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Aim: To compare the intensity of postoperative pain after primary root canal treatment of asymptomatic teeth when using ultrasonically (UAI) or laser‐activated irrigation (LAI). Methodology: In this superiority randomized clinical trial (ClinicalTrials.gov ID: NCT03981237) with parallel design, fifty‐six patients with an asymptomatic tooth in need of primary root canal treatment were enrolled. After chemo‐mechanical canal preparation using rotary instruments and NaOCl irrigation, teeth were randomly assigned to two groups and patients were blinded to the final irrigation protocol. In the UAI group (n = 28), 60s activation with an Irrisafe tip was done per canal. In the LAI group (n = 28), NaOCl was activated with a pulsed Er:YAG (2940 nm) laser, equipped with a conical tip, with settings of 50 µs, 20 mJ at 15 Hz for 60 s. Patients recorded their pain intensity 6, 24, 48 and 72 h after treatment on a 100 mm visual analogue scale (VAS), as well as their analgesic consumption. Pain levels and incidence were compared across groups using the Mann–Whitney U‐test and chi‐square test. Results: Overall, mean postoperative pain intensity was low, with the majority of patients having no or minimal pain 24 h postoperatively. At 6 h postoperatively, pain intensity and incidence were significantly higher in the UAI group compared to the LAI group (P < 0.05). For the other time intervals, no significant differences in postoperative pain incidence or intensity were found. The frequency of analgesic intake did not differ significantly between the two groups. Neither of the activation methods resulted in any adverse effects. Conclusions: Ultrasonically and laser‐activated irrigation resulted in low and comparable levels of postoperative pain in asymptomatic patients receiving primary root canal treatment. [ABSTRACT FROM AUTHOR]

Piercing of the tongue and perioral regions is an increasingly popular expression of body art, with more patients coming in for a routine check-up with tongue and/or lip piercings. Several complications of oral piercing have been reported, some of which are life-threatening. In the present clinical survey the prevalence of both tongue and lip piercing complications in oral health was assessed in a group of 50 patients. The most common dental problem registered was chipping of the teeth, especially in association with tongue piercing. Gingival recession was seen as a result of lip piercing with studs. Postprocedural complications included oedema, haemorrhage and infection. Therefore, dentists and oral and maxillofacial surgeons should be given more authority to advise patients with oral and facial piercings or those who plan to acquire this type of body art. [ABSTRACT FROM AUTHOR]

Depraet FJHW, De Bruyne MAA, De Moor RJG.The sealing ability of an epoxy resin root canal sealer after Nd:YAG laser irradiation of the root canal.International Endodontic Journal,38,302–309, 2005.To evaluateex vivothe effect of Nd:YAG laser irradiation with and without black ink on instrumented root canal walls, and the degree of both coronal and apical microleakage of filled root canals.Seventy-two single-rooted teeth were instrumented up to a size 40 K-file, and then divided into six groups of 10 teeth: groups 1 and 4 remained unlased and acted as control groups, groups 2 and 5 were treated with a Nd:YAG laser (Fidelis Plus, Herzele, Belgium), groups 3 and 6 were treated with a laser and black ink; the remaining 12 teeth served as positive and negative controls. The laser was operated at 1.5 W, 15 Hz, four times for 5 s with a 20-s interval. Groups 4–6 were filled using cold lateral condensation of gutta-percha and AH26. After storage in water for 48 h at 37 °C, through-and-through leakage (LinμL day−1) was measured for 48 h under a pressure of 1.2 atm using a fluid transport model and recorded asL = 0 (L1), 0 < L ≤ 10 (L2),L > 10 (L3). After the assessment of leakage with the fluid transport model, the teeth were immersed in rhodamine B solution for 48 h at 37 °C. Apical and coronal dye leakage was scored after longitudinal splitting of these teeth. All teeth of groups 1–3 were split longitudinally and observed under SEM for evaluation of remaining smear layer.Through-and-through leakage was only observed in the group lased with black ink (two samples– L2). Apical and coronal dye leakage was observed in all groups; there were no statistically significant differences amongst the three experimental groups. The through-and-through leakage, measured with the fluid transport model in two teeth of group 6, was confirmed in the dye leakage test (rhodamine B dye was observed along the total length of the root filling). There was evidence of melted and ablated root canal dentine in the laser-treated groups. These findings were more obvious in root canals lased in association with black ink. All apical foramina in the lased group remained patent.Nd:YAG laser irradiation with black ink increased the amount of melted and ablated dentine areas compared with that without black ink. Nd:YAG lasing in association with black ink did not result in a reduction of either coronal or apical microleakage in root filled teeth. [ABSTRACT FROM AUTHOR]

De Bruyne MAA, De Moor RJG. The use of glass ionomer cements in both conventional and surgical endodontics. International Endodontic Journal, 37, 91–104, 2004. The capacity to bond to dental tissues, especially to dentine, their long-term fluoride release and their biocompatibility make glass ionomer cements (GICs) advantageous for use in endodontics, as well as in restorative dentistry. This review provides information on the basic properties of GICs, such as adhesion, antimicrobial effects and biocompatibility, particularly as they relate to use in endodontics. Indications for the use of GICs in endodontics are orthograde root canal sealing, root-end filling, repair of perforations and root resorption defects, treatment of vertical fractures and maintenance of the coronal seal. The paper includes a review on each of these indications. It is concluded that in spite of the critical handling characteristics and the inconclusive findings regarding sealing ability and antimicrobial activity, there is substantial evidence to confirm their satisfactory clinical performance. Both soft tissue and bone compatibility make them suitable for use during endodontic surgery. [ABSTRACT FROM AUTHOR]

De Bruyne MAA, De Moor RJG, Raes FM. Necrosis of the gingiva caused by calcium hydroxide: a case report. International Endodontic Journal, 33, 67–71, 2000. Case report The present case demonstrates the possible detrimental effect of an overextension of a calcium hydroxide intracanal dressing into the periradicular and soft tissue after iatrogenic buccal root perforation of a maxillary central incisor. At first this perforation was not recognized by the dentist, which resulted in the introduction of a large amount of non-setting calcium hydroxide paste under the gingival tissues through a dehiscence on the buccal side of the root. This report describes the consequences and management of the necrosis of the buccal gingiva and mucosa, and the subsequent treatment and follow-up of the root perforation. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "A Micro-Computed Tomographic Evaluation of Apical Root Canal Preparation Using Three Instrumentation Techniques."

Abstract Background Olfactory receptors work at the interface between the chemical world of volatile molecules and the perception of scent in the brain. Their main purpose is to translate chemical space into information that can be processed by neural circuits. Assuming that these receptors have evolved to cope with this task, the analysis of their coding strategy promises to yield valuable insight in how to encode chemical information in an efficient way. Results We mimicked olfactory coding by modeling responses of primary olfactory neurons to small molecules using a large set of physicochemical molecular descriptors and artificial neural networks. We then tested these models by recording in vivo receptor neuron responses to a new set of odorants and successfully predicted the responses of five out of seven receptor neurons. Correlation coefficients ranged from 0.66 to 0.85, demonstrating the applicability of our approach for the analysis of olfactory receptor activation data. The molecular descriptors that are best-suited for response prediction vary for different receptor neurons, implying that each receptor neuron detects a different aspect of chemical space. Finally, we demonstrate that receptor responses themselves can be used as descriptors in a predictive model of neuron activation. Conclusion The chemical meaning of molecular descriptors helps understand structure-response relationships for olfactory receptors and their "receptive fields". Moreover, it is possible to predict receptor neuron activation from chemical structure using machine-learning techniques, although this is still complicated by a lack of training data.

Prolonged heart-rate adjusted QT intervals on the electrocardiogram (ECG) are associated with an increased risk for coronary heart disease and sudden death. However, the diagnosis of the prolonged QT interval is hampered by lack of standards. We studied variations in the prevalence of prolonged QT, based on different common definitions, in a large nonhospitalized population, and compared our results with other studies applying the same definitions. The study population consisted of 2,200 men and 3,366 women participants of the Rotterdam Study, > or =55 years old. The QT interval was computed by our Modular ECG Analysis System (MEANS). Three different formulas to adjust QT for heart rate were used: Bazett's formula (QTc), a linear regression equation (QTlr), and the QT index (QTI). Prolonged QT occurred frequently in both men and women, and its prevalence increased with age. Women had longer heart-rate adjusted QT intervals than men (mean QTc 433 ms vs 422 ms), and mean values for QTlr were lower than for QTc (mean QTlr 422 ms in women and 412 ms in men). Prevalence was highest for prolonged QTlr (31% in men and 26% in women) and lowest for prolonged QTI (6% in men and 9% in women). Comparison with other studies applying the same correction formulas showed large discrepancies in prevalence estimates of prolonged QTc and QTlr, and to a lesser degree of prolonged QTI, possibly due to differences in measurement techniques. Future research is needed to relate QT interval to prognosis, to obtain measurement technique specific reference values of heart-rate adjusted QT measurements, and to obtain age- and sex-specific threshold values for prolonged QT. Such data are needed to use the QT interval with confidence. [ABSTRACT FROM AUTHOR]

Purpose: Evaluating the presence of class 3, 4, and 5 genetic variants in inherited retinal disease (IRD) genes in patients with retinopathy of unknown origin (RUO)., Methods: Multicentric retrospective study of RUO cases diagnosed between January 2012 and February 2022. General and ophthalmologic history, complete ophthalmologic examination, antiretinal antibodies, and IRD gene panel results were analyzed in every patient. Four RUO categories were defined: nonparaneoplastic autoimmune retinopathy, unilateral pigmentary retinopathy, asymmetrical pigmentary retinopathy, and acute zonal occult outer retinopathy., Results: The authors included 12 patients (9 females) across these four RUO categories. Mean age at inclusion was 45.6 years (20-68 years). Seven patients demonstrated class 3 variants in IRD genes. Of these, two also demonstrated class 5 variants in other IRD genes. The remaining five patients had negative panel results. IRD gene panel analysis allowed diagnosis refinement in 1 (8.3%) nonparaneoplastic autoimmune retinopathy patient in the RUO cohort. When considering the nonparaneoplastic autoimmune retinopathy subpopulation only, a higher diagnostic yield of 20% (1/5 patients) was achieved., Conclusion: Every suspected nonparaneoplastic autoimmune retinopathy patient should benefit from gene panel testing to not overlook undiagnosed IRDs. By contrast, unilateral pigmentary retinopathy, asymmetrical pigmentary retinopathy, and acute zonal occult outer retinopathy subpopulations did not benefit from genetic testing in this study.

Usher syndrome (USH) is the most common cause of deafblindness. USH is autosomal recessively inherited and characterized by rod-cone dystrophy or retinitis pigmentosa (RP), often accompanied by sensorineural hearing loss. Variants in >15 genes have been identified as causative for clinically and genetically distinct subtypes. Among the ultra-rare and recently discovered genes is ARSG, coding for the lysosomal sulfatase Arylsulfatase G. This subtype was assigned as "USH IV" with a late onset of RP and usually late-onset progressive SNHL without vestibular involvement. Here, we describe nine new subjects and the clinical description of four cases with the USH IV phenotype bearing seven novel and two known pathogenic variants. Functional experiments indicated the complete loss of sulfatase enzymatic activity upon ectopic expression of mutated ARSG cDNA. Interestingly, we identified a homozygous missense variant, p.(Arg99His), previously described in dogs with neuronal ceroid lipofuscinosis. Our study expands the genetic landscape of ARSG-USH IV and the number of known subjects by more than 30%. These findings highlight that USH IV likely has been underdiagnosed and emphasize the need to test molecularly unresolved subjects with deafblindness syndrome. Finally, testing of ARSG should be considered for the genetic work-up of apparent isolated inherited retinal diseases., (© 2024 The Author(s). Clinical Genetics published by John Wiley & Sons Ltd.)

The industrial yeast Komagataella phaffii (formerly named Pichia pastoris) is commonly used to synthesize recombinant proteins, many of which are used as human therapeutics or in food. However, the basic strain, named NRRL Y-11430, from which all commercial hosts are derived, is not available without restrictions on its use. Comparative genome sequencing leaves little doubt that NRRL Y-11430 is derived from a K. phaffii type strain deposited in the UC Davis Phaff Yeast Strain Collection in 1954. We analysed four equivalent type strains in several culture collections and identified the NCYC 2543 strain, from which we started to develop an open-access Pichia chassis strain that anyone can use to produce recombinant proteins to industry standards. NRRL Y-11430 is readily transformable, which we found to be due to a HOC1 open-reading-frame truncation that alters cell-wall mannan. We introduced the HOC1 open-reading-frame truncation into NCYC 2543, which increased the transformability and improved secretion of some but not all of our tested proteins. We provide our genome-sequenced type strain, the hoc1 tr derivative that we named OPENPichia as well as a synthetic, modular expression vector toolkit under liberal end-user distribution licences as an unencumbered OPENPichia resource for the microbial biotechnology community., (© 2024. The Author(s).)

In this study, transmission electron microscopy (TEM) and cryo-scanning electron microscopy (cryo-SEM) were evaluated for their ability to detect lipid bodies in microalgae. To do so, Phaeodactylum tricornutum and Nannochloropsis oculata cells were harvested in both the mid-exponential and early stationary growth phase. Two different cryo-SEM cutting methods were compared: cryo-planing and freeze-fracturing. The results showed that, despite the longer preparation time, TEM visualisation preceded by cryo-immobilisation allows a clear detection of lipid bodies and is preferable to cryo-SEM. Using freeze-fracturing, lipid bodies were rarely detected. This was only feasible if crystalline layers in the internal structure, most likely related to sterol esters or di-saturated triacylglycerols, were revealed. Furthermore, lipid bodies could not be detected using cryo-planing. Cryo-SEM is also not the preferred technique to recognise other organelles besides lipid bodies, yet it did reveal chloroplasts in both species and filament-containing organelles in cryo-planed Nannochloropsis oculata samples., (© 2023 Royal Microscopical Society.)

Background: 5' untranslated regions (5'UTRs) are essential modulators of protein translation. Predicting the impact of 5'UTR variants is challenging and rarely performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and functional assays to evaluate 5'UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs)., Methods: We performed an isoform-level re-analysis of retinal RNA-seq data to identify the protein-coding transcripts of 378 IRD genes with highest expression in retina. We evaluated the coverage of their 5'UTRs by different whole exome sequencing (WES) kits. The selected 5'UTRs were analyzed in whole genome sequencing (WGS) and WES data from IRD sub-cohorts from the 100,000 Genomes Project (n = 2397 WGS) and an in-house database (n = 1682 WES), respectively. Identified variants were annotated for 5'UTR-relevant features and classified into seven categories based on their predicted functional consequence. We developed a variant prioritization strategy by integrating population frequency, specific criteria for each category, and family and phenotypic data. A selection of candidate variants underwent functional validation using diverse approaches., Results: Isoform-level re-quantification of retinal gene expression revealed 76 IRD genes with a non-canonical retina-enriched isoform, of which 20 display a fully distinct 5'UTR compared to that of their canonical isoform. Depending on the probe design, 3-20% of IRD genes have 5'UTRs fully captured by WES. After analyzing these regions in both cohorts, we prioritized 11 (likely) pathogenic variants in 10 genes (ARL3, MERTK, NDP, NMNAT1, NPHP4, PAX6, PRPF31, PRPF4, RDH12, RD3), of which 7 were novel. Functional analyses further supported the pathogenicity of three variants. Mis-splicing was demonstrated for the PRPF31:c.-9+1G>T variant. The MERTK:c.-125G>A variant, overlapping a transcriptional start site, was shown to significantly reduce both luciferase mRNA levels and activity. The RDH12:c.-123C>T variant was found in cis with the hypomorphic RDH12:c.701G>A (p.Arg234His) variant in 11 patients. This 5'UTR variant, predicted to introduce an upstream open reading frame, was shown to result in reduced RDH12 protein but unaltered mRNA levels., Conclusions: This study demonstrates the importance of 5'UTR variants implicated in IRDs and provides a systematic approach for 5'UTR annotation and validation that is applicable to other inherited diseases., (© 2024. The Author(s).)

Background: The Apfel simplified risk score includes four risk factors: female sex, non-smoking status, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use. The score is calculated preoperatively, so postoperative opioid use must be predicted. We aimed to determine whether anaesthetists can predict patients' postoperative opioid use and dose., Methods: Specialist anaesthetists from eight hospitals preoperatively predicted opioid use and dose in the post-anaesthesia care unit (PACU) and for the first 24 h postoperatively, which was compared with actual opioid use and dose. Opioid doses were converted to oral morphine equivalents (MEQ). Correlations between predicted and actual opioid use and dose were analysed with Spearman's rho and linear regression., Results: A total of 487 anaesthetist-patient pairs were included. Anaesthetists overpredicted opioid use (398 [82%] predicted vs 251 [52%] actual patients requiring opioids in the PACU; 396 [81%] predicted vs 291 [60%] actual in the first 24 h) (Spearman's rho [95% confidence interval] 0.24 [0.16-0.33], P <0.001 in the PACU; 0.36 [0.28-0.44], P <0.001 in the first 24 h). Anaesthetists also overpredicted opioid dose (median [inter-quartile range] 12 [8-20] mg predicted MEQ vs 4 [0-18] mg actual MEQ in the PACU; 32 [18-60] mg vs 24 [0-65] mg MEQ in the first 24 h) (Spearman's rho 0.21 [0.13-0.29], P <0.001 in the PACU; 0.53 [0.40-0.60], P <0.001 in the first 24 h)., Conclusions: Specialist anaesthetists cannot accurately predict opioid use or dose in the PACU or the first 24 postoperative hours. The Apfel risk criterion for postoperative opioid use may be inaccurate in clinical practice., (© 2023 The Authors.)

Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing., Competing Interests: PS is an employee of Molecular Loop Biosciences Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Panneman, Hitti-Malin, Holtes, de Bruijn, Reurink, Boonen, Khan, Ali, Andréasson, De Baere, Banfi, Bauwens, Ben-Yosef, Bocquet, De Bruyne, Cerda, Coppieters, Farinelli, Guignard, Inglehearn, Karali, Kjellström, Koenekoop, de Koning, Leroy, McKibbin, Meunier, Nikopoulos, Nishiguchi, Poulter, Rivolta, Rodríguez de la Rúa, Saunders, Simonelli, Tatour, Testa, Thiadens, Toomes, Tracewska, Tran, Ushida, Vaclavik, Verhoeven, van de Vorst, Gilissen, Hoischen, Cremers and Roosing.)

Serial Block Face Scanning Electron Microscopy (SBF-SEM) is one of several volume electron microscopy (vEM) techniques whose purpose is to reveal the nanostructure of cells and tissues in three dimensions. As one of the earliest, and possibly most widely adopted of the disruptive vEM techniques there have been hundreds of publications using the method, although very few comparative studies of specimen preparation parameters. While some studies have focused on staining and specimen acquisition no comparison of resin embedding has yet been conducted. To this end we have surveyed the SBF-SEM literature to determine which resins are commonly used and compared them in both cellular and fixed tissue samples in an attempt to optimize sample preparation for: effectiveness of resin infiltration, resistance to charging and beam damage and clarity of image in the resulting data set. Here we present the results and discuss the various factors that go into optimizing specimen preparation for SBF-SEM., (Copyright © 2023 Elsevier Inc. All rights reserved.)

EMILIN1 (elastin-microfibril-interface-located-protein-1) is a structural component of the elastic fiber network and localizes to the interface between the fibrillin microfibril scaffold and the elastin core. How EMILIN1 contributes to connective tissue integrity is not fully understood. Here, we report bi-allelic EMILIN1 loss-of-function variants causative for an entity combining cutis laxa, arterial tortuosity, aneurysm formation, and bone fragility, resembling autosomal-recessive cutis laxa type 1B, due to EFEMP2 (FBLN4) deficiency. In both humans and mice, absence of EMILIN1 impairs EFEMP2 extracellular matrix deposition and LOX activity resulting in impaired elastogenesis, reduced collagen crosslinking, and aberrant growth factor signaling. Collagen fiber ultrastructure and histopathology in EMILIN1- or EFEMP2-deficient skin and aorta corroborate these findings and murine Emilin1 -/- femora show abnormal trabecular bone formation and strength. Altogether, EMILIN1 connects elastic fiber network with collagen fibril formation, relevant for both bone and vascular tissue homeostasis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)