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1.
bioRxiv ; 2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38895331

ABSTRACT

Background: Suture anchor failures can lead to revision surgeries which are costly and burdensome for patients. The durability of musculoskeletal reconstructions is therefore partly affected by the design of the suture anchors. Purpose: The purpose of the study was to quantify the strength of different suture anchors whose sizes are suitable for attaching artificial Achilles and tibialis cranialis tendons in a rabbit model, as well as determine the effect of cyclic loading on the anchoring strength. Method: Four anchors (two with embedded eyelet and two with raised eyelet, n=5 per group) were tested with cyclical loading (1000 cycles and 4.5 mm/sec) and without cycling, to inform the failure loads and mode of failure of the suture anchors. An eyebolt screw with smooth eyelet was used as a control for the test groups. Results: All samples in all groups completed 1000 cycles and failed via suture breakage in both test conditions. All anchors had failure loads exceeding the peak Achilles tendon force in rabbits during hopping gait. The data analysis showed an effect of anchor type on the maximum tensile force at failure ( F max ) in all suture categories but not an effect of loading condition. Also, the Anika anchor had a significantly less adverse effect on suture strength compared to Arthrex anchor (p=0.015), IMEX anchor (p=0.004) and Jorvet anchor (p<0.001). We observed a greater percentage of failure at the mid-section for the anchors with the raised eyelets compared to the anchors with embedded eyelets, which all failed at the knot. Conclusion: Anchors with embedded eyelets had clinically preferred mode of failure with less adverse effects on suture and, may be more reliable than anchors with raised eyelets for attaching artificial Achilles and tibialis cranialis tendons in rabbits.

2.
Vet Surg ; 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38840447

ABSTRACT

OBJECTIVE: To assess a three-dimensional (3-D)-printed laryngeal clamp (LC) designed to enhance the anchoring of laryngeal prostheses at the cricoid cartilage. STUDY DESIGN: Ex vivo biomechanical study. SAMPLE POPULATION: A total of 22 equine larynges. METHODS: Two experimental groups included larynges with standard prosthetic laryngoplasty (PL; n = 10) and larynges with prosthetic laryngoplasty modified with laryngeal clamps (PLLC; n = 10). All constructs underwent 3000 cycles of tension loading and a single tension to failure. Recorded biomechanical parameters included maximum load, actuator displacement, and construct failure. Finite element analysis (FEA) was performed on one PL and one PLLC construct. RESULTS: The maximum load at single tension to failure was 183.7 ± 46.8 N for the PL construct and 292.7 ± 82.3 N for the PLLC construct (p = .003). Actuator displacement at 30 N was 1.7 ± 0.5 mm and 2.7 ± 0.7 mm for the PL and PLLC constructs, respectively (p = .011). The cause of PL constructs failure was mostly tearing through the cartilage whereas the PLLC constructs failed through fracture of the cricoid cartilage (p = .000). FEA revealed an 11-fold reduction in the maximum equivalent plastic strain, a four-fold reduction in maximum compressive stress, and a two-fold increase in the volume of engaged cartilage in PLLC constructs. CONCLUSION: The PLLC constructs demonstrated superior performance in biomechanical testing and FEA compared to standard PL constructs. CLINICAL SIGNIFICANCE: The use of 3-D-printed laryngeal clamps may enhance the outcomes of laryngoplasty in horses. In vivo studies are necessary to determine the feasibility of performing laryngoplasty using the laryngeal clamp in horses.

3.
bioRxiv ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38746085

ABSTRACT

Objective: The purpose of this study was to investigate the factors associated with outcomes of attaching artificial tendons to bone using suture anchors for replacement of biological tendons in rabbits. Study Design: Metal suture anchors with braided composite sutures of varying sizes (USP #1, #2, or #5) were used to secure artificial tendons replacing both the Achilles and tibialis cranialis tendons in 12 New Zealand White rabbits. Artificial tendons were implanted either at the time of (immediate replacement, n=8), or four weeks after (delayed replacement, n=4) resection of the biological tendon. Hindlimb radiographs of the rabbits were obtained immediately after surgery and approximately every other week until the study endpoint (16 weeks post-surgery). Results: All suture anchors used for the tibialis cranialis artificial tendons remained secure and did not fail during the study. The suture linkage between the Achilles artificial tendon and anchor failed in 9 of 12 rabbits. In all cases, the mode of failure was suture breakage distant from the knot. Based on radiographic analysis, the mean estimated failure timepoint was 5.3±2.3 weeks post-surgery, with a range of 2-10 weeks. Analysis of variance (ANOVA) tests revealed no significant effect of tendon implantation timing or suture size on either the timing or frequency of suture anchor failure. Conclusion: Based on the mode of failure, suture mechanical properties, and suture anchor design, we suspect that the cause of failure was wear of the suture against the edges of the eyelet in the suture anchor post, which reduced the suture strength below in vivo loads. Suture anchor designs differed for the tibialis cranialis and did not fail during the period of study. Future studies are needed to optimize suture anchor mechanical performance under different loading conditions and suture anchor design features.

4.
J Am Vet Med Assoc ; 262(7): 1-6, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38640950

ABSTRACT

OBJECTIVE: To examine the prevalence of nasolacrimal duct (NLD) obstruction in hospital populations and assess signalment, diagnostics, and clinical approaches for alpacas and llamas diagnosed with NLD atresia or obstruction. ANIMALS: 29 alpacas and 2 llamas. CLINICAL PRESENTATION: Medical records were reviewed to identify camelids with NLD evaluated between 2000 and 2023. Signalment, history, physical examination data, diagnosis, and treatments were recorded. Follow-up information was gathered via phone and email questionnaire. Data were evaluated to determine prevalence and describe signalment and treatments for NLD disease. RESULTS: 31 camelids met the inclusion criteria. A total of 8,027 alpacas and 1,998 llamas were seen within the study period at 1 teaching institution. The prevalence of NLD obstruction for this population of alpacas was 0.3% (26/8,027). Nineteen of 31 (61%) camelids presented at 1 year of age or younger. The most common physical exam finding was ocular discharge (68%). The most common diagnosis was NLD atresia (16/31 [51%]). Patency was established by surgical opening or lavage of the NLD. Long-term follow-up was available for 13 alpacas and 2 llamas, of which 11 (73%) had successful outcomes. CLINICAL RELEVANCE: Results indicate that NLD obstruction is a condition that most commonly affects alpacas < 1 year of age and is associated with a good prognosis for treatment success.


Subject(s)
Camelids, New World , Lacrimal Duct Obstruction , Animals , Lacrimal Duct Obstruction/veterinary , Lacrimal Duct Obstruction/epidemiology , Male , Female , Prevalence , Nasolacrimal Duct/pathology , Hospitals, Animal , Retrospective Studies
5.
J Orthop Surg Res ; 19(1): 108, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38303012

ABSTRACT

BACKGROUND: Artificial tendons may be an effective alternative to autologous and allogenic tendon grafts for repairing critically sized tendon defects. The goal of this study was to quantify the in vivo hindlimb biomechanics (ground contact pressure and sagittal-plane motion) during hopping gait of rabbits having a critically sized tendon defect of the tibialis cranialis and either with or without repair using an artificial tendon. METHODS: In five rabbits, the tibialis cranialis tendon of the left hindlimb was surgically replaced with a polyester, silicone-coated artificial tendon (PET-SI); five operated control rabbits underwent complete surgical excision of the biological tibialis cranialis tendon in the left hindlimb with no replacement (TE). RESULTS: At 8 weeks post-surgery, peak vertical ground contact force in the left hindlimb was statistically significantly less compared to baseline for the TE group (p = 0.0215). Statistical parametric mapping (SPM) analysis showed that, compared to baseline, the knee was significantly more extended during stance at 2 weeks post-surgery and during the swing phase of stride at 2 and 8 weeks post-surgery for the TE group (p < 0.05). Also, the ankle was significantly more plantarflexed during swing at 2 and 8 weeks postoperative for the TE group (p < 0.05). In contrast, there were no significant differences in the SPM analysis among timepoints in the PET-SI group for the knee or ankle. CONCLUSIONS: Our findings suggest that the artificial tibialis cranialis tendon effectively replaced the biomechanical function of the native tendon. Future studies should investigate (1) effects of artificial tendons on other (e.g., neuromuscular) tissues and systems and (2) biomechanical outcomes when there is a delay between tendon injury and artificial tendon implantation.


Subject(s)
Silicones , Tendon Injuries , Animals , Rabbits , Polyesters , Tendons/surgery , Ankle , Tendon Injuries/surgery , Biomechanical Phenomena
6.
Angew Chem Int Ed Engl ; 63(4): e202313556, 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-37801443

ABSTRACT

With their highly reactive respective C-Na and N-Na bonds, organosodium and sodium amide reagents could be viewed as obvious replacements or even superior reagents to the popular, widely utilised organolithiums. However, they have seen very limited applications in synthesis due mainly to poor solubility in common solvents and their limited stability. That notwithstanding in recent years there has been a surge of interest in bringing these sustainable metal reagents into the forefront of organometallics in synthesis. Showcasing the growth in utilisation of organosodium complexes within several areas of synthetic chemistry, this Minireview discusses promising new methods that have been recently reported with the goal of taming these powerful reagents. Special emphasis is placed on coordination and aggregation effects in these reagents which can impart profound changes in their solubility and reactivity. Differences in observed reactivity between more nucleophilic aryl and alkyl sodium reagents and the less nucleophilic but highly basic sodium amides are discussed along with current mechanistic understanding of their reactivities. Overall, this review aims to inspire growth in this exciting field of research to allow for the integration of organosodium complexes within common important synthetic transformations.

7.
Vaccine ; 42(3): 713-722, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38142214

ABSTRACT

INTRODUCTION: Cytomegalovirus (CMV) is the most common cause of congenital infection and affected children often have permanent neurodevelopmental sequelae, including hearing loss and intellectual disability. Vaccines to prevent transmission of CMV during pregnancy are a public health priority. This first-in-humans dose-ranging, randomized, placebo-controlled, observer-blinded study evaluated the safety and immunogenicity of an enveloped virus-like particle (eVLP) vaccine expressing a modified form of the CMV glycoprotein B (gB). METHODS: Healthy CMV-seronegative 18 to 40-year-olds at 3 Canadian study sites were randomized to one of 4 dose formulations (0.5 µg, 1 µg, or 2 µg gB content with alum) or 1 µg gB without alum, or placebo, given intramuscularly on days 0, 56 and 168. Outcome measures were solicited and unsolicited adverse events (AE), severe AE, gB and AD-2 epitope binding antibody titers and avidity, and neutralizing antibody (nAb) titers to CMV measured in fibroblast and epithelial cell infection assays. RESULTS: Among 125 participants, the most common solicited local and general AEs were pain and headache, respectively. A dose-dependent increase in gB binding, avidity and nAb titers was observed after doses 2 and 3, with the highest titers in the alum-adjuvanted 2.0 µg dose recipients after the third dose; in the latter 24 % had responses to the broadly neutralizing AD-2 epitope. Neutralizing activity to CMV infection of fibroblasts was seen in 100 % of 2.0 µg alum-adjuvanted dose recipients, and to epithelial cell infection in 31 %. Epithelial cell nAb titers were positively correlated with higher geometric mean CMV gB binding titers. CONCLUSIONS: An eVLP CMV vaccine was immunogenic in healthy CMV-seronegative adults and no safety signals were seen. Alum adjuvantation increased immunogenicity as did higher antigen content and a three dose schedule. This phase 1 trial supports further development of this eVLP CMV vaccine candidate.


Subject(s)
Alum Compounds , Cytomegalovirus Infections , Cytomegalovirus Vaccines , Vaccines, Virus-Like Particle , Adult , Child , Pregnancy , Female , Humans , Cytomegalovirus , Antibodies, Viral , Canada , Cytomegalovirus Infections/prevention & control , Vaccination , Aluminum Hydroxide , Adjuvants, Immunologic , Epitopes , Antibodies, Neutralizing , Immunogenicity, Vaccine
8.
J Exp Orthop ; 10(1): 111, 2023 Nov 07.
Article in English | MEDLINE | ID: mdl-37934300

ABSTRACT

PURPOSE: Cortical porosis, secondary to either vascular injury or stress-shielding, is a comorbidity of fracture fixation using compression bone plating. Locking plate constructs have unique mechanics of load transmission and lack of reliance on contact pressures for fixation stability, so secondary cortical porosis adjacent to the plate has not been widely investigated. Therefore, this study aimed to assess the effects of long-term locking plate fixation on cortical dimensions and density in a caprine tibial segmental ostectomy model. METHODS: Data was acquired from a population of goats enrolled in ongoing orthopedic research which utilized locking plate fixation of 2 cm tibial diaphyseal segmental defects to evaluate bone healing over periods of 3, 6, 9, and 12 months. Quantitative data included tibial cortical width measurements and three-dimensionally reconstructed slab density measurements, both assessed using computed tomographic examinations performed at the time of plate removal. Additional surgical and demographic variables were analyzed for effect on cortical widths and density, and all cis-cortex measurements were compared to both the trans-cortex and to the contralateral limbs. RESULTS: The tibial cis-cortex was significantly wider and more irregular than the trans-cortex at the same level. This width asymmetry differed in both magnitude and direction from the contralateral limb. The bone underlying the plate was significantly less dense than the trans-cortex, and this cortical density difference was significantly greater than that of the contralateral limb. These cortical changes were independent of both duration of fixation and degree of ostectomy bone healing. CONCLUSIONS: This study provides evidence that cortical bone loss consistent with cortical porosity is a comorbidity of locking plate fixation in a caprine tibial ostectomy model. Further research is necessary to identify risk factors for locking-plate-associated bone loss and to inform clinical decisions in cases necessitating long-term locking plate fixation.

9.
Polymers (Basel) ; 15(18)2023 Sep 07.
Article in English | MEDLINE | ID: mdl-37765540

ABSTRACT

Neural injuries affect millions globally, significantly impacting their quality of life. The inability of these injuries to heal, limited ability to regenerate, and the lack of available treatments make regenerative medicine and tissue engineering a promising field of research for developing methods for nerve repair. This review evaluates the use of natural and synthetic polymers, and the fabrication methods applied that influence a cell's behavior. Methods include cross-linking hydrogels, incorporation of nanoparticles, and 3D printing with and without live cells. The endogenous cells within the injured area and any exogenous cells seeded on the polymer construct play a vital role in regulating healthy neural activity. This review evaluates the body's local and systemic reactions to the implanted materials. Although numerous variables are involved, many of these materials and methods have exhibited the potential to provide a biomaterial environment that promotes biocompatibility and the regeneration of a physical and functional nerve. Future studies may evaluate advanced methods for modifying material properties and characterizing the tissue-biomaterial interface for clinical applications.

10.
BMC Res Notes ; 16(1): 177, 2023 Aug 18.
Article in English | MEDLINE | ID: mdl-37596624

ABSTRACT

Blood chemistry may provide indicators to greater feed efficient cattle. As a side objective to previous research, 17 Angus heifers approximately two years old underwent a feed efficiency trial to determine residual feed intake (RFI) and identify variation in blood chemistry in beef cattle divergent in feed efficiency. Heifers were categorized as high- or low-RFI based ± 0.25 standard deviations around mean RFI. Blood samples were analyzed using an i-STAT handheld blood analyzer to measure sodium, potassium, glucose, blood urea nitrogen (BUN), creatinine, hematocrit, and hemoglobin. BUN was greater in high-RFI heifers (µ = 8.7 mg/dL) contrasted to low-RFI heifers (µ = 6.5 mg/dL; P = 0.01), whereas glucose was greater in low-RFI heifers (µ = 78.1 mg/dL) contrasted to high-RFI heifers (µ = 82.0 mg/dL; P = 0.05). No other blood chemistry parameters differed by RFI. The greater abundance of BUN in high-RFI heifers may indicate inefficient utilization of protein or mobilization of tissue protein for non-protein use. Greater blood glucose concentrations in low-RFI heifers may indicate greater utilization of energy precursors, such as volatile fatty acids, or metabolites. These data suggest there are readily measurable indicators of physiological variation in nutrient utilization; however, this warrants additional studies to explore.


Subject(s)
Eating , Glucose , Cattle , Animals , Female , Creatinine , Hematocrit , Nutrients
12.
J Exp Orthop ; 10(1): 38, 2023 Apr 03.
Article in English | MEDLINE | ID: mdl-37010659

ABSTRACT

PURPOSE: Locking plate fixation of caprine tibial segmental defects is widely utilized for translational modeling of human osteopathology, and it is a useful research model in tissue engineering and orthopedic biomaterials research due to its inherent stability while maintaining unobstructed visualization of the gap defect and associated healing. However, research regarding surgical technique and long-term complications associated with this fixation method are lacking. The goal of this study was to assess the effects of surgeon-selected factors including locking plate length, plate positioning, and relative extent of tibial coverage on fixation failure, in the form of postoperative fracture. METHODS: In vitro, the effect of plate length was evaluated using single cycle compressive load to failure mechanical testing of locking plate fixations of caprine tibial gap defects. In vivo, effects of plate length, positioning, and relative tibial coverage were evaluated using data from a population of goats enrolled in ongoing orthopedic research which utilized locking plate fixation of 2 cm tibial diaphyseal segmental defects to evaluate bone healing over 3, 6, 9, and 12 months. RESULTS: In vitro, no significant differences in maximum compressive load or total strain were noted between fixations using 14 cm locking plates and 18 cm locking plates. In vivo, both plate length and tibial coverage ratio were significantly associated with postoperative fixation failure. The incidence of any cortical fracture in goats stabilized with a 14 cm plate was 57%, as compared with 3% in goats stabilized with an 18 cm plate. Craniocaudal and mediolateral angular positioning variables were not significantly associated with fixation failure. Decreasing distance between the gap defect and the proximal screw of the distal bone segment was associated with increased incidence of fracture, suggesting an effect on proximodistal positioning on overall fixation stability. CONCLUSIONS: This study emphasizes the differences between in vitro modeling and in vivo application of surgical fixation methods, and, based on the in vivo results, maximization of plate-to-tibia coverage is recommended when using locking plate fixation of the goat tibial segmental defect as a model in orthopedic research.

13.
J Biomech ; 151: 111520, 2023 04.
Article in English | MEDLINE | ID: mdl-36944293

ABSTRACT

Artificial tendons may be valuable clinical devices for replacing damaged or missing biological tendons. In this preliminary study, we quantified the effect of polyester-suture-based artificial tendons on movement biomechanics. New Zealand White rabbits underwent surgical replacement of either the Achilles (n = 2) or tibialis cranialis (TC, n = 2) biological tendons with artificial tendons. Once pre-surgery and weekly from 2 to 6 weeks post-surgery, we quantified hindlimb kinematics and ground contact pressures during the stance phase of hopping gait. Post-surgical movement biomechanics were either consistent or improved over time in both groups. However, the Achilles group had greater overall biomechanical and muscle deficits than the TC group. In the TC group, at 6 weeks post-surgery, foot angles were about 10° greater than those in healthy controls during the first 30 % of stance. At 6 weeks post-surgery, the Achilles group exhibited lesser (i.e., more dorsiflexed) ankle angles (minimum angle = 31.5 ± 9.4°) and vertical ground reaction forces (37.4 ± 2.6 %BW) during stance than those in healthy controls (65.0 ± 11.2° and 50.2 ± 8.3 %BW, respectively). Future studies are needed to quantify long-term biomechanical function with artificial tendons, the effect of artificial tendons on muscle function and structure, and the effect of formal rehabilitation.


Subject(s)
Achilles Tendon , Foot , Animals , Rabbits , Biomechanical Phenomena , Foot/physiology , Ankle , Gait/physiology , Achilles Tendon/physiology
14.
Infect Dis Model ; 8(1): 294-308, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36819739

ABSTRACT

With the declaration of the COVID-19 pandemic by the World Health Organization on March 11, 2020, the University of Tennessee College of Veterinary Medicine (UTCVM), like other institutions, restructured their services to reduce the potential spread of the COVID-19 virus while simultaneously providing critical and essential veterinary services. A mathematical model was developed to predict the change in the level of possible COVID-19 infections due to the increased number of potential contacts within the UTCVM hospital. A system of ordinary differential equations with different compartments for UTCVM individuals and the Knox county population was formulated to show the dynamics of transmission and the number of confirmed cases. Key transmission rates in the model were estimated using COVID-19 case data from the surrounding county and UTCVM personnel. Simulations from this model show the increasing number of COVID-19 cases among UTCVM personnel as the number of daily clients and the number of veterinary staff in the clinic are increased. We also investigate how changes within the Knox county community impact the UTCVM hospital. These scenarios show the importance of understanding the effects of re-opening scenarios in veterinary teaching hospitals.

15.
Angew Chem Int Ed Engl ; 62(11): e202218498, 2023 Mar 06.
Article in English | MEDLINE | ID: mdl-36636916

ABSTRACT

Deaggregating the alkyl sodium NaCH2 SiMe3 with polydentate nitrogen ligands enables the preparation and characterisation of new, hydrocarbon soluble chelated alkylsodium reagents. Equipped with significantly enhanced metalating power over their organolithium counterparts, these systems can promote controlled sodiation of weakly acidic benzylic C-H bonds from a series of toluene derivatives under mild stoichiometric conditions. This has been demonstrated through the benzylic aroylation of toluenes with Weinreb amides, that delivers a wide range of 2-arylacetophenones in good to excellent yields. Success in isolating and determining the structures of key organometallic intermediates has provided useful mechanistic insight into these new sodium-mediated transformations.

16.
Med J (Ft Sam Houst Tex) ; (Per 23-1/2/3): 3-10, 2023.
Article in English | MEDLINE | ID: mdl-36607292

ABSTRACT

BACKGROUND: Correct identification and rapid intervention of a traumatic pneumothorax is necessary to avoid hemodynamic collapse and subsequent morbidity and mortality. The purpose of this clinical review is to summarize the evaluation and best treatment strategies to improve outcomes in combat casualties. Blunt, explosive, and penetrating trauma are the 3 etiologies for causing a traumatic pneumothorax. Blunt trauma tends to be more common, but all etiologies require similar treatment. The current standard to diagnose pneumothorax is through imaging to include ultrasound, chest x-ray, or computed tomography. A physical exam aids in the diagnosis especially when few other resources are available. Recent studies on the treatment of a small, closed pneumothorax involve conservative care, which includes close observation of the patient and monitoring supplemental oxygen. For a large, closed pneumothorax, conservative treatment is still a possible option, but manual aspiration may be required. Less often, a needle or tube thoracostomy is needed to reinflate the lung. Large, open pneumothoraxes require the most invasive treatment with current guidelines recommending tube thoracostomy. More invasive management options can result in higher rates of complications. Given the significant variability in practice patterns, most notable in resource limited settings, the areas for potential research are presented.


Subject(s)
Pneumothorax , Thoracic Injuries , Humans , Pneumothorax/diagnostic imaging , Pneumothorax/etiology , Thoracostomy/adverse effects , Thoracostomy/methods , Chest Tubes/adverse effects , Thoracic Injuries/complications , Thoracic Injuries/diagnosis , Thoracic Injuries/therapy , Lung
17.
Equine Vet J ; 55(2): 171-181, 2023 Mar.
Article in English | MEDLINE | ID: mdl-35569040

ABSTRACT

Equine tibial fractures are relatively infrequent in racing and non-racing sport horses, but limitations in successful treatment of tibial fractures in adult horses result in relatively high mortality compared with other musculoskeletal injuries. The aetiology of tibial fracture can be classified into two general categories: traumatic impact or fatigue failure. Tibial stress fractures, also known as fatigue fractures, are often rated as the second most common stress fracture in racing Thoroughbreds; young age, early stage in race training, and initiation of training after a period of rest are the reported risk factors. Both impact and fatigue fracture propagation are dependent on the magnitude of force applied and on the local composition/alignment of mineralised collagen in the tibial lamella. Extensive research has characterised the pattern of strain distribution and stress remodelling within the equine tibia, but in vivo measurement of load and angular moments are currently not feasible. Further research is warranted to correlate biomechanical theory of tibia fatigue fracture propagation with current histopathological data. Preventative measures for fatigue fractures aim to optimise diagnostic efficiency, reduce the interval between injury and diagnosis and modify racing and training conditions to reduce non-specific fracture risk. Treatment options for complete tibial fractures in adult horses are limited, but with careful case selection, successful outcomes have been reported after open reduction and internal fixation. On the other hand, tibial stress fractures and minimally displaced incomplete fractures are typically treated conservatively and have good prognosis for athletic recovery. This review aims to describe the current literature regarding tibial fracture aetiology, prevalence, risk factors, fracture biomechanics, treatment, prognosis and prevention.


Subject(s)
Fractures, Stress , Horse Diseases , Physical Conditioning, Animal , Sports , Tibial Fractures , Horses , Animals , Fractures, Stress/diagnosis , Fractures, Stress/veterinary , Physical Conditioning, Animal/adverse effects , Tibial Fractures/veterinary , Tibial Fractures/epidemiology , Tibial Fractures/etiology , Prognosis , Horse Diseases/therapy
18.
Protein Sci ; 32(1): e4518, 2023 01.
Article in English | MEDLINE | ID: mdl-36412553

ABSTRACT

Tyrosinase related protein 1 (TYRP1) is the most abundant melanosomal protein of the melanocyte, where plays an important role in the synthesis of eumelanin, possibly catalyzing the oxidation of 5,6-dihydroxyindole-2-carboxylic acid to 5,6-quinone-2-carboxylic acid. Mutations to the TYRP1 gene can result in oculocutaneous albinism type 3 (OCA3), a rare disease characterized by reduced synthesis of melanin in skin, hair, and eyes. To investigate the effect of genetic mutations on the TYRP1 structure, function, and stability, we engineered the intramelanosomal domain of TYRP1 and its mutant variants mimicking either OCA3-related changes, C30R, H215Y, D308N, and R326H or R87G mutant variant, analogous to OCA1-related pathogenic effect in tyrosinase. Proteins were produced in Trichoplusia Ni larvae, then purified, and analyzed by biochemical methods. Data shows that D308N and R326H mutants keep the native conformations and demonstrate no change in their stability and enzymatic activity. In contrast, mutations C30R and R87G localized in the Cys-rich domain show the variants misfolding during the purification process. The H215Y variant disrupts the binding of Zn2+ in the active site and thus reduces the strength of the enzyme/substrate interactions. Our results, consistent with the clinical and in silico studies, show that mutations at the protein surface are expected to have a negligible phenotype change compared to that of TYRP1. For the mutations with severe phenotype changes, which were localized in the Cys-rich domain or the active site, we confirmed a complete or partial protein misfolding as the possible mechanism of protein malfunction caused by OCA3 inherited mutations.


Subject(s)
Albinism, Oculocutaneous , Monophenol Monooxygenase , Humans , Monophenol Monooxygenase/genetics , Monophenol Monooxygenase/chemistry , Monophenol Monooxygenase/metabolism , Albinism, Oculocutaneous/genetics , Albinism, Oculocutaneous/pathology , Mutation , Membrane Glycoproteins , Oxidoreductases
19.
20.
Am J Vet Res ; 83(12)2022 11 28.
Article in English | MEDLINE | ID: mdl-36462173

Subject(s)
Global Health , Animals
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