Identification of dental implant systems from low-quality and distorted dental radiographs using AI trained on a large multi-center dataset.

Most artificial intelligence (AI) studies have attempted to identify dental implant systems (DISs) while excluding low-quality and distorted dental radiographs, limiting their actual clinical use. This study aimed to evaluate the effectiveness of an AI model, trained on a large and multi-center dataset, in identifying different types of DIS in low-quality and distorted dental radiographs. Based on the fine-tuned pre-trained ResNet-50 algorithm, 156,965 panoramic and periapical radiological images were used as training and validation datasets, and 530 low-quality and distorted images of four types (including those not perpendicular to the axis of the fixture, radiation overexposure, cut off the apex of the fixture, and containing foreign bodies) were used as test datasets. Moreover, the accuracy performance of low-quality and distorted DIS classification was compared using AI and five periodontists. Based on a test dataset, the performance evaluation of the AI model achieved accuracy, precision, recall, and F1 score metrics of 95.05%, 95.91%, 92.49%, and 94.17%, respectively. However, five periodontists performed the classification of nine types of DISs based on four different types of low-quality and distorted radiographs, achieving a mean overall accuracy of 37.2 ± 29.0%. Within the limitations of this study, AI demonstrated superior accuracy in identifying DIS from low-quality or distorted radiographs, outperforming dental professionals in classification tasks. However, for actual clinical application of AI, extensive standardization research on low-quality and distorted radiographic images is essential.

Alternative polyadenylation determines the functional landscape of inverted Alu repeats.

Inverted Alu repeats (IRAlus) are abundantly found in the transcriptome, especially in introns and 3' untranslated regions (UTRs). Yet, the biological significance of IRAlus embedded in 3' UTRs remains largely unknown. Here, we find that 3' UTR IRAlus silences genes involved in essential signaling pathways. We utilize J2 antibody to directly capture and map the double-stranded RNA structure of 3' UTR IRAlus in the transcriptome. Bioinformatic analysis reveals alternative polyadenylation as a major axis of IRAlus-mediated gene regulation. Notably, the expression of mouse double minute 2 (MDM2), an inhibitor of p53, is upregulated by the exclusion of IRAlus during UTR shortening, which is exploited to silence p53 during tumorigenesis. Moreover, the transcriptome-wide UTR lengthening in neural progenitor cells results in the global downregulation of genes associated with neurodegenerative diseases, including amyotrophic lateral sclerosis, via IRAlus inclusion. Our study establishes the functional landscape of 3' UTR IRAlus and its role in human pathophysiology.

Unique inverse association between allergic rhinitis and periodontitis: a nationwide population-based study.

The increase in fine dust levels in the atmosphere has been associated with a growth in the incidence of environmental diseases, including allergic rhinitis (AR). Nasal obstruction caused by AR can impact the conditions in the oral cavity. The aim of this study was to determine the association between AR and periodontitis in the Republic of Korea. This study was based on data from the Seventh Korea National Health and Nutrition Examination Survey (KNHANES VII-1, 2016), which was conducted by the Korea Centers for Disease Control and Prevention. The study included 6129 adults older than 19 years. Sociodemographic information and medical variables including history of treatment of periodontitis (HTP) reflecting diagnosis of periodontitis and diagnosis of diseases such as AR were extracted from the data. HTP and AR were reported for 22.81 ± 0.84% (weighted percentage ± standard error) and 15.32 ± 0.63% of the studied population, respectively. A diagnosis of AR was reported for 11.07 ± 1.28% of those with HTP and for 17.55 ± 1.84% of those without HTP. From these, it was inferred that the prevalence of HTP was 1.536-fold higher in the non-AR group than in their counterparts with AR. Significant association was found between AR and HTP among those aged ≤ 64 years and the odds ratio (OR) of AR group for HTP was 0.62 (95% confidence interval:0.44-0.87; P = 0.0057). From this result, it can be inferred that patients diagnosed AR have lower risk of periodontitis.

Suboptimal Mitochondrial Activity Facilitates Nuclear Heat Shock Responses for Proteostasis and Genome Stability.

Thermal stress induces dynamic changes in nuclear proteins and relevant physiology as a part of the heat shock response (HSR). However, how the nuclear HSR is fine-tuned for cellular homeostasis remains elusive. Here, we show that mitochondrial activity plays an important role in nuclear proteostasis and genome stability through two distinct HSR pathways. Mitochondrial ribosomal protein (MRP) depletion enhanced the nucleolar granule formation of HSP70 and ubiquitin during HSR while facilitating the recovery of damaged nuclear proteins and impaired nucleocytoplasmic transport. Treatment of the mitochondrial proton gradient uncoupler masked MRP-depletion effects, implicating oxidative phosphorylation in these nuclear HSRs. On the other hand, MRP depletion and a reactive oxygen species (ROS) scavenger non-additively decreased mitochondrial ROS generation during HSR, thereby protecting the nuclear genome from DNA damage. These results suggest that suboptimal mitochondrial activity sustains nuclear homeostasis under cellular stress, providing plausible evidence for optimal endosymbiotic evolution via mitochondria-to-nuclear communication.

Effect of photodynamic therapy according to differences in photosensitizers on Staphylococcus aureus biofilm on titanium.

PURPOSE: This study aimed to evaluate the antimicrobial effect of photodynamic therapy (PDT) against Staphylococcus aureus biofilm on a titanium surface and to compare the differences in the effect of PDT using toluidine blue O (TBO) and methylene blue (MB) as a photosensitizer. METHODS: The bacterial strain S. aureus ATCC 25,923 was used. Sandblasted and acid-etched (SLA) disks were divided into the following six groups: phosphate buffer saline (PBS), TBO, MB, PBS with laser (PBS + L), TBO with laser (TBO + L), and MB with laser (MB + L). The laser group samples were irradiated by a cold diode laser for 60 s. After treatment, the number of surviving bacteria was calculated by counting the colony-forming units (CFUs) and confocal laser scanning microscopy (CLSM) was applied to observe the bacteria on the disk surface. RESULTS: The TBO + L and MB + L groups showed significantly lower CFU/ml than the other groups (p < 0.01). The TBO + L group showed significantly lower CFU/ml than the MB + L group (p = 0.032). There was no significant difference between the PBS, TBO, MB, and PBS + L groups. Within the limitations of this in vitro study, PDT with TBO and MB can effectively reduce S. aureus biofilm on SLA titanium surfaces. TBO is more effective than MB as a photosensitizer. PDT with TBO may be applied to the treatment of peri­implant disease in the future.

Temporal changes of periodontal tissue pathology in a periodontitis animal model.

PURPOSE: This study aimed to characterize the early stages of periodontal disease and determine the optimal period for its evaluation in a mouse model. The association between the duration of ligation and its effect on the dentogingival area in mice was evaluated using micro-computed tomography (CT) and histological analysis. METHODS: Ninety mice were allocated to an untreated control group or a ligation group in which periodontitis was induced by a 6-0 silk ligation around the left second maxillary molar. Mice were sacrificed at 1, 2, 3, 4, 5, 8, 11, and 14 days after ligature placement. Alveolar bone destruction was evaluated using micro-CT. Histological analysis was performed to assess the immune-inflammatory processes in the periodontal tissue. RESULTS: No significant difference in alveolar bone loss was found compared to the control group until day 3 after ligature placement, and a gradual increase in alveolar bone loss was observed from 4 to 8 days following ligature placement. No significant between-group differences were observed after 8 days. The histological analysis demonstrated that the inflammatory response was evident from day 4. CONCLUSIONS: Our findings in a mouse model provide experimental evidence that ligature-induced periodontitis models offer a consistent progression of disease with marginal attachment down-growth, inflammatory infiltration, and alveolar bone loss.

Long-term effect of implant-abutment connection type on marginal bone loss and survival of dental implants.

PURPOSE: This study aimed to compare the long-term survival rate and peri-implant marginal bone loss between different types of dental implant-abutment connections. METHODS: Implants with external or internal abutment connections, which were fitted at Gangneung-Wonju National University Dental Hospital from November 2011 to December 2015 and followed up for >5 years, were retrospectively investigated. Cumulative survival rates were evaluated for >5 years, and peri-implant marginal bone loss was evaluated at 1- and 5-year follow-up examinations after functional loading. RESULTS: The 8-year cumulative survival rates were 93.3% and 90.7% in the external and internal connection types, respectively (P=0.353). The mean values of marginal bone loss were 1.23 mm (external) and 0.72 mm (internal) (P<0.001) after 1 year of loading, and 1.20 mm and 1.00 mm for external and internal abutment connections, respectively (P=0.137) after 5 years. Implant length (longer, P=0.018), smoking status (heavy, P=0.001), and prosthetic type (bridge, P=0.004) were associated with significantly greater marginal bone loss, and the use of screw-cement-retained prosthesis was significantly associated (P=0.027) with less marginal bone loss. CONCLUSIONS: There was no significant difference in the cumulative survival rate between implants with external and internal abutment connections. After 1 year of loading, marginal bone loss was greater around the implants with an external abutment connection. However, no significant difference between the external and internal connection groups was found after 5 years. Both types of abutment connections are viable treatment options for the reconstruction of partially edentulous ridges.

Deep learning improves implant classification by dental professionals: a multi-center evaluation of accuracy and efficiency.

PURPOSE: The aim of this study was to evaluate and compare the accuracy performance of dental professionals in the classification of different types of dental implant systems (DISs) using panoramic radiographic images with and without the assistance of a deep learning (DL) algorithm. METHODS: Using a self-reported questionnaire, the classification accuracy of dental professionals (including 5 board-certified periodontists, 8 periodontology residents, and 31 dentists not specialized in implantology working at 3 dental hospitals) with and without the assistance of an automated DL algorithm were determined and compared. The accuracy, sensitivity, specificity, confusion matrix, receiver operating characteristic (ROC) curves, and area under the ROC curves were calculated to evaluate the classification performance of the DL algorithm and dental professionals. RESULTS: Using the DL algorithm led to a statistically significant improvement in the average classification accuracy of DISs (mean accuracy: 78.88%) compared to that without the assistance of the DL algorithm (mean accuracy: 63.13%, P<0.05). In particular, when assisted by the DL algorithm, board-certified periodontists (mean accuracy: 88.56%) showed higher average accuracy than did the DL algorithm, and dentists not specialized in implantology (mean accuracy: 77.83%) showed the largest improvement, reaching an average accuracy similar to that of the algorithm (mean accuracy: 80.56%). CONCLUSIONS: The automated DL algorithm classified DISs with accuracy and performance comparable to those of board-certified periodontists, and it may be useful for dental professionals for the classification of various types of DISs encountered in clinical practice.

Antimicrobial photothermal therapy using diode laser with indocyanine green on Streptococcus gordonii biofilm attached to zirconia surface.

PURPOSE: The purpose of this study was to evaluate the antimicrobial effects of photothermal therapy using indocyanine green (ICG) and an 810-nm infrared diode laser on Streptococcus gordonii biofilm attached to zirconia surfaces in vitro. METHODS: A biofilm was formed using the static method on zirconia disks placed in a 24-well plate. The biofilms were subdivided into the following six treatment groups: control, commercial photodynamic therapy (PDT), chlorhexidine gluconate (CHX), laser only (L, 810-nm infrared diode), ICG, and laser with ICG (PTT). After treatment, each disk was agitated and the solution with detached bacteria was spread directly on a blood agar plate. Cells were cultured under anaerobic conditions and colony-forming units were counted. Confocal laser-scanning microscopy was used to assess the survival according to the height of the biofilm. RESULTS: The PTT, PDT, and CHX groups showed a significant reduction in S. gordonii viability (p<0.05), while the L and ICG groups showed no significant difference compared to the control group (p = 0.32, p = 0.97; respectively). In confocal laser-scanning microscopy images, the PTT, PDT, and CHX groups presented most of the dead bacteria in both the upper and lower levels of biofilm. CONCLUSION: Within the limitations of this in vitro study, PTT with ICG was effective in significantly reducing the viability of S. gordonii bacteria on zirconia. Further studies are needed to establish a standardized PTT protocol to treat peri­implant diseases.

The E3 ubiquitin ligase adaptor Tango10 links the core circadian clock to neuropeptide and behavioral rhythms.

Circadian transcriptional timekeepers in pacemaker neurons drive profound daily rhythms in sleep and wake. Here we reveal a molecular pathway that links core transcriptional oscillators to neuronal and behavioral rhythms. Using two independent genetic screens, we identified mutants of Transport and Golgi organization 10 (Tango10) with poor behavioral rhythmicity. Tango10 expression in pacemaker neurons expressing the neuropeptide PIGMENT-DISPERSING FACTOR (PDF) is required for robust rhythms. Loss of Tango10 results in elevated PDF accumulation in nerve terminals even in mutants lacking a functional core clock. TANGO10 protein itself is rhythmically expressed in PDF terminals. Mass spectrometry of TANGO10 complexes reveals interactions with the E3 ubiquitin ligase CULLIN 3 (CUL3). CUL3 depletion phenocopies Tango10 mutant effects on PDF even in the absence of the core clock gene timeless Patch clamp electrophysiology in Tango10 mutant neurons demonstrates elevated spontaneous firing potentially due to reduced voltage-gated Shaker-like potassium currents. We propose that Tango10/Cul3 transduces molecular oscillations from the core clock to neuropeptide release important for behavioral rhythms.

Metabolic flux from the Krebs cycle to glutamate transmission tunes a neural brake on seizure onset.

Kohlschütter-Tönz syndrome (KTS) manifests as neurological dysfunctions, including early-onset seizures. Mutations in the citrate transporter SLC13A5 are associated with KTS, yet their underlying mechanisms remain elusive. Here, we report that a Drosophila SLC13A5 homolog, I'm not dead yet (Indy), constitutes a neurometabolic pathway that suppresses seizure. Loss of Indy function in glutamatergic neurons caused "bang-induced" seizure-like behaviors. In fact, glutamate biosynthesis from the citric acid cycle was limiting in Indy mutants for seizure-suppressing glutamate transmission. Oral administration of the rate-limiting α-ketoglutarate in the metabolic pathway rescued low glutamate levels in Indy mutants and ameliorated their seizure-like behaviors. This metabolic control of the seizure susceptibility was mapped to a pair of glutamatergic neurons, reversible by optogenetic controls of their activity, and further relayed onto fan-shaped body neurons via the ionotropic glutamate receptors. Accordingly, our findings reveal a micro-circuit that links neural metabolism to seizure, providing important clues to KTS-associated neurodevelopmental deficits.

ZNF598 co-translationally titrates poly(GR) protein implicated in the pathogenesis of C9ORF72-associated ALS/FTD.

C9ORF72-derived dipeptide repeat proteins have emerged as the pathogenic cause of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). However, the mechanisms underlying their expression are not fully understood. Here, we demonstrate that ZNF598, the rate-limiting factor for ribosome-associated quality control (RQC), co-translationally titrates the expression of C9ORF72-derived poly(GR) protein. A Drosophila genetic screen identified key RQC factors as potent modifiers of poly(GR)-induced neurodegeneration. ZNF598 overexpression in human neuroblastoma cells inhibited the nuclear accumulation of poly(GR) protein and decreased its cytotoxicity, whereas ZNF598 deletion had opposing effects. Poly(GR)-encoding sequences in the reporter RNAs caused translational stalling and generated ribosome-associated translation products, sharing molecular signatures with canonical RQC substrates. Furthermore, ZNF598 and listerin 1, the RQC E3 ubiquitin-protein ligase, promoted poly(GR) degradation via the ubiquitin-proteasome pathway. An ALS-relevant ZNF598R69C mutant displayed loss-of-function effects on poly(GR) expression, as well as on general RQC. Moreover, RQC function was impaired in C9-ALS patient-derived neurons, whereas lentiviral overexpression of ZNF598 lowered their poly(GR) expression and suppressed proapoptotic caspase-3 activation. Taken together, we propose that an adaptive nature of the RQC-relevant ZNF598 activity allows the co-translational surveillance to cope with the atypical expression of pathogenic poly(GR) protein, thereby acquiring a neuroprotective function in C9-ALS/FTD.

The trinity of ribosome-associated quality control and stress signaling for proteostasis and neuronal physiology.

Translating ribosomes accompany co-translational regulation of nascent polypeptide chains, including subcellular targeting, protein folding, and covalent modifications. Ribosome-associated quality control (RQC) is a co-translational surveillance mechanism triggered by ribosomal collisions, an indication of atypical translation. The ribosome-associated E3 ligase ZNF598 ubiquitinates small subunit proteins at the stalled ribosomes. A series of RQC factors are then recruited to dissociate and triage aberrant translation intermediates. Regulatory ribosomal stalling may occur on endogenous transcripts for quality gene expression, whereas ribosomal collisions are more globally induced by ribotoxic stressors such as translation inhibitors, ribotoxins, and UV radiation. The latter are sensed by ribosome-associated kinases GCN2 and ZAKα, activating integrated stress response (ISR) and ribotoxic stress response (RSR), respectively. Hierarchical crosstalks among RQC, ISR, and RSR pathways are readily detectable since the collided ribosome is their common substrate for activation. Given the strong implications of RQC factors in neuronal physiology and neurological disorders, the interplay between RQC and ribosome-associated stress signaling may sustain proteostasis, adaptively determine cell fate, and contribute to neural pathogenesis. The elucidation of underlying molecular principles in relevant human diseases should thus provide unexplored therapeutic opportunities. [BMB Reports 2021; 54(9): 439-450].

A Performance Comparison between Automated Deep Learning and Dental Professionals in Classification of Dental Implant Systems from Dental Imaging: A Multi-Center Study.

In this study, the efficacy of the automated deep convolutional neural network (DCNN) was evaluated for the classification of dental implant systems (DISs) and the accuracy of the performance was compared against that of dental professionals using dental radiographic images collected from three dental hospitals. A total of 11,980 panoramic and periapical radiographic images with six different types of DISs were divided into training (n = 9584) and testing (n = 2396) datasets. To compare the accuracy of the trained automated DCNN with dental professionals (including six board-certified periodontists, eight periodontology residents, and 11 residents not specialized in periodontology), 180 images were randomly selected from the test dataset. The accuracy of the automated DCNN based on the AUC, Youden index, sensitivity, and specificity, were 0.954, 0.808, 0.955, and 0.853, respectively. The automated DCNN outperformed most of the participating dental professionals, including board-certified periodontists, periodontal residents, and residents not specialized in periodontology. The automated DCNN was highly effective in classifying similar shapes of different types of DISs based on dental radiographic images. Further studies are necessary to determine the efficacy and feasibility of applying an automated DCNN in clinical practice.

A sleep-like state in Hydra unravels conserved sleep mechanisms during the evolutionary development of the central nervous system.

Sleep behaviors are observed even in nematodes and arthropods, yet little is known about how sleep-regulatory mechanisms have emerged during evolution. Here, we report a sleep-like state in the cnidarian Hydra vulgaris with a primitive nervous organization. Hydra sleep was shaped by homeostasis and necessary for cell proliferation, but it lacked free-running circadian rhythms. Instead, we detected 4-hour rhythms that might be generated by ultradian oscillators underlying Hydra sleep. Microarray analysis in sleep-deprived Hydra revealed sleep-dependent expression of 212 genes, including cGMP-dependent protein kinase 1 (PRKG1) and ornithine aminotransferase. Sleep-promoting effects of melatonin, GABA, and PRKG1 were conserved in Hydra However, arousing dopamine unexpectedly induced Hydra sleep. Opposing effects of ornithine metabolism on sleep were also evident between Hydra and Drosophila, suggesting the evolutionary switch of their sleep-regulatory functions. Thus, sleep-relevant physiology and sleep-regulatory components may have already been acquired at molecular levels in a brain-less metazoan phylum and reprogrammed accordingly.

Correlation analysis of gingival recession after orthodontic treatment in the anterior region: an evaluation of soft and hard tissues.

PURPOSE: The aim of this study was to investigate and identify the main causes of periodontal tissue change associated with labial gingival recession by examining the anterior region of patients who underwent orthodontic treatment. METHODS: In total, 45 patients who had undergone orthodontic treatment from January 2010 to December 2015 were included. Before and after the orthodontic treatment, sectioned images from 3-dimensional digital model scanning and cone-beam computed tomography images in the same region were superimposed to measure periodontal parameters. The initial labial gingival thickness (IGT) and the initial labial alveolar bone thickness (IBT) were measured at 4 mm below the cementoenamel junction (CEJ), and the change of the labial gingival margin was defined as the change of the distance from the CEJ to the gingival margin. Additionally, the jaw, tooth position, tooth inclination, tooth rotation, and history of orthognathic surgery were investigated to determine the various factors that could have affected anterior periodontal tissue changes. RESULTS: The mean IGT and IBT were 0.77±0.29 mm and 0.77±0.32 mm, respectively. The mean gingival recession was 0.14±0.57 mm. Tooth inclination had a significant association with gingival recession, and as tooth inclination increased labially, gingival recession increased by approximately 0.2 mm per 1°. CONCLUSIONS: In conclusion, the IGT, IBT, tooth position, tooth rotation, and history of orthognathic surgery did not affect labial gingival recession. However, tooth inclination showed a significant association with labial gingival recession of the anterior teeth after orthodontic treatment.

Soft tissue expander for vertically atrophied alveolar ridges: Prospective, multicenter, randomized controlled trial.

OBJECTIVES: Conventional guided bone regeneration (GBR) limits the amount of bone graft due to limited soft tissue expansion. We hypothesize that the use of tissue expander will successfully augment soft tissue prior to bone graft, allowing for sufficient amount of grafting which will lead to a more stable and effective vertical bone graft. The authors aimed to evaluate effectiveness of the novel self-inflating tissue expander for vertical augmentation in terms of soft tissue expansion, clinical outcomes, and related complications. MATERIAL AND METHODS: A prospective, multicenter, randomized controlled trial was performed on patients requiring vertical augmentation. For experimental group patients, the tissue expander was subperiosteally implanted and followed by a tunneling bone graft without full flap reflection. Control patients underwent conventional vertical GBR. Primary objectives were to evaluate the dimensional changes of soft tissue and radiographic vertical bone gain and retention. As a secondary outcome, clinical complications and thickness changes of expanded overlying tissue were assessed and analyzed. RESULTS: Twenty-three patients in each group were included. During a 4-week expansion, two of the experimental group showed over-expansion and one showed mucosal perforation associated with previous severe scars. The other patients showed uneventful expansion and mean tissue augmentation was 6.88 ± 1.64 mm vertically. Ultrasonographic measurements of overlying gingiva revealed no thinning after tissue expansion (p > .05). Significantly higher vertical bone gain was shown in the experimental group (5.12 ± 1.25 mm) compared with that in the control patients (4.22 ± 1.15 mm; p < .05). After a 6-month retention period, the mean vertical bone measurement of the controls had decreased to 1.90 mm (55.0% reduction), which was a significantly greater decrease than that in the experimental group (mean 3.55 mm, 30.7% reduction; p < .05). CONCLUSION: Our results demonstrated the effectiveness of tissue expanders followed by tunneling bone graft for vertical augmentation; however, studies comparing the two techniques without tissue expanders are needed to elucidate the net effect of tissue expansion.

Evaluation of prognosis related to compliance with supportive periodontal treatment in patients with chronic periodontitis: a clinical retrospective study.

PURPOSE: The purpose of this study was to evaluate the prognostic effect of patient compliance with supportive periodontal treatment (PC-SPT). Chronic periodontitis patients were classified based on their compliance level, and factors affecting PC-SPT and the prognosis of PC-SPT were investigated. METHODS: This study selected 206 patients who started SPT after receiving periodontal treatment between 2010 and 2012. Patients who continued SPT through February 2016 were included. The patients were classified according to whether they exhibited complete compliance (100% of visits), excellent compliance (≥70% of visits), incomplete compliance (<70% of visits), or non-compliance (only 2 visits). Patient characteristics that could affect PC-SPT, such as age, sex, distance of the clinic from their residence, implantation, and periodontal treatment, were investigated. The number of newly decayed and extracted teeth, alveolar bone level changes around the teeth and implants, and implant removal were examined to evaluate the prognosis of PC-SPT. RESULTS: Sex and the presence of an implant significantly affected PC-SPT. Additionally, the number of newly decayed and extracted teeth and changes in alveolar bone levels around the teeth and implants were significant prognostic factors related to PC-SPT. CONCLUSIONS: PC-SPT in chronic periodontitis patients will help maintain periodontal health and prevent further periodontal disease.

Drosophila CrebB is a Substrate of the Nonsense-Mediated mRNA Decay Pathway that Sustains Circadian Behaviors.

Post-transcriptional regulation underlies the circadian control of gene expression and animal behaviors. However, the role of mRNA surveillance via the nonsense-mediated mRNA decay (NMD) pathway in circadian rhythms remains elusive. Here, we report that Drosophila NMD pathway acts in a subset of circadian pacemaker neurons to maintain robust 24 h rhythms of free-running locomotor activity. RNA interference-mediated depletion of key NMD factors in timeless-expressing clock cells decreased the amplitude of circadian locomotor behaviors. Transgenic manipulation of the NMD pathway in clock neurons expressing a neuropeptide PIGMENT-DISPERSING FACTOR (PDF) was sufficient to dampen or lengthen free-running locomotor rhythms. Confocal imaging of a transgenic NMD reporter revealed that arrhythmic Clock mutants exhibited stronger NMD activity in PDF-expressing neurons than wild-type. We further found that hypomorphic mutations in Suppressor with morphogenetic effect on genitalia 5 (Smg5 ) or Smg6 impaired circadian behaviors. These NMD mutants normally developed PDF-expressing clock neurons and displayed daily oscillations in the transcript levels of core clock genes. By contrast, the loss of Smg5 or Smg6 function affected the relative transcript levels of cAMP response element-binding protein B (CrebB ) in an isoform-specific manner. Moreover, the overexpression of a transcriptional repressor form of CrebB rescued free-running locomotor rhythms in Smg5-depleted flies. These data demonstrate that CrebB is a rate-limiting substrate of the genetic NMD pathway important for the behavioral output of circadian clocks in Drosophila.

Characteristics of Local Delivery Agents for Treating Peri-Implantitis on Dental Implant Surfaces: A Preclinical Study.

Local delivery agents (LDAs) are widely used in peri-implantitis treatments. The aim of this study was to identify LDAs remaining on the dental implant surfaces and to analyze the components of these residues after applying various cleaning methods. Implants were prepared with a sand-blasted, large-grit, acid-etched surface. Four kinds of LDAs were applied on the implant surfaces: chlorhexidine gel (group 2), tetracycline solution (group 3), and 2 kinds of minocycline hydrochloride agents (groups 4 and 5). Group 1 received normal saline as a control. Two cleaning methods were applied for different durations as follows: (1) running distilled water for 10 seconds (subgroup A), 5 minutes (subgroup B), and 15 minutes (subgroup C); and (2) water spray of a dental-unit chair for 10 seconds (subgroup D) and 5 minutes (subgroup E). Scanning electron microscopy and energy-dispersive x-ray spectroscopy were used to analyze the surface morphology and residue components for all implants. The amount of LDA removed from the implant surfaces in groups 1, 2, 3, and 5 increased with the cleaning duration and pressure. However, Minocline remained coated on the implant surfaces in group 4 under all cleaning conditions. Minocline could not be cleaned off well by water due to its hydrophobicity. Therefore, directly using this agent on implant surfaces with peri-implantitis should be carefully considered. The presence of LDA residues without drug efficacies on implant surfaces might interfere with reosseointegration and act as a reservoir of microorganisms.