MEDIAL-LATERAL HIP POSITIONS PREDICTED KINETIC ASYMMETRIES DURING BILATERAL SQUATS IN COLLEGIATE ATHLETES FOLLOWING ACLR

Anterior cruciate ligament (ACL) re-injury rates are high in collegiate athletes, and double-leg squats are commonly used following ACL reconstruction (ACLR). The purpose was to quantify the correlations between the medial-lateral shoulder/hip kinematics and bilateral kinetic asymmetries during double-leg squats in collegiate athletes at two assessments. Seventeen collegiate athletes performed three double-leg squats 0-6 months and/or 6-12 months following ACLR. Medial-lateral shoulder/hip positions and bending angles were calculated. Medial-lateral hip positions were significant and strongly correlated with ground reaction force and knee moment asymmetries. A commercially available camera may be used to capture the frontal plane motion as a low-cost and more convenient tool to monitor bilateral kinetic asymmetries during double-leg squats in patients following ACLR

Calcitonin receptor N-glycosylation enhances peptide hormone affinity by controlling receptor dynamics

The class B G protein-coupled receptor (GPCR) calcitonin receptor (CTR) is a drug target for osteoporosis and diabetes. N-glycosylation of asparagine 130 in its extracellular domain (ECD) enhances calcitonin hormone affinity with the proximal GlcNAc residue mediating this effect through an unknown mechanism. Here, we present two crystal structures of salmon calcitonin-bound, GlcNAc-bearing CTR ECD at 1.78 and 2.85 Å resolutions and analyze the mechanism of the glycan effect. The N130 GlcNAc does not contact the hormone. Surprisingly, the structures are nearly identical to a structure of hormone-bound, N-glycan-free ECD, which suggested that the GlcNAc might affect CTR dynamics not observed in the static crystallographic snapshots. Hydrogen-deuterium exchange mass spectrometry and molecular dynamics simulations revealed that glycosylation stabilized a β-sheet adjacent to the N130 GlcNAc and the N-terminal α-helix near the peptide-binding site, while increasing flexibility of the peptide-binding site turret loop. These changes due to N-glycosylation increased the ligand on-rate and decreased its off rate. The glycan effect extended to RAMP-CTR amylin receptor complexes and was also conserved in the related CGRP receptor. These results reveal that N-glycosylation can modulate GPCR function by altering receptor dynamics

Identification of the calcitonin receptor in osteoarthritic chondrocytes

<p>Abstract</p> <p>Background</p> <p>Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA). However, the presence of the calcitonin receptor (CTR) in articular cartilage chondrocytes is yet to be identified. In this study, we sought to further investigate the expression of the CTR in naïve human OA articular chondrocytes to gain further confirmation of the existents of the CTR in articular cartilage.</p> <p>Methods</p> <p>Total RNA was purified from primary chondrocytes from articular cartilage biopsies from four OA patients undergoing total knee replacement. High quality cDNA was produced using a dedicated reverse transcription polymerase chain reaction (RT-PCR) protocol. From this a nested PCR assay amplifying the full coding region of the CTR mRNA was completed. Western blotting and immunohistochemistry were used to characterize CTR protein on protein level in chondrocytes.</p> <p>Results</p> <p>The full coding transcript of the CTR isoform 2 was identified in all four individuals. DNA sequencing revealed a number of allelic variants of the gene including two potentially novel polymorphisms: a frame shift mutation, +473del, producing a shorter form of the receptor protein, and a single nucleotide polymorphism in the 3' non coding region of the transcript, +1443 C>T. A 53 kDa protein band, consistent with non-glycosylated CTR isoform 2, was detected in chondrocytes with a similar size to that expressed in osteoclasts. Moreover the CTR was identified in the plasma membrane and the chondrocyte lacuna of both primary chondrocytes and OA cartilage section.</p> <p>Conclusions</p> <p>Human OA articular cartilage chondrocytes do indeed express the CTR, which makes the articular a pharmacological target of salmon calcitonin. In addition, the results support previous findings suggesting that calcitonin has a direct anabolic effect on articular cartilage.</p

Correlation between Chest X-Ray Severity in COVID-19 and Age in Mexican-Mestizo Patients: An Observational Cross-Sectional Study

Introduction. Chest X-ray (CXR) is used for the initial triage of patients with suspected COVID-19. Studies of CXR scoring in the European population found a higher score in males than in females and significantly correlated with age. Because there have not been studies in the Mexican-mestizo community, we aimed to compare the differences in CXR scores between males and females and their correlation with age after controlling comorbidities like diabetes and hypertension. Materials and Methods. A retrospective study of 1000 CXR of Mexican-mestizo patients with SARS-CoV-2 infection, confirmed by RT-PCR. Significant differences between age, age groups, symptoms, comorbidities, and CXR scores between males and females used the Mann-Whitney U, Chi-square tests (χ2), and Kruskal-Wallis tests. The relationship between the total CXR score and age was measured with the Spearman rank correlation coefficient (Rs); partial correlation analysis controlled the effect of symptoms, risk factors, and comorbidities. Results. The total CXR score did not show a difference between males and females grouped by age. There was a positive, low correlation between the total CXR score and age in males, Rs=0.260,

Correlation between Chest X-Ray Severity in COVID-19 and Age in Mexican-Mestizo Patients: An Observational Cross-Sectional Study

Introduction. Chest X-ray (CXR) is used for the initial triage of patients with suspected COVID-19. Studies of CXR scoring in the European population found a higher score in males than in females and significantly correlated with age. Because there have not been studies in the Mexican-mestizo community, we aimed to compare the differences in CXR scores between males and females and their correlation with age after controlling comorbidities like diabetes and hypertension. Materials and Methods. A retrospective study of 1000 CXR of Mexican-mestizo patients with SARS-CoV-2 infection, confirmed by RT-PCR. Significant differences between age, age groups, symptoms, comorbidities, and CXR scores between males and females used the Mann–Whitney U, Chi-square tests (χ2), and Kruskal–Wallis tests. The relationship between the total CXR score and age was measured with the Spearman rank correlation coefficient (Rs); partial correlation analysis controlled the effect of symptoms, risk factors, and comorbidities. Results. The total CXR score did not show a difference between males and females grouped by age. There was a positive, low correlation between the total CXR score and age in males, Rs=0.260, p<0.001 (N=616), and in females, Rs=0.170, p=0.001 (N=384). Age only explained a <9% variance of CXR severity. Rs decreased its magnitude (from Rs=0.152 to Rs=0.046) and lost its significance (change in p value from p<0.001 to p=0.145) after controlling the effect of hypertension. Conclusions. There is no significant difference in CXR score between males and females in the Mexican-mestizo population grouped by age. Hypertension cancels the significance of CXR severity with age pointing to its role in the pathophysiology of COVID-19. Further research using stratified groups by age and gender in other populations needs to be published