Abdominal aortic aneurysm is associated with a variant in low-density lipoprotein receptor-related protein 1

Abdominal aortic aneurysm (AAA) is a common cause of morbidity and mortality and has a significant heritability. We carried out a genome-wide association discovery study of 1866 patients with AAA and 5435 controls and replication of promising signals (lead SNP with a p value < 1 × 10-5) in 2871 additional cases and 32,687 controls and performed further follow-up in 1491 AAA and 11,060 controls. In the discovery study, nine loci demonstrated association with AAA (p < 1 × 10-5). In the replication sample, the lead SNP at one of these loci, rs1466535, located within intron 1 of low-density-lipoprotein receptor-related protein 1 (LRP1) demonstrated significant association (p = 0.0042). We confirmed the association of rs1466535 and AAA in our follow-up study (p = 0.035). In a combined analysis (6228 AAA and 49182 controls), rs1466535 had a consistent effect size and direction in all sample sets (combined p = 4.52 × 10-10, odds ratio 1.15 [1.10-1.21]). No associations were seen for either rs1466535 or the 12q13.3 locus in independent association studies of coronary artery disease, blood pressure, diabetes, or hyperlipidaemia, suggesting that this locus is specific to AAA. Gene-expression studies demonstrated a trend toward increased LRP1 expression for the rs1466535 CC genotype in arterial tissues; there was a significant (p = 0.029) 1.19-fold (1.04-1.36) increase in LRP1 expression in CC homozygotes compared to TT homozygotes in aortic adventitia. Functional studies demonstrated that rs1466535 might alter a SREBP-1 binding site and influence enhancer activity at the locus. In conclusion, this study has identified a biologically plausible genetic variant associated specifically with AAA, and we suggest that this variant has a possible functional role in LRP1 expression

Genome-wide association identifies nine common variants associated with fasting proinsulin levels and provides new insights into the pathophysiology of type 2 diabetes.

OBJECTIVE: Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology. RESEARCH DESIGN AND METHODS: We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates. RESULTS: Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets. CONCLUSIONS: We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis

Recording the maxillomandibular relationship with the Aqualizer system prior to occlusal splint therapy for treating temporomandibular disorders: a randomized controlled trial

Abstract Temporomandibular disorders (TMD) present a public health issue and are one of the most common musculoskeletal conditions causing chronic pain. This study compares the outcomes of occlusal splint therapy in patients with TMD following two different maxillomandibular relationship (MMR) registration techniques. 40 TMD patients were randomly allocated to MMR registration with the Aqualizer system (AQU) or with chin point guidance (CPG) prior to fabricating occlusal splints. TMD symptoms, subjective pain intensity, and quality of life (QoL) were recorded at baseline and after 3 and 6 months. The treatment led to an overall reduction of TMD symptoms in both groups (Conover test, p  0.8). AQU-based occlusal splints led to a better improvement of TMJ pain with maximum opening compared to CPG-based occlusal splints (Cohen’s d = 0.9; CPG d = 0.13). In both groups, occlusal splint treatment had little to no effect on correcting lateral mandible deviation or improving restricted jaw opening. After 6 months occlusal splints in both groups had a large effect on improving subjective pain intensity (Cohen’s d > 0.8), however, patients reported a higher QoL in the AQU group compared to the CPG group (Mann–Whitney-U-test, p < 0.05). The results of this study support the premise that occlusal splints are effective in relieving pain-related TMD symptoms. The Aqualizer can be considered for determining MMR in cases, where guided registration techniques are not possible. Trial registration: DRKS00031998

Impact of COVID-19 on Dental Care during a National Lockdown: A Retrospective Observational Study

The coronavirus disease 19 (COVID-19) has challenged dental health professions. This study analyzes its impact on urgent dental care in the Department of Conservative Dentistry and Periodontology, University Hospital Munich and Bavaria, Germany. Patient numbers without and with positive/suspected COVID-19 infection, their reasons for attendance, and treatments were retrospectively recorded (February–July 2020) and linked to local COVID-19 infection numbers, control measures, and numbers/reasons for closures of private dental practices in Bavaria, Germany. Patient numbers decreased within the urgent care unit and the private dental practices followed by a complete recovery by the end of July. While non-emergency visits dropped to almost zero during the first lockdown, pain-related treatments were administered invariably also in patients with positive/suspected COVID-19 infections. Reasons for practice closures were lack of personal protective equipment (PPE), lack of employees, staff’s increased health risks, and infected staff, which accounted for 0.72% (3.6% closures in total). Pain-driven urgent dental care remains a constant necessity even in times of high infection risk, and measures established at the beginning of the pandemic seem to have provided a safe environment for patients as well as oral health care providers. PPE storage is important to ensure patients’ treatment under high-risk conditions, and its storage and provision by regulatory units might guarantee a stable and safe oral health care system in the future

A comprehensive in vitro comparison of the biological and physicochemical properties of bioactive root canal sealers

Objectives To evaluate the biological and physicochemical features of bioactive root canal sealers. Materials and methods Human periodontal ligament fibroblasts (hPDLF) and human osteoblasts (hOB) were exposed to eluates of three bioactive root canal sealers, GuttaFlow (R) bioseal (GF), BioRoot (TM) RCS (BR), and TotalFill (R) BC Sealer (TF), and the epoxy resin-based sealer AH plus (R) (AH). Cytotoxicity and cellular inflammatory response were evaluated. The osteogenic potential was examined using human mesenchymal stem cells (hMSC). Film thickness, flowability, and pH were assessed. Root canal treatment was performed on human extracted teeth to evaluate the sealers' tightness towards bacterial penetration. The antibacterial activity against common pathogens in primary root canal infections was tested. Results AH was severely cytotoxic to hPDLF and hOB (p < 0.001). The bioactive sealers were generally less cytotoxic. IL-6 levels in hPDLF were elevated in the presence of AH (p < 0.05). AH and GF suppressed IL-6 production in hOB (p < 0.05). AH and BR stimulated the PGE(2) production in hPDLF and hOB (p < 0.05). BR was the only sealer that led to calcium deposits in hMSC (p < 0.05). TF and AH showed the lowest film thickness and the highest flowability. Bacterial tightness was best in teeth filled with AH and BR. All sealers showed similar antimicrobial activity, but the overall antimicrobial efficacy was moderate as the bacteria were reduced by just one log scale (p < 0.05). Conclusions This study revealed favorable in vitro results regarding the biocompatibility of the bioactive root canal sealers

Special Teaching Formats during the COVID-19 Pandemic—A Survey with Implications for a Crisis-Proof Education

Modern teaching formats have not been considered necessary during the COVID-19 pandemic with uncertain acceptance by students. The study’s aim was to describe and evaluate all measures undertaken for theoretical and practical knowledge/skill transfer, which included objective structured practical examinations (OSPEs) covering a communication skills training. The students’ performance in the OSPE as well as the theoretical knowledge level were assessed, of which the latter was compared with previous terms. In conservative dentistry and periodontology (4th and 5th year courses), theoretical teaching formats were provided online and completed by a multiple-choice test. Practical education continued without patients in small groups using the phantom-head, 3D printed teeth, and objective structured practical examinations (OSPEs) including communication skills training. Formats were evaluated by a questionnaire. The organization was rated as very good/good (88.6%), besides poor Internet connection (22.8%) and Zoom® (14.2%) causing problems. Lectures with audio were best approved (1.48), followed by practical videos (1.54), live stream lectures (1.81), treatment checklists (1.81), and virtual problem-based learning (2.1). Lectures such as .pdf files without audio, articles, or scripts were rated worse (2.15–2.30). Phantom-heads were considered the best substitute for patient treatment (59.5%), while additional methodical efforts for more realistic settings led to increased appraisal. However, students performed significantly worse in the multiple-choice test compared to the previous terms (p &lt; 0.0001) and the OSPEs revealed deficits in the students’ communication skills. In the future, permanent available lectures with audio and efforts toward realistic treatment settings in the case of suspended patient treatment will be pursued

The perceived destination image of Indonesia: An assessment on travel blogs written by the industry’s top markets

The tourist gaze theory suggests that tourists are taught by the destination marketing organisation to know how, when, and where to look. However, the birth of travel blogs has challenged this image as they offer the public “unfiltered” information. Travel bloggers have become more powerful in influencing the decision making of potential tourists. This study employs textual and photographic content analysis to investigate the destination image of Indonesia held by the industry’s key markets; Singapore and Australia. 106 blog entries and over 1,500 pictures were content analysed, and the results suggest that overall tourists tended to have positive images of Indonesia. International tourists are still very much concentrated in the traditionally popular places such as Bali and Jakarta. Negative images of Indonesia include inadequate infrastructure, ineffective wildlife protection, and westernisation of Bali. Natural and cultural resources are proven in this thesis to be Indonesia’s top tourism products. Influenced by their cultural backgrounds, Singaporean and Australian bloggers have demonstrated a dissimilar tourist gaze. The current study also analysed the bloggers’ image of Indonesia as opposed to the image projected by the government through the national tourism brand “Wonderful Indonesia”. The results indicate a narrow gap between the two images. Implications for Indonesian tourism practitioners include stronger law enforcement to preserve local culture and natural attractions, and recognising the market’s preference to promote other destinations. Recommendations for future research are discussed