Lack of association between ENAM gene polymorphism and dental caries in primary and permanent teeth in Czech children

Clinical Oral Investigations - The enamelin gene (ENAM) polymorphism (rs12640848) was recently associated with dental caries in primary teeth in Polish children. The aims of the present study were...     

Influence of Extraoral Apicoectomy on Revascularization of an Autotransplanted Tooth: A Case Report

Autotransplantation is considered a standard procedure with a poorer prognosis for mature than for immature teeth. In this case report, the root tip of an almost fully developed tooth was resected during autotransplantation to fit into a deficient recipient site. As a positive side effect, the apical foramen was enlarged, with potential improvement of the probability of revascularization. Clinical and radiologic follow-up examinations up to 18 months indicated revascularization and uneventful periodontal regeneration and thus successful autotransplantation. This case supports the hypothesis that intraoperative apicoectomy can improve the prognosis for revascularization of mature autotransplanted teeth. Further prospective controlled clinical studies are needed to confirm this innovative surgical approach.     

Wnt‐3a‐activated human fibroblasts promote human keratinocyte proliferation and matrix destruction

Aberrant Wnt regulation, detectable by nuclear translocation of beta‐catenin, is a hallmark of many cancers including skin squamous cell carcinomas (SCCs). By analyzing primary human skin SCCs, we demonstrate that nuclear beta‐catenin is not restricted to SCC cells but also detected in stromal fibroblasts, suggesting an important role for aberrant Wnt regulation also in the tumor microenvironment. When human keratinocytes and fibroblasts were treated with Wnt‐3a, fibroblasts proved to be more responsive. Accordingly, Wnt‐3a did not alter HaCaT cell functions in a cell‐autonomous manner. However, when organotypic cultures (OTCs) were treated with Wnt‐3a, HaCaT keratinocytes responded with increased proliferation. As nuclear beta‐catenin was induced only in the fibroblasts, this argued for a Wnt‐dependent, paracrine keratinocyte stimulation. Global gene expression analysis of Wnt‐3a‐stimulated fibroblasts identified genes encoding interleukin‐8 (IL‐8) and C‐C motif chemokine 2 (CCL‐2) as well as matrix metalloproteinase‐1 (MMP‐1) as Wnt‐3a targets. In agreement, we show that IL‐8 and CCL‐2 were secreted in high amounts by Wnt‐3a‐stimulated fibroblasts also in OTCs. The functional role of IL‐8 and CCL‐2 as keratinocyte growth regulators was confirmed by directly stimulating HaCaT cell proliferation in conventional cultures. Most important, neutralizing antibodies against IL‐8 and CCL‐2 abolished the Wnt‐dependent HaCaT cell hyperproliferation in OTCs. Additionally, MMP‐1 was expressed in high amounts in Wnt‐3a‐stimulated OTCs and degraded the stromal matrix. Thus, our data show that Wnt‐3a stimulates fibroblasts to secrete both keratinocyte proliferation‐inducing cytokines and stroma‐degrading metalloproteinases, thereby providing evidence for a novel Wnt deregulation in the tumor‐stroma directly contributing to skin cancer progression.     

Accuracy of ultrasound for predicting pathologic response during neoadjuvant therapy for breast cancer

Early assessment of response to neoadjuvant chemotherapy (NAC) for breast cancer allows therapy to be tailored; however, optimal response assessment methods have not been established. We estimated the accuracy of ultrasound (US) to predict pathologic complete response (pCR) using common response criteria and pCR definitions, and estimated incremental accuracy over known prognostic variables. Participants undergoing US after two cycles in the GeparTrio trial randomised to no change in NAC were eligible. US response by World Health Organisation (WHO) criteria (1D or 2D) and Response Evaluation Criteria In Solid Tumours (RECIST) was assessed. Four pCR definitions were applied. Sensitivity (correct prediction of pCR), specificity (correct prediction of no‐pCR) and diagnostic odds ratios (DORs) were calculated. Areas under the curve (AUCs) were derived from logistic regression including patient variables with and without US. In 832 patients, DORs decreased as pCR definitions became less stringent (p = 0.01). For WHO‐2D, DORs were as follows: 4.07 (ypT0,ypN0), 3.75 (ypT0/is,ypN0), 3.14 (ypT0/is,ypN+/?) and 2.65 (ypT0/is/1a,ypN+/?). DORs did not differ between US criteria (p = 0.60). High sensitivity and lower specificity were found for WHO‐2D and RECIST; WHO‐1D was highly specific with low sensitivity. Sensitivity was highest for WHO‐2D predicting ypT0,ypN0 (sensitivity = 81.7%, specificity = 47.6% vs. 42.3% and 80.4% for WHO‐1D). Adding US to models including patient variables (age, T‐stage, histology and subtype) improved AUCs for predicting pCR by 2–3%. In conclusion, US accuracy is highest for predicting ypT0,ypN0, shown to be most prognostic of long‐term survival. WHO‐2D and RECIST maximise sensitivity; WHO‐1D maximises specificity. US modestly improves the prediction of pCR by patient characteristics.     

The use of fractionated Kraft lignin to improve the mechanical and biological properties of PVA-based scaffolds

The mechanical properties of poly(vinyl alcohol) (PVA)-based scaffolds were successfully improved. The improvements in mechanical properties correlated with the amount of Kraft lignin in PVA matrices. The critical property for any scaffold is its capacity to allow cells to ingrow and survive within its internal structure. The ingrowth of cells was tested using bioreactors creating simulated in vivo conditions. In the context of all the mentioned parameters, the most advantageous properties were exhibited by the scaffold containing 99 wt% PVA and 1 wt% Kraft lignin. The composites with 1 wt% Kraft lignin exhibited sufficient mechanical stability, a lack of cytotoxicity, and mainly the ability to allow the ingrowth of cells into the scaffold in a rotation bioreactor.

The mechanical properties of poly(vinyl alcohol) (PVA)-based scaffolds were successfully improved.     

Do anatomic variants of the acromion shape in the frontal plane influence pain and function in calcifying tendinitis of the shoulder?

Purpose  

To evaluate the relationship of a large acromion index and calcifying tendinitis of the supraspinatus tendon at the shoulder.     

Agreement of duplex ultrasonography vs. computed tomography angiography for evaluation of native and in-stent SFA re-stenosis--findings from a randomized controlled trial

Background

Multidetector CT angiography (CTA) is a non-invasive imaging technique for evaluation of peripheral vascular disease. CTA might be particularly useful for assessment of intermediate- and long-term morphological outcome after endovascular treatment. Validation of CTA vs. the current imaging standard, colour Doppler ultrasonography (CDUS), for quantification of native and in-stent re-stenosis in the superficial femoral artery (SFA) is required.

Methods

Seventy randomized patients who underwent stent implantation (n = 47) or balloon angioplasty (n = 23) underwent 6-month follow-up with CDUS and CTA. CTA was compared with CDUS in both sub-groups of patients in terms of binary re-stenosis (>50% lumen narrowing) and re-occlusion. Agreement between CTA and CDUS was assessed using Kappa (κ) statistics with 95% confidence intervals, and correlation coefficients.

Results

Binary re-stenosis was detected in 16/70 (22.9%) patients by CTA and 17/70 (24.3%) patients by CDUS (κ = 0.88, 95% CI: 0.80–0.96). Re-stenosis rates after balloon angioplasty were 39.1% (9/23) on CTA and CDUS (κ = 0.82, 95% CI: 0.66–0.98), and after stent implantation 14.9% (7/47) on CTA and 17.0% (8/47) on CDUS (κ = 0.92, 95% CI: 0.84–1.00). Re-occlusions were detected in 3/70 (4.3%) patients by both CTA and CDUS (κ = 0.65; 95% CI 0.54–0.76). Significant correlations (r = 0.85, p < 0.001) were noted between degree of re-stenosis on CTA and peak velocity ratio on CDUS. The correlation coefficient was higher in patients after balloon angioplasty (r = 0.94, p < 0.001) than in patients after stent implantation (r = 0.71, p < 0.001).

Conclusion

CTA and CDUS show excellent agreement for evaluation of native and in-stent re-stenosis after endovascular treatment of SFA obstructions. CTA is an appropriate non-invasive imaging modality for follow-up after endovascular therapy.     

Long-Term Outcomes of Pre-emptive Valganciclovir Compared with Valacyclovir Prophylaxis for Prevention of Cytomegalovirus in Renal Transplantation

Prevention of cytomegalovirus (CMV) is essential in organ transplantation. The two main strategies are pre-emptive therapy, in which one screens for and treats asymptomatic CMV viremia, and universal antiviral prophylaxis. We compared these strategies and examined long-term outcomes in a randomized, open-label, single-center trial. We randomly assigned 70 renal transplant recipients (CMV-seropositive recipient or donor) to 3-month prophylaxis with valacyclovir (n=34) or pre-emptive valganciclovir for significant CMV viremia detected at predefined assessments through month 12 (n=36). Among the 55 patients who had a protocol biopsy specimen available at 3 years to allow assessment of the primary outcome, 9 (38%) of 24 patients in the prophylaxis group and 6 (19%) of 31 patients in the pre-emptive therapy group had moderate to severe interstitial fibrosis and tubular atrophy (odds ratio, 2.50; 95% confidence interval, 0.74-8.43; P=0.22). The prophylaxis group had significantly higher intrarenal mRNA expression of genes involved in fibrogenesis. The occurrence of CMV disease was similar in both groups, but pre-emptive therapy improved 4-year graft survival (92% versus 74%; P=0.049) as a result of worse outcomes in patients with late-onset CMV viremia. In conclusion, compared with valacyclovir prophylaxis, pre-emptive valganciclovir therapy may lead to less severe interstitial fibrosis and tubular atrophy and to significantly better graft survival.