RESUMEN
TBL1XR1, which encodes transducing ß-like 1 X-linked receptor 1, is implicated in both Pierpont syndrome and intellectual developmental disorder, autosomal dominant-41 (MRD-41, OMIM #616944). While both conditions are autosomal dominant, variants associated with Pierpont syndrome are believed to behave in a dominant negative fashion, whereas those causing MRD-41 result in haploinsufficiency. Here, we present a patient with a de novo novel variant in TBL1XR1 (c.977G > A,p.S326N) identified by trio exome sequencing. Though a different variant at this same residue has previously been associated with MRD-41, our patient's presentation is suggestive of Pierpont syndrome. The patient's clinical phenotype, which includes short stature, developmental delay, dysmorphic craniofacial features, and plantar fat pads, more closely resembles that of known patients with Pierpont syndrome than MRD-41. Furthermore, this missense variant is directly adjacent to one previously associated with Pierpont syndrome and exists in the same region as all variants associated with Pierpont, on the inner surface of a WD40 ring. We propose this variant is a newly identified cause of Pierpont syndrome.
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Discapacidades del Desarrollo , Discapacidad Intelectual , Humanos , Niño , Discapacidades del Desarrollo/genética , Discapacidades del Desarrollo/patología , Facies , Discapacidad Intelectual/genética , Fenotipo , Proteínas Represoras/genética , Receptores Citoplasmáticos y Nucleares/genéticaRESUMEN
Objective: To compare wound complication rates between orthopedic closure (OC) and plastic multilayered closure (PMC) in patients undergoing primary posterior spinal fusion for neuromuscular scoliosis (NMS). We hypothesize that multilayered closure will be associated with better postoperative outcomes. Methods: We collected data on pediatric patients diagnosed with NMS who underwent first time spinal instrumentation between 1 January 2018 and 31 May 2021. Patient demographics, length of surgery, spinal levels fused and operative variables, wound complication rate, treatments, and need for wound washout were reviewed in depth and recorded. Results: In total, 86 patients were reviewed: 46 with OC and 40 with PMC. There was a significant increase in operating room (OR) time with PMC compared with OC (6.7±1.2 vs 7.3±1.3, p=0.016). There was no difference in complication rate, mean postoperative day of complication or unplanned return to the OR for OC and PMC, respectively. There was a slightly significant increase in the number of patients going home with a drain in the PMC cohort compared with the OC cohort (2.1% vs 15%, p=0.046). Conclusions: PMC demonstrated longer OR times than OC and did not demonstrate a statistically significant reduction in wound complications or unplanned returns to the OR. However, other studies have demonstrated statistical and clinical significance with these variables. Surgical programs should review internal patient volumes and outcomes for spinal fusion in NMS patients and consider if PMC after spinal fusions in pediatric patients with NMS or other scoliosis subtypes is an appropriate option in their institution to minimize postoperative wound complications.
RESUMEN
AIM: To assess the influence of root canal treatment on serum high-sensitivity C-reactive protein (hsCRP) levels in systemically healthy human adults. METHODOLOGY: Fifteen individuals aged 20-40 years diagnosed with apical periodontitis [Periapical Index (PAI) score ≥3] who were otherwise healthy took part in this prospective interventional study. Patients with moderate to severe periodontitis, systemic diseases and traditional cardiac risk factors (hypertension, diabetes, dyslipidemia and smoking) were excluded. Root canal treatment was completed in two visits with an inter-appointment calcium hydroxide intracanal medicament. After 6 months, healing of apical periodontitis was evaluated clinically and radiographically, and serum hsCRP levels were recorded. A paired sample T-test was used to compare the mean hsCRP values between the pre- and post-treatment groups. The Mann-Whitney U test was used to compare hsCRP values between patients with PAI scores of 3 and 4, and the Wilcoxon signed-rank test was used to compare pre- and postoperative PAI scores. RESULTS: The mean preoperative baseline serum hsCRP level was 2.88 ± 1.06 mg L-1 which can be associated with a moderate risk for cardiovascular disease (CVD). Based on the preoperative hsCRP levels, eight of the 15 patients were categorized as high risk (hsCRP > 3 mg L-1 ) and the other seven as medium risk (hsCRP 1-3 mg L-1 ) for CVD. The mean preoperative hsCRP value of patients with a PAI score of 3 was 2.88 ± 1.19 mg L-1 , and the mean preoperative hsCRP of patients with a PAI score of 4 was 2.87 ± 0.15 mg L-1 , which was not significantly different (P = 0.942). Six months after root canal treatment, the mean PAI score had significantly reduced from 3.2 ± 0.42 to 1.4 ± 0.69 (P = 0.003). The PAI score had reduced to ≤2 in 87% of the patients, and the mean serum hsCRP levels had significantly reduced to 1.34 ± 0.52 mg L-1 (P < 0.001). Ten of the 15 patients had a reduction in their CVD risk status. CONCLUSIONS: This study suggests that root canal treatment can reduce serum hsCRP levels in systemically healthy individuals with apical periodontitis.
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Proteína C-Reactiva , Periodontitis Periapical , Adulto , Cavidad Pulpar , Humanos , Periodontitis Periapical/terapia , Estudios Prospectivos , Tratamiento del Conducto Radicular , Adulto JovenRESUMEN
Prevention of viral-induced respiratory disease begins with an understanding of the factors that increase or decrease susceptibility to viral infection. The primary receptor for most adenoviruses is the coxsackievirus and adenovirus receptor (CAR), a cell-cell adhesion protein normally localized at the basolateral surface of polarized epithelia and involved in neutrophil transepithelial migration. Recently, an alternate isoform of CAR, CAREx8, has been identified at the apical surface of polarized airway epithelia and is implicated in viral infection from the apical surface. We hypothesized that the endogenous role of CAREx8 may be to facilitate host innate immunity. We show that IL-8, a proinflammatory cytokine and a neutrophil chemoattractant, stimulates the protein expression and apical localization of CAREx8 via activation of AKT/S6K and inhibition of GSK3ß. Apical CAREx8 tethers infiltrating neutrophils at the apical surface of a polarized epithelium. Moreover, neutrophils present on the apical-epithelial surface enhance adenovirus entry into the epithelium. These findings suggest that adenovirus evolved to co-opt an innate immune response pathway that stimulates the expression of its primary receptor, apical CAREx8, to allow the initial infection the intact epithelium. In addition, CAREx8 is a new target for the development of novel therapeutics for both respiratory inflammatory disease and adenoviral infection.
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Infecciones por Adenoviridae/inmunología , Adenoviridae , Células Epiteliales/metabolismo , Inmunidad Innata/inmunología , Infecciones por Adenoviridae/metabolismo , Animales , Células Cultivadas , Epitelio/metabolismo , Humanos , Ratones , Neutrófilos/inmunología , Receptores Virales/metabolismoRESUMEN
The Coxsackievirus and adenovirus receptor (CAR) is an essential cellular protein that is involved in cell-cell adhesion, protein trafficking, and viral infection. The major isoform of CAR is selectively sorted to the basolateral membrane of polarized epithelial cells where it co-localizes with the cellular scaffolding protein membrane-associated guanylate kinase with inverted domain structure-1 (MAGI-1). Previously, we demonstrated CAR interacts with MAGI-1 through a PDZ-domain dependent interaction. Here, we show that the PDZ3 domain of MAGI-1 is exclusively responsible for the high affinity interaction between the seven exon isoform of CAR and MAGI-1 using yeast-two-hybrid analysis and confirming this interaction biochemically and in cellular lysates by in vitro pull down assay and co-immunoprecipitation. The high affinity interaction between the PDZ3 domain and CAR C-terminus was measured by fluorescence resonance energy transfer. Further, we investigated the biological relevance of this high affinity interaction between CAR and the PDZ3 domain of MAGI-1 and found that it does not alter CAR-mediated adenovirus infection. By contrast, interruption of this high affinity interaction altered the localization of MAGI-1 indicating that CAR is able to traffic MAGI-1 to cell junctions. These data deepen the molecular understanding of the interaction between CAR and MAGI-1 and indicate that although CAR plays a role in trafficking PDZ-based scaffolding proteins to cellular junctions, association with a high affinity intracellular binding partner does not significantly alter adenovirus binding and entry via CAR.