A comparison of skeletal and dental changes in patients with a Class II relationship treated with clear aligner mandibular advancement and Herbst appliance followed by comprehensive orthodontic treatment.

INTRODUCTION: The objective of this study was to compare the skeletal and dental changes of patients with a Class II relationship treated with clear aligner mandibular advancement (MA) and Herbst appliances followed by comprehensive orthodontic treatment. METHODS: The participants included 20 patients treated with MA and 20 with the Herbst appliance. Orthodontic records were taken before treatment, after the functional appliance, and completion of phase II treatment. The skeletal and dental changes across the 3-time periods were evaluated using a matched paired t test for each treatment. A 2-sample t test was used to examine the changes across periods between 2 treatment groups (P <0.05). RESULTS: Significant reduction in overjet, overbite, and change in molar relationship were obtained by both appliances with similar skeletal and dental contributions. This was contributed by a forward movement of the mandible and mandibular molars, backward movement of the maxillary molars, and retraction of the maxillary incisors. After phase II treatment, both appliances could maintain the skeletal and dental changes achieved during the advancement phase. Greater change in overbite (2.4 mm vs 1.4 mm), an eruption of maxillary incisors (0.9 mm vs 0.1 mm), and proclination of mandibular incisors were found with the Herbst group (3.9° vs -2.1°). The average total treatment time was similar with the 2 appliances. CONCLUSIONS: Both functional appliances were equally effective in reducing the overjet and overbite and achieving a Class I molar relationship with a similar length of treatment time. The Herbst design lacked control of the mandibular incisor proclination, and clear aligners offered better vertical control and management of the mandibular incisor inclination.

Improved functional status in patients undergoing cement and rebar reconstruction with total hip arthroplasty for uncontained metastatic tumors of the acetabulum.

BACKGROUND AND OBJECTIVE: Metastatic cancer of the acetabulum can produce marked pain and disability for patients. Several reconstruction techniques for such lesions have been described, with variable outcomes. The purpose of this study was to determine functional outcomes and complication rate for patients undergoing cement rebar reconstruction using posterior column screws with total hip arthroplasty for large, uncontained lesions of the acetabulum. METHODS: Twenty-two consecutive patients who underwent cement rebar reconstruction with posterior column screws and total hip arthroplasty for metastatic tumors of the acetabulum between 2014 and 2017 were identified. All cases were reviewed for patient demographics, surgical parameters, implant survival, complications, and functional status following these procedures. RESULTS: There was a significant increase in the proportion of patients able to ambulate post-surgery (95.5%) compared with presurgery (22.7%) (p < 0.001). Mean musculoskeletal tumor society score postoperatively was 17.9 (60%). Average operative time was 174 min and average estimated blood loss was 689 mL. Seven patients required an intraoperative or postoperative blood transfusion. Three patients had postoperative complications (14%), two of whom required revision (9%). CONCLUSION: Reconstruction using cement rebar with posterior column screws and total hip arthroplasty is a safe, reproducible approach that may greatly improve functional outcomes with a low rate of intraoperative or postoperative complications.

Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer.

The mutant form of the GTPase KRAS is a key driver of pancreatic cancer but remains a challenging therapeutic target. Exosomes are extracellular vesicles generated by all cells, and are naturally present in the blood. Here we show that enhanced retention of exosomes, compared to liposomes, in the circulation of mice is likely due to CD47-mediated protection of exosomes from phagocytosis by monocytes and macrophages. Exosomes derived from normal fibroblast-like mesenchymal cells were engineered to carry short interfering RNA or short hairpin RNA specific to oncogenic KrasG12D, a common mutation in pancreatic cancer. Compared to liposomes, the engineered exosomes (known as iExosomes) target oncogenic KRAS with an enhanced efficacy that is dependent on CD47, and is facilitated by macropinocytosis. Treatment with iExosomes suppressed cancer in multiple mouse models of pancreatic cancer and significantly increased overall survival. Our results demonstrate an approach for direct and specific targeting of oncogenic KRAS in tumours using iExosomes.

Detection of the pathological exposure of pulp using an artificial intelligence tool: a multicentric study over periapical radiographs.

BACKGROUND: Introducing artificial intelligence (AI) into the medical field proved beneficial in automating tasks and streamlining the practitioners' lives. Hence, this study was conducted to design and evaluate an AI tool called Make Sure Caries Detector and Classifier (MSc) for detecting pathological exposure of pulp on digital periapical radiographs and to compare its performance with dentists. METHODS: This study was a diagnostic, multi-centric study, with 3461 digital periapical radiographs from three countries and seven centers. MSc was built using Yolov5-x model, and it was used for exposed and unexposed pulp detection. The dataset was split into a train, validate, and test dataset; the ratio was 8-1-1 to prevent overfitting. 345 images with 752 labels were randomly allocated to test MSc. The performance metrics used to test MSc performance included mean average precision (mAP), precision, F1 score, recall, and area under receiver operating characteristic curve (AUC). The metrics used to compare the performance with that of 10 certified dentists were: right diagnosis exposed (RDE), right diagnosis not exposed (RDNE), false diagnosis exposed (FDE), false diagnosis not exposed (FDNE), missed diagnosis (MD), and over diagnosis (OD). RESULTS: MSc achieved a performance of more than 90% in all metrics examined: an average precision of 0.928, recall of 0.918, F1-score of 0.922, and AUC of 0.956 (P<.05). The results showed a higher mean of 1.94 for all right (correct) diagnosis parameters in MSc group, while a higher mean of 0.64 for all wrong diagnosis parameters in the dentists group (P<.05). CONCLUSIONS: The designed MSc tool proved itself reliable in the detection and differentiating between exposed and unexposed pulp in the internally validated model. It also showed a better performance for the detection of exposed and unexposed pulp when compared to the 10 dentists' consensus.

Characterization of Microplastic-Associated Biofilm Development along a Freshwater-Estuarine Gradient.

Microplastic contamination is an increasing concern worldwide. Biofilms rapidly develop on surfaces in aquatic habitats, but the processes of biofilm formation and variation in bacterial community succession on different microplastics introduced into freshwater and estuarine environments are not well understood. In this study, the biofilm bacterial communities that developed on three different types of microplastics that are prevalent in the environment, high-density polyethylene (HDPE), polyethylene terephthalate (PET), and polystyrene (PS), was investigated. Virgin microplastics were incubated in microcosms over a period of 31 days with water collected along a freshwater-estuarine gradient of the Raritan River in New Jersey. Through long-read MinION sequencing of bacterial ribosomal operons, we were able to examine biofilm bacterial communities at a species- and strain-level resolution. Results indicated that both salinity level and microplastic type impacted biofilm formation and promoted colonization by distinct microbial communities. Limnobacter thiooxidans was found to be one of the most abundant microplastics colonizing-bacteria, and it is hypothesized that different types of microplastics could select for different strains. Our findings indicate that multiple groups of highly similar L. thiooxidans rRNA operons could be discerned within the community profiles. Phylogenetic reconstruction further established that various Linmobacter species uniquely colonized the different microplastics from the different sampling sites. Our findings indicate that microplastics support abundant and diverse bacterial communities and that the various types of microplastics can influence how different bacterial biofilms develop, which may have ecological impacts on aquatic ecosystems.

Investigation of the optimal medium and application strategy for foot-and-mouth disease vaccine antigen production.

AIMS: For the effective production of 146S particles, which determines foot-and-mouth disease (FMD) vaccine efficacy, we aimed to identify the optimal medium that is easy-to-use, productive and economically affordable for the large-scale production of FMD vaccine. METHODS AND RESULTS: Nine combinations of cell growth media and replacement media were tested for virus propagation. Apart from the replacement strategy, we tested a simple addition strategy involving the addition of 30% v/v of fresh medium to the total spent medium using the Cellvento BHK-200 (Vento). Unlike other tested media that produced poor yields of 146S particles when the spent media were not eliminated, Vento exhibited high productivity with the 30% addition strategy. CONCLUSIONS: Considering its lower price and media consumption compared to those of other media that require media replacement, the 30% addition strategy of Vento is highly effective. Furthermore, owing to its simple application strategy, it makes the scale-up process easy and helps in saving the time and labour involved in spent media removal. SIGNIFICANCE AND IMPACT OF THE STUDY: Through the first comparative assessment of commercial media for the 146S particle recovery, this study suggests the best practical medium for the industrial-scale production of FMD vaccines.

A case of oral foreign-body granuloma due to diatoms.

Diatoms are photosynthetic algae with a siliceous exoskeleton. Diatoms are utilized by a wide array of industries for applications such as filtration and pest control. Unsubstantiated claims have also propelled their societal reach to trendy oral and topical uses. This case highlights a rare case of an oral granuloma secondary to diatoms. An 80-year-old woman presented with a mobile, firm, asymptomatic submucosal mass on her lower left mandibular vestibular mucosa. Histopathology showed a non-caseating granulomatous reaction to diatoms. Her only verified contact with a diatomaceous earth product was a dental impression using alginate after upper front teeth trauma 5 months before. Although there have been several cases of allergic contact dermatitis attributed to diatoms, there are no reported cases of diatom-induced granuloma formation found in the literature. There are, however, ample data on granulomas initiated by silica. Given the silica-based composition of diatoms, and the broad use of diatoms in industry and alternative medicine, it is unclear why diatom-induced granulomas are not more widely described. This report may alert clinicians to the existence of diatom granulomas and incline them to tailor their history to cover questions about possible exposure when evaluating patients presenting with a localized oral lesion.

STIM1 knock-down decreases the affinity of obinutuzumab for CD20 by altering CD20 localization to Triton-soluble membrane.

Obinutuzumab is thought to exert its effects through its high antibody-dependent cellular cytotoxicity (ADCC) via glyco-engineering of the Fc region. In addition, obinutuzumab causes direct binding-induced cell death (DCD) only by specifically binding to its target CD20, a Ca2+ channel. However, the specific features of CD20 related to obinutuzumab binding-induction of cell death are not clearly understood. In this study, we evaluated the relationship between the Ca2+ channel features of CD20 as a store-operated Ca2+ channel (SOC) and obinutuzumab binding-induced cell death. Ca2+ channel function and biochemical analysis revealed that CD20 is an Orai1- and stromal interaction molecule (STIM1)-dependent Ca2+ pore. However, binding of obinutuzumab on CD20 did not have any effect on Ca2+ influx activity of CD20; the direct cell death rate mediated by obinutuzumab binding was almost equivalent with or without the extracellular Ca2+ condition. Given the apparent interaction between STIM1 and CD20, we observed Triton-X solubilized obinutuzumab-bound CD20 accompanied by STIM1. Subsequently, obinutuzumab binding and cell death were decreased by STIM1 knock-down in Ramos B cells. Thus, STIM1 directly contributes to cell death by increasing the affinity of cells for obinutuzumab by transferring CD20 to the Triton-soluble membrane region.

A novel mobile application to determine mandibular and tongue laterality discrimination in women with chronic temporomandibular disorder.

BACKGROUND: Chronic pain from temporomandibular disorders (TMDs) is caused by a somatosensory disturbance due to sustained activation of central nervous system nociceptive pathways, which can induce changes in neuroplasticity in the thalamus, basal ganglia and limbic system, as well as disturbances in the somatosensory, prefrontal and orbitofrontal cortex and cognitive impairment. The main objective of this study was to determine the discrimination capacity of mandibular and tongue laterality between women with chronic TMDs and asymptomatic women. MATERIAL AND METHODS: This descriptive-comparative study examined 2 groups with a total of 30 women. All participants were between the ages of 23 and 66 years and were assigned to the chronic TMD group or the asymptomatic group according to the inclusion criteria. We employed a mobile application developed specifically for this study to measure the accuracy and reaction time (RT) of mandibular and tongue laterality discrimination. RESULTS: The chronic TMD group had a lower success rate in laterality discrimination (mean mandibular accuracy of 40% and mean tongue accuracy of 67%) than the asymptomatic group (mean mandibular accuracy of 61% and mean tongue accuracy of 90%). These results showed statistically significant differences between the groups for mandibular laterality discrimination (d, 1.14; p<0.01) and tongue laterality discrimination (d, 0.79; p=0.03). The asymptomatic group had faster RTs than the chronic TMD group. The data revealed statistically significant differences for the right mandibular RT (d, 0.89; p=0.02) and right tongue RT (d, 0.83; p=0.03). However, there were no significant differences for left mandibular and left tongue RT. CONCLUSIONS: We found that the women with chronic TMDs had a lower success rate and slower RTs in the discrimination of mandibular laterality when compared with the asymptomatic women.

Investigation of the esthetic outcomes of white spot lesion treatments.

OBJECTIVE: The present study compared the ability of bleaching, resin infiltration and microabrasion to restore the appearance of existing white spot lesions (WSL) on tooth surfaces as close as possible to that of the original healthy enamel. MATERIALS AND METHODS: Sixty extracted human teeth with WSL were randomly assigned to three treatment groups (20/group). Prior to treatment, the colour of the surrounding healthy enamel and the WSL were measured as the baseline and pre-treatment (PreRX) colours respectively using spectrophotometer based on CIE L*A*B. The L-value was used for the statistical comparison. WSLs in each group were treated respectively by bleaching, infiltration or microabrasion following the manufacturer's instructions. Colour measurement was repeated after treatment. Both intragroup and intergroup comparisons were performed using ANOVA followed by Tukey's multiple comparison test (α=0.05). RESULT: In all groups the mean L-values were significantly higher in PreRX WSL (P < 0.01; Tukey) compared to baseline (sound enamel). After treatment the difference in mean L-value between baseline and WSL increased significantly (P < 0.01, Tukey) in Bleaching and Microabrasion groups by 1.4% and 1% respectively, but decreased in Infiltration group by 3.4%. Thus resin infiltration decreased the L-value of the WSL, bringing it closer to the L-value of the sound enamel while bleaching and microabrasion increased the L-value. CONCLUSIONS: Among the three treatment modalities investigated in this study, resin infiltration was the most effective in masking the WSLs.

New bracketing luminescence ages constrain the Sima de los Huesos hominin fossils (Atapuerca, Spain) to MIS 12.

Recent chronological studies of the Sima de los Huesos (SH) hominin fossil site, Atapuerca, Spain, have established a close minimum age of at least 430 ka for sedimentary material immediately overlying the human remains. However, a firm maximum age limit still needs to be established for the SH fossils in order to better constrain the timing for the onset of Neandertal speciation. In the present study, we address this important chronological gap at SH by providing direct ages for the sediment deposits that host, and immediately underlie, the hominin fossils. Depositional ages were obtained using single-grain thermally-transferred optically stimulated luminescence (TT-OSL), a technique that has yielded reliable 'extended-range' luminescence chronologies at several independently dated Atapuerca sites. Four single-grain TT-OSL depositional ages of 453 ± 56 ka, 437 ± 38 ka, 457 ± 41 ka and 460 ± 39 ka were obtained for the red clay lithostratigraphic units (LU-5 and LU-6) found underlying and encasing the SH hominin bones. A Bayesian age-depth model was constructed using previously published chronologies, as well as the new single-grain TT-OSL ages for LU-5 and LU-6, in order to derive combined age estimates for individual lithostratigraphic units preserved at SH. The combined modeled ranges reveal that the hominin-bearing layer (LU-6) was deposited between 455 ± 17 ka and 440 ± 15 ka (mean lower and upper boundary 68.2% probability range ± 1σ uncertainty, respectively), with a mean age of 448 ± 15 ka. These new bracketing ages suggest that the hominin fossils at SH were most likely deposited within Marine Isotope Stage (MIS) 12, enabling more precise temporal constraint on the early evolution of the Neandertal lineage. The SH fossils represent the oldest reliably dated hominin remains displaying Neandertal features across Eurasia. These Neandertal features are first observed in the facial skeleton, including the mandible and teeth, as well as the temporomandibular joint, and appear consistently across the SH collection. Our chronological findings suggest that the appearance of these Neandertal traits may have been associated with the climatic demise of MIS 12 and the ecological changes that occurred in Iberia during this period. Other Middle Pleistocene hominin fossils from Europe dated to MIS 12-11, or later, show different morphological trends, with some lacking Neandertal specializations. The latest SH dating results enable improved temporal correlations with these contrasting hominin records from Europe, and suggest a complex picture for hominin evolution during the Middle Pleistocene.

What influences use of dental services by the Korean disabled people? The role of perceived barriers in dental care system.

OBJECTIVE: To identify the perceived barriers to dental care for disabled people in South Korea using the revised Andersen's model of access to health care. BASIC RESEARCH DESIGN: Cross-sectional analytic interview study. PARTICIPANTS: Korean people with a disability residing in residential facilities, or those at home who attend vocational rehabilitation facilities, special schools, or welfare facilities, were sampled from Seoul and non-Seoul areas in 2016 and were interviewed face-to-face. In total, 456 disabled Koreans, or their primary caregivers participated. RESULTS: Household income, disability duration and perceived barriers in the dental care system were perceived to impact on dental care utilisation, while the need for dental care services did not significantly explain the use of dental care by disabled people in South Korea. Those with low household incomes were less likely to use dental care services, compared to people with moderate and high household incomes. As disability duration increased, disabled people were more likely to use dental services. Those who perceived the barriers to dental care as higher were less likely to use dental services. CONCLUSION: These data suggest that policies are needed to support disabled people with low household incomes. Lowering barriers in the dental care system may encourage people with disabilities to access timely and adequate dental services.

Magnetically Coated Bioabsorbable Stents for Renormalization of Arterial Vessel Walls after Stent Implantation.

The insertion of a stent in diseased arteries is a common endovascular procedure that can be compromised by the development of short- and long-term inflammatory responses leading to restenosis and thrombosis, respectively. While treatment with drugs, either systemic or localized, has decreased the incidence of restenosis and thrombosis these complications persist and are associated with a high mortality in those that present with stent thrombosis. We reasoned that if stents could be made to undergo accelerated endothelialization in the deployed region, then such an approach would further decrease the occurrence of stent thrombosis and restenosis thereby improving clinical outcomes. Toward that objective, the first step necessitated efficient capture of progenitor stem cells, which eventually would become the new endothelium. To achieve this objective, we engineered intrinsic ferromagnetism within nonmagnetizable, biodegradable magnesium (Mg) bare metal stents. Mg stents were coated with biodegradable polylactide (PLA) polymer embedding magnetizable iron-platinum (FePt) alloy nanoparticles, nanomagnetic particles, nMags, which increased the surface area and hence magnetization of the stent. nMags uniformly distributed on stents enabled capture, under flow, up to 50 mL/min, of systemically injected iron-oxide-labeled (IO-labeled) progenitor stem cells. Critical parameters enhancing capture efficiency were optimized, and we demonstrated the generality of the approach by showing that nMag-coated stents can capture different cell types. Our work is a potential paradigm shift in engineering stents because implants are rendered as tissue in the body, and this "natural stealthiness" reduces or eliminates issues associated with pro-inflammatory immune responses postimplantation.

Is calcium phosphate augmentation a viable option for osteoporotic hip fractures?

The use of calcium phosphate bone cement has been described to allow for retention of reduction. Therefore, we evaluated whether augmentation with resorbable calcium phosphate could improve fracture stability in osteoporotic hip fractures. The results showed that augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures. INTRODUCTION: The aim with this study was to measure whether augmentation with resorbable calcium phosphate cement could improve fracture stability in osteoporotic hip fractures. METHODS: We retrospectively reviewed 82 patients who underwent closed reduction and internal fixation with proximal femoral nail (PFN) for unstable intertrochanteric fractures between 2014 and 2017. In 42 of 82 patients, patients were treated with a PFN alone (group I). These patients were compared with 40 patients for whom the same device combined with calcium phosphate cement for augmentation was used (group II). Questionnaire surveys or telephone interviews were conducted and patients completed a self-report Harris hip score (HHS) and visual analog scale (VAS) scores. Radiographic outcomes including mean sliding distance of screw, femoral shortening, and varus collapse were compared. Postoperative complications were compared. RESULTS: Clinical outcomes at 6 months after surgery were equivalent in both groups. Screw sliding, femoral shortening, and varus collapse were all significantly reduced in the cemented group at the last follow-up (p < 0.001, p = 0.005, p < 0.001, respectively). A total of 9 (21%) complications occurred in group I. In contrast, 2 (5%) complications were seen in group II (p = 0.029). CONCLUSIONS: Augmentation with calcium phosphate cement significantly improved the stability of intertrochanteric fractures fixed with a PFN and reduced overall failure rates. We believe augmentation with resorbable calcium phosphate cement for osteoporotic hip fractures is a reasonable option in selected patients.

Influence of dietary nitrate food forms on nitrate metabolism and blood pressure in healthy normotensive adults.

Inorganic nitrate (NO3-) supplementation has been shown to improve cardiovascular health indices in healthy adults. The purpose of this study was to investigate how the vehicle of NO3- administration can influence NO3- metabolism and the subsequent blood pressure response. Ten healthy males consumed an acute equimolar dose of NO3- (∼5.76 mmol) in the form of a concentrated beetroot juice drink (BR; 55 mL), a non-concentrated beetroot juice drink (BL; 456 mL) and a solid beetroot flapjack (BF; 60 g). A drink containing soluble beetroot crystals (BC; ∼1.40 mmol NO3-) and a control drink (CON; 70 mL deionised water) were also ingested. BP and plasma, salivary and urinary [NO3-] and [NO2-] were determined before and up to 24 h after ingestion. All NO3--rich vehicles elevated plasma, salivary and urinary nitric oxide metabolites compared with baseline and CON (P<0.05). The peak increases in plasma [NO2-] were greater in BF (371 ± 136 nM) and BR (369 ± 167 nM) compared to BL (283 ± 93 nM; all P<0.05) and BC (232 ± 51 nM). BR, but not BF, BL and BC, reduced systolic (∼5 mmHg) and mean arterial pressure (∼3-4 mmHg; P<0.05), whereas BF reduced diastolic BP (∼4 mmHg; P < 0.05). Although plasma [NO2-] was elevated in all conditions, the consumption of a small, concentrated NO3--rich fluid (BR) was the most effective means of reducing BP. These findings have implications for the use of dietary NO3-supplements when the main objective is to maintain or improve indices of cardiovascular health.

Dental implications in Hajdu-Cheney syndrome: A novel case report and review of the literature.

OBJECTIVE: To identify the molecular genetic etiology of an individual with a dysmorphic face, unusual teeth mobility, and root resorption. SUBJECTS AND METHODS: DNA samples were collected from a trio of family members, and whole-exome sequencing was performed. RESULTS: Mutational analysis revealed a de novo mutation (c.6787C>T) in the last exon of the NOTCH2 gene. This mutation would introduce a premature stop codon [p.(Gln2263*)] and generate a truncated protein without C-terminus, escaping from the nonsense-mediated decay system. Sanger sequencing confirmed that this mutation was generated spontaneously. CONCLUSIONS: In this study, we identified a novel nonsense mutation in the last exon of the NOTCH2 gene causing Hajdu-Cheney syndrome. We described the genotype and phenotype correlation and the related dental complications. These results will advance the understanding of the NOTCH2 signaling in periodontitis and root resorption.

Clinical audit training improves undergraduates' performance in root canal therapy.

AIM: To evaluate the effectiveness of clinical audit-feedback cycle as an educational tool in improving the technical quality of root canal therapy (RCT) and compliance with record keeping performed by dental undergraduates. METHODS: Clinical audit learning was introduced in Year 3 of a 5-year curriculum for dental undergraduates. During classroom activities, students were briefed on clinical audit, selected their audit topics in groups of 5 or 6 students, and prepared and presented their audit protocols. One chosen topic was RCT, in which 3 different cohorts of Year 3 students conducted retrospective audits of patients' records in 2012, 2014 and 2015 for their compliance with recommended record keeping criteria and their performance in RCT. Students were trained by and calibrated against an endodontist (κ ≥ 0.8). After each audit, the findings were reported in class, and recommendations were made for improvement in performance of RCT and record keeping. Students' compliance with published guidelines was presented and their RCT performances in each year were compared using the chi-square test. RESULTS: Overall compliance with of record keeping guidelines was 44.1% in 2012, 79.6% in 2014 and 94.6% in 2015 (P = .001). In the 2012 audit, acceptable extension, condensation and the absence of mishap were observed in 72.4, 75.7% and 91.5%; in the 2014 audit, 95.1%, 64.8% and 51.4%; and in 2015 audit, 96.4%, 82.1% and 92.8% of cases, respectively. In 2015, 76.8% of root canal fillings met all 3 technical quality criteria when compared to 48.6% in 2014 and 44.7% in 2012 (P = .001). CONCLUSION: Clinical audit-feedback cycle is an effective educational tool for improving dental undergraduates' compliance with record keeping and performance in the technical quality of RCT.

Influence of iodide ingestion on nitrate metabolism and blood pressure following short-term dietary nitrate supplementation in healthy normotensive adults.

Uptake of inorganic nitrate (NO3-) into the salivary circulation is a rate-limiting step for dietary NO3- metabolism in mammals. It has been suggested that salivary NO3- uptake occurs in competition with inorganic iodide (I-). Therefore, this study tested the hypothesis that I- supplementation would interfere with NO3- metabolism and blunt blood pressure reductions after dietary NO3- supplementation. Nine healthy adults (4 male, mean ± SD, age 20 ± 1 yr) reported to the laboratory for initial baseline assessment (control) and following six day supplementation periods with 140 mL·day-1 NO3--rich beetroot juice (8.4 mmol NO3-·day-1) and 198 mg potassium gluconate·day-1 (nitrate), and 140 mL·day-1 NO3--rich beetroot juice and 450 µg potassium iodide·day-1 (nitrate + iodide) in a randomized, cross-over experiment. Salivary [I-] was higher in the nitrate + iodide compared to the control and NIT trials (P < 0.05). Salivary and plasma [NO3-] and [NO2-] were higher in the nitrate and nitrate + iodide trials compared to the control trial (P < 0.05). Plasma [NO3-] was higher (474 ± 127 vs. 438 ± 117 µM) and the salivary-plasma [NO3-] ratio was lower (14 ± 6 vs. 20 ± 6 µM), indicative of a lower salivary NO3- uptake, in the nitrate + iodide trial compared to the nitrate trial (P < 0.05). Plasma and salivary [NO2-] were not different between the nitrate and nitrate + iodide trials (P > 0.05). Systolic blood pressure was lower than control (112 ± 13 mmHg) in the nitrate (106 ± 13 mmHg) and nitrate + iodide (106 ± 11 mmHg) trials (P < 0.05), with no differences between the nitrate and nitrate + iodide trials (P > 0.05). In conclusion, co-ingesting NO3- and I- perturbed salivary NO3- uptake, but the increase in salivary and plasma [NO2-] and the lowering of blood pressure were similar compared to NO3- ingestion alone. Therefore, increased dietary I- intake, which is recommended in several countries worldwide as an initiative to offset hypothyroidism, does not appear to compromise the blood pressure reduction afforded by increased dietary NO3- intake.

Genetic alterations in mesiodens as revealed by targeted next-generation sequencing and gene co-occurrence network analysis.

OBJECTIVE: Mesiodens is the most common type of supernumerary tooth which includes a population prevalence of 0.15%-1.9%. Alongside evidence that the condition is heritable, mutations in single genes have been reported in few human supernumerary tooth cases. Gene sequencing methods in tradition way are time-consuming and labor-intensive, whereas next-generation sequencing and bioinformatics are cost-effective for large samples and target sizes. MATERIALS AND METHODS: We describe the application of a targeted next-generation sequencing (NGS) and bioinformatics approach to samples from 17 mesiodens patients. Subjects were diagnosed on the basis of panoramic radiograph. A total of 101 candidate genes which were captured custom genes were sequenced on the Illumina HiSeq 2500. Multistep bioinformatics processing was performed including variant identification, base calling, and in silico analysis of putative disease-causing variants. RESULTS: Targeted capture identified 88 non-synonymous, rare, exonic variants involving 42 of the 101 candidate genes. Moreover, we investigated gene co-occurrence relationships between the genomic alterations and identified 88 significant relationships among 18 most recurrent driver alterations. CONCLUSION: Our search for co-occurring genetic alterations revealed that such alterations interact cooperatively to drive mesiodens. We discovered a gene co-occurrence network in mesiodens patients with functionally enriched gene groups in the sonic hedgehog (SHH), bone morphogenetic proteins (BMP), and wingless integrated (WNT) signaling pathways.

Genetic analysis of hereditary gingival fibromatosis using whole exome sequencing and bioinformatics.

OBJECTIVES: Our study aims to identify genetic variants associated with hereditary gingival fibromatosis (HGF) by applying whole-exome sequencing (WES) and bioinformatics analyses such as gene set enrichment analysis (GSEA) and protein functional network study. SUBJECTS AND METHODS: Two affected siblings whose grandparents and parents have normal gingiva were chosen for our investigation. Saliva collected from the patients and their parents were used for WES. GSEA and protein functional network study were performed to find gene groups in a biological coordination which are associated with HGF. RESULTS: Genetic variants for homozygotes and compound heterozygotes were analyzed and translated into 845 genes. The result from protein functional network study showed that these genetic variants were mainly observed in genes affecting fibronectin as well as the immune and autoimmune system. Additionally, three mutated genes in our HGF patients, TMCO1, RIN2, and INSR, were found through human phenotype ontology (HPO) to have potential to contribute to gingival hyperplasia. CONCLUSIONS: Genetic analysis of HGF in this study implicated mutations in fibronectin and the immune system as triggering abnormal gingival fibromatosis.