Mechanism of low-intensity pulse ultrasound combined with Rhodiola to promote bone formation in spinal fusion.

This study aimed to explore the influence and mechanism of low-intensity pulsed ultrasound (LIPUS) combined with Rhodiola bone penetration on the formation of spinal fusion bone. Sixty clean-grade New Zealand white rabbits were selected for randomization and divided into combined group and Rhodiola group, with 30 rabbits in each group to construct a rabbit lumbar intervertebral fusion model, using Rhodiola intervention and Rhodiola combined with LIPUS intervention protocol, respectively. The axial strength, axial stiffness, maximum compressive load, vascular endothelial growth factor (VEGF), cycloxygenase-2 (COX-2), prostaglandin E2 (PGE2) and transforming growth factor-ß (TGF-ß) were compared after HE staining, immunohistochemistry and biomechanical detection. Spine fusion rate was 100.00%; the combined bone graft tissue had implanted bone cell degeneration, cell necrosis and cell hyperplasia, chondrocytes differentiated into trabecular bone and some hematopoietic cells, severe cell necrosis and fiber cell proliferation and late bone formation in the Rhodiola group, VEGF, COX-2, PGE2, TGF-ß, axial strength, axial stiffness, and maximum compression load in the combined group significantly increased (P<0.05). Spinal fusion using LIPUS combined with Rhodiola can enhance biomechanical properties and promote the role of PGE2, COX-2, VEGF, TGF-ß expression and bone formation, and this protocol is worthy of clinical application.

The effects of simvastatin on the bone microstructure and mechanics of ovariectomized mice: a micro-CT and micro-finite element analysis study.

BACKGROUND: Osteoporosis is a major health concern for postmenopausal women, and the effect of simvastatin (Sim) on bone metabolism is controversial. This study aimed to investigate the effect of simvastatin on the bone microstructure and bone mechanical properties in ovariectomized (OVX) mice. METHODS: 24 female C57BL/6J mice (8-week-old) were randomly allocated into three groups including the OVX + Sim group, the OVX group and the control group. At 8 weeks after operation, the L4 vertebral bones were dissected completely for micro-Computed Tomography (micro-CT) scanning and micro-finite element analysis (µFEA). The differences between three groups were compared using ANOVA with a LSD correction, and the relationship between bone microstructure and mechanical properties was analyzed using linear regression. RESULTS: Bone volume fraction, trabecular number, connectivity density and trabecular tissue mineral density in the OVX + Sim group were significantly higher than those in the OVX group (P < 0.05). For the mechanical properties detected via µFEA, the OVX + Sim group had lower total deformation, equivalent elastic strain and equivalent stress compared to the OVX group (P < 0.05). In the three groups, the mechanical parameters were significantly correlated with bone volume fraction and trabecular bone mineral density. CONCLUSIONS: The findings suggested that simvastatin had a potential role in the treatment of osteoporosis. The results of this study could guide future research on simvastatin and support the development of simvastatin-based treatments to improve bone health.

Biomechanical changes of tree shrew posterior sclera during experimental myopia, after retrobulbar vehicle injections, and crosslinking using genipin.

Myopia is a common ocular condition characterized by biomechanical weakening revealed by increasing creep rate, cyclic softening scleral thinning, change of collagen fibril crimping, and excessive elongation of the posterior sclera resulting in blurred vision. Animal studies support scleral crosslinking as a potential treatment for myopia control by strengthening the weakened sclera and slowing scleral expansion. While multiple studies investigated aspects of the biomechanical weakening and strengthening effects in myopia and after scleral crosslinking, a comprehensive analysis of the underlying mechanical changes including the effect of vehicle injections is still missing. The purpose of this study was to provide a comprehensive analysis of biomechanical changes by scleral inflation testing in experimental myopia, after retrobulbar vehicle injections and scleral crosslinking using genipin in tree shrews. Our results suggest that biomechanical weakening in myopia involves an increased creep rate and higher strain levels at which collagen fibers uncrimp. Both weakening effects were reduced after scleral crosslinking using genipin at doses that were effective in slowing myopia progression. Vehicle injections increased mechanical hysteresis and had a small but significant effect on slowing myopia progression. Also, our results support scleral crosslinking as a potential treatment modality that can prevent or counteract scleral weakening effects in myopia. Furthermore, vehicle solutions may cause independent biomechanical effects, which should be considered when developing and evaluating scleral crosslinking procedures.

Quality and kinematic characteristics of Bali bulls frozen semen with purified green tea extract epigallocatechin-3-gallate antioxidant addition in diluent.

Background: The preservation of semen quality and kinematic characteristics during cryopreservation is crucial for the reproductive success and genetic management of livestock, particularly in Bali bulls. Aim: This study aimed to investigate the effect of adding purified green tea extract antioxidant Epigallocatechin-3-gallate (EGCG) in tris egg yolk diluent on the quality and kinematic characteristics of frozen semen from Bali bulls. Methods: Fresh and frozen semen samples were obtained from Bali bull and divided into four different treatment groups. P0 contained semen samples + diluent, while P1 to P3 consisted of semen samples + diluent supplemented with EGCG levels of 0.1, 0.15, and 0.2 mg/100 ml, respectively. Data were analyzed using One-way ANOVA and followed by Duncan's test if significant differences were found (p<0.05). Parameters observed included the assessment of fresh semen quality, kinematic analysis, post-thawing sperm viability, and abnormality. Results: The results indicated that the assessment of fresh semen quality showed macroscopic and microscopic semen quality according to SNI 4869-1:2021. Kinematic analysis revealed significant differences in DSL and STR parameters between P0 and P3 (p<0.05). EGCG supplementation also caused significant differences in motility between P0 and P3 (p<0.05). Viability and spermatozoa abnormality with EGCG supplementation did not show significant differences (p>0.05). Conclusion: The best results for motility, kinematics, and sperm morphology variables were found in P1 as it did not exhibit a decrease in motility, kinematics, and sperm morphology. Viability did not show significant differences between P1, P2, and P3, but the best results were found in P2 as it did not exhibit a decrease in viability with mean and standard deviation (66.84 ± 7.88). Abnormality variables also did not show significant differences between P1, P2, and P3, but the best results were found in P2 as it did not exhibit a decrease in abnormality with mean and standard deviation (23.80 ± 7.36).

Hyaluronic Acid/Platelet-Rich Plasma Mixture Improves Temporomandibular Joint Biomechanics: A Systematic Review.

Hyaluronic acid (HA) is the main component of the temporomandibular joint (TMJ) synovial fluid. Arthritis in temporomandibular disorders (TMDs) disrupts HA metabolism, resulting in shorter polymeric chain predominance and increased friction. Intra-articular injections of HA supplement the larger molecules of this glycosaminoglycan, and the platelet-rich plasma (PRP) delivered in this way releases growth factors, suppressing inflammation. This PRISMA-compliant PROSPERO-registered (CRD42024564382) systematic review aimed to assess the validity of mixing HA with PRP in the injectable treatment of TMJ disorders. We searched the medical literature for eligible randomized clinical trials using BASE, Google Scholar, PubMed and Scopus engines on 9 May 2024, with no time frame limit. Selected reports were assessed for risk of bias using the Cochrane RoB2 tool. Numerical data were collected on articular pain and mandibular mobility. We provided mean differences from baseline and between study and control groups at each observation point. The efficacy of TMD treatment with HA/PRP versus HA or PRP alone was assessed meta-analytically. Of 171 identified records, we selected 6 studies. In the 6-month follow-up, the mean advantage of PRP supplementation with HA was 2.52 (SE = 2.44; d = 0.83) mm and the benefit of adding PRP to HA was 1.47 (SE = 2.68; d = 0.34) mm in mandibular abduction. The pain-improvement scores were -1.33 (SE = 1.02; d = -1.05) and -1.18 (SE = 0.92; d = 0.80), respectively. Presumably, the HA/PRP range of therapeutic efficiency includes cases non-respondent to HA or PRP alone.

Dopaminergic manipulations affect the modulation and meta-modulation of movement speed: Evidence from two pharmacological interventions.

A body of research implicates dopamine in the average speed of simple movements. However, naturalistic movements span a range of different shaped trajectories and rarely proceed at a single constant speed. Instead, speed is reduced when drawing "corners" compared to "straights" (i.e., speed modulation), and the extent of this slowing down is dependent upon the global shape of the movement trajectory (i.e., speed meta-modulation) - for example whether the shape is an ellipse or a rounded square. At present, it is not known how (or whether) dopaminergic function controls continuous changes in speed during movement execution. The current paper reports effects on these kinematic features of movement following two forms of dopamine manipulation: Study One highlights movement differences in individuals with PD both ON and OFF their dopaminergic medication (N = 32); Study Two highlights movement differences in individuals from the general population on haloperidol (a dopamine receptor blocker, or "antagonist") and placebo (N = 43). Evidence is presented implicating dopamine in speed, speed modulation and speed meta-modulation, whereby low dopamine conditions are associated with reductions in these variables. These findings move beyond vigour models implicating dopamine in average movement speed, and towards a conceptualisation that involves the modulation of speed as a function of contextual information.

Mitigating aging and doxorubicin induced bone loss in mature mice via mechanobiology based treatments.

Aging leads to a reduced anabolic response to mechanical stimuli and a loss of bone mass and structural integrity. Chemotherapy agents such as doxorubicin exacerbate the degeneration of aging skeleton and further subject older cancer patients to a higher fracture risk. To alleviate this clinical problem, we proposed and tested a novel mechanobiology-based therapy. Building upon prior findings that i) Yoda1, the Piezo1 agonist, promoted bone growth in young adult mice and suppressed bone resorption markers in aged mice, and ii) moderate tibial loading protected bone from breast cancer-induced osteolysis, we hypothesized that combined Yoda1 and moderate loading would improve the structural integrity of adult and aged skeletons in vivo and protect bones from deterioration after chemotherapy. We first examined the effects of 4-week Yoda1 (dose 5 mg/kg, 5 times/week) and moderate tibial loading (4.5 N peak load, 4 Hz, 300 cycles for 5 days/week), individually and combined, on mature mice (∼50 weeks of age). Combined Yoda1 and loading was found to mitigate age-associated cortical and trabecular bone loss better than individual interventions. As expected, the non-treated controls experienced an average drop of cortical polar moment of inertia (Ct.pMOI) by -4.3 % over four weeks and the bone deterioration occurred in the majority (64 %) of the samples. Relative to no treatment, loading alone, Yoda1 alone, and combined Yoda1 and loading increased Ct.pMOI by +7.3 %, +9.5 %, +12.0 % and increased the % of samples with positive Ct.pMOI changes by +32 %, +26 %, and +43 %, respectively, suggesting an additive protection of aging-related bone loss for the combined therapy. We further tested if the treatment efficacy was preserved in mature mice following two weeks (six injections) of doxorubicin at the dose of 2.5 or 5 mg/kg. As expected, doxorubicin increased osteocyte apoptosis, altered bone remodeling, and impaired bone structure. However, the effects induced by DOX were too severe to be rescued by Yoda1 and loading, alone or combined, although loading and Yoda1 individually, or combined, increased the number of mice showing positive responsiveness by 0 %, +15 %, and +29 % relative to no intervention after doxorubicin exposure. Overall, this study supported the potentials and challenges of the Yoda1-based strategy in mitigating the detrimental skeletal effects caused by aging and doxorubicin.

The fluoroquinolones may positively affect tendon healing after surgical repair.

OBJECTIVES: This study aimed to evaluate the biomechanical and histological effects of fluoroquinolones on surgically repaired tendon healing. MATERIALS AND METHODS: The Achilles tendons of 40 Wistar rats (mean weight: 213.5 g; range 201 to 242 g) were bilaterally surgically cut and repaired. The rats were randomly divided into four groups: the first and third groups were designated as control groups and did not receive drug therapy, whereas the second and fourth groups received 300 mg/kg ciprofloxacin for a week after the surgical procedure. The first and second groups had both tendons dissected at the end of the first week, while the third and fourth groups were dissected at the end of the third week. The left tendons were examined biomechanically, while the right tendons were examined histologically. RESULTS: Statistical analysis revealed that the mean maximum tensile forces of tendons in the first and second groups were 5.2±1.84 N (range, 2.9 to 8.5 N) and 11.1±2.65 N (range, 7.3 to 13.9 N), respectively, which was found to be statistically significant (p< 0.05). At the end of the third week, mean maximum tensile forces of the third and fourth groups were determined to be 20.7±5.0 N (range, 22.1 to 29.8 N) and 28.7±4.6 N (range, 22.1 to 36.8 N), respectively, which was also statistically significant (p< 0.05). Histologically, our results were compatible. CONCLUSION: This study demonstrated that ciprofloxacin did not exhibit the expected adverse effects on surgically repaired tendon healing in the early stages but likely contributed to healing in the short term by affecting the inflammatory phase.

Oral dehydroepiandrosterone supplementation enhances osteoporotic fracture healing in the OVX rats.

Osteoporosis easily causes delayed fracture union, even non-union. It has been demonstrated that dehydroepiandrosterone (DHEA) supplementation can increase estrogen levels and improve bone mineral density (BMD) in the elderly, while the role of DHEA on fracture healing remains unknown. This study aimed to elucidate the impact of DHEA supplementation on osteoporotic fracture healing. Seventy-two female Sprague-Dawley rats were used. Forty-eight rats received ovariectomy (OVX), and the remaining rats received a sham OVX operation (sham group). A right transverse femoral osteotomy was performed in all rats at 12 weeks post-OVX. OVX rats were randomly allocated into 2 groups (n = 24 in each group): (i) ovariectomized rats (control group) and (ii) ovariectomized rats treated with DHEA (DHEA group, 5 mg/kg/day). The DHEA supplementation was initiated on the first day post-fracture for 3, 6, and 12 weeks. Fracture healing was evaluated by radiography, histology, biomechanical analysis, and dual-energy X-ray absorptiometry (DEXA). Serum biomarkers were analyzed using enzyme-linked immunosorbent assay (ELISA). At 3 and 6 weeks, radiographs revealed reduced calluses formation and lower radiographic scores in the control group than in other groups. The sham and DHEA groups showed higher BMD and bone mineral content (BMC) at the fracture site than the control group after fracture. Histological analysis revealed the fracture callus was remodeled better in the sham and DHEA groups than in the control group. At the early phase of healing, DHEA supplementation increased osteoblast number, callus area, and cartilage area than the control group. An increased bone area was observed in the DHEA group than in the control group at the late phase of healing. Additionally, improved biomechanical characteristics were observed in both the sham and DHEA groups than those in the control group post-fracture. ELISA showed higher levels of insulin-like growth factor-1 (IGF-1) and 17ß-estradiol (E2) in the DHEA group than in the control group post-fracture. Furthermore, the DHEA group exhibited significantly elevated alkaline phosphatase (ALP) and osteocalcin (OC) levels compared to the control group at 6 and 12 weeks. The DHEA group and the control group did not exhibit a notable difference in TRAP-5b levels. The present study demonstrated that the DHEA treatment has a favorable impact on osteoporotic fracture healing by enhancing callus formation, consolidation, and strength in the OVX rats.

Does vanillic acid affect fracture healing? An experimental study in a rat model of femur fracture.

BACKGROUND AND OBJECTIVES: We aimed to determine the effects of vanillic acid (VA) on fracture healing radiologically, histologically, immunohistochemically, and biomechanically using a rat femur open fracture injury model. METHODS: 32 male Wistar-Albino rats were used and divided into two groups: the study group (VA) and the control group. From the time they were operated on until they were sacrificed, the rats in the study group were given 100 mg/kg/day VA by oral gavage. After sacrification, the femurs were analyzed. RESULTS: It was observed that the Huo histological scoring was significantly higher in the VA group (p = 0.001), and the ratio of the amount of callus tissue compared to intact bone tissue was significantly higher. While no significant difference was observed in immunohistochemical H-scores in ColI antibody staining (p = 1.000), a borderline significant difference in favor of VA was observed in ColIII antibody staining (p = 0.078). In biomechanical analysis, failure load (N), total energy (J), maximum stress (MPa), and stiffness (N/mm) measurements were significantly higher in the VA group (p = 0.040, p = 0.021, p = 0.015, and p = 0.035, respectively). CONCLUSION: It has been observed that VA, with its antioxidative properties, increases fracture healing in rats, in which an open fracture model was created. We are hopeful that such an antioxidant, which is common in nature, will increase fracture healing. Since this study is the first to examine the effect of VA on fracture healing, further studies are needed.

Biomechanical outcomes of pharmacological therapies for post-traumatic arthrofibrosis in preclinical animal models: a systematic review and meta-analysis.

PURPOSE/AIM OF THE STUDY: There is still no evidence of which drug has the greatest therapeutic potential for post-traumatic arthrofibrosis. The aim of this study is to systematically review the literature for quality evidence and perform a meta-analysis about the pharmacological therapies of post-traumatic arthrofibrosis in preclinical models. MATERIALS AND METHODS: A comprehensive and systematic search strategy was performed in three databases (MEDLINE, EMBASE and Web of Science) retrieving studies on the effectiveness of pharmacological therapies in the management of post-traumatic arthrofibrosis using preclinical models in terms of biomechanical outcomes. Risk of bias assessment was performed using the SYRCLE's risk of bias tool. A meta-analysis using a random-effects model was conducted if a minimum of three studies reported homogeneous outcomes for drugs with the same action mechanism. RESULTS: Forty-six studies were included in the systematic review and evaluated for risk of bias. Drugs from 6 different action mechanisms of 21 studies were included in the meta-analysis. Overall, the methodological quality of the studies was poor. Statistically significant overall effect in favor of reducing contracture was present for anti-histamines (Chi2 p = 0.75, I2 = 0%; SMD (Standardized Mean Difference) = -1.30, 95%CI: -1.64 to -0.95, p < 0.00001) and NSAIDs (Chi2 p = 0.01, I2 = 63%; SMD= -0.93, 95%CI: -1.58 to -0.28, p = 0.005). CONCLUSIONS: Anti-histamines, particularly ketotifen, have the strongest evidence of efficacy for prevention of post-traumatic arthrofibrosis. Some studies suggest a potential role for NSAIDs, particularly celecoxib, although heterogeneity among the included studies is significant.

Effect of cilostazol on healing of achilles tendon ruptures: an experimental study on rats.

PURPOSE: This study aimed to evaluate whether cilostazol (phosphodiesterase III inhibitor) could enhance the healing of Achilles tendon ruptures in rats. MATERIALS AND METHODS: The Achilles tendons of 24 healthy male adult rats were incised and repaired. The rats were randomly allocated to cilostazol and control groups. The cilostazol group received daily intragastric administration of 50 mg/kg cilostazol for 28 days, while the control group did not receive any medication. The rats were sacrificed on the 30th day, and the Achilles tendon was evaluated for biomechanical properties, histopathological characteristics, and immunohistochemical analysis. RESULTS: All rats completed the experiment. The Movin sum score of the control group was significantly higher (p = 0.008) than that of the cilostazol group, with means of 11 ± 0.63 and 7.50 ± 1.15, respectively. Similarly, the mean Bonar score was significantly higher (p = 0.026) in the control group compared to the cilostazol group (8.33 ± 1.50 vs. 5.5 ± 0.54, respectively). Moreover, the Type I/Type III Collagen ratio was notably higher (p = 0.016) in the cilostazol group (52.2 ± 8.4) than in the control group (34.6 ± 10.2). The load to failure was substantially higher in the cilostazol group than in the control group (p = 0.034), suggesting that the tendons in the cilostazol group were stronger and exhibited greater resistance to failure. CONCLUSIONS: The results of this study suggest that cilostazol treatment significantly improves the biomechanical and histopathological parameters of the healing Achilles tendon in rats. Cilostazol might be a valuable supplementary therapy in treating Achilles tendon ruptures in humans. Additional clinical studies are, however, required to verify these outcomes.

The effect of papaverine on tendon healing and adhesion in rats following Achilles tendon repair.

OBJECTIVES: The study aimed to examine the histopathological and biomechanical effects of papaverine administered intraperitoneally and locally on Achilles tendon healing in a rat model. MATERIALS AND METHODS: Forty-eight adult male Sprague-Dawley rats (range, 300 to 400 g) were used in this study conducted between October and November 2022. The rats were divided into three groups, with each group further subdivided into two for sacrifice on either the 15th (early period) or 30th (late period) day after surgery. The first (control) group received no treatment following Achilles tendon repair, while papaverine was intraperitoneally administered every other day for 10 days in the second group and locally in the third group after surgery. On the 15th and 30th days, the rats were sacrificed, and their Achilles tendons were subjected to biomechanical testing and histopathological evaluation. RESULTS: Histopathologically, there were no significant differences among the groups on the 15th day. However, on the 30th day, the locally applied papaverine group exhibited superior histopathological outcomes compared to the control group (p<0.05). Concerning the highest tensile strength values before rupture, the biomechanical assessment showed that the group receiving local papaverine treatment in the early period and both the group with systemic papaverine treatment and the one with local papaverine treatment in the late period displayed a statistically significant advantage compared to the control group (p<0.05). CONCLUSION: Locally administered papaverine has positive biomechanical effects in the early period and exhibits a positive correlation both histopathologically and biomechanically in the late period. Novel therapeutic options may be provided for patients through these findings.

Micro tensile tester measurement of biomechanical properties and adhesion force of microtubule-polymerization-inhibited cancer cells.

Both mechanical and adhesion properties of cancer cells are complex and reciprocally related to migration, invasion, and metastasis with large cell deformation. Therefore, we evaluated these properties for human cervical cancer cells (HeLa) simultaneously using our previously developed micro tensile tester system. For efficient evaluation, we developed image analysis software to modify the system. The software can analyze the tensile force in real time. The modified system can evaluate the tensile stiffness of cells to which a large deformation is applied, also evaluate the adhesion strength of cancer cells that adhered to a culture substrate and were cultured for several days with their adhesion maturation. We used the modified system to simultaneously evaluate the stiffness of the cancer cells to which a large deformation was applied and their adhesion strength. The obtained results revealed that the middle phase of tensile stiffness and adhesion force of the microtubule-depolymerized group treated with colchicine (an anti-cancer drug) (stiffness, 13.4 ± 7.5 nN/%; adhesion force, 460.6 ± 258.2 nN) were over two times larger than those of the control group (stiffness, 5.0 ± 3.5 nN/%; adhesion force, 168.2 ± 98.0 nN). Additionally, the same trend was confirmed with the detailed evaluation of cell surface stiffness using an atomic force microscope. Confocal fluorescence microscope observations showed that the stress fibers (SFs) of colchicine-treated cells were aligned in the same direction, and focal adhesions (FAs) of the cells developed around both ends of the SFs and aligned parallel to the developed direction of the SFs. There was a possibility that the microtubule depolymerization by the colchicine treatment induced the development of SFs and FAs and subsequently caused an increment of cell stiffness and adhesion force. From the above results, we concluded the modified system would be applicable to cancer detection and anti-cancer drug efficacy tests.

Six months of voluntary alcohol consumption in male cynomolgus macaques reduces intracortical bone porosity without altering mineralization or mechanical properties.

Chronic heavy alcohol consumption is a risk factor for low trauma bone fracture. Using a non-human primate model of voluntary alcohol consumption, we investigated the effects of 6 months of ethanol intake on cortical bone in cynomolgus macaques (Macaca fascicularis). Young adult (6.4 ± 0.1 years old, mean ± SE) male cynomolgus macaques (n = 17) were subjected to a 4-month graded ethanol induction period, followed by voluntary self-administration of water or ethanol (4 % w/v) for 22 h/d, 7 d/wk. for 6 months. Control animals (n = 6) consumed an isocaloric maltose-dextrin solution. Tibial response was evaluated using densitometry, microcomputed tomography, histomorphometry, biomechanical testing, and Raman spectroscopy. Global bone response was evaluated using biochemical markers of bone turnover. Monkeys in the ethanol group consumed an average of 2.3 ± 0.2 g/kg/d ethanol resulting in a blood ethanol concentration of 90 ± 12 mg/dl in longitudinal samples taken 7 h after the daily session began. Ethanol consumption had no effect on tibia length, mass, density, mechanical properties, or mineralization (p > 0.642). However, compared to controls, ethanol intake resulted in a dose-dependent reduction in intracortical bone porosity (Spearman rank correlation = -0.770; p < 0.0001) and compared to baseline, a strong tendency (p = 0.058) for lower plasma CTX, a biochemical marker of global bone resorption. These findings are important because suppressed cortical bone remodeling can result in a decrease in bone quality. In conclusion, intracortical bone porosity was reduced to subnormal values 6 months following initiation of voluntary ethanol consumption but other measures of tibia architecture, mineralization, or mechanics were not altered.

Combining anabolic loading and raloxifene improves bone quantity and some quality measures in a mouse model of osteogenesis imperfecta.

Osteogenesis imperfecta (OI) increases fracture risk due to changes in bone quantity and quality caused by mutations in collagen and its processing proteins. Current therapeutics improve bone quantity, but do not treat the underlying quality deficiencies. Male and female G610C+/- mice, a murine model of OI, were treated with a combination of raloxifene and in vivo axial tibial compressive loading starting at 10 weeks of age and continuing for 6 weeks to improve bone quantity and quality. Bone geometry and mechanical properties were measured to determine whole bone and tissue-level material properties. A colocalized Raman/nanoindentation system was used to measure chemical composition and nanomechanical properties in newly formed bone compared to old bone to determine if bone formed during the treatment regimen differed in quality compared to bone formed prior to treatment. Lastly, lacunar geometry and osteocyte apoptosis were assessed. OI mice were able to build bone in response to the loading, but this response was less robust than in control mice. Raloxifene improved some bone material properties in female but not male OI mice. Raloxifene did not alter nanomechanical properties, but loading did. Lacunar geometry was largely unchanged with raloxifene and loading. However, osteocyte apoptosis was increased with loading in raloxifene treated female mice. Overall, combination treatment with raloxifene and loading resulted in positive but subtle changes to bone quality.

l-carnitine enhances the kinematics and protects the sperm membranes of chilled and frozen-thawed Peruvian Paso horse spermatozoa.

l-carnitine (LC) transports fatty acids to the mitochondria for energy production, reducing lipid availability for peroxidation through ß-oxidation. This research examines the effect of LC supplementation to two skimmed milk-based extenders on the cryosurvival of chilled (5°C) and frozen-thawed Peruvian Paso horse spermatozoa .An initial experiment determined the optimal LC concentration (0, 1, 5, 10, 25, and 50 mM) when added to INRA-96® and UHT (skimmed milk + 6% egg yolk) extenders, using nine ejaculates from three stallions chilled for up to 96 h. Subsequently, the effect of 25 mM LC supplementation (the optimal concentration) on chilling (INRA-96) and freezing (INRA-Freeze®) extenders was evaluated using eight pooled samples from sixteen ejaculates (2 ejaculates/pool) from four stallions. Results indicated that all LC concentrations produced significantly higher values (P<0.05) for kinematic variables (total [TM] and progressive motilities, curvilinear [VCL] and straight-line [VSL] velocity, and beat-cross frequency [BCF]), and the integrity of plasma/acrosome membranes (IPIA) compared to non-supplemented chilled sperm samples for up to 96 h with both extenders. Moreover, the use of 25 mM LC was more efficient (P<0.05) in preserving the post-chilled values of velocity, BCF, and IPIA for the long term than lower LC concentrations (1-10 mM). Post-thaw values of total motility, the amplitude of lateral head displacement (ALH), and IPIA were significantly improved (P<0.05) when INRA-Freeze extender was supplemented with 25 mM LC. In conclusion, supplementation of l-carnitine to skimmed milk-based extenders enhanced kinematic variables and protected the membrane integrity in chilled and frozen-thawed Peruvian Paso horse spermatozoa.

Botulinum neurotoxin type A responders among children with spastic cerebral palsy: Pattern-specific effects.

AIM: To identify short-term effects of botulinum neurotoxin type A (BoNT) injections on gait and clinical impairments, in children with spastic cerebral palsy (CP), based on baseline gait pattern-specific subgroups. METHOD: Short-term effects of BoNT injections in the medial hamstrings and gastrocnemius were defined in a retrospective convenience sample of 117 children with CP (median age: 6 years 4 months; GMFCS I/II/III: 70/31/16; unilateral/bilateral: 56/61) who had received gait analyses before and 2 months post-BoNT. First, baseline gait patterns were classified. Statistical and meaningful changes were calculated between pre- and post-BoNT lower limb sagittal plane kinematic waveforms, the gait profile score, and non-dimensional spatiotemporal parameters for the entire sample and for pattern-specific subgroups. These gait waveforms per CP subgroup at pre- and post-BoNT were also compared to typically developing gait and composite scores for spasticity, weakness, and selectivity were compared between the two conditions. RESULTS: Kinematic improvements post-BoNT were identified at the ankle and knee for the entire sample, and for subgroups with apparent equinus and jump gait. Limbs with baseline patterns of dropfoot and to a lesser extent true equinus showed clear improvements only at the ankle. In apparent equinus, jump gait, and dropfoot, spasticity improved post-BoNT, without leading to increased weakness or diminished selectivity. Compared to typical gait, knee and hip motion improved in the crouch gait subgroup post-BoNT. CONCLUSION: This comprehensive analysis highlighted the importance of investigating BoNT effects on gait and clinical impairments according to baseline gait patterns. These findings may help identify good treatment responders.

Impact of Collagen Crosslinking on Dislocated Human Shoulder Capsules-Effect on Structural and Mechanical Properties.

Classical treatments of shoulder instability are associated with recurrence. To determine whether the modification of the capsule properties may be an alternative procedure, the effect of crosslinking treatment on the structure and mechanical properties of diseased human shoulder capsules was investigated. Joint capsules harvested from patients during shoulder surgery (n = 5) were treated or not with UV and/or riboflavin (0.1%, 1.0% and 2.5%). The structure and the mechanical properties of the capsules were determined by atomic force microscopy. The effect of treatments on cell death was investigated. Collagen fibrils were well-aligned and adjacent to each other with a D-periodicity of 66.9 ± 3.2 nm and a diameter of 71.8 ± 15.4 nm in control untreated capsules. No effect of treatments was observed on the organization of the collagen fibrils nor on their intrinsic characteristics, including D-periodicity or their mean diameter. The treatments also did not induce cell death. In contrast, UV + 2.5% riboflavin induced capsule stiffness, as revealed by the increased Young's modulus values (p < 0.0001 for each patient). Our results showed that the crosslinking procedure changed the biomechanics of diseased capsules, while keeping their structural organisation unchanged at the single fibril level. The UV/riboflavin crosslinking procedure may be a promising way to preserve the functions of collagen-based tissues and tune their elasticity for clinically relevant treatments.

Physiological tremor is suppressed and force steadiness is enhanced with increased availability of serotonin regardless of muscle fatigue.

Although there is evidence that 5-HT acts as an excitatory neuromodulator to enhance maximal force generation, it is largely unknown how 5-HT activity influences the ability to sustain a constant force during steady-state contractions. A total of 22 healthy individuals participated in the study, where elbow flexion force was assessed during brief isometric contractions at 10% maximal voluntary contraction (MVC), 60% MVC, MVC, and during a sustained MVC. The selective serotonin reuptake inhibitor, paroxetine, suppressed physiological tremor and increased force steadiness when performing the isometric contractions. In particular, a main effect of drug was detected for peak power of force within the 8-12 Hz range (P = 0.004) and the coefficient of variation (CV) of force (P < 0.001). A second experiment was performed where intermittent isometric elbow flexions (20% MVC sustained for 2 min) were repeatedly performed so that serotonergic effects on physiological tremor and force steadiness could be assessed during the development of fatigue. Main effects of drug were once again detected for peak power of force in the 8-12 Hz range (P = 0.002) and CV of force (P = 0.003), where paroxetine suppressed physiological tremor and increased force steadiness when the elbow flexors were fatigued. The findings of this study suggest that enhanced availability of 5-HT in humans has a profound influence of maintaining constant force during steady-state contractions. The action of 5-HT appears to suppress fluctuations in force regardless of the fatigue state of the muscle.NEW & NOTEWORTHY Converging lines of research indicate that enhanced serotonin availability increases maximal force generation. However, it is largely unknown how serotonin influences the ability to sustain a constant force. We performed two experiments to assess physiological tremor and force steadiness in unfatigued and fatigued muscle when serotonin availability was enhanced in the central nervous system. Enhanced availability of serotonin reduced physiological tremor amplitude and improved steadiness regardless of muscle fatigue.