Parathyroid hormone 1–34 enhances extracellular matrix deposition and organization during flexor tendon repair

Parathyroid hormone (PTH) 1–34 is known to enhance fracture healing. Tendon repair is analogous to bone healing in its dependence on the proliferation and differentiation of mesenchymal stem cells, matrix formation, and tissue remodeling.^1,2,3 We hypothesized that PTH 1–34 enhances tendon healing in a flexor digitorum longus (FDL) tendon repair model. C57Bl/6J mice were treated with either intraperitoneal PTH 1–34 or vehicle‐control (PBS). Tendons were harvested at 3–28 days for histology, gene expression, and biomechanical testing. The metatarsophalangeal joint range of motion was reduced 1.5–2‐fold in PTH 1–34 mice compared to control mice. The gliding coefficient, a measure of adhesion formation, was 2–3.5‐fold higher in PTH 1–34 mice. At 14 days post‐repair, the tensile strength was twofold higher in PTH 1–34 specimens, but at 28 days there were no differences. PTH 1–34 mice had increased fibrous tissue deposition that correlated with elevated expression of collagens and fibronectin as seen on quantitative PCR. PTH 1–34 accelerated the deposition of reparative tissue but increased adhesion formation. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 33:17–24, 2015.     

Efficacy of manual therapy on psychological status and pain in patients with neck pain: A randomized clinical trial

Objectives:To compare the effectiveness of Maitland versus Mulligan mobilization techniques on pain, functional disability, and psychological status in patients with neck pain.Methods:Forty-four patients with nonspecific neck pain were randomly assigned to the Maitland group (n=22 patients received Maitland therapy [central or unilateral postero-anterior pressure] for 2 sessions/week for 3 weeks) and Mulligan group (n=22 patients received Mulligan sustained natural apophyseal glides for 2 sessions/week for 3 weeks). This study was conducted at the Rehabilitation Clinic, King Abdulaziz Hospital, Jeddah, Kingdom of Saudi Arabia between December 2016 to May 2017. The outcome measures were the numeric pain rating scale score, neck disability index score, beck depression inventory score, State-trait anxiety inventory score, fear avoidance beliefs questionnaire, and pain catastrophic scale results. The independent t-test, Shapiro-Wilk test, and paired t-test were used in data analysis.Results:There were significant improvements in mean values of the numeric pain rating scale, neck disability index, beck depression inventory, state-trait anxiety inventory scores, and pain catastrophic scale results after the interventions in both groups (p<0.05, all except fear avoidance beliefs results in mulligan group p>0.05), and there were no significant differences in mean values between the groups (p>0.05).Conclusion:In patients with nonspecific neck pain, Maitland and Mulligan mobilization techniques have positive effects on neck pain, functional disability, and selected psychological features with no significant difference between them.     

New quinazolinone-based derivatives as DHFR/EGFR-TK inhibitors: Synthesis,molecular modeling simulations,and anticancer activity

New 2-mercapto-quinazolin-4-one analogs were synthesized and tested for their in vitro anticancer activity, dihydrofolate reductase (DHFR) inhibition, and epidermal growth factor tyrosine kinase (EGFR-TK) inhibition activities. Compound 24 , which is characterized by a 2-benzyl-thio function, showed broad-spectrum anticancer activity with high safety profile and selectivity index. The concentrations of 24 causing 50% growth inhibition (GI₅₀) and total cell growth inhibition (TGI) and its lethal concentration 50 (LC₅₀) were 15.1, 52.5, and 91.2 µM, respectively, using 5-fluorouracil as a positive control. Also, it showed EGFR-TK inhibitory activity with IC₅₀ = 13.40 nM compared to gefitinib (IC₅₀ = 18.14 nM) and DHFR inhibitory potency with 0.30 μM compared to methotrexate (MTX; IC₅₀ = 0.08 μM). In addition, compound 24 caused cell cycle arrest and apoptosis on COLO-205 colon cancer cells. Compounds 37, 21 , and 54 showed remarkable DHFR inhibitory activity with IC₅₀ values of 0.03, 0.08, and 0.08 μM, respectively. The inhibitory properties of these compounds are due to an electron-withdrawing group on the quinazolinone ring, except for compound 54 . In a molecular modeling study, compound 24 showed the same binding mode as gefitinib as it interacted with the amino acid Lys745 via π–π interaction. Compound 37 showed a similar binding mode as MTX through the binding interaction with Lys68, Asn64 via hydrogen bond acceptor, and Phe31 via arene–arene interaction. The obtained model and substitution pattern could be used for further development.     

Completeness and accuracy of data in spine registries: an independent audit-based study

European Spine Journal - Clinical registries are used for quality management and clinical research. Due to the importance and implications of both aims, completeness and high quality of data are of...