scholarly journals A Comparison of Two-Dimensional and Three-Dimensional Techniques for Kinematic Analysis of the Sagittal Motion of Sheep Hindlimbs During Walking on a Treadmill

2021 ◽  
Vol 8 ◽  
Author(s):  
Camila Cardoso Diogo ◽  
José Arthur Camassa ◽  
Bárbara Fonseca ◽  
Luís Maltez da Costa ◽  
José Eduardo Pereira ◽  
...  

Compared to rodents, sheep offer several attractive features as an experimental model for testing different medical and surgical interventions related to pathological gait caused by neurological diseases and injuries. To use sheep for development of novel treatment strategies in the field of neuroscience, it is key to establish the relevant kinematic features of locomotion in this species. To use sheep for development of novel treatment strategies in the field of neuroscience, it is crucial to understand fundamental baseline characteristics of locomotion in this species. Despite their relevance for medical research, little is known about the locomotion in the ovine model, and next to nothing about the three-dimensional (3D) kinematics of the hindlimb. This study is the first to perform and compare two-dimensional (2D) and 3D hindlimb kinematics of the sagittal motion during treadmill walking in the ovine model. Our results show that the most significant differences took place throughout the swing phase of the gait cycle were for the distal joints, ankle and metatarsophalangeal joint, whereas the hip and knee joints were much less affected. The results provide evidence of the inadequacy of a 2D approach to the computation of joint kinematics in clinically normal sheep during treadmill walking when the interest is centered on the hoof's joints. The findings from the present investigation are likely to be useful for an accurate, quantitative and objective assessment of functionally altered gait and its underlying neuronal mechanisms and biomechanical consequences.

2020 ◽  
Author(s):  
Camila Cardoso Diogo ◽  
Bárbara Fonseca ◽  
Francisca S.M. Almeida ◽  
Luís Maltez da Costa ◽  
José Eduardo Pereira ◽  
...  

Abstract Background: Analysis of locomotion is often used as a measure for impairment and recovery following experimental peripheral nerve injury. Compared to rodents, sheep offer several attractive features as an experimental model for studying peripheral nerve regeneration. There are no studies on locomotion outcomes after peripheral nerve injury and repair in the sheep model. In the present study, we performed and compared two-dimensional (2D) and, for the first time, three-dimensional (3D) hindlimb kinematics during obstacle avoidance in the ovine model. This study aimed to obtain kinematic data to serve as a template for an objective assessment of the ankle joint motion in future studies of common peroneal nerve (CP) injury and repair in the ovine model. Results: The strategy used by the sheep to bring the hindlimb over a moderately high obstacle, set to 10% of its hindlimb length, was the pronounced knee, ankle and metatarsophalangeal flexion when approaching and clearing the obstacle. Despite the overall time course kinematic patterns about the hip, knee, ankle, and metatarsophalangeal were identical, we found significant differences between values of the 2D and 3D joint angular motion. Conclusions: Our results show that the most apparent changes that occurred during the gait cycle were for the ankle and metatarsophalangeal joints, whereas the hip and knee joints were much less affected. Data and techniques described here are likely to be useful for an objective assessment of altered gait after CP injury and repair in an ovine model.


2021 ◽  
Vol 51 (6) ◽  
Author(s):  
Camila Cardoso Diogo ◽  
Bárbara Fonseca ◽  
Francisca Soares Marques de Almeida ◽  
Luís Maltez da Costa ◽  
José Eduardo Pereira ◽  
...  

ABSTRACT: Analysis of locomotion is often used as a measure for impairment and recovery following experimental peripheral nerve injury. Compared to rodents, sheep offer several advantages for studying peripheral nerve regeneration. In the present study, we compared for the first time, two-dimensional (2D) and three-dimensional (3D) hindlimb kinematics during obstacle avoidance in the ovine model. This study obtained kinematic data to serve as a template for an objective assessment of the ankle joint motion in future studies of common peroneal nerve (CP) injury and repair in the ovine model. The strategy used by the sheep to bring the hindlimb over a moderately high obstacle, set to 10% of its hindlimb length, was pronounced knee, ankle and metatarsophalangeal flexion when approaching and clearing the obstacle. Despite the overall time course kinematic patterns about the hip, knee, ankle, and metatarsophalangeal were identical, we found significant differences between values of the 2D and 3D joint angular motion. Our results showed that the most apparent changes that occurred during the gait cycle were for the ankle (2D-measured STANCEmax: 157±2.4 degrees vs. 3D-measured STANCEmax: 151±1.2 degrees; P<.05) and metatarsophalangeal joints (2D-measured STANCEmin: 151±2.2 degrees vs. 3D-measured STANCEmin: 162 ± 2.2 degrees; P<.01 and 2D-measured TO: 163±4.9 degrees vs. 3D-measured TO: 177±1.4 degrees; P<.05), whereas the hip and knee joints were much less affected. Data and techniques described here are useful for an objective assessment of altered gait after CP injury and repairin an ovine model.


2020 ◽  
pp. 972-987
Author(s):  
Ramez N. Eskander ◽  
Julia Elvin ◽  
Laurie Gay ◽  
Jeffrey S. Ross ◽  
Vincent A. Miller ◽  
...  

PURPOSE High-grade neuroendocrine cervical cancer (HGNECC) is an uncommon malignancy with limited therapeutic options; treatment is patterned after the histologically similar small-cell lung cancer (SCLC). To better understand HGNECC biology, we report its genomic landscape. PATIENTS AND METHODS Ninety-seven patients with HGNECC underwent comprehensive genomic profiling (182-315 genes). These results were subsequently compared with a cohort of 1,800 SCLCs. RESULTS The median age of patients with HGNECC was 40.5 years; 83 patients (85.6%) harbored high-risk human papillomavirus (HPV). Overall, 294 genomic alterations (GAs) were identified (median, 2 GAs/sample; average, 3.0 GAs/sample, range, 0-25 GAs/sample) in 109 distinct genes. The most frequently altered genes were PIK3CA (19.6% of cohort), MYC (15.5%), TP53 (15.5%), and PTEN (14.4%). RB1 GAs occurred in 4% versus 32% of HPV-positive versus HPV-negative tumors ( P < .0001). GAs in HGNECC involved the following pathways: PI3K/AKT/mTOR (41.2%); RAS/MEK (11.3%); homologous recombination (9.3%); and ERBB (7.2%). Two tumors (2.1%) had high tumor mutational burden (TMB; both with MSH2 alterations); 16 (16.5%) had intermediate TMB. Seventy-one patients (73%) had ≥ 1 alteration that was theoretically druggable. Comparing HGNECC with SCLC, significant differences in TMB, microsatellite instability, HPV-positive status, and in PIK3CA, MYC, PTEN, TP53, ARID1A, and RB1 alteration rates were found. CONCLUSION This large cohort of patients with HGNECC demonstrated a genomic landscape distinct from SCLC, calling into question the biologic and therapeutic relevance of the histologic similarities between the entities. Furthermore, 73% of HGNECC tumors had potentially actionable alterations, suggesting novel treatment strategies for this aggressive malignancy.


Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5435
Author(s):  
Maiko Matsushita

Introduction of tyrosine kinase inhibitors (TKIs) has improved the prognosis of patients with chronic myelogenous leukemia (CML), and treatment-free remission (TFR) is now a treatment goal. However, about half of the patients experience molecular relapse after cessation of TKIs, suggesting that leukemic stem cells (LSCs) are resistant to TKIs. Eradication of the remaining LSCs using immunotherapies including interferon-alpha, vaccinations, CAR-T cells, and other drugs would be a key strategy to achieve TFR.


2021 ◽  
Vol 135 (10) ◽  
pp. 1289-1293
Author(s):  
Gregor Werba ◽  
Tamas A. Gonda

Abstract Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.


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