Transoral, retromolar, para-tonsillar approach to the styloid process in 6 patients with Eagle's syndrome

Objectives: Eagle's syndrome is caused by an elongated or mineralised styloid process and characterised by facial and pharyngeal pain, odynophagia and dysphagia. Diagnosis is based on clinical findings. However radiologic imaging, like panoramic radiograph, helps to confirm the diagnosis. There are different treatments of the Eagle's syndrome. Anti-inflammatory medication (carbamazepime, corticosteroids) and/or surgical interventions are established. The aim of the different surgical techniques is to resect the elongated styloid process near the skull base. Study Design: A transoral, retromolar, para-tonsillar approach was performed to expose and resect the elongated calcified styloid process in a consecutive series of six patients. The use of different angled ring curettes, generally used in hypophysis surgery, facilitated the preparation of the styloid process through the surrounding tissue to the skull base, without a compromise to the surrounding tissue. Clinical examinations were performed pre- and postoperatively (3 month and after 1 year after surgery) in all patients. Results: No intra- or postoperative complications were observed. The hypophysis ring curettes facilitated the preparation of the styloid process to the skull base. Conclusions: The transoral, retromolar, para-tonsillar approach is a secure and fast method to resect an elongated symptomatic styloid process. Side effects of the classical transoral trans-tonsillar approach did not occur

Prediction of regulatory targets of alternative isoforms of the epidermal growth factor receptor in a glioblastoma cell line.

BackgroundThe epidermal growth factor receptor (EGFR) is a major regulator of proliferation in tumor cells. Elevated expression levels of EGFR are associated with prognosis and clinical outcomes of patients in a variety of tumor types. There are at least four splice variants of the mRNA encoding four protein isoforms of EGFR in humans, named I through IV. EGFR isoform I is the full-length protein, whereas isoforms II-IV are shorter protein isoforms. Nevertheless, all EGFR isoforms bind the epidermal growth factor (EGF). Although EGFR is an essential target of long-established and successful tumor therapeutics, the exact function and biomarker potential of alternative EGFR isoforms II-IV are unclear, motivating more in-depth analyses. Hence, we analyzed transcriptome data from glioblastoma cell line SF767 to predict target genes regulated by EGFR isoforms II-IV, but not by EGFR isoform I nor other receptors such as HER2, HER3, or HER4.ResultsWe analyzed the differential expression of potential target genes in a glioblastoma cell line in two nested RNAi experimental conditions and one negative control, contrasting expression with EGF stimulation against expression without EGF stimulation. In one RNAi experiment, we selectively knocked down EGFR splice variant I, while in the other we knocked down all four EGFR splice variants, so the associated effects of EGFR II-IV knock-down can only be inferred indirectly. For this type of nested experimental design, we developed a two-step bioinformatics approach based on the Bayesian Information Criterion for predicting putative target genes of EGFR isoforms II-IV. Finally, we experimentally validated a set of six putative target genes, and we found that qPCR validations confirmed the predictions in all cases.ConclusionsBy performing RNAi experiments for three poorly investigated EGFR isoforms, we were able to successfully predict 1140 putative target genes specifically regulated by EGFR isoforms II-IV using the developed Bayesian Gene Selection Criterion (BGSC) approach. This approach is easily utilizable for the analysis of data of other nested experimental designs, and we provide an implementation in R that is easily adaptable to similar data or experimental designs together with all raw datasets used in this study in the BGSC repository, https://github.com/GrosseLab/BGSC

RNA-binding proteins as regulators of migration, invasion and metastasis in oral squamous cell carcinoma

Nearly 7.5% of all human protein-coding genes have been assigned to the class of RNA-binding proteins (RBPs), and over the past decade, RBPs have been increasingly recognized as important regulators of molecular and cellular homeostasis. RBPs regulate the post-transcriptional processing of their target RNAs, i.e., alternative splicing, polyadenylation, stability and turnover, localization, or translation as well as editing and chemical modification, thereby tuning gene expression programs of diverse cellular processes such as cell survival and malignant spread. Importantly, metastases are the major cause of cancer-associated deaths in general, and particularly in oral cancers, which account for 2% of the global cancer mortality. However, the roles and architecture of RBPs and RBP-controlled expression networks during the diverse steps of the metastatic cascade are only incompletely understood. In this review, we will offer a brief overview about RBPs and their general contribution to post-transcriptional regulation of gene expression. Subsequently, we will highlight selected examples of RBPs that have been shown to play a role in oral cancer cell migration, invasion, and metastasis. Last but not least, we will present targeting strategies that have been developed to interfere with the function of some of these RBPsPublikationsfond ML

Dental pulp stem cells for salivary gland regeneration : where are we today?

Xerostomia is the phenomenon of dry mouth and is mostly caused by hypofunction of the salivary glands. This hypofunction can be caused by tumors, head and neck irradiation, hormonal changes, inflammation or autoimmune disease such as Sjögren’s syndrome. It is associated with a tremendous decrease in health-related quality of life due to impairment of articulation, ingestion and oral immune defenses. Current treatment concepts mainly consist of saliva substitutes and parasympathomimetic drugs, but the outcome of these therapies is deficient. Regenerative medicine is a promising approach for the treatment of compromised tissue. For this purpose, stem cells can be utilized due to their ability to differentiate into various cell types. Dental pulp stem cells are adult stem cells that can be easily harvested from extracted teeth. They can form tissues of all three germ layers and are therefore becoming more and more popular for tissue engineering. Another potential benefit of these cells is their immunomodulatory effect. They suppress proinflammatory pathways of lymphocytes and could therefore probably be used for the treatment of chronic inflammation and autoimmune disease. These attributes make dental pulp stem cells an interesting tool for the regeneration of salivary glands and the treatment of xerostomia. Nevertheless, clinical studies are still missing. This review will highlight the current strategies for using dental pulp stem cells in the regeneration of salivary gland tissue

A novel splice variant of the stem cell marker LGR5/GPR49 is correlated with the risk of tumor-related death in soft-tissue sarcoma patients

<p>Abstract</p> <p>Background</p> <p>The human leucine-rich, repeat-containing G protein-coupled receptor (LGR) 5, also called GPR49, is a marker of stem cells in adult intestinal epithelium, stomach and hair follicles. LGR5/GPR49 is overexpressed in tumors of the colon, ovary and liver and in basal cell carcinomas. Moreover, an expression in skeletal muscle tissues was also detected. However, there has been no investigation regarding the expression and function of LGR5/GPR49 in soft-tissue sarcomas (STS) yet.</p> <p>Methods</p> <p>Seventy-seven frozen tumor samples from adult STS patients were studied using quantitative real-time TaqMan™ PCR analysis. The mRNA levels of wild type <it>LGR5/GPR49 </it>and a newly identified splice variant of <it>LGR5/GPR49 </it>lacking exon 5 (that we called <it>GPR49Δ5</it>) were quantified.</p> <p>Results</p> <p>A low mRNA expression level of <it>GPR49Δ5</it>, but not wild type <it>LGR5/GPR49</it>, was significantly correlated with a poor prognosis for the disease-associated survival of STS patients (RR = 2.6; P = 0.026; multivariate Cox's regression hazard analysis). Furthermore, a low mRNA expression level of <it>GPR49Δ5 </it>was associated with a shorter recurrence-free survival (P = 0.043). However, tumor onset in patients with a lower expression level of <it>GPR49Δ5 </it>mRNA occurred 7.5 years later (P = 0.04) than in patients with a higher tumor level of <it>GPR49Δ5 </it>mRNA.</p> <p>Conclusion</p> <p>An attenuated mRNA level of the newly identified transcript variant <it>GPR49Δ5 </it>is a negative prognostic marker for disease-associated and recurrence-free survival in STS patients. Additionally, a lower <it>GPR49Δ5 </it>mRNA level is associated with a later age of tumor onset. A putative role of <it>GPR49Δ5 </it>expression in tumorigenesis and tumor progression of soft tissue sarcomas is suggested.</p

Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation

Background: Trends over time and possible socio-spatial inequalities in the incidence and care of type 1 diabetes mellitus (T1D) in children and adolescents are important parameters for the planning of target-specific treatment structures. Methodology: The incidence and prevalence of type 1 diabetes, diabetic ketoacidosis and severe hypoglycaemia as well as the HbA1c value are presented for under 18-year-olds based on data from the nationwide Diabetes Prospective Follow-up Registry (DPV) and the diabetes registry of North Rhine-Westphalia. Indicators were mapped by sex over time between 2014 and 2020, and stratified by sex, age and regional socioeconomic deprivation for 2020. Results: In 2020, the incidence was 29.2 per 100,000 person-years and the prevalence was 235.5 per 100,000 persons, with the figures being higher in boys than in girls in either case. The median HbA1c value was 7.5%. Ketoacidosis manifested in 3.4% of treated children and adolescents, significantly more often in regions with very high (4.5%) deprivation than in regions with very low deprivation (2.4%). The proportion of severe hypoglycaemia cases was 3.0%. Between 2014 and 2020, the incidence, prevalence and HbA1c levels changed little, while the proportions of ketoacidosis and severe hypoglycaemia decreased. Conclusions: The decrease in acute complications indicates that type 1 diabetes care has improved. Similar to previous studies, the results suggest an inequality in care by regional socioeconomic situation

Incidence, prevalence and care of type 1 diabetes in children and adolescents in Germany: Time trends and regional socioeconomic situation

Background: Trends over time and possible socio-spatial inequalities in the incidence and care of type 1 diabetes mellitus (T1D) in children and adolescents are important parameters for the planning of target-specific treatment structures. Methodology: The incidence and prevalence of type 1 diabetes, diabetic ketoacidosis and severe hypoglycaemia as well as the HbA1c value are presented for under 18-year-olds based on data from the nationwide Diabetes Prospective Follow-up Registry (DPV) and the diabetes registry of North Rhine-Westphalia. Indicators were mapped by sex over time between 2014 and 2020, and stratified by sex, age and regional socioeconomic deprivation for 2020. Results: In 2020, the incidence was 29.2 per 100,000 person-years and the prevalence was 235.5 per 100,000 persons, with the figures being higher in boys than in girls in either case. The median HbA1c value was 7.5%. Ketoacidosis manifested in 3.4% of treated children and adolescents, significantly more often in regions with very high (4.5%) deprivation than in regions with very low deprivation (2.4%). The proportion of severe hypoglycaemia cases was 3.0%. Between 2014 and 2020, the incidence, prevalence and HbA1c levels changed little, while the proportions of ketoacidosis and severe hypoglycaemia decreased. Conclusions: The decrease in acute complications indicates that type 1 diabetes care has improved. Similar to previous studies, the results suggest an inequality in care by regional socioeconomic situation

Expected Basal Insulin Requirement during CSII therapy by Age Group, Sex and BMI, based on 25,718 Young People with Type 1 Diabetes in the DPV Registry.

Background Since the introduction of insulin pumps into the therapy of paediatric subjects, different approaches have been taken to find optimal basal rates. Previously, the DPV registry provided circadian basal rate patterns for different age groups. As the number of pump users has increased recently and short-acting insulin analogues are now predominant, we performed a new analysis with a larger data pool. Methods We included all recent basal profiles from T1D patients between 1 and 25 years from the DPV 2021 data pool. We excluded night-time-only pump users, human regular insulin users, and daily basal rates 1.0 U/kgBW/d. Results In the analysis of profiles from 25,718 young persons with T1D, differences in the daily pattern of basal rates were found between age groups. In addition, we saw significant (p<0.001) differences in total daily basal dose between genders in all age groups except adults. In addition, the shape of the expected basal-rate pattern differed by BMI, HbA1c and use of continuous glucose monitoring. Discussion This analysis demonstrates multiple factors influencing basal patterns and insulin requirement, including age group, gender, overweight, HbA1c, bolus frequency and sensor use. As circadian basal rates are still mandatory for initiating insulin pump therapy with or without automation, a multimodal approach is necessary to estimate optimal basal rates

Area deprivation and demographic factors associated with diabetes technology use in adults with type 1 diabetes in Germany

IntroductionDiabetes technology improves glycemic control and quality of life for many people with type 1 diabetes (T1D). However, inequalities in access to diabetes technology exist in many countries. In Germany, disparities in technology use have been described in pediatric T1D, but no data for adults are available so far. We therefore aimed to analyze whether demographic factors and area deprivation are associated with technology use in a representative population of adults with T1D.Materials and methodsIn adults with T1D from the German prospective diabetes follow-up registry (DPV), we analyzed the use of continuous subcutaneous insulin infusion (CSII), continuous glucose monitoring (CGM), and sensor augmented pump therapy (SAP, with and without automated insulin delivery) in 2019-2021 by age group, gender, migration background, and area deprivation using multiple adjusted regression models. Area deprivation, defined as a relative lack of area-based resources, was measured by quintiles of the German index of Multiple Deprivation (GIMD 2015, from Q1, least deprived, to Q5, most deprived districts).ResultsAmong 13,351 adults with T1D, the use of technology decreased significantly with older age: CSII use fell from 56.1% in the 18−&lt;25-year age group to 3.1% in the ≥80-year age group, CGM use from 75.3% to 28.2%, and SAP use from 45.1% to 1.5% (all p for trend &lt;0.001). The use of technology was also significantly higher in women than in men (CSII: 39.2% vs. 27.6%; CGM: 61.9% vs. 58.0%; SAP: 28.7% vs. 19.6%, all p &lt;0.001), and in individuals without migration background than in those with migration background (CSII: 38.8% vs. 27.6%; CGM: 71.1% vs. 61.4%; SAP: 30.5% vs. 21.3%, all p &lt;0.001). Associations with area deprivation were not linear: the use of each technology decreased only from Q2 to Q4.DiscussionOur real-world data provide evidence that higher age, male gender, and migration background are currently associated with lower use of diabetes technology in adults with T1D in Germany. Associations with area deprivation are more complex, probably due to correlations with other factors, like the higher proportion of migrants in less deprived areas or the federal structure of the German health care system