Lagrangian Split-Step Method for Viscoelastic Flows.

This research addresses and resolves current challenges in meshless Lagrangian methods for simulating viscoelastic materials. A split-step scheme, or pressure Poisson reformulation of the Navier-Stokes equations, is introduced for incompressible viscoelastic flows in a Lagrangian context. The Lagrangian differencing dynamics (LDD) method, which is a thoroughly validated Lagrangian method for Newtonian and non-Newtonian incompressible flows, is extended to solve the introduced split-step scheme to simulate viscoelastic flows based on the Oldroyd-B constitutive model. To validate and evaluate the new method's capabilities, the following benchmarks were used: lid-driven cavity flow, droplet impact response, 4:1 planar sudden contraction, and die swelling. These findings highlight the LDD method's effectiveness in accurately simulating viscoelastic flows and capturing large deformations and memory effects. Even though the extra stress was directly modeled without any regularization approach, the method produced stable simulations for high Weissenberg numbers. The stability and performance of the the Lagrangian numerics for complex temporal evolution of material properties and stress responses encourage its use for industrial problems dealing with polymers.

Psoriatic arthritis increases the risk of venous thromboembolism following degenerative lumbar spine surgery: An analysis of U.S. Nationwide Inpatient Sample 2005-2018.

Background: This retrospective study aimed to determine the risk of venous thromboembolism (VTE) in patients with PsA after surgery for lumbar degenerative disease (LDD). Methods: The study data of adults aged ≥20 years admitted to U.S. hospitals with diagnoses of LDD and undergoing spinal decompression or fusion between 2005 and 2018 were extracted from the National Inpatient Sample (NIS) database. Patients were further divided into two groups based on a diagnosis of PsA or not via codes ICD-9: 696.0 and ICD-10: L40.50. Patients with missing information were excluded. Propensity score matching (PSM) was employed to enhance comparability between groups. Logistic regression was used to determine associations between PsA and various outcomes, including complications, unfavorable discharge, and prolonged length of stay (LOS). Results: Data on 471,283 patients with LDD was extracted from the NIS database.from 2005 to 2018. Before propensity score matching, patients with PsA had higher proportions of overall morbidity (8.8 % vs. 6.9 %), VTE (1.4 % vs. 0.7 %), and unfavorable discharge (20.8 % vs. 16.9 %). After matching, patients with PsA still had higher VTE incidence and unfavorable discharge proportions. After adjustments, multivariable regression analysis indicated that patients with PsA had a higher risk of unfavorable discharge (aOR: 1.26, 95 % CI: 1.03-1.55) and VTE (aOR: 1.99, 95 % CI: 1.05-3.75). Conclusions: Among patients undergoing surgery for LDD, pre-existing PsA may be associated with increased risks of unfavorable discharge and VTE occurrence. The findings may benefit preoperative risk stratifications before LDD surgeries.

Efficacy of Cucurmin and Aloevera Extracts Gel as Local Drugs Delivery Agents.

Introduction: The usage of antimicrobials as local drug delivery (LDD) agents in the treatment of periodontitis has posed limitations due to the development of bacterial resistance, high cost, and unavailability, thus indicating the need for safer and economic alternatives. Methodology: A split-mouth randomized clinical trial was carried out on 10 patients. Three sites in different quadrants were assigned, treatment modality of scaling and root planing (SRP) alone, SRP with LDD of curcumin gel, and SRP with LDD of 99% pure aloe vera gel, respectively. Clinical parameters were recorded at baseline and on 30th day postoperatively. Results: Curcumin and aloe vera in addition to SRP demonstrated improvements in clinical parameters, though 99% aloe vera extract produced more statistically significant results when used as an LDD agent, as shown in intergroup comparisons for changes in periodontal parameters. Conclusion: Curcumin 10mg (Curenext) and 99% aloe vera extract as LDD along with regular mechanical debridement is a promising therapy in the treatment of chronic periodontitis.

Latest Developments in Minimally Invasive Spinal Treatment in Slovakia and Its Comparison with an Open Approach for the Treatment of Lumbar Degenerative Diseases.

The study describes the benefits of MIS-TLIF (minimally invasive transforaminal lumbar interbody fusion) and compares them with OTLIF (open transforaminal lumbar interbody fusion). It compares blood loss, length of hospitalization stays (LOS), operation time, and return of the patient to the environment. A total of 250 adults (109 males and 141 females), mean age 59.5 ± 12.6, who underwent MIS-TLIF in the Neurosurgery Clinic (NSC) Ruzomberok, Slovakia, because of lumbar degenerative diseases (LDD), participated in this retrospective study. Data were obtained from the patients' medical records and from the standardized Oswestry Disability Index (ODI) index questionnaire. To compare ODI in our study sample, we used the Student's Paired Sample Test. To compare the MIS-TLIF and OTLIF approaches, a meta-analysis was conducted. Confidence intervals were 95% CI. The test of homogeneity (Chi-square (Q)) and the degree of heterogeneity (I2 test) among the included studies were used. Statistical analyses were two-sided (α = 0.05). All monitored parameters were significantly better in MIS-TLIF group: blood loss (p < 0.001), operation time (p < 0.001), and ODI changes (p < 0.001). LOS (p < 0.042) were close to the significance level. ODI in the study sample decreased by 33.44% points after MIS-TLIF, and it significantly increased as well (p < 0.001). The percentage of patients who were satisfied with the surgery they underwent was 84.8%. The study confirmed that the MIS-TLIF method is in general gentler for the patient and allows the faster regeneration of patient's health status compared to OTLIF.

A meta-analysis of prognostic factors in surgical treatment of foot drop due to lumbar degenerative diseases.

Objective: Lumbar decompression surgery is an effective treatment for foot drop caused by LDD, but there is controversy about the prognostic factors affecting its efficacy. This study aimed to investigate the factors influencing the surgical outcome of foot drop due to LDD. Methods: A systematic database search of PubMed, Embase, Web of Science, Cochrane Library and Clinical Trials was performed for relevant articles published until May 2022. Two reviewers independently screened the literature, extracted data, and evaluated the quality of the studies based on the inclusion and exclusion criteria. The quality of the studies was evaluated using the Newcastle-Ottawa Scale (NOS), and STATA 16.0 software was used for meta-analysis. Results: A total of 730 relevant articles were initially identified and 9 articles were finally included in this study for data extraction and mea-analysis. The results of metaanalysis showed that patients with preoperative moderate muscle strength (2-3/5 on the Medical Research Council scale) had better prognosis compared to those with severe muscle weakness. Additionally, the presence of diabetes mellitus was associated with a poorer prognosis for patients with foot drop due to LDD. The OR values (95%CI) of these two factors were 5.882 (4.449, 7.776) and 5.657 (2.094,15.280) respectively. Conclusions: Patients with moderate muscle strength have a better prognosis compared to those with severe muscle weakness. The presence of diabetes mellitus is associated with a poorer prognosis for patients with foot drop due to LDD. These factors should be considered when predicting the surgical outcome of foot drop due to LDD.

The role of oceanic currents in the dispersal and connectivity of the mangrove Rhizophora mangle on the Southwest Atlantic region.

Dispersal is a crucial mechanism to living beings, allowing them to reach new resources such that populations and species can occupy new environments. However, directly observing the dispersal mechanisms of widespread species can be costly or even impractical, which is the case for mangrove trees. The influence of ocean currents on mangrove dispersal is increasingly evident; however, few studies mechanistically relate the patterns of population distribution with the dispersal by oceanic currents under an integrated framework. Here, we evaluate the role of oceanic currents on connectivity of Rhizophora mangle along the Southwest Atlantic. We inferred population genetic structure and migration rates, simulated the displacement of propagules and tested our hypotheses with Mantel tests and redundancy analysis. We observed populations structured in two major groups, north and south, which is corroborated by other studies with Rhizophora and other coastal plants. Inferred recent migration rates do not indicate ongoing gene flow between sites. Conversely, long-term migration rates were low across groups and contrasting dispersal patterns within each one, which is consistent with long-distance dispersal events. Our hypothesis tests suggest that both isolation by distance and isolation by oceanography (derived from the oceanic currents) can explain the neutral genetic variation of R. mangle in the region. Our findings expand current knowledge of mangrove connectivity and highlight how the association of molecular methods with oceanographic simulations improve the interpretation of the dispersal process. This integrative approach is a cost- and time-efficient strategy to include dispersal and connectivity data into marine protected areas planning and management.

Pharmacological Evidence Suggests That Slo3 Channel Is the Principal K+ Channel in Boar Spermatozoa.

Sperm ion channels are associated with the quality and type of flagellar movement, and their differential regulation is crucial for sperm function during specific phases. The principal potassium ion channel is responsible for the majority of K+ ion flux, resulting in membrane hyperpolarization, and is essential for sperm capacitation-related signaling pathways. The molecular identity of the principal K+ channel varies greatly between different species, and there is a lack of information about boar K+ channels. We aimed to determine the channel identity of boar sperm contributing to the primary K+ current using pharmacological dissection. A series of Slo1 and Slo3 channel modulators were used for treatment. Sperm motility and related kinematic parameters were monitored using a computer-assisted sperm analysis system under non-capacitated conditions. Time-lapse flow cytometry with fluorochromes was used to measure changes in different intracellular ionic concentrations, and conventional flow cytometry was used to determine the acrosome reaction. Membrane depolarization, reduction in acrosome reaction, and motility parameters were observed upon the inhibition of the Slo3 channel, suggesting that the Slo3 gene encodes the main K+ channel in boar spermatozoa. The Slo3 channel was localized on the sperm flagellum, and the inhibition of Slo3 did not reduce sperm viability. These results may aid potential animal-model-based extrapolations and help to ameliorate motility and related parameters, leading to improved assisted reproductive methods in industrial livestock production.

Are current machine learning applications comparable to radiologist classification of degenerate and herniated discs and Modic change? A systematic review and meta-analysis.

INTRODUCTION: Low back pain is the leading contributor to disability burden globally. It is commonly due to degeneration of the lumbar intervertebral discs (LDD). Magnetic resonance imaging (MRI) is the current best tool to visualize and diagnose LDD, but places high time demands on clinical radiologists. Automated reading of spine MRIs could improve speed, accuracy, reliability and cost effectiveness in radiology departments. The aim of this review and meta-analysis was to determine if current machine learning algorithms perform well identifying disc degeneration, herniation, bulge and Modic change compared to radiologists. METHODS: A PRISMA systematic review protocol was developed and four electronic databases and reference lists were searched. Strict inclusion and exclusion criteria were defined. A PROBAST risk of bias and applicability analysis was performed. RESULTS: 1350 articles were extracted. Duplicates were removed and title and abstract searching identified original research articles that used machine learning (ML) algorithms to identify disc degeneration, herniation, bulge and Modic change from MRIs. 27 studies were included in the review; 25 and 14 studies were included multi-variate and bivariate meta-analysis, respectively. Studies used machine learning algorithms to assess LDD, disc herniation, bulge and Modic change. Models using deep learning, support vector machine, k-nearest neighbors, random forest and naïve Bayes algorithms were included. Meta-analyses found no differences in algorithm or classification performance. When algorithms were tested in replication or external validation studies, they did not perform as well as when assessed in developmental studies. Data augmentation improved algorithm performance when compared to models used with smaller datasets, there were no performance differences between augmented data and large datasets. DISCUSSION: This review highlights several shortcomings of current approaches, including few validation attempts or use of large sample sizes. To the best of the authors' knowledge, this is the first systematic review to explore this topic. We suggest the utilization of deep learning coupled with semi- or unsupervised learning approaches. Use of all information contained in MRI data will improve accuracy. Clear and complete reporting of study design, statistics and results will improve the reliability and quality of published literature.

The Analysis of Preoperative Roussouly Classification on Pain Scores and Radiological Data in Lateral Lumbar Interbody Fusion for Patients with Lumbar Degenerative Disease.

STUDY DESIGN: A retrospective observational study. OBJECTIVE: The type of sagittal profile defined by Roussouly has affected spinal degeneration and surgical outcome. This study aimed to investigate the effect of preoperative Roussouly classification on pain intensity and radiological data of patients with lumbar degenerative disease who underwent indirect decompression with lateral lumbar interbody fusion (LLIF). METHODS: We retrospectively investigated 102 patients who underwent LLIF without direct decompression. Patients were subdivided into 4 groups according to the Roussouly classification determined from preoperative full-length and lateral spine X-rays, and classified according to Roussouly types I, II, and IV in the nonstandard group and Roussouly type III in the standard group. RESULTS: The nonstandard group showed improved sagittal vertical axis and lumbar lordosis after LLIF surgery, but the midsagittal canal diameter and axial central canal area of the thecal sac using T2-weighted sagittal and axial magnetic resonance imaging were smaller than those in the standard group. On the other hand, each numeric rating scale score 1 year after surgery improved in all patients. Changes in numeric rating scale scores in low back pain, leg pain, and numbness were not statistically significant between Roussouly classification types. CONCLUSIONS: These results suggest that the nonstandard group may have less indirect decompression effect from LLIF than the standard group. In the short term, we show for the first time after LLIF surgery that preoperative sagittal spinal alignment and the pelvic position may not significantly impact pain improvement.

Hybrid Lymphatic Drug Delivery Vehicles as a New Avenue for Targeted Therapy: Lymphatic Trafficking, Applications, Challenges, and Future Horizons.

Lymphatic drug targeting is an effective approach for targeting immunomodulators, and chemotherapeutic drugs at a specific organ or cellular location. The cellular, paracellular, and dendritic cell trafficking machinery are involved in the lymphatic transport of therapeutic agents. The engineering of triggered and hybrid lymphatic drug delivery systems (LDDS) is a promising strategy to fight cancer metastasis and microbial pandemics. Hybrid lymphatic drug delivery systems can be tailored and developed by grafting the conventional LDDS with biological agents. Thus, hybrid LDDS could collect the benefits of conventional and biological delivery systems. Moreover, the fabrication of triggered LDDS increases drug accumulation in the lymphatic system in the response to an internal stimulus such as pH, and redox status or external such as magnetic field, temperature, and light. Stimuli-responsive LDD systems prevent premature release of payload and mediate selective drug biodistribution. This improves therapeutic impact and reduces the systemic side effect of anticancer, immunomodulatory, and antimicrobial therapeutics. This review highlights the challenges and future horizons of nanoscaled-triggered LDDS and their influence on the lymphatic trafficking of therapeutic molecules.

Superhydrophobicity mechanism of refoliated quaking aspen leaves after complete defoliation by LDD (gypsy, spongy) moth caterpillars.

Complete defoliation of trees due to periodic LDD (Lymantria dispar dispar) moth outbreaks in many parts of the world is a significant stress factor for the survival of individual trees and entire forests over vast areas. This study addresses such a mid-summer defoliation event in Ontario, Canada for quaking aspen trees during 2021. It is shown that complete refoliation in the same year is possible for these trees, albeit with significantly smaller leaf size. Regrown leaves showed the well-known non-wetting behaviour typically observed for the quaking aspen tree without a defoliation event. These leaves have the same hierarchical dual-scale surface structure consisting of nanometre-size epicuticular wax (ECW) crystals superimposed on micrometre-sized papillae. This structure provides for the Cassie-Baxter non-wetting state with a very high water contact angle on the adaxial surface of the leaves. Subtle differences in the leaf surface morphology of the refoliation leaves compared with the regular growth leaves are likely due to environmental factors such as seasonal temperature during the leaf growth period after budbreak.

TPGS decorated NLC shift gefitinib from portal absorption into lymphatic delivery: Intracellular trafficking, biodistribution and bioavailability studies.

Lymphatic drug delivery (LDD) is an attractive option for the prevention and treatment of cancer metastasis. This study aims to develop TPGS decorated nanostructure lipid carrier gefitinib loaded (TPGS-NLC-GEF). Biocompatibility and cytotoxicity were studied using erythrocytes and A549 cell lines. Furthermore, cellular uptake of the prepared TPGS-NLC was studied using 5-carboxyfluorescein (5-CF). Pharmacokinetic, biodistribution, and chylomicron-block flow studies were performed using male Wister Albino rats to investigate the influence of TPGS-NLC on plasma concentration-time profile, organ deposition, and LDD of GEF. The present results indicated that the prepared TPGS-NLC and TPGS-NLC-GEF formulation had a particle size range of 268 and 288 nm with a negative zeta-potential value of - 29.3 and - 26.5 mV, respectively. The in-vitro release showed burst drug release followed by sustained release. In addition, the biosafety in the term of the hemocompatibility study showed that the prepared formulation was safe at the therapeutic level. Additionally, an in-vitro cytotoxicity study showed that the TPGS-NLC was able to enhance the activity of GEF against the A549 cell line. The cellular uptake study showed the ability of TPGS-NLC to enhance 5-CF internalization by 12.6-fold compared to the 5-CF solution. Furthermore, the in-vivo study showed that TPGS-NLC was able to enhance GEF bioavailability (1.5-fold) through lymphatic system which was confirmed via the indirect chylomicron-block flow method. The tissue distribution study showed the ability of lipid nanoparticles to enhance lung drug deposition by 5.8-fold compared to a GEF suspension. This study concluded that GEF-NLC-GEF is an encouraging approach for the treatment of metastatic lung cancer through lymphatic delivery, enhanced bioavailability, and reduced systemic toxicity.

Persistent expression of NLRP3 in spinal microglia promotes development of lumbar disc degeneration.

Introduction: Activated microglia play a critical role in the development of lumbar disc degeneration (LDD), which is a severe disease that causes neuropathic pain in affected people. Interleukin 1ß (IL-1ß) is a proinflammatory cytokine produced and secreted by activated microglia to induce the inflammation and the subsequent degradation of the disease discs. Recent findings suggest that activation of IL-1ß in cells usually requires the involvement of NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-induced formation of inflammasome. However, the importance of NLRP3 in spinal microglia in LDD is not known and thus addressed in the current study. Methods: NLRP3 expression was examined in the spinal discs. Correlation of NLRP3 levels in microglia with the pain score of the LDD patients or Thompson classification of the degeneration level of the patients was determined. The effects of persistent expression or depletion of NLRP3 on phagocytosis potential and production of proinflammatory cytokines in microglia were tested in vitro, while their effects on the severity of LDD and LDD-associated neuropathic pain were assessed in a mouse model for LDD. Results: NLRP3 was exclusively expressed in microglia in the spinal discs. NLRP3 levels in microglia strongly correlated with the pain score of the LDD patients, and modestly correlated with the Thompson classification of the degeneration level of the patients. Persistent NLRP3 expression in microglia increased both their phagocytosis potential and production of proinflammatory cytokines, while NLRP3-depleted microglia decreased both their phagocytosis potential and production of proinflammatory cytokines. In a mouse model for LDD, persistent NLRP3 activation in microglia significantly increased the severity of LDD and LDD-associated neuropathic pain, while specific depletion of NLRP3 in microglia significantly attenuated the severity of LDD and reduced the LDD-associated neuropathic pain. Conclusions: Persistent activation of NLRP3 in spinal microglia promotes development of LDD, while suppression of NLRP3 in microglia could be a promising strategy for LDD therapy.

Inhibition of angiogenetic macrophages reduces disc degeneration-associated pain.

Abnormal angiogenesis and innervation in avascular discs during lumbar disc degeneration (LDD) cause severe back pain. These pathological alterations in the degenerating discs are induced by cytokines partially produced and secreted by inflammatory cells, among which macrophages are the most frequently ones detected at the legion site. However, the role of macrophages as well as their polarization in regulation of innervation and angiogenesis in the degenerating discs is unclear. In this study, we analyzed macrophages in the degenerating discs from patients and detected a specific macrophage subtype that expresses high levels of vascular endothelial growth factor A (VEGF-A). Co-expression of M2 macrophage markers in this macrophage subtype suggested that they were a M2d-like subtype. High levels of VEGF-A and genes associated with angiogenesis were also detected in LDD specimens compared to control heathy discs from a public database, consistent with our finding. Moreover, the levels of VEGF-A in disc macrophages were strongly correlated to the pain score of the examined patients, but not to the Thompson classification of the degeneration level of the patients. In vitro, overexpressing VEGF-A in macrophages increased the tube formation, proliferation and migration of co-cultured endothelial cells, and increased the innervation of embryonic spinal cord explant into the co-cultured area for macrophages and skeletal myocytes. In vivo, an orthotopic injection of adeno-associated virus carrying siRNA for VEGF-A under a macrophage-specific CD68 promoter significantly reduced the number of VEGF-A-positive disc macrophages and alleviated the pain in LDD-mice. Together, these data suggest that inhibition of angiogenetic potential of macrophages may reduce disc degeneration-associated pain through suppression of angiogenesis and innervation, as a promising therapy for LDD-associated pain.

Engineered Nanoscale Lipid-Based Formulation as Potential Enhancer of Gefitinib Lymphatic Delivery: Cytotoxicity and Apoptotic Studies Against the A549 Cell Line.

The present study aimed to engineer a nanoscale lipid-based lymphatic drug delivery system with D-α-Tocopherol polyethylene glycol 1000 succinate to combat the lymphatic metastasis of lung cancer. The nanoscale lipid-based systems including GEF-SLN, GEF-NLC, and GEF-LE were prepared and pharmaceutically characterized. In addition, the most stable formulation (GEF-NLC) was subjected to an in vitro release study. Afterward, the optimized GEF-NLC was engineered with TPGS (GEF-TPGS-NLC) and subjected to in vitro cytotoxicity, and apoptotic studies using the A549 cells line as a surrogate model for lung cancer. The present results revealed that particle size and polydispersity index of freshly prepared formulations were ranging from 198 to 280 nm and 0.106 to 0.240, respectively, with negative zeta potential ranging from - 14 to - 27.6.mV. An in vitro release study showed that sustained drug release was attained from GEF-NLC containing a high concentration of lipid. In addition, GEF-NLC and GEF-TPGS-NLC showed remarkable entrapment efficiency above 89% and exhibited sustained release profiles. Cytotoxicity showed that IC50 of pure GEF was 11.15 µg/ml which decreased to 7.05 µg/ml for GEF-TPGS-NLC. The apoptotic study revealed that GEF-TPGS-NLC significantly decreased the number of living cells from 67 to 58% when compared with pure GEF. The present results revealed that the nanoscale and lipid composition of the fabricated SLN, NLC, and LE could mediate the lymphatic uptake of GEF to combat the lymphatic tumor metastasis. Particularly, GEF-TPGS-NLC is a promising LDDS to increase the therapeutic outcomes of GEF during the treatment of metastatic lung cancer.

Molecular phylogenetics, speciation, and long distance dispersal in tardigrade evolution: A case study of the genus Milnesium.

Microorganisms (sensu lato, i.e., including micrometazoans) are thought to have cosmopolitan geographic distributions due to their theoretically unlimited dispersal capabilities, a consequence of their tiny size, population dynamics, and resistant forms. However, several molecular studies of microorganisms have identified biogeographic patterns indicating cryptic speciation and/or weak species definitions. Using a multi-locus approach with the genus Milnesium (Tardigrada), we aimed to determine the genetic structure of populations worldwide and the effects of long distance dispersal (LDD) on genetic connectivity and relationships across the six continents. Our results on this micrometazoan's genetic structure and LDD at global and micro-local scales indicate contrasting patterns not easily explained by a unique or simple phenomenon. Overall, we report three key findings: (i) confirmation of long distance dispersal for tardigrades, (ii) populations with globally-shared or endemic micro-local haplotypes, and (iii) a supported genetic structure instead of the homogeneous genetic distribution hypothesized for microorganisms with LDD capabilities. Moreover, incongruences between our morphological and molecular results suggest that species delimitation within the genus Milnesium could be problematic due to homoplasy. Duality found for Milnesium populations at the global scale, namely, a molecular phylogenetic structure mixed with widely distributed haplotypes (but without any apparent biogeographic structure), is similar to patterns observed for some unicellular, prokaryotic and eukaryotic, microorganisms. Factors influencing these patterns are discussed within an evolutionary framework.

Population assignment tests uncover rare long-distance marine larval dispersal events.

Long-distance dispersal (LDD) is consequential to metapopulation ecology and evolution. In systems where dispersal is undertaken by small propagules, such as larvae in the ocean, documenting LDD is especially challenging. Genetic parentage analysis has gained traction as a method for measuring larval dispersal, but such studies are generally spatially limited, leaving LDD understudied in marine species. We addressed this knowledge gap by uncovering LDD with population assignment tests in the coral reef fish Elacatinus lori, a species whose short-distance dispersal has been well-characterized by parentage analysis. When adults (n = 931) collected throughout the species' range were categorized into three source populations, assignment accuracy exceeded 99%, demonstrating low rates of gene flow between populations in the adult generation. After establishing high assignment confidence, we assigned settlers (n = 3,828) to source populations. Within the settler cohort, <0.1% of individuals were identified as long-distance dispersers from other populations. These results demonstrate an exceptionally low level of connectivity between E. lori populations, despite the potential for ocean currents to facilitate LDD. More broadly, these findings illustrate the value of combining genetic parentage analysis and population assignment tests to uncover short- and long-distance dispersal, respectively.

Prevention of lumbar disc degeneration through co-manipulation of insulin-like growth factor 1 and vascular endothelial growth factor.

BACKGROUND: Associated with abnormal angiogenesis and disc dysfunction, lumbar disc degeneration (LDD) appears to be an important disease suffered by elderly people. Previous studies have highlighted the importance of insufficient insulin-like growth factor 1 (IGF1) and excessive vascular endothelial growth factor (VEGF) in the development and progression of LDD, though a practical therapeutic strategy is lacking. METHODS: The expression of IGF1 and VEGF was assessed in LDD specimens compared to normal disc tissue as a control. A gene therapy approach was performed, in which an adeno-associated virus (AAV) carrying both IGF1 and shVEGF (AAV-IGF1/shVEGF) was orthotopically injected to the rats that had undergone LDD. The alterations in IGF1 and VEGF levels in the treated disc tissue were confirmed by immunohistochemistry. The outcome of this therapy was assessed by disc cell death using an annexin V-FITC assay and by assessing lumbar proteoglycan and collagen II levels using ELISA. RESULTS: IGF1 expression was significantly downregulated in LDD, while VEGF expression was significantly upregulated in LDD, compared to normal controls. Combined AAV-IGF1/shVEGF treatment simultaneously corrected the insufficient IGF1 and the excessive VEGF in LDD rats. Moreover, AAV-IGF1/shVEGF significantly reduced disc cell death in the vertebral pulp and annulus fibrosus and significantly enhanced the lumbar proteoglycan and collagen II levels. CONCLUSIONS: The simultaneous increase in IGF1 and depletion of VEGF effectively prevented the development of LDD, suggesting its potential as a novel therapeutic approach for LDD which is clinically translatable.

A randomized trial on the application of a nurse-led early rehabilitation program after minimally invasive lumbar internal fixation.

BACKGROUND: Lumbar degenerative disease (LDD) is a narrowing of the spinal canal and intervertebral foramina caused by aging and degeneration of lumbar spine tissue. Minimally invasive internal lumbar spine fixation is emerging in the treatment of LDD. However, no standard early rehabilitation protocol for orthopedic robot-assisted minimally invasive internal lumbar spine fixation exits. To investigate the effect of a nurse-led early rehabilitation program in the postoperative recovery of patients with lumbar degenerative lesions undergoing orthopedic robot-assisted minimally invasive lumbar internal fixation. METHODS: Eighty patients with minimally invasive orthopedic robot-assisted lumbar degenerative lesions admitted to our hospital between January 2019 and January 2021 were recruited to this study. The patients were randomly allocated to a control group (n=40), involving conventional care, and an observation group (n=38; 40 initially and 2 later excluded) including a nurse-led early rehabilitation program added on the basis of the control group. The primary outcomes were the general postoperative conditions, scores of daily living ability, the degree of low back pain and functional recovery. Participants were also compared in terms of their compliance with the care regimen and the incidence of complications. RESULTS: Participants in the observation group had a significantly shorter first time on the floor after surgery (P<0.001) and shorter hospital stay (P=0.003). Meanwhile, participants in the observation group had higher Barthel index (BI) scores (P=0.039), lower visual analogue scale (VAS) scores (P=0.028), and Oswestry disability index (ODI) scores (P=0.002) at 3 days postoperatively, and there was no difference in the three scores between the two groups at 1 month postoperatively (all P>0.05). The compliance of participants in the observation group was significantly higher than that of the control group (P<0.001). Participants in the observation group were less likely to experience constipation (P=0.043) and bloating (P=0.012) within 1 month after surgery. CONCLUSIONS: Implementation of a nurse-led early rehabilitation program in patients undergoing orthopedic robotic-assisted minimally invasive treatment of lumbar degenerative lesions can significantly improve patient compliance, significantly shorten postoperative flooring and hospitalization time, reduce the incidence of gastrointestinal adverse events, and accelerate postoperative recovery. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100048698.

Lagrangian Differencing Dynamics for Time-Independent Non-Newtonian Materials.

This paper introduces a novel meshless and Lagrangian approach for simulating non-Newtonian flows, named Lagrangian Differencing Dynamics (LDD). Second-order-consistent spatial operators are used to directly discretize and solve generalized Navier-Stokes equations in a strong formulation. The solution is obtained using a split-step scheme, i.e., by decoupling the solutions of the pressure and velocity. The pressure is obtained by solving a Poisson equation, and the velocity is solved in a semi-implicit formulation. The matrix-free solution to the equations, and Lagrangian advection of mesh-free nodes allowed for a fully parallelized implementation on the CPU and GPU, which ensured an affordable computing time and large time steps. A set of four benchmarks are presented to demonstrate the robustness and accuracy of the proposed formulation. The tested two- and three-dimensional simulations used Power Law, Casson and Bingham models. An Abram slump test and a dam break test were performed using the Bingham model, yielding visual and numerical results in accordance with the experimental data. A square lid-driven cavity was tested using the Casson model, while the Power Law model was used for a skewed lid-driven cavity test. The simulation results of the lid-driven cavity tests are in good agreement with velocity profiles and stream lines of published reports. A fully implicit scheme will be introduced in future work. As the method precisely reproduces the pressure field, non-Newtonian models that strongly depend on the pressure will be validated.