Expanding the spectrum of PTH1R mutations in patients with primary failure of tooth eruption

Objectives

Primary failure of tooth eruption (PFE) is a rare autosomal-dominant disease characterized by severe lateral open bite as a consequence of incomplete eruption of posterior teeth. Heterozygous mutations in the parathyroid hormone 1 receptor (PTH1R) gene have been shown to cause PFE likely due to protein haploinsufficiency. To further expand on the mutational spectrum of PFE-associated mutations, we report here on the sequencing results of the PTH1R gene in 70 index PFE cases.

Materials and methods

Sanger sequencing of the PTH1R coding exons and their immediate flanking intronic sequences was performed with DNA samples from 70 index PFE cases.

Results

We identified a total of 30 unique variants, of which 12 were classified as pathogenic based on their deleterious consequences on PTH1R protein while 16 changes were characterized as unclassified variants with as yet unknown effects on disease pathology. The remaining two variants represent common polymorphisms.

Conclusions

Our data significantly increase the number of presently known unique PFE-causing PTH1R mutations and provide a series of variants with unclear pathogenicity which will require further in vitro assaying to determine their effects on protein structure and function.

Clinical relevance

Management of PTH1R-associated PFE is problematic, in particular when teeth are exposed to orthodontic force. Therefore, upon clinical suspicion of PFE, molecular DNA testing is indicated to support decision making for further treatment options.     

Bioactive asterosaponins from the starfish Culcita novaeguineae

Two new sulfated steroidal pentaglycosides（asterosaponins）,novaeguinosides Ⅰ（2） and （Ⅱ）2,along with the known regularoside B（1）were isolated from the starfish Culcita novaeguineae.Their structures were elucidated by extensive NMR techniques as well as chemical evidence.     

The emerging dental workforce: long-term career expectations and influences. A quantitative study of final year dental students' views on their long-term career from one London Dental School

Background  

Research into the motivation and expectations of the emerging workforce and their short-term expectations has already been reported with a view to informing professional and policy decisions. The objective of this component of the research programme was to examine the long-term goals and perceived influences on final year dental students' professional careers.     

EMPHYSEMATOUS PYELONEPHRITIS RESPONDING TO MEDICAL THERAPY

We describe two type 2 diabetic patients with unilateral emphysematous pyelonephritis who responded to medical treatment alone. Escherichia coli was isolated in both patients. The presence of gas was confirmed early by ultrasound and CT scan of abdomen. Following treatment, good functional recovery was demonstrable in the affected kidneys by isotope renogram. We stress the need for early diagnosis of this condition and aggressive treatment with broad spectrum antibiotics.     

胶原-壳聚糖复合材料的制备及生物安全性检测

目的:制备胶原-壳聚糖复合细胞载体,并对该载体进行系统的生物学性能检测。方法:实验于2003-07/2006-06在天津市医药科学研究所完成。将胶原溶液和壳聚糖溶液按照一定比例(9∶1)混匀,交联后真空冷冻干燥,制成胶原-壳聚糖复合载体,对该载体进行复合材料性状及理化性能检测。并采用急性全身毒性试验、皮内刺激试验、皮肤致敏试验、溶血试验、细胞毒性试验和致突变试验进行生物学性能检测。结果:①胶原-壳聚糖复合材料具有三维立体多孔结构,适合细胞的三维生长,能为新生组织提供良好的支架。②急性全身毒性试验、皮内刺激试验均阴性,致敏率仅为6.25%,细胞毒性为0级,无诱变能力。结论:从仿生学角度出发,制备出可生物降解的胶原-壳聚糖复合材料,经过系统的生物学评价发现,胶原-壳聚糖复合材料具有良好的生物安全性,对机体无毒,不致突变,对细胞有较强的亲和作用,利于细胞生长和分化。     

Risk Stratification of Patients With Severe Heart Failure Awaiting Heart Transplantation—Prospective National Registry POLKARD HF

Most methods used in the risk assessment of heart transplant candidates do not include new biomarkers.

Aims

The aim of the study was to examine the value of NTproBNP and hsCRP and their combined use together with HFSS score in the risk assessment of patients with heart failure enlisted for heart transplantation.

Methods

Data of 658 patients enlisted for heart transplantation in all active transplantation centers were stored in a prospective registry. The composite end point-death or urgent transplantation was recorded during the follow-up.

Results

Death or urgent transplantation was recorded in 161 (24%) of pts. 102 (15%) patients died and 59 (9%) were transplanted urgently. Kaplan-Meier curves for risk of death or urgent transplantation where highly significant when pts were stratified by the quartiles of NT proBNP (P < .000001) or quartiles according to the hsCRP level on admission (P < .002). In the multivariate Cox proportional hazard model, the significance was observed for NTproBNP (P < .01) and HFSS (P < .02), and borderline significance for hsCRP (P = .057). When ROC analyses of the area under the curve (AUC) values were considered, AUC area was for HFSS – 0.645, for NTproBNP – 0.653 and for hsCRP – 0.566. When all those variables were included together in the model, the AUC value rose to 0.6943. Based on those results a weighted risk model with all three parameters was proposed.

Conclusion

HFSS, NTproBNP and hsCRP levels are independent stratification variables of survival or need for urgent heart transplantation. Their predictive value is moderately increased when they are analyzed together.