural), and chloramphenicol in real sample shows the limit-of-detection 0.1 µg mL-1, 0.005 µg mL-1, 0.01 µg mL-1; the linearity range 0.1-5 µg mL-1, 0.005-0.25 µg mL-1, 0.01-1 µg mL-1; and the linear fits R2 ≥ 0.980, 0.991, 0.986. Moreover, we show that tip-ESI can also afford sequential molecular ionization of untreated viscous samples, which is difficult to achieve by conventional ESI. We conclude that tip-ESI-MS is a versatile analytical approach for the rapid chemical analysis of untreated food samples.

Impact of vertical alveoloplasty on changes in keratinized mucosa width following full-arch immediate implant placement and rehabilitations: A prospective case series.

PURPOSE: This prospective case series aimed to investigate the effect of vertical alveoloplasty on the changes in keratinized mucosa width (KMW) following full-arch immediate implant placement and rehabilitation. MATERIALS AND METHODS: A total of 17 potential edentulous patients were enrolled and received implant placement and full-arch implant-supported immediate rehabilitations. The main outcome was to analyze the effect of vertical alveoloplasty on the changes in KMW. The amount of vertical alveoloplasty during implant surgery as well as the changes in KMW at buccal aspects from the day of surgery to 6 months post-surgery were recorded on the implant-level using a periodontal probe. The secondary outcome was to analyze the other possible factors that affected the changes in KMW. The included factors were the initial KMW, the distribution of implants in the maxilla and mandible, the distribution of implants in the anterior and posterior regions, the distribution of implants in extraction sockets and healed ridges, and gender. Mann-Whitney non-parametric tests and multiple linear regression adjusted by generalized estimating equations (GEE) were used to statistically analyze the data. RESULTS: A total of 121 implant positions were analyzed. The KMW was 4.1± 2.0 mm on the day of the surgery and 4.1± 1.7 mm 6 months post-surgery. The mean changes in KMW following 6 months were -0.1± 1.6 mm (p = 0.824). From the results of GEE, the vertical amount of alveoloplasty had no significant effect on changes in KMW. Both initial KMW and the distribution of implants in the anterior and posterior regions had significant impacts on the changes in KMW (p < 0.0001). CONCLUSION: The amount of vertical alveoloplasty during implant surgery has no significant impact on the KMW. The KMW remained stable from baseline to 6 months after alveoloplasty, implant placement, and immediate rehabilitations in potential edentulous arches. The initial KMW and the distribution of implants in the anterior and posterior regions were the possible factors affecting changes in KMW.

Titanium nanotopography enhances mechano-response of osteocyte three-dimensional network toward osteoblast activation.

The bone turnover capability influences the acquisition and maintenance of osseointegration. The architectures of osteocyte three-dimensional (3D) networks determine the direction and activity of bone turnover through osteocyte intercellular crosstalk, which exchanges prostaglandins through gap junctions in response to mechanical loading. Titanium nanosurfaces with anisotropically patterned dense nanospikes promote the development of osteocyte lacunar-canalicular networks. We investigated the effects of titanium nanosurfaces on intercellular network development and regulatory capabilities of bone turnover in osteocytes under cyclic compressive loading. MLO-Y4 mouse osteocyte-like cell lines embedded in type I collagen 3D gels on titanium nanosurfaces promoted the formation of intercellular networks and gap junctions even under static culture conditions, in contrast to the poor intercellular connectivity in machined titanium surfaces. The osteocyte 3D network on the titanium nanosurfaces further enhanced gap junction formation after additional culturing under cyclic compressive loading simulating masticatory loading, beyond the degree observed on machined titanium surfaces. A prostaglandin synthesis inhibitor cancelled the dual effects of titanium nanosurfaces and cyclic compressive loading on the upregulation of gap junction-related genes in the osteocyte 3D culture. Supernatants from osteocyte monolayer culture on titanium nanosurfaces promoted osteocyte maturation and intercellular connections with gap junctions. With cyclic loading, titanium nanosurfaces induced expression of the regulatory factors of bone turnover in osteocyte 3D cultures, toward higher osteoblast activation than that observed on machined surfaces. Titanium nanosurfaces with anisotropically patterned dense nanospikes promoted intercellular 3D network development and regulatory function toward osteoblast activation in osteocytes activated by cyclic compressive loading, through intercellular crosstalk by prostaglandin.

A hybrid finite-discrete element method for modelling cracking processes in sandy mudstone containing a single edge-flaw under cyclic dynamic loading.

Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.

Spinal loads during dynamic full flexion and return to standing posture in different age and sex groups: A musculoskeletal model study.

During forward flexion, spine motion varies due to age and sex differences. Previous studies showed that lumbar/pelvis range of flexion (RoF) and lumbo-pelvic ratio (L/P) are age/sex dependent. How variation of these parameters affects lumbar loading in a normal population requires further assessment. We aimed to estimate lumbar loads during dynamic flexion-return cycle and the differences in peak loads (compression) and corresponding trunk inclinations due to variation in lumbar/pelvis RoF and L/P. Based on in vivo L/P (0.11-3.44), temporal phases of flexion (early, middle, and later), the lumbar (45-55°) and hip (60-79°) RoF; full flexion-return cycles of six seconds were reconstructed for three age groups (20-35, 36-50 and 50+ yrs.) in both sexes. Six inverse dynamic analyses were performed with a 50th percentile model, and differences in peak loads and corresponding trunk inclinations were calculated. Peak loads at L4-L5 were 179 N higher in younger males versus females, but 228 N and 210 N lower in middle-aged and older males, respectively, compared to females. Females exhibited higher trunk inclinations (6°-20°) than males across all age groups. Age related differences in L4-L5 peak loads and corresponding trunk inclinations were found up to 415 N and 19° in males and 152 N and 13° in females. With aging, peak loads were reduced in males but were found non-monotonic in females, whereas trunk inclinations at peak loads were reduced in both sexes from young to middle/old age groups. In conclusion, lumbar loading and corresponding trunk inclinations varied notably due to age/sex differences. Such data may help distinguishing normal or pathological condition of the lumbar spine.

Accuracy of navigation guided implant surgery for immediate loading complete arch restorations: Prospective clinical trial.

OBJECTIVES: To assess navigation accuracy for complete-arch implant placement with immediate loading of digitally prefabricated provisional. MATERIALS AND METHODS: Consecutive edentulous and terminal dentition patients requiring at least one complete-arch FDP were treated between December 2020 and January 2022. Accuracy was evaluated by superimposing pre-operative and post-operative cone beam computed tomography (CBCT), recording linear (mm) and angular (degrees) deviations. T-tests were performed to investigate the potential effect of the registration algorithm (fiducial-based vs. fiducial-free), type of references for the fiducial-free algorithm (teeth vs. bone screws), site characteristic (healed vs. post-extractive), implant angulation (axial vs. tilted), type of arch (maxilla vs. mandible) on the accuracy with p-value <0.05. RESULTS: Twenty-five patients, 36 complete-arches, and 161 implants were placed. The overall mean angular deviation was 2.19° (SD 1.26°). The global platform and apex mean deviations were 1.17 mm (SD 0.57 mm), and 1.30 mm (SD 0.62 mm). Meaningful global platform (p = 0.0009) and apical (p = 0.0109) deviations were experienced only between healed and post-extraction sites. None of the analyzed variables significantly influenced angular deviation. Minor single-axis deviations were reported for the type of jaw (y-axis at implant platform and apex), registration algorithm (y-axis platform and z-axis deviations), and type of references for the fiducial-free algorithm. No statistically significant differences were found in relation to implant angulation. CONCLUSIONS: Within the study limitations navigation was reliable for complete-arch implant placement with immediate loading digitally pre-fabricated FDP. AI-driven surface anatomy identification and calibration protocol made fiducial-free registration as accurate as fiducial-based, teeth and bone screws equal as references. Implant site characteristics were the only statistically significant variable with healed sites reporting higher accuracy compared to post-extractive. Live-tracked navigation surgery enhanced operator performance and accuracy regardless of implant angulation and type of jaw. A mean safety room of about 1 mm and 2° should be considered.

Anterior variable angle locking neutralisation plate superiority over traditional tension band wiring for treating transverse patella fractures.

Purpose: This paper investigates the biomechanical benefits of using hybrid constructs that combine cannulated screws with tension band wiring (TBW) cerclage compared to cannulated screws with anterior Variable Angle locking neutralisation plates (VA LNP). These enhancements can bear heavier loads and maintain the repaired patella's integrity, in contrast to traditional methods. Method: Eighteen fresh-frozen human cadaver patellae were carefully fractured transversely at their midpoints using a saw. They were then divided into two groups of nine for subsequent utilisation. Fixation methods included Cannulated Screw Fixation added with either TBW or VA LNP Fixation Technique. Cyclic loading simulations (500 cycles) were conducted to mimic knee motion, tracking fracture displacement with Optotrak. After that, the constructs were secured over a servo-hydraulic testing machine to determine the load-to-failure on axial mode. Results: The average fracture displacement for the anterior neutralisation plate group was 0.09 ± 0.12 mm, compared to 0.77 ± 0.54 mm for the tension band wiring with cannulated screw group after 500 cyclic loading. This result is statistically significant (p = 0.004). The anterior neutralisation plate group exhibited a mean load-to-failure of 1359 ± 21.53 N, whereas the tension band wiring group showed 780.1 ± 22.62 N, resulting in a significant difference between the groups (p = 0.007). Conclusion: This research highlights the superior biomechanical advantage of VA LNP over TBW for treating simple transverse patella fractures with two cannulated screws. It also highlights how the TBW is still a valuable option considering the load-to-failure limit. Level of Evidence: Not Applicable.

Relevance of instrumented gait analysis in the prediction of the rebound phenomenon after guided growth intervention.

Predictors of rebound after correction of coronal plane deformities using temporary hemiepiphysiodesis (TH) are not well defined. The following research questions were tested: (1) Is the dynamic knee joint load useful to improve rebound prediction accuracy? (2) Does a large initial deformity play a critical role in rebound development? (3) Are BMI and a young age risk factors for rebound? Fifty children and adolescents with idiopathic knee valgus malalignment were included. A deviation of the mechanical femorotibial angle (MFA) of ≥ 3° into valgus between explantation and the one-year follow-up period was chosen to classify a rebound. A rebound was detected in 22 of the 50 patients (44%). Two predictors of rebound were identified: 1. reduced peak lateral knee joint contact force in the first half of the stance phase at the time of explantation (72.7% prediction); 2. minor initial deformity according to the MFA (70.5% prediction). The best prediction (75%) was obtained by including both parameters in the binary logistic regression method. A TH should not be advised in patients with a minor initial deformity of the leg axis. Dynamic knee joint loading using gait analysis and musculoskeletal modeling can be used to determine the optimum time to remove the plates.

Probabilistic Finite Element Analysis of Human Rib Biomechanics: A Framework for Improved Generalizability.

In dynamic impact events, thoracic injuries often involve rib fractures, which are closely related to injury severity. Previous studies have investigated the behavior of isolated ribs under impact loading conditions, but often neglected the variability in anatomical shape and tissue material properties. In this study, we used probabilistic finite element analysis and statistical shape modeling to investigate the effect of population-wide variability in rib cortical bone tissue mechanical properties and rib shape on the biomechanical response of the rib to impact loading. Using the probabilistic finite element analysis results, a response surface model was generated to rapidly investigate the biomechanical response of an isolated rib under dynamic anterior-posterior load given the variability in rib morphometry and tissue material properties. The response surface was used to generate pre-fracture force-displacement computational corridors for the overall population and a population sub-group of older mid-sized males. When compared to the experimental data, the computational mean response had a RMSE of 4.28N (peak force 94N) and 6.11N (peak force 116N) for the overall population and sub-group respectively, whereas the normalized area metric when comparing the experimental and computational corridors ranged from 3.32% to 22.65% for the population and 10.90% to 32.81% for the sub-group. Furthermore, probabilistic sensitivities were computed in which the contribution of uncertainty and variability of the parameters of interest was quantified. The study found that rib cortical bone elastic modulus, rib morphometry and cortical thickness are the random variables that produce the largest variability in the predicted force-displacement response. The proposed framework offers a novel approach for accounting biological variability in a representative population and has the potential to improve the generalizability of findings in biomechanical studies.

Nitric oxide contributes to rapid sclerostin protein loss following mechanical load.

In response to mechanical loading of bone, osteocytes produce nitric oxide (NO•) and decrease sclerostin protein expression, leading to an increase in bone mass. However, it is unclear whether NO• production and sclerostin protein loss are mechanistically linked, and, if so, the nature of their hierarchical relationship within an established mechano-transduction pathway. Prior work showed that following fluid-shear stress (FSS), osteocytes produce NOX2-derived reactive oxygen species, inducing calcium (Ca2+) influx. Increased intracellular Ca2+ results in calcium-calmodulin dependent protein kinase II (CaMKII) activation, which regulates the lysosomal degradation of sclerostin protein. Here, we extend our discoveries, identifying NO• as a regulator of sclerostin degradation downstream of mechano-activated CaMKII. Pharmacological inhibition of nitric oxide synthase (NOS) activity in Ocy454 osteocyte-like cells prevented FSS-induced sclerostin protein loss. Conversely, short-term treatment with a NO• donor in Ocy454 cells or isolated murine long bones was sufficient to induce the rapid decrease in sclerostin protein abundance, independent of changes in Sost gene expression. Ocy454 cells express all three NOS genes, and transfection with siRNAs targeting eNOS/Nos3 was sufficient to prevent FSS-induced loss of sclerostin protein, while siRNAs targeting iNOS/Nos2 mildly blunted the loss of sclerostin but did not reach statistical significance. Similarly, siRNAs targeting both eNOS/Nos3 and iNOS/Nos2 prevented FSS-induced NO• production. Together, these data show iNOS/Nos2 and eNOS/Nos3 are the primary producers of FSS-dependent NO•, and that NO• is necessary and sufficient for sclerostin protein control. Further, selective inhibition of elements within this sclerostin-controlling mechano-transduction pathway indicated that NO• production occurs downstream of CaMKII activation. Targeting Camk2d and Camk2g with siRNA in Ocy454 cells prevented NO• production following FSS, indicating that CaMKII is needed for NO• production. However, NO• donation (1min) resulted in a significant increase in CaMKII activation, suggesting that NO• may have the ability to tune CaMKII response. Together, these data support that CaMKII is necessary for, and may be modulated by NO•, and that the interaction of these two signals is involved in the control of sclerostin protein abundance, consistent with a role in bone anabolic responses.

Deciphering the impact of organic loading rate and digestate recirculation on the occurrence patterns of antibiotics and antibiotic resistance genes in dry anaerobic digestion of kitchen waste.

Organic loading rate (OLR) is crucial for determining the stability of dry anaerobic digestion (AD). Digestate recirculation contributes to reactor stability and enhances methane production. Nevertheless, the understanding of how OLR and digestate recirculation affect the abundance and diversity of antibiotics and antibiotic resistance genes (ARGs), as well as the mechanisms involved in the dissemination of ARGs, remains limited. This study thoroughly investigated this critical issue through a long-term pilot-scale experiment. The metabolome analyses revealed the enrichment of various antibiotics, such as aminoglycoside, tetracycline, and macrolide, under low OLR conditions (OLR ≤ 4.0 g·VS/L·d) and the reactor instability. Antibiotics abundance decreased by approximately 19.66-31.69 % during high OLR operation (OLR ≥ 6.0 g·VS/L·d) with digestate recirculation. The metagenome analyses demonstrated that although low OLR promoted reactor stability, it facilitated the proliferation of antibiotic-resistant bacteria, such as Pseudomonas, and triggered functional profiles related to ATP generation, oxidative stress response, EPS secretion, and cell membrane permeability, thereby facilitating horizontal gene transfer (HGT) of ARGs. However, under stable operation at an OLR of 6.0 g·VS/L·d, there was a decrease in ARGs abundance but a notable increase in human pathogenic bacteria (HPB) and mobile genetic elements (MGEs). Subsequently, during reactor instability, the abundance of ARGs and HPB increased. Notably, during digestate recirculation at OLR levels of 6.0 and 7.0 g·VS/L·d, the process attenuated the risk of ARGs spread by reducing the diversity of ARGs hosts, minimizing interactions among ARGs hosts, ARGs, and MGEs, and weakening functional profiles associated with HGT of ARGs. Overall, digestate recirculation aids in reducing the abundance of antibiotics and ARGs under high OLR conditions. These findings provide advanced insights into how OLR and digestate recirculation affect the occurrence patterns of antibiotics and ARGs in dry AD.

An in-situ biochar-enhanced anaerobic membrane bioreactor for swine wastewater treatment under various organic loading rates.

A biochar-assisted anaerobic membrane bioreactor (BC-AnMBR) was conducted to evaluate the performance in treating swine wastewater with different organic loading rates (OLR) ranging from 0.38 to 1.13 kg-COD/(m3.d). Results indicated that adding spent coffee grounds biochar (SCG-BC) improved the organic removal efficiency compared to the conventional AnMBR, with an overall COD removal rate of > 95.01%. Meanwhile, methane production of up to 0.22 LCH4/gCOD with an improvement of 45.45% was achieved under a high OLR of 1.13 kg-COD/(m3.d). Furthermore, the transmembrane pressure (TMP) in the BC-AnMBR system was stable at 4.5 kPa, and no irreversible membrane fouling occurred within 125 days. Microbial community analysis revealed that the addition of SCG-BC increased the relative abundance of autotrophic methanogenic archaea, particularly Methanosarcina (from 0.11% to 11.16%) and Methanothrix (from 16.34% to 24.05%). More importantly, Desulfobacterota and Firmicutes phylum with direct interspecific electron transfer (DIET) capabilities were also enriched with autotrophic methanogens. Analysis of the electron transfer pathway showed that the concentration of c-type cytochromes increased by 38.60% in the presence of SCG-BC, and thus facilitated the establishment of DIET and maintained high activity of the electron transfer system even at high OLR. In short, the BC-AnMBR system performs well under various OLR conditions and is stable in the recovery energy system for swine wastewater.