Early radiographic osseointegration of a novel highly porous 3D-printed titanium collar for megaprostheses compared to a previous generation smooth HA-coated collar.

PURPOSE: Extracortical osseointegration at the collar-bone interface of megaprostheses is associated with improved implant stability, lower rates of stem fracture and loosening. The use of hydroxy-apatite (HA-) coated collars showed mixed results in previously published reports. A novel collar system has recently become available utilizing additive manufacturing technology to create a highly porous titanium collar with a calcium-phosphate coated surface. The aim of this study was to evaluate our early experience with this novel collar and compare it to the previously used HA-coated model. METHODS: Twenty patients who underwent megaprostheses implantation utilizing the novel collar system were case matched to 20 patients who had previously undergone a HA-coated collar. A minimum radiological follow-up of three months was available in all included patients. Osseointegration was evaluated using postoperative plain radiographs in two planes based on a previously published semi-quantitative score. RESULTS: Compared to the HA-coated collar the use of the novel highly porous collar was associated with a higher proportion of cases demonstrating osseointegration at the bone-collar interface (80% vs. 65%). Application of the highly porous collar led to a significantly shortened time to reach the final ongrowth score (173 ± 89 days vs. 299 ± 165 days, p < 0.05). At one year follow-up, 90% of the novel collars had reached their final osseoingration grade compared to 50% in the HA-coated collar group (p < 0.001). Radiological osseointegration was seen in 71% for highly porous collars where the indication was revision arthroplasty, compared to 27% in reported in the literature. CONCLUSION: These results indicate more reliable and accelerated osseointegration at the bone-collar interface of a novel highly porous collar system compared to a previously used HA-coated collar. Further studies are warranted to confirm these findings.

Randomized Controlled Trial Comparing Nylon and Chromic Gut Sutures After Minor Hand Surgery.

PURPOSE: We sought to compare overall satisfaction with treatment and satisfaction with initial wound healing after closure of office hand and upper extremity surgery wounds using polyamide compared to Chromic gut sutures. METHODS: We compared 62 patients randomized to polyamide suture closure of an office hand and upper extremity incision (mostly carpal tunnel release and trigger finger release) to 50 patients closed with Chromic gut suture. Patients rated overall treatment satisfaction, satisfaction with initial healing, pain intensity, and upper extremity-specific activity tolerance. RESULTS: Accounting for potential confounding in multivariable linear and logistic regression analysis, we found the following: (1) overall satisfaction with care was unrelated to suture type; (2) satisfaction with initial wound healing and appearance was lower among people with no other comorbidities, but unrelated to suture type; (3) there were no factors independently associated with pain intensity; and (4) excisional biopsy was associated with greater activity tolerance. CONCLUSIONS: Our findings suggests that Chromic sutures are a viable alternative to polyamide sutures after office hand surgery, provided that the care team anticipates and develops strategies for concerns that may arise if the sutures take an extended period to fall off. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Informed Consent from a Historical, Societal, Ethical, Legal, and Practical Perspective.

Informed consent is often perceived as a regulatory obligation without recognizing its educational potential in the dynamic provider/patient relationship. This article discusses the complex interaction of ethics, society, and law through a historical and practical perspective. The purpose is to provide general dentists and specialists with a comprehensive understanding of the complexity and practical dimensions of informed consent.

Nonepithelial Tumors of the Larynx: Single-Institution 13-Year Review with Radiologic-Pathologic Correlation.

Nonepithelial tumors of the larynx are rare and represent a minority of all laryngeal neoplasms. Imaging has an important role in the diagnosis, treatment planning, and surveillance of these entities. However, unfamiliarity with these neoplasms can cause diagnostic difficulties for radiologists, especially because many of the imaging findings are nonspecific. By using a systematic approach based on clinical history, patient age and gender, lesion location, endoscopic results, and specific imaging findings, the differential diagnosis can often be narrowed. These tumors typically affect the submucosal layer, so if a tumor has an intact mucosa at endoscopy, a nonepithelial neoplasm is the most likely diagnosis. Nonepithelial tumors of the larynx can arise from the laryngeal cartilage or muscle or from the surrounding lymphoid tissue or blood vessels. Consequently, imaging findings typically correspond to the specific cell type from which it originated. Recognizing specific features (eg, metaplastic bone formation, macroscopic fat, or enhancement pattern) can often help narrow the differential diagnosis. In addition, identification of noncircumscribed borders of the lesion and invasion of the adjacent structures is key to diagnosis of a malignant process rather than a benign neoplasm. Understanding the pathologic correlation is fundamental to understanding the radiologic manifestations and is ultimately crucial for differentiation of nonepithelial laryngeal neoplasms. Online supplemental material is available for this article. ©RSNA, 2020.

Three-percent sucrose acts as a thermostabilizer for cell-adapted foot-and-mouth disease virus without any negative effect on viral growth.

AIMS: As cell-adapted foot-and-mouth disease virus (FMDV) with H56R mutation in VP3 has reduced thermostability, this study aimed to investigate the effect of thermostabilizers on cell-adapted FMDV for vaccine production. METHODS AND RESULTS: We examined the effect of 3% sucrose, 10% (or 25%) glycerol or 10% FBS on cell-adapted FMDV O/SKR/JC/2014, containing H56R mutation in VP3, as vaccine seed virus at -80, 4, 25 or 37°C for 2, 4 or 7 days. The stabilizing effect of 3% sucrose on O/SKR/JC/2014 was observed at 25, 37°C, and after repeated freeze-thaw cycles. Additionally, we tested the effect of 3% sucrose on the growth of FMDV or cells and did not observe any decrease in either viral growth or cell viability. CONCLUSIONS: Our study showed the protective effect of 3% sucrose on FMDV infectivity at various temperatures; this virus stock in 3% sucrose could be used for infecting cells without the removal of sucrose. SIGNIFICANCE AND IMPACT OF THE STUDY: We suggest that 3% sucrose-containing medium could be beneficial for the stable storage and transport of cell-adapted FMDV.

Pilot GWAS of caries in African-Americans shows genetic heterogeneity.

BACKGROUND: Dental caries is the most common chronic disease in the US and disproportionately affects racial/ethnic minorities. Caries is heritable, and though genetic heterogeneity exists between ancestries for a substantial portion of loci associated with complex disease, a genome-wide association study (GWAS) of caries specifically in African Americans has not been performed previously. METHODS: We performed exploratory GWAS of dental caries in 109 African American adults (age > 18) and 96 children (age 3-12) from the Center for Oral Health Research in Appalachia (COHRA1 cohort). Caries phenotypes (DMFS, DMFT, dft, and dfs indices) assessed by dental exams were tested for association with 5 million genotyped or imputed single nucleotide polymorphisms (SNPs), separately in the two age groups. The GWAS was performed using linear regression with adjustment for age, sex, and two principal components of ancestry. A maximum of 1 million adaptive permutations were run to determine empirical significance. RESULTS: No loci met the threshold for genome-wide significance, though some of the strongest signals were near genes previously implicated in caries such as antimicrobial peptide DEFB1 (rs2515501; p = 4.54 × 10- 6) and TUFT1 (rs11805632; p = 5.15 × 10- 6). Effect estimates of lead SNPs at suggestive loci were compared between African Americans and Caucasians (adults N = 918; children N = 983). Significant (p < 5 × 10- 8) genetic heterogeneity for caries risk was found between racial groups for 50% of the suggestive loci in children, and 12-18% of the suggestive loci in adults. CONCLUSIONS: The genetic heterogeneity results suggest that there may be differences in the contributions of genetic variants to caries across racial groups, and highlight the critical need for the inclusion of minorities in subsequent and larger genetic studies of caries in order to meet the goals of precision medicine and to reduce oral health disparities.

Locally delivered ethyl-2,5-dihydroxybenzoate using 3D printed bone implant for promotion of bone regeneration in a osteoporotic animal model.

Osteoporosis is a disease characterized by low bone mass, most commonly caused by an increase in bone resorption that is not matched by sufficient bone formation. The most common complications of postmenopausal osteoporosis are bone-related defects and fractures. Fracture healing is a multifactorial bone regeneration process, influenced by both biological and mechanical factors related to age, osteoporosis and stability of the osteosynthesis. During the treatment of bone defects in osteoporotic conditions, imbalanced bone remodeling is the leading cause for implant failure. To overcome these problems, ethyl-2,5-dihydroxybenzoate (E-2,5-DHB), a drug that promotes bone formation and inhibits bone resorption, was used. E-2,5-DHB-incorporating titanium (Ti) implants using poly(lactic-co-glycolic acid) (PLGA) coating for local delivery of E-2,5-DHB were developed and the effects on bone healing of femoral defects were evaluated in an osteoporotic model. The release of E-2,5-DHB resulted in decreased bone resorption and increased bone formation around the implant. Thus, it was confirmed that, in the osteoporotic model, bone healing was increased and implant fixation was enhanced. These results suggested that E-2,5-DHB-coated Ti implants have great potential as an ultimate local drug delivery system for bone tissue scaffolds.

A new combination therapy for asthma using dual-function dexamethasone-conjugated polyethylenimine and vitamin D binding protein siRNA.

Asthma is a multifactorial disease that is influenced by the interaction of genetic and environmental factors. Because of its complex nature, there is no cure for asthma currently. Instead, reliever and controller medications are used to treat asthma. Unfortunately, conventional treatments do not work in some severe cases of asthma. In addition, there may be adverse, systemic effects of long-term treatment with high-dose inhaled corticosteroids (ICSs) as a controller medication. Therefore, we attempted to develop a novel combination therapy for asthma. Our regimen included dexamethasone as a controller medication and vitamin D binding protein (VDBP) small interfering RNA (siRNA) as a novel target therapeutic. The dexamethasone moiety of DEXA-PEI (dexamethasone-conjugated polyethylenimine) was used as an ICS, combined with anti-VDBP treatment via delivery of VDBP siRNA, using DEXA-PEI as a siRNA carrier molecule. Treatment with DEXA-PEI/VDBP siRNA effectively reduced the ovalbumin sensitization/challenge-induced enhancement of airway inflammation, goblet cell hyperplasia and expression of interleukin (IL)-4, IL-13 and CCL11. These findings suggest that the DEXA-PEI/VDBP siRNA can be developed as a potent asthma therapeutic by dose-reducing ICSs and using a multitarget therapeutic method.

Role of PIN1 on in vivo periodontal tissue and in vitro cells.

BACKGROUND: Although expression of peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) was reported in bone tissue, the precise role of PIN1 in periodontal tissue and cells remain unclear. MATERIAL & METHODS: To elucidate the roles of PIN1 in periodontal tissue, its expression in periodontal tissue and cells, and effects on in vitro 4 osteoblast differentiation and the underlying signaling mechanisms were evaluated. RESULTS: PIN1 was expressed in mouse periodontal tissues including periodontal ligament cells (PDLCs), cementoblasts and osteoblasts at the developing root formation stage (postnatal, PN14) and functional stage of tooth (PN28). Treatment of PIN1 inhibitor juglone, and gene silencing by RNA interference promoted osteoblast differentiation in PDLCs and cementoblasts, whereas the overexpression of PIN1 inhibited. Moreover, osteogenic medium-induced activation of AMPK, mTOR, Akt, ERK, p38 and NF-jB pathways were enhanced by PIN1 siRNA, but attenuated by PIN1 overexpression. Runx2 expressions were induced by PIN1 siRNA, but downregulated by PIN1 overexpression. CONCLUSION: In summary, this study is the first to demonstrate that PIN1 is expressed in developing periodontal tissue, and in vitro PDLCs and cementoblasts. PIN1 inhibition stimulates osteoblast differentiation, and thus may play an important role in periodontal regeneration.

Clinical effectiveness of late maxillary protraction in cleft lip and palate: A methods paper.

OBJECTIVES: A prospective parallel cohort trial was conducted to compare outcomes of patients treated with maxillary protraction vs LeFort 1 maxillary advancement surgery. SETTING AND SAMPLE POPULATION: The primary site for the clinical trial is Children's Hospital Los Angeles; the satellite test site is Seattle Children's Hospital. All patients have isolated cleft lip and palate and a skeletal Class III malocclusion. MATERIAL AND METHODS: A total of 50 patients, ages 11-14, will be recruited for the maxillary protraction cohort. The maxillary surgery cohort consists of 50 patients, ages 16-21, who will undergo LeFort 1 maxillary advancement surgery. Patients with additional medical or cognitive handicaps were excluded from the study. RESULTS: Current recruitment of patients is on track to complete the study within the proposed recruitment period. CONCLUSION: This observational trial is collecting information that will examine dental, skeletal, financial and quality-of-life issues from both research cohorts.

Does Maximal External Tibial Component Rotation Influence Tibiofemoral Load Distribution in the Primary Knee Arthroplasty Setting: A Comparison of Neutral vs Maximal Anatomical External Rotatory States.

BACKGROUND: Tibial component rotation at time of knee arthroplasty can influence conformity, load transmission across the polyethylene surface, and perhaps ultimately determined survivorship. Optimal tibial component rotation on the cut surface is reliant on standard per operative manual stressing. This subjective assessment aims to balance constraint and stability of the articulation through a full arc of movement. METHODS: Using a cadaveric model, computer navigation and under defined, previously validated loaded conditions mimicking the in vivo setting, the influence of maximal tibial component external rotation compared with the neutral state was examined for changes in laxity and tibiofemoral continuous load using 3D displacement measurement and an orthosensor continuous load sensor implanted within the polyethylene spacer in a simulated single radius total knee arthroplasty. RESULTS: No significant difference was found throughout arc of motion (0-115 degrees of flexion) for maximal varus and/or valgus or rotatory laxity between the 2 states. The neutral state achieved equivalence for mediolateral load distribution at each point of flexion. We have found that external rotation of the tibial component increased medial compartment load in comparison with the neutral position. Compared with the neutral state, external rotation consistently effected a marginal, but not significant reduction in lateral load under similar loading conditions. The effects were most pronounced in midflexion. CONCLUSION: On the basis of these findings, we would advocate for the midtibial tubercle point to determine tibial component rotation and caution against component external rotation.

Nasotracheal intubation in patients with limited mouth opening: a comparison between fibreoptic intubation and the Trachway®.

In patients with limited mouth opening, traditional laryngoscopy and videolaryngoscopes are not useful when performing nasotracheal intubation. Eighty patients with limited mouth opening who required nasotracheal intubation were randomly assigned to either fibreoptic intubation (n = 40) or the Trachway(®) (n = 40). Using the modified nasal intubation difficulty scale, 22 (55%) patients who received fibreoptic intubation were categorised as no difficulty compared with 40 (100%) patients in the Trachway group (p < 0.001). Mean (SD) total intubation time was 71.8 (23.3) s in patients who received fibreoptic intubation compared with 35.4 (9.8) s in the Trachway group (p < 0.001). We conclude that the Trachway technique for nasotracheal intubation is quicker and easier compared with fibreoptic intubation in patients with limited mouth opening.

Putative mechanisms mediating tolerance for audiovisual stimulus onset asynchrony.

Audiovisual (AV) speech perception is robust to temporal asynchronies between visual and auditory stimuli. We investigated the neural mechanisms that facilitate tolerance for audiovisual stimulus onset asynchrony (AVOA) with EEG. Individuals were presented with AV words that were asynchronous in onsets of voice and mouth movement and judged whether they were synchronous or not. Behaviorally, individuals tolerated (perceived as synchronous) longer AVOAs when mouth movement preceded the speech (V-A) stimuli than when the speech preceded mouth movement (A-V). Neurophysiologically, the P1-N1-P2 auditory evoked potentials (AEPs), time-locked to sound onsets and known to arise in and surrounding the primary auditory cortex (PAC), were smaller for the in-sync than the out-of-sync percepts. Spectral power of oscillatory activity in the beta band (14-30 Hz) following the AEPs was larger during the in-sync than out-of-sync perception for both A-V and V-A conditions. However, alpha power (8-14 Hz), also following AEPs, was larger for the in-sync than out-of-sync percepts only in the V-A condition. These results demonstrate that AVOA tolerance is enhanced by inhibiting low-level auditory activity (e.g., AEPs representing generators in and surrounding PAC) that code for acoustic onsets. By reducing sensitivity to acoustic onsets, visual-to-auditory onset mapping is weakened, allowing for greater AVOA tolerance. In contrast, beta and alpha results suggest the involvement of higher-level neural processes that may code for language cues (phonetic, lexical), selective attention, and binding of AV percepts, allowing for wider neural windows of temporal integration, i.e., greater AVOA tolerance.

Macrophage-specific TLR2 signaling mediates pathogen-induced TNF-dependent inflammatory oral bone loss.

Porphyromonas gingivalis is a primary etiological agent of chronic periodontal disease, an infection-driven chronic inflammatory disease that leads to the resorption of tooth-supporting alveolar bone. We previously reported that TLR2 is required for P. gingivalis-induced alveolar bone loss in vivo, and our in vitro work implicated TNF as a key downstream mediator. In this study, we show that TNF-deficient (Tnf(-/-)) mice are resistant to alveolar bone loss following oral infection with P. gingivalis, and thus establish a central role for TNF in experimental periodontal disease. Using bone marrow-derived macrophages (BMDM) from wild-type and gene-specific knockout mice, we demonstrate that the initial inflammatory response to P. gingivalis in naive macrophages is MyD88 dependent and requires cooperative signaling of TLR2 and TLR4. The ability of P. gingivalis to activate cells via TLR2 or TLR4 was confirmed in TLR2- or TLR4-transformed human embryonic kidney cells. Additional studies using bacterial mutants demonstrated a role for fimbriae in the modulation of TLR-mediated activation of NF-κB. Whereas both TLR2 and TLR4 contributed to TNF production in naive macrophages, P. gingivalis preferentially exploited TLR2 in endotoxin-tolerant BMDM to trigger excessive TNF production. We found that TNF induced surface TLR2 expression and augmented TLR-induced cytokine production in P. gingivalis-stimulated BMDM, establishing a previously unidentified TNF-dependent feedback loop. Adoptive transfer of TLR2-expressing macrophages to TLR2-deficient mice restored the ability of P. gingivalis to induce alveolar bone loss in vivo. Collectively, our results identify a TLR2- and TNF-dependent macrophage-specific mechanism underlying pathogen-induced inflammatory bone loss in vivo.

Cone-beam computed tomography education and exposure in oral and maxillofacial surgery training programs in the United States.

PURPOSE: The purpose of this study was to estimate the penetration of cone-beam computed tomography (CBCT) in oral and maxillofacial surgery (OMS) residency programs in the United States. In addition, this study was designed to assess the education and training, relevance, and image interpretation responsibility of CBCT as experienced by OMS residents. MATERIALS AND METHODS: The authors performed a cross-sectional study of all 102 US-based OMS program directors (PDs) from January 1, 2014 through April 30, 2014. Study variables included questions about 4 key factors in CBCT in OMS programs: access, education and training, relevance, and image interpretation responsibility. Data analysis was a product of the percentage of positive responses to each question. RESULTS: Fifty-four PDs participated in the study. The results showed that 87% of responding OMS programs have access to CBCT and that CBCT is used primarily for dental implant-related procedures. CONCLUSION: OMS residents are actively involved in CBCT use in their residency. OMS residents' access to CBCT is increasing, and their education, training, and image interpretation responsibility is increasing.

Evaluation of extractables in processed and unprocessed polymer materials used for pharmaceutical applications.

Polymeric materials are often used in pharmaceutical packaging, delivery systems, and manufacturing components. There is continued concern that chemical entities from polymeric components may leach into various dosage forms, particularly those that are comprised of liquids such as parenterals, injectables, ophthalmics, and inhalation products. In some cases, polymeric components are subjected to routine extractables testing as a control measure. To reduce the risk of discovering leachables during stability studies late in the development process, or components that may fail extractables release criteria, it is proposed that extractables testing on polymer resins may be useful as a screening tool. Two studies have been performed to evaluate whether the extractables profile generated from a polymer resin is representative of the extractables profile of components made from that same resin. The ELSIE Consortium pilot program examined polyvinyl chloride and polyethylene, and another study evaluated polypropylene and a copolymer of polycarbonate and acrylonitrile butadiene styrene. The test materials were comprised of polymer resin and processed resin or molded components. Volatile, semi-volatile, and nonvolatile chemical profiles were evaluated after headspace sampling and extraction with solvents of varying polarity and pH. The findings from these studies indicate that there may or may not be differences between extractables profiles obtained from resins and processed forms of the resin depending on the type of material, the compounds of interest, and extraction conditions used. Extractables testing of polymer resins is useful for material screening and in certain situations may replace routine component testing.

Controlled Extraction Studies Applied to Polyvinyl Chloride and Polyethylene Materials: Conclusions from the ELSIE Controlled Extraction Pilot Study.

The effective management of leachables in pharmaceutical products is a critical aspect of their development. This can be facilitated if extractables information on the materials used in a packaging or delivery system is available to assist companies in selecting materials that will be compatible with the drug product formulation and suitable for the intended use. The Extractables and Leachables Safety Information Exchange (ELSIE) materials working group developed and executed a comprehensive extraction study protocol that included a number of extraction solvents, extraction techniques, and a variety of analytical techniques. This was performed on two test materials, polyethylene (PE) and polyvinyl chloride (PVC), that were selected due to their common use in pharmaceutical packaging. The purpose of the study was to investigate if the protocol could be simplified such that (i) a reduced number or even a single extraction technique could be used and (ii) a reduced number of solvents could be used to obtain information that is useful for material selection regardless of product type. Results indicate that, at least for the PVC, such reductions are feasible. Additionally, the studies indicate that levels of extractable elemental impurities in the two test materials were low and further confirm the importance of using orthogonal analytical detection techniques to gain adequate understanding of extraction profiles.

Community periodontal treatment needs in South Korea.

OBJECTIVES: This study aimed to assess the relationship between socio-economic factors and community periodontal treatment needs in Korea. METHODS: Data were obtained from the year 2009 Korean National Health and Nutrition Examination Survey. Our analysis included 7510 survey participants over the age of 19 years. To assess the relationship between socio-economic factors and the need for periodontal scaling, we performed multivariate logistic regression analyses for data with a complex sampling structure. PASW statistics 19.0 (SPSS Inc., Chicago, IL, USA) was used to perform the statistical analyses, and the results were expressed as odds ratios (OR) with corresponding 95% confidence intervals (CIs). RESULTS: A very high percentage of Korean adults required periodontal scaling (71.5%). After adjusting for sex, age, and socio-economic factors, the need for periodontal scaling was associated with low levels of education (OR: 1.41, 95% CI: 1.03-1.93), low incomes (OR: 1.27, 95% CI: 1.01-1.60), employment as a service and sales worker (OR: 1.39, 95% CI: 1.10-1.77), and employment as a manual worker (OR: 1.31, 95% CI: 1.02-1.69). CONCLUSIONS: In South Korea, the need for periodontal scaling was associated with socio-economic factors, such as low levels of education, low incomes, employment as a service and sales worker and employment as a manual worker. Consequently, clinical and community dental hygienists should consider adults with these risk factors as belonging to high-priority subgroups to whom they should respond first.

Risk of osteonecrosis in patients taking bisphosphonates for prevention of osteoporosis: a systematic review and meta-analysis.

SUMMARY: We aimed to systematically review observational studies evaluating use of bisphosphonates (BPs) and risk of osteonecrosis of jaw (ONJ) or other sites among non-cancer patients. INTRODUCTION: PubMed, EMBASE, and Cochrane Library were screened from database inception to Dec 2012. METHODS: Two reviewers independently identified cohort and case-control studies evaluating the use of oral or intravenous (IV) BPs and the risk of ONJ and extracted the characteristics of the studies and risk estimates. Pooled estimates of odds ratios and 95 % confidence intervals (CI) were derived by random effects meta-analysis. Subgroup analyses were carried according to patients' characteristics and route of BP use. RESULTS: We identified 12 studies, including 2,652 cases and 1,571,997 controls. Use of BPs was associated with a significantly increased risk of ONJ or ON of other sites [odds ratio (OR) 2.32; 95 % CI 1.38-3.91; I (2) = 91 %]. The summary OR was 2.91 (95 % CI 1.62-5.22; I (2) = 85.9 %) for adjusted studies. Use of BPs were associated with higher risk on ONJ (OR 2.57; 95 % CI 1.37-4.84; I (2) = 92.2 %) than ON of other sites (OR 1.79; 95 % CI 0.71-4.47; I (2) = 83.3 %). Meta-regression analysis did not find design characteristics or outcome definitions to be significant sources of heterogeneity. CONCLUSION: The available evidence suggests that use of BPs in cancer patients is associated with a substantial risk for ONJ. Patients receiving IV BP are at highest risk.

Genome-wide association study of primary dentition pit-and-fissure and smooth surface caries.

Dental caries continues to be the most common chronic disease in children today. Despite the substantial involvement of genetics in the process of caries development, the specific genes contributing to dental caries remain largely unknown. We performed separate genome-wide association studies of smooth and pit-and-fissure tooth surface caries experience in the primary dentitions of self-reported white children in two samples from Iowa and rural Appalachia. In total, 1,006 children (ages 3-12 years) were included for smooth surface analysis, and 979 children (ages 4-14 years) for pit-and-fissure surface analysis. Associations were tested for more than 1.2 million single nucleotide polymorphisms, either genotyped or imputed. We detected genome-wide significant signals in KPNA4 (p value = 2.0E-9), and suggestive signals in ITGAL (p value = 2.1E-7) and PLUNC family genes (p value = 2.0E-6), thus nominating these novel loci as putative caries susceptibility genes. We also replicated associations observed in previous studies for MPPED2 (p value = 6.9E-6), AJAP1 (p value = 1.6E-6) and RPS6KA2 (p value = 7.3E-6). Replication of these associations in additional samples, as well as experimental studies to determine the biological functions of associated genetic variants, are warranted. Ultimately, efforts such as this may lead to a better understanding of caries etiology, and could eventually facilitate the development of new interventions and preventive measures.