Craniofacial Morphology and Occlusal Variation in Monozygous and Dizygous Twins

A study of 60 pairs of twins, 30 monozygous and 30 dizygous, finding a strong genetic component overlaid by functional adaptation most prominent in the dental area

Teaching Culturally Sensitive Care to Dental Students: A Multidisciplinary Approach

Dental schools must prepare future dentists to deliver culturally sensitive care to diverse patient populations, but there is little agreement on how best to teach these skills to students. This article examines this question by exploring the historical and theoretical foundations of this area of education in dentistry, analyzes what is needed for students to learn to provide culturally sensitive care in a dental setting, and identifies the discipline-specific skills students must master to develop this competence. The problems associated with single-discipline, lecture-based approaches to teaching culturally sensitive care are outlined, and the advantages of an interdisciplinary, patient-centered, skills-based approach to teaching culturally sensitive care are described. The authors advocate for an approach to teaching culturally sensitive care that builds upon learning in the behavioral sciences, ethics, and public health. Component skills and perspectives offered by each of these curriculum areas are identified, and their contributions to the teaching of culturally sensitive care are described. Finally, the need to consider the timing of this instruction in the dental curriculum is examined, along with instructional advantages associated with an approach that is shared by faculty across the curriculum

The Economic Costs and Benefits of Dental Education: An Empirical Analysis

The rising costs associated with obtaining a dental education have caused some to question the financial benefit of pursuing a dental degree. There is a concern that recent graduates may have difficulty finding professional opportunities that provide the income necessary to service their accumulated educational debt. The aim of this study was to evaluate the trends in educational costs to aid in making an accurate appraisal of the financial benefit of a dental education. Adjusted into constant dollar terms, data from a variety of sources were collected for economic variables such as tuition, fees, student indebtedness, and dentists’ earnings. These variables were then analyzed to determine the true costs and benefits of obtaining a dental education. The results showed that, over the course of the last decade, educational costs increased faster than the real net income of practicing dentists, which led to a decline in the return on investment in dental education. However, regardless of an applicant’s choice of public or private dental school, there continues to be a positive economic return on students’ commitment of both financial resources and time to receive a dental education

Galvanic Corrosion between Various Combinations of Orthodontic Brackets and Archwires

Introduction: The purpose of this study was to compare galvanic currents generated by different combinations of commonly used brackets and archwires. Methods: As-received stainless steel, nickel-titanium, and betatitanium wires were coupled to stainless steel and titanium brackets in an artificial saliva medium. The galvanic current and amount of charge transferred for each pair were monitored with a zero resistance ammeter for 10 hours. Results: Two-way analysis of variance (ANOVA) showed a significant difference in charge and galvanic currents when factored for type of bracket (P\0.001), but no significant difference between them when factored by type of wire (P .0.05). Specifically, a brazed stainless steel bracket was significantly greater in charge transferred and 10-hour galvanic current than metal injection molded stainless steel and titanium brackets (P\0.001), which were not different from each other (P .0.05). Conclusions: The method of bracket manufacturing might be of equal or more relevance to galvanic corrosion susceptibility than bracket composition

Homologous recombination DNA repair defects in PALB2- associated breast cancers

Abstract: Mono-allelic germline pathogenic variants in the Partner And Localizer of BRCA2 (PALB2) gene predispose to a high-risk of breast cancer development, consistent with the role of PALB2 in homologous recombination (HR) DNA repair. Here, we sought to define the repertoire of somatic genetic alterations in PALB2-associated breast cancers (BCs), and whether PALB2-associated BCs display bi-allelic inactivation of PALB2 and/or genomic features of HR-deficiency (HRD). Twenty-four breast cancer patients with pathogenic PALB2 germline mutations were analyzed by whole-exome sequencing (WES, n = 16) or targeted capture massively parallel sequencing (410 cancer genes, n = 8). Somatic genetic alterations, loss of heterozygosity (LOH) of the PALB2 wild-type allele, large-scale state transitions (LSTs) and mutational signatures were defined. PALB2-associated BCs were found to be heterogeneous at the genetic level, with PIK3CA (29%), PALB2 (21%), TP53 (21%), and NOTCH3 (17%) being the genes most frequently affected by somatic mutations. Bi-allelic PALB2 inactivation was found in 16 of the 24 cases (67%), either through LOH (n = 11) or second somatic mutations (n = 5) of the wild-type allele. High LST scores were found in all 12 PALB2-associated BCs with bi-allelic PALB2 inactivation sequenced by WES, of which eight displayed the HRD-related mutational signature 3. In addition, bi-allelic inactivation of PALB2 was significantly associated with high LST scores. Our findings suggest that the identification of bi-allelic PALB2 inactivation in PALB2-associated BCs is required for the personalization of HR-directed therapies, such as platinum salts and/or PARP inhibitors, as the vast majority of PALB2-associated BCs without PALB2 bi-allelic inactivation lack genomic features of HRD

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers

Funder: Breast Cancer Now (BCN); doi: https://doi.org/10.13039/100009794Funder: Cancer Research UK (CRUK); doi: https://doi.org/10.13039/501100000289Funder: RCUK | Medical Research Council (MRC); doi: https://doi.org/10.13039/501100000265Funder: U.S. Department of Health & Human Services | National Institutes of Health (NIH)Funder: Wellcome Trust (Wellcome); doi: https://doi.org/10.13039/100004440Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013)); doi: https://doi.org/10.13039/100011199; Grant(s): HEALTH-F2-2009-223175, HEALTH-F2-2009-223175Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); doi: https://doi.org/10.13039/501100000024Funder: Quebec Breast cancer Foundation Genome QuebecFunder: U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM); doi: https://doi.org/10.13039/100000092Funder: EC | EC Seventh Framework Programm | FP7 Ideas: European Research Council (FP7-IDEAS-ERC - Specific Programme: "Ideas" Implementing the Seventh Framework Programme of the European Community for Research, Technological Development and Demonstration Activities (2007 to 2013))Funder: European Union’s Horizon 2020Funder: Deutsche Krebshilfe (German Cancer Aid); doi: https://doi.org/10.13039/501100005972Funder: BCAST - European Union’s Horizon 2020Funder: Breast Cancer Now; doi: https://doi.org/10.13039/501100007913Abstract: Background: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. Methods: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. Results: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (−49.2%, 95% CI −56.1% to −41.1%, P = 3.1 × 10–18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (−26.7%, 95% CI −39.4% to −11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82–0.91, P = 6.9 × 10–8). Conclusions: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women

Travel Distances by Wisconsin Medicaid Enrollees Who Visit Emergency Departments for Dental Care

Objectives: Prior studies document increased numbers of nontraumatic dental condition (NTDC) visits to U.S. emergency departments (EDs). However, the influence of travel distance on ED use for NTDCs, particularly for Medicaid enrollees has hitherto received little attention. The authors examined the effect of travel distance on Wisconsin Medicaid enrollees’ NTDC visits to EDs after adjustment for covariates. Methods: NTDC-related visits claims data for Wisconsin Medicaid (2001-2009) was analyzed. For each enrollee, travel distance to the nearest of 130 EDs in Wisconsin was determined. The number of NTDC visits per person-year was aggregated by ZIP+4 of residence. Negative binomial regression adjusting for the expected number of visits based on race, sex, age of the residents and calendar year was used to evaluate the effect of travel distance, urbanicity, and dentist-population ratio on rate of visits. Results: Enrollees residing in rural counties, entire dental health professional shortage areas, areas with dentist population ratios \u3e20,000: 1 and non-Hispanic Whites travelled the furthest, compared to nearest mean ED distance of 2.9 miles. Enrollees residing 3 miles away or further had significantly lower rates of NTDC visits to EDs. Conclusions: This study demonstrates that distance is a barrier to making NTDC-related visits to EDs. Rates of NTDC visits decreased as travel distance to the nearest ED increased for Medicaid enrollees