BRAF overexpression is associated with BRAF V600E mutation in papillary thyroid carcinomas.

A common mutation in the BRAF gene, comprising the T1799A nucleotide transversion, which leads to the V600E amino acid substitution in the BRAF protein, has been observed in about 50% of papillary thyroid carcinomas (PTCs). However, BRAF protein expression has been rarely examined in such tumors. Clinical studies have shown important associations between BRAF mutation and clinical parameters in PTC, such as progression, invasion, and recurrence. The aim of this study was to evaluate the association between BRAF protein overexpression and the BRAF V600E mutation in a group of PTC patients. The study group included 116 patients with PTC from Araújo Jorge Hospital, Goiânia, Goiás, Brazil. Immunohistochemistry was utilized to analyze BRAF protein expression. Presence of the BRAF V600E mutation was determined by polymerase chain reaction amplification and restriction fragment length polymorphism, and confirmed by direct sequencing. The chi-square test with Yates correction and the Fisher exact test were used for statistical analysis. BRAF overexpression was detected in 55 patients with PTC (47.4%) and the BRAF V600E mutation was observed in 74 patients (63.8%). In the studied group, significant associations were observed between the BRAF V600E mutation and BRAF protein overexpression (P = 0.0115), and also between BRAF overexpression and extra-thyroid extension of the tumor (P = 0.0111). This study demonstrated a significant association between BRAF overexpression and the BRAF V600E mutation in PTC, highlighting the importance of these molecular events in the process of PTC carcinogenesis.

Changes in lower limb co-contraction and stiffness by toddlers with Down syndrome and toddlers with typical development during the acquisition of independent gait.

During gait acquisition, children learn to use their changing resources to meet the requirements of the task. Compared to typically developing toddlers (TD), toddlers with Down syndrome (DS) have functionally different musculoskeletal characteristics, such as hypotonia, and joint and ligament laxity, that could produce a reduced passive stiffness. The interplay between this inherently lower passive stiffness and the demands of walking may result in different strategies during gait acquisition. This study compared normalized global stiffness and lower limb's co-contraction indices (CCI) used by toddlers with TD (n=12) and with DS (n=12), during the early stages of gait acquisition. Stiffness and CCI were normalized by gravitational torque (mLg) in both phases of gait (stance, swing). Five longitudinal evaluations were conducted from the onset of locomotion until three months post-acquisition. All children were video taped and had electromyographic (EMG) recordings from muscle pairs of one leg, which were used to calculate CCI of hip, knee, ankle, and total leg CCI. Body and lower limb stiffness were calculated according to a hybrid pendulum resonance equation. Results from ANOVAs revealed no group differences on stiffness or on CCI's during stance but children with DS showed greater CCI during swing. Despite the structural musculoskeletal differences between toddlers with TD and with DS, the similarities observed in their processes of gait development suggest functional equivalences.