Search

Summary: Background: Few noninvasive methods are available for equine hoof wall evaluation. The highly organised wall structures and composition of proteoglycans and collagens may make this region amenable to quantitative MRI (qMRI) techniques of T1ρ and T2 mapping to identify pathology related to proteoglycan content and collagen organisation respectively. Objective: To establish normative T1ρ and T2 values of the equine hoof wall of 3‐year‐old Quarter Horses with histological comparison. Study design: Cadaveric anatomical study. Methods: Six cadaveric left thoracic feet from 3‐year‐old racing Quarter Horses with no reported lameness were evaluated using T1ρ and T2 mapping. Mapping was performed at six regions of interest at the toe of each hoof including proximal and distal regions of the inner epidermis, stratum lamellatum and corium. Histology was evaluated for standard hoof morphology and proteoglycan staining. Results: T2 values of the stratum lamellatum and corium were similar (42.9 [95% CI: 41.6–44.2] ms and 44 [95% CI: 42.7–45.3] ms respectively), but both were significantly different to the inner epidermis (35.8 [95% CI: 34.5–37.1] ms, P<0.001). T1ρ values for the inner epidermis, stratum lamellatum and corium were significantly different (25.1 [95% CI: 23.1–27.1] ms, 44.4 [95% CI: 42.4–46.4] ms and 50.1 [95% CI: 48.1–52.1] ms, respectively, P<0.001). Histology demonstrated normal organised morphology. Proteoglycan staining was only visible in the stratum lamellatum and corium. Main limitations: Cadaveric study with frozen samples used. Conclusions: Variation of qMRI metrics through the depth of the equine hoof wall was found. Although the highly ordered environment of collagen may contribute to T2 values, there was lack of evidence to support proteoglycan content as a major contributor of T1ρ values. It is possible T1ρ values had a greater dependence on total water content as the lowest values were seen in the epidermis. Additional research using qMRI is needed to determine mapping values in different disease states. [ABSTRACT FROM AUTHOR]

Reasons for performing study: Post operative imaging in subjects with orthopaedic implants is challenging across all modalities. Magnetic resonance imaging (MRI) is preferred to assess human post operative musculoskeletal complications, as soft tissue and bones are evaluated without using ionising radiation. However, with conventional MRI pulse sequences, metal creates susceptibility artefact that distorts anatomy. Assessment of the post operative equine patient is arguably more challenging due to the volume of metal present, and MRI is often not performed in horses with implants. Novel pulse sequences such as multiacquisition variable resonance image combination (MAVRIC) now provide improved visibility in the vicinity of surgical-grade implants and offer an option for imaging horses with metal implants. Objectives: To compare conspicuity of regional anatomy in an equine fracture-repair model using MAVRIC, narrow receiver bandwidth (NBW) fast spin echo (FSE), and wide receiver bandwidth (WBW) FSE sequences. Study design: Nonrandomised in vitro experiment. Methods: MAVRIC, NBW FSE and WBW FSE were performed on 9 cadaveric distal limbs with fractures and stainless steel implants in the third metacarpal bone and proximal phalanx. Objective measures of artefact reduction were performed by calculating the total artefact area in each transverse image as a percentage of the total anatomic area. The number of transverse images in which fracture lines were visible was tabulated for each sequence. Regional soft tissue conspicuity was assessed subjectively. Results: Overall anatomic delineation was improved using MAVRIC compared with NBW FSE; delineation of structures closest to the metal implants was improved using MAVRIC compared with WBW FSE and NBW FSE. Total artefact area was the highest for NBW FSE and lowest for MAVRIC; the total number of transverse slices with a visible fracture line was highest in MAVRIC and lowest in NBW FSE. Conclusion: MAVRIC and WBW FSE are feasible additions to minimise artefact around implants. [ABSTRACT FROM AUTHOR]

Objective: The transverse relaxation time constant, T2, of articular cartilage has been proposed as a biomarker for osteoarthritis (OA). Previous studies have not clearly defined the relationship between cartilage T2 values and clinical methods of grading OA or known factors associated with OA. This study compared T2 values of patellar cartilage grouped by radiographic stage of patello-femoral OA and by body mass index (BMI).Methods: T2 values of patellar cartilage were calculated for 113 subjects using images acquired on a 1.5 T clinical scanner. Radiographs of the patello-femoral joint were graded for OA grading using the Kellgren-Lawrence scale.Results: No differences of T2 values were found across the stages of OA (P = 0.25), but the factor of BMI did have a significant effect (P < 0.0001) on T2 value.Conclusions: The results indicate the T2 values are not sensitive to changes in radiographic stages of OA. In addition, differences of T2 values with BMI signify structural changes occurring within the patello-femoral joint and that BMI may be considered a factor for a potential increase of T2 values. Future studies comparing different OA grading methods with T2 mapping may highlight the sensitivity of T2 mapping in a clinical setting. [ABSTRACT FROM AUTHOR]

Recent research has unveiled numerous important functions of protein glycosylation in development, homeostasis, and diseases. A type of glycosylation taking the center stage is protein O-mannosylation, a posttranslational modification conserved in a wide range of organisms, from yeast to humans. In animals, protein O-mannosylation plays a crucial role in the nervous system, whereas protein O-mannosylation defects cause severe neurological abnormalities and congenital muscular dystrophies. However, the molecular and cellular mechanisms underlying protein O-mannosylation functions and biosynthesis remain not well understood. This review outlines recent studies on protein O-mannosylation while focusing on the functions in the nervous system, summarizes the current knowledge about protein O-mannosylation biosynthesis, and discusses the pathologies associated with protein O-mannosylation defects. The evolutionary perspective revealed by studies in the Drosophila model system are also highlighted. Finally, the review touches upon important knowledge gaps in the field and discusses critical questions for future research on the molecular and cellular mechanisms associated with protein O-mannosylation functions., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Modification by sialylated glycans can affect protein functions, underlying mechanisms that control animal development and physiology. Sialylation relies on a dedicated pathway involving evolutionarily conserved enzymes, including CMP-sialic acid synthetase (CSAS) and sialyltransferase (SiaT) that mediate the activation of sialic acid and its transfer onto glycan termini, respectively. In Drosophila , CSAS and DSiaT genes function in the nervous system, affecting neural transmission and excitability. We found that these genes function in different cells: the function of CSAS is restricted to glia, while DSiaT functions in neurons. This partition of the sialylation pathway allows for regulation of neural functions via a glia-mediated control of neural sialylation. The sialylation genes were shown to be required for tolerance to heat and oxidative stress and for maintenance of the normal level of voltage-gated sodium channels. Our results uncovered a unique bipartite sialylation pathway that mediates glia-neuron coupling and regulates neural excitability and stress tolerance., Competing Interests: HS, BN, BU, BA, IM, PM, MK, SB, KA, RV, DL, MT, HB, VP No competing interests declared, (© 2023, Scott, Novikov et al.)

Mutations in protein O-mannosyltransferases (POMTs) result in severe brain defects and congenital muscular dystrophies characterized by abnormal glycosylation of α-dystroglycan (α-Dg). However, neurological phenotypes of POMT mutants are not well understood, and the functional substrates of POMTs other than α-Dg remain unknown. Using a Drosophila model, here we reveal that Dg alone cannot account for the phenotypes of POMT mutants, and identify Protein tyrosine phosphatase 69D (PTP69D) as a gene interacting with POMTs in producing the abdomen rotation phenotype. Using RNAi-mediated knockdown, mutant alleles, and a dominant-negative form of PTP69D, we reveal that PTP69D is required for the wiring of larval sensory axons. We also found that PTP69D and POMT genes interact in this process, and that their interactions lead to complex synergistic or antagonistic effects on axon wiring phenotypes, depending on the mode of genetic manipulation. Using glycoproteomic approaches, we further characterized the glycosylation of the PTP69D transgenic construct expressed in genetic strains with different levels of POMT activity. We found that the PTP69D construct carries many O-linked mannose modifications when expressed in Drosophila with wild-type or ectopically upregulated expression of POMTs. These modifications were absent in POMT mutants, suggesting that PTP69D is a substrate of POMT-mediated O-mannosylation. Taken together, our results indicate that PTP69D is a novel functional substrate of POMTs that is required for axon connectivity. This mechanism of POMT-mediated regulation of receptor-type protein tyrosine phosphatase functions could potentially be conserved in mammals and may shed new light on the etiology of neurological defects in muscular dystrophies., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the longitudinal reproducibility and variations of cartilage T1ρ and T2 measurements using different coils, MR systems and sites., Methods: Single-Site study: Phantom data were collected monthly for up to 29 months on four GE 3T MR systems. Data from phantoms and human subjects were collected on two MR systems using the same model of coil; and were collected on one MR system using two models of coils. Multi-site study: Three participating sites used the same model of MR systems and coils, and identical imaging protocols. Phantom data were collected monthly. Human subjects were scanned and rescanned on the same day at each site. Two traveling human subjects were scanned at all three sites., Results: Single-Site Study: The phantom longitudinal RMS-CVs ranged from 1.8% to 2.7% for T1ρ and 1.8-2.8% for T2. Significant differences were found in T1ρ and T2 values using different MR systems and coils. Multi-Site Study: The phantom longitudinal RMS-CVs ranged from 1.3% to 2.6% for T1ρ and 1.2-2.7% for T2. Across three sites (n = 16), the in vivo scan-rescan RMS-CV was 3.1% and 4.0% for T1ρ and T2, respectively. Phantom T1ρ and T2 values were significantly different between three sites but highly correlated (R > 0.99). No significant difference was found in T1ρ and T2 values of traveling controls, with cross-site RMS-CV as 4.9% and 4.4% for T1ρ and T2, respectively., Conclusion: With careful quality control and cross-calibration, quantitative MRI can be readily applied in multi-site studies and clinical trials for evaluating cartilage degeneration., (Copyright © 2015 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

A three-dimensional (3D) knee joint computational model was developed and validated to predict knee joint contact forces and pressures for different degrees of malalignment. A 3D computational knee model was created from high-resolution radiological images to emulate passive sagittal rotation (full-extension to 65°-flexion) and weight acceptance. A cadaveric knee mounted on a six-degree-of-freedom robot was subjected to matching boundary and loading conditions. A ligament-tuning process minimised kinematic differences between the robotically loaded cadaver specimen and the finite element (FE) model. The model was validated by measured intra-articular force and pressure measurements. Percent full scale error between FE-predicted and in vitro-measured values in the medial and lateral compartments were 6.67% and 5.94%, respectively, for normalised peak pressure values, and 7.56% and 4.48%, respectively, for normalised force values. The knee model can accurately predict normalised intra-articular pressure and forces for different loading conditions and could be further developed for subject-specific surgical planning.

Objective: To correlate meniscal T2* relaxation times using ultra-short echo time (UTE) magnetic resonance imaging (MRI) with quantitative microscopic methods, and to determine the effect of meniscal repair on post-operative cartilage T2 values., Design: A medial meniscal tear was created and repaired in the anterior horn of one limb of 28 crossbred mature ewes. MR scans for morphological evaluation, meniscal T2* values, and cartilage T2 values were acquired at 0, 4 and 8 months post-operatively for the Tear and Non-Op limb. Samples of menisci from both limbs were analyzed using multiphoton microscopy (MPM) analysis and biomechanical testing., Results: Significantly prolonged meniscal T2* values were found in repaired limbs than in control limbs, P < 0.0001. No regional differences of T2* were detected for either the repaired or control limbs in the anterior horn. Repaired limbs had prolonged cartilage T2 values, primarily anteriorly, and tended to have lower biomechanical force to failure at 8 months than Non-Op limbs. MPM autofluorescence and second harmonic generation data correlated with T2* values at 8 months (ρ = -0.48, P = 0.06)., Conclusions: T2* mapping is sensitive to detecting temporal and zonal differences of meniscal structure and composition. Meniscal MPM and cartilage T2 values indicate changes in tissue integrity in the presence of meniscal repair., (Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Language barriers frequently impede the ability of the health care professional to provide the highest quality health care to his or her patients. Spanish speaking people are rapidly becoming the largest minority population in the United States. In order to facilitate access to appropriate medical care that would not be inhibited by miscommunication or lack of a trained translator, the MedSpanish Web Site was developed for use in the Emergency Department. The site contains common Spanish vocabularies, including translations and audio clips, that would be used in such a setting. The various sections are formatted so that they could easily become pocket cards rather than relying on the availability of a computer in a medical emergency. While MedSpanish is not designed to replace a trained translator, it does offer an effective alternative if such translations services are not available.

The objective of this study was to evaluate the expression of mRNA for transforming growth factor-alpha in the bovine mammary gland. Total RNA from 23 cows at various stages of development was isolated from mammary parenchyma and subjected to Northern blot analysis using human transforming growth factor-alpha 32P-labeled deoxycytosine triphosphate cDNA probe. When blots were washed through 1x sodium chloride and sodium citrate plus 1% SDS at 60 degrees C, a 4.8-kb band was observed in all RNA samples. When stringency was increased to .1x, mRNA transcripts were observed only for cows at d 233, 240, and 244 of gestation. After the high stringency washes, major bands were observed at 7.4 and 3.3 kb and minor bands on d 233 at 5.4, 2.3, and 1.6 kb. No additional transcripts were detected in RNA from mammary glands of nonpregnant cows during involution, lactating cows, or estrogen-treated heifers. These data indicate that transcripts similar to transforming growth factor-alpha are present in the bovine mammary gland. The expression pattern could represent alternatively spliced transcripts that were produced during an important period of mammary development prior to parturition.