JUMONJI (JMJ) is a nuclear factor that is critical for normal cardiovascular development, evidenced by the analysis of jmj homozygous mutant mice. However, the molecular function of JMJ remains to be elucidated. In the present study, we investigated whether JMJ is a transcriptional modulator. Reporter gene assays using the GAL4-DNA binding domain fused to JMJ and a reporter gene consisting of the GAL4 binding sites upstream of a luciferase reporter gene indicated that JMJ functions as a powerful transcriptional repressor. The DNA binding motif of JMJ was determined using CASTing experiments by incubating a random oligonucleotide library with the GST-JMJ fusion protein coupled to agarose beads. Among the selected binding oligonucleotides, the high affinity DNA binding sequences were identified by gel retardation assays. JMJ repressed expression of the reporter genes containing the high affinity JMJ binding sequences, indicating that JMJ is a DNA-binding transcriptional repressor. The domains for transcriptional repression, DNA binding, and nuclear localization signal were mapped by mutational analyses using reporter gene assays, gel retardation assays, and immunostaining experiments, respectively. The present data demonstrate for the first time that JMJ functions as a DNA-binding transcriptional repressor. Therefore, JMJ may play a critical role in transcription factor cascade to regulate expression of heart-specific genes and normal cardiac development.
Kawasaki disease (KD) produces endothelial inflammation, which may lead to dilatation and aneurysms of coronary and peripheral arteries. Previous studies have suggested that these patients can present endothelial dysfunction that can predispose to coronary vascular events late after KD. The purpose of this study was to determine the cardiovascular risk profile and endothelial function of Chilean children with history of KD. In a prospective case-control study, 11 patients with history of KD (age 10.6 +/- 2.0 years, interval from initial episode 8.1 +/- 3.6 years) and 11 healthy, age-, gender-, and BMI z score-matched controls were evaluated with blood pressure (BP), a fasting lipid profile, high sensitivity C-reactive protein (hsCRP), and flow-mediated dilatation of the brachial artery (FMD). One KD patient (9.1%) had persistent coronary aneurysms. There was a significant difference of mean and log-transformed concentrations of hsCRP between case and control groups (2.3 +/- 3.0 vs 0.5 +/- 0.3 mg/l, P = 0.045). None of the patients with elevated hsCRP had persistent coronary arterial lesions. No difference was found in systolic BP z score between the case and control groups. Diastolic BP z score was significantly higher in cases than controls (P = 0.039). There were no significant differences of FMD between cases and controls. Mean fasting total cholesterol, high-density and low-density lipoprotein, and triglycerides in cases were normal, with no significant difference vs controls. This study shows that Chilean children with history of KD have increased levels of hsCRP, possibly reflecting persistent low-grade inflammation. The prognostic value of hsCRP in KD patients deserves further investigation.
Background: The deep peroneal nerve (DPN) plays a role in afferent nociceptive dorsal midfoot joint pain perception. DPN neurectomy for treatment of symptomatic dorsal midfoot osteoarthritis allows early mobilization and weightbearing. The purpose of our study was to evaluate the patient satisfaction and pain relief after DPN neurectomy for treatment of chronic dorsal midfoot pain due to osteoarthritis. Methods: In this retrospective, IRB-approved, questionnaire-based study, we evaluated 48 patients (55 feet) with an average follow-up of 35.1 (range, 16-51) months who underwent DPN neurectomy at our institution between September 2017 and February 2021. There were 38 women and 10 men, 41 unilateral (22 right, 19 left) and 7 bilateral procedures, with an average age of 67.8 (range, 35-88) years at the time of surgery. A questionnaire that included questions regarding postsurgical dorsal midfoot pain relief, surgical result satisfaction, and current functional limitations was administered via telephone. Demographic information, patient responses, and complications were recorded. Results: Of the 48 patients, 80.8% were satisfied with the result of the surgery in relieving their dorsal midfoot pain, 84.6% would repeat the surgery under the same circumstances, 83.8% would recommend the surgery to a friend, 10.4% reported they wish they had undergone arthrodesis, 91.7% reported pain relief in the first 6 months, and 55.6% reported current activity limitations. Six feet (10.9%) underwent a second procedure with an average postoperative time of 20.5 (range, 1-36) months. Complications included 1 hematoma and deep wound infection, 1 DPN neuroma and superficial peroneal nerve entrapment, and 4 patients with inadequate pain relief. Conclusion: In this cohort, DPN neurectomy appeared to be a reasonable surgical alternative to arthrodesis for the management of chronic dorsal midfoot pain due to midfoot osteoarthritis after failed nonoperative management. Level of Evidence: Level IV, retrospective case series.
Ankle arthritis is a debilitating disease marked by pain and limited function. Total ankle arthroplasty improves pain while preserving motion and offers an alternative to the traditional treatment of ankle fusion. Gait analysis and functional outcomes tools can provide an objective balanced analysis of ankle replacement for the treatment of ankle arthritis. Twenty‐nine patients with end‐stage ankle arthritis were evaluated before and after ankle arthroplasty. Multi‐segment foot and ankle kinematics were assessed annually following surgery (average 3.5 years, range 1–6 years) using the Milwaukee Foot Model and a Vicon video motion analysis system. Functional outcomes (American Orthopedic Foot and Ankle Society [AOFAS] ankle/hindfoot scale, short form 36 [SF‐36] questionnaire) and temporal‐spatial parameters were also assessed. Kinematic results were compared to findings from a previously collected group of healthy ambulators. AOFAS and SF‐36 mean scores improved postoperatively. Walking speed and stride length increased after surgery. There were significant improvements in tibial sagittal range of motion in terminal stance and hindfoot sagittal range of motion in preswing. Decreased external rotation of the tibia and increased external rotation of the hindfoot were noted throughout the gait cycle. Pain and function improved after ankle replacement as supported by better outcomes scores, increased temporal‐spatial parameters, and significant improvement in tibial sagittal range of motion during terminal stance and hindfoot sagittal range of motion during preswing. While multi‐segment foot kinematics were improved, they were not restored to control values. Statement of clinical significance: Total ankle arthroplasty does not fully normalize mutli‐segment gait kinematics despite improved patient‐reported outcomes and gait mechanics.
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