Early posttraumatic ankle osteoarthritis following ankle fracture-dislocations in a sub-Saharan African setting.

INTRODUCTION: Ankle fracture-dislocation (AFD) represents a major threat to the joint and a potential source of complication and functional disability. This study was performed to assess the outcome of AFD in a resource-limited setting and factors associated with the posttraumatic ankle osteoarthritis (PTAOA). We hypothesized that conservative treatment after AFD was associated with higher risk of PTAOA compared to surgical treatment. PATIENTS AND METHODS: Data from 52 consecutive patients (mean age 37.2±11.1years, with 57.7% n=30, males) who were treated and followed in a teaching hospital for AFD during a period of six years were collected. Forty-four of these patients were obtained at the time of the study for a retrospective evaluation. Functional outcome was assessed using the American Orthopaedic Foot and Ankle Society (AOFAS), ankle-hindfoot scale, and the patient's global satisfaction index. Radiographs were performed and analyzed for PTAOA. Logistic regression was used to determine factors associated with the presence of PTAOA. RESULTS: PTAOA was found in 19 (43.2%) patients after an average follow-up period of 27.2±18.3months. Anatomic fracture reduction was achieved in 22 (50%) patients, while the talus was centered in the mortise in 30 (68.2%) patients. Despite these poor anatomical results, the clinical outcome was good to excellent in 33 (75%) patients, and 88.6% was satisfied or very satisfied. Factors associated with the presence of PTAOA were the non-anatomical reduction (OR=11.07; p=0.007, 95% CI: 2.096-58.77) and the time elapsed since trauma (OR=1.073; p=0.007, 95% CI: 1.109-1.129). CONCLUSION: This study indicates that AFDs are associated with high rate of early and severe PTAOA. Non-anatomical realignment and a delay since trauma were positive predictors of PTAOA. There was no difference regarding the occurrence of PTAOA after AFD whatever the type of treatment, surgical or conservative. LEVEL OF EVIDENCE: IV; retrospective cohort study.

Androglobin gene expression patterns and FOXJ1-dependent regulation indicate its functional association with ciliogenesis.

Androglobin (ADGB) represents the latest addition to the globin superfamily in metazoans. The chimeric protein comprises a calpain domain and a unique circularly permutated globin domain. ADGB expression levels are most abundant in mammalian testis, but its cell-type-specific expression, regulation, and function have remained unexplored. Analyzing bulk and single-cell mRNA-Seq data from mammalian tissues, we found that-in addition to the testes-ADGB is prominently expressed in the female reproductive tract, lungs, and brain, specifically being associated with cell types forming motile cilia. Correlation analysis suggested coregulation of ADGB with FOXJ1, a crucial transcription factor of ciliogenesis. Investigating the transcriptional regulation of the ADGB gene, we characterized its promoter using epigenomic datasets, exogenous promoter-dependent luciferase assays, and CRISPR/dCas9-VPR-mediated activation approaches. Reporter gene assays revealed that FOXJ1 indeed substantially enhanced luciferase activity driven by the ADGB promoter. ChIP assays confirmed binding of FOXJ1 to the endogenous ADGB promoter region. We dissected the minimal sequence required for FOXJ1-dependent regulation and fine mapped the FOXJ1 binding site to two evolutionarily conserved regions within the ADGB promoter. FOXJ1 overexpression significantly increased endogenous ADGB mRNA levels in HEK293 and MCF-7 cells. Similar results were observed upon RFX2 overexpression, another key transcription factor in ciliogenesis. The complex transcriptional regulation of the ADGB locus was illustrated by identifying a distal enhancer, responsible for synergistic regulation by RFX2 and FOXJ1. Finally, cell culture studies indicated an ADGB-dependent increase in the number of ciliated cells upon overexpression of the full-length protein, confirming a ciliogenesis-associated role of ADGB in mammals.

Loss of Neuroglobin Expression Alters Cdkn1a/Cdk6-Expression Resulting in Increased Proliferation of Neural Stem Cells.

In the quest to unravel its functional significance, neuroglobin (Ngb), a brain-specific neuroprotective protein, has recently been proposed as an actor in neurodevelopment. As neural stem cells (NSCs) are fundamental during brain development, the present study aimed at investigating the role of Ngb in the growth and proliferation of NSCs by comparing an Ngb-floxed (Ngbfl-)NSC line, equivalent to the wild-type cellular situation, with an in-house created Ngb knockout (NgbKO-)NSC line. NgbKO-NSCs were characterized by an increased growth and proliferation capacity in vitro, supported by RNA sequencing and western blot results reporting the downregulation of Cdkn1a and the upregulation of Cdk6, both enhancing the cell cycle. Based on additional gene ontology enrichment and pathway analyses, we hypothesize that the loss of Ngb affects multiple cellular signaling pathways with the most important being the Akt-Tp53 axis.

Critical re-evaluation of neuroglobin expression reveals conserved patterns among mammals.

Neuroglobin (Ngb) is a respiratory protein that is almost exclusively expressed in the vertebrate nervous system. Despite many years of research, the exact function and even the expression sites of Ngb are still a matter of debate. However, to investigate hypotheses surrounding the potential roles of Ngb, a detailed knowledge of its major and minor expression sites is indispensable. We have therefore evaluated Ngb expression by extensive bioinformatic analysis using publicly available transcriptome data (RNA-Seq). During mammalian brain development, we observed low embryonic expression of Ngb mRNA and an increase after birth, arguing against a role of Ngb in fetal hypoxia tolerance. In adult mouse brain, we found highest Ngb mRNA levels in the hypothalamus, where expression was up to 100-fold stronger than in cerebral cortex, cerebellum or hippocampus, as confirmed by qRT-PCR and Western blotting. High Ngb expression in the hypothalamus was found conserved in humans and other mammals. Thus, Ngb mRNA is expressed at a basal level in many mammalian brain regions, but shows distinctive regional peaks. RNA-Seq analysis further revealed only low levels of Ngb mRNA in retina and testes and no signal in standard tumor cell lines, thus raising questions concerning previous studies and functional hypotheses. In conclusion, this broad-scale expression study may point to distinct Ngb functions for high- and low-expressing cells and tissues and argues against a single, generic role of Ngb as an oxygen supplier or as an endogenous protectant in all nerve cells.

Prediction of drainage effectiveness during endoscopic stenting of malignant hilar strictures: the role of liver volume assessment.

BACKGROUND: The optimal endoscopic approach to the drainage of malignant hilar strictures remains controversial, especially with regard to the extent of desirable drainage and unilateral or bilateral stenting. OBJECTIVE: To identify useful criteria for predicting successful endoscopic drainage. DESIGN AND SETTING: Retrospective 2-center study in the greater Paris area in France. PATIENTS: A total of 107 patients who had undergone endoscopic stenting for hilar tumors Bismuth type II, III, or IV and a set of contemporaneous cross-sectional imaging data available. INTERVENTIONS: The relative volumetry of the 3 main hepatic sectors (left, right anterior, and right posterior) was assessed on CT scans. The liver volume drained was estimated and classified into 1 of 3 classes: less than 30%, 30% to 50%, and more than 50% of the total liver volume. MAIN OUTCOME MEASUREMENTS: The primary outcome was effective drainage, defined as a decrease in the bilirubin level of more than 50% at 30 days after drainage. Secondary outcomes were early cholangitis rate and survival. RESULTS: The main factor associated with drainage effectiveness was a liver volume drained of more than 50% (odds ratio 4.5, P = .001), especially in Bismuth III strictures. Intubating an atrophic sector (<30%) was useless and increased the risk of cholangitis (odds ratio 3.04, P = .01). A drainage > 50% was associated with a longer median survival (119 vs 59 days, P = .005). LIMITATIONS: Heterogeneous population and volume assessment methodology to improve in further prospective studies. CONCLUSION: Draining more than 50% of the liver volume, which frequently requires bilateral stent placement, seems to be an important predictor of drainage effectiveness in malignant, especially Bismuth III, hilar strictures. A pre-ERCP assessment of hepatic volume distribution on cross-sectional imaging may optimize endoscopic procedures.

[Duodenal duplication revealed by acute pancreatitis: endoscopic treatment]. / Duplication duodénale révélée par une pancréatite aiguë: traitement endoscopique.

We report the case of a 17 year old man who presented with several episodes of acute pancreatitis due to a duodenal duplication. This was successfully treated by an incision by sphincterotome during interventional duodenoscopy. The patient is symptom free without recurrence 20 months after endoscopic treatment.