Structured genome-wide association methods can be used to find population substructure, determine significant SNPs, and subsequently narrow down the field of SNPs to those most significant for determining disease risk. Beginning with more than 500,000 SNPs and rheumatoid arthritis (RA) phenotype data for cases and controls, we used a three-part clustering approach that found 684 SNPs significant for determining RA after accounting for clusters, and of those, 168 SNPs with differing odds across clusters. These 168 SNPs were used to create 16 population subgroups, each revealing a unique pattern of minor allele frequencies. The subgroups showed some commonality in multi-dimensional scaling plots, however, and were combined into five RA risk categories, each with odds differing from the other categories with pvalues less than 0.0001. Thus, based on SNP information from 168 SNPs it may be possible to assign an individual into one of five distinct RA risk categories.

In dentistry today, endosseous implants have become a generally favorable treatment option for edentulous spaces in the oral cavity because of proven biocompatibility, potential for esthetics, and good long term prognosis.(1) However, there are risk factors to consider that may affect and impair the osseointegration of an implant. A possible risk factor is type 2 diabetes mellitus (T2DM), a metabolic disorder characterized by insulin resistance at the target tissue site and progressive destruction of the pancreatic beta cells that ultimately results in prolonged periods of hyperglycemia.(2) When the serum glucose levels were persistently high, it was shown to impair bone metabolism and thus, has the potential to impair implant osseointegration.(3)

Craniofacial defects can result from congenital malformations, trauma, tumor resection,periodontal disease, post-extraction ridge remodeling, and peri-implantitis. Regenerationof bone is critical to achieving functional and esthetic outcomes in the rehabilitation ofsuch defects. Traditional strategies for osseous regeneration include a multiple ofsurgical techniques utilizing autologous bone, cadaver-sourced allogeneic or xenogeneicbone, synthetic bone biomaterials, barrier membranes, or combinations thereof(Wikesjö, Qahash 2009). The need to enhance the predictability of regeneration inespecially large defects that cannot heal adequately without intervention (critical-sizedefects) has led to recent development of protein- and cell-based technologies.[Introduction, first paragraph]

Matching-diameter and platform shift abutments were randomized to 40 dental implants placed into 5 dogs following mucoperiosteal flap elevation. 1x5 (width x height) mm peri-implant gap defects were surgically created in randomly assigned jaw quadrants. All implants were placed 2 mm subcrestally. Mucoperiosteal flaps were sutured around the abutments for primary intention healing. Radiographs were recorded immediately, 4-, and 8 weeks postsurgery when block biopsies were removed for histometric analysis. The histological examination showed the junctional epithelium was arrested coronal to the implant platform without significant differences among experimental conditions. Crestal bone height demonstrated no significant differences among groups at buccal or lingual sites. Bone-implant contact reached 0.4 mm below the platform at buccal sites. Higher variability was observed at lingual sites without differences among groups. Platform shift abutments offer negligible benefit compared to conventional abutments to maintain peri-implant crestal bone and soft tissue contours.

Liver disease is an important health concern and a significant source of morbidity and mortality in the United States and worldwide. NEDD8 (neural-precursor-cell-expressed developmentally down-regulated 8) is a novel ubiquitin-like protein modifier. The conjugation of NEDD8 to target proteins, termed neddylation, requires NEDD8 specific E1, E2 and E3 ligases. Neddylation participates in various cellular processes. However, whether neddylation regulates liver development and function is completely unknown. We created mice with hepatocyte specific deletion of NAE1, a subunit of the only NEDD8 E1 enzyme, and identified that they display severe hepatomegaly, hypertriglyceridemia, and hypercholesterolemia from 10 days after birth. By postnatal 14 days, their liver cytoarchitecture is completely disrupted, along with formation of numerous biliary cysts, fibrosis and hypoglycemia, which ultimately result in liver failure and premature death by 6 weeks. Mechanistically, NAE1 deficiency in hepatocytes caused reduced hepatocytespecific gene expression but increased biliary/oval cell gene expression in liver. In vitro, NAE1 inhibition by MLN4924 and CRISPR/Cas9-mediated NAE1 deletion in HepG2 cells recapitulated in vivo findings with repressed expression of hepatocyte specific genes but elevated biliary/oval cell gene expression. Together, these data highlight an essential role for neddylation in regulating hepatocyte lineage commitment and function as well as polycyst formation through trans/de-differentiation of hepatocytes.

Implant dentistry has become a widely accepted modality to replace missing teeth. However, dental implants are susceptible to biofilm-mediated inflammatory lesions (peri-implant mucositis / peri-implantitis), similar to that seen around natural teeth (gingivitis / periodontitis). These lesions, in turn, threaten the longevity of implants as anchors for dental prostheses. Because of the similarity in etiology and presentation, comparable treatment modalities are applied to resolve peri-implant and periodontal inflammatory lesions. Such a shared treatment includes mechanical debridement, with or without surgical repositioning of the soft tissue complex. However, most contemporary dental implants feature threads to engage the alveolar bone and a micro/nano-textured surface to stimulate bone-implant contact (osseointegration). Therefore, when the implant threads become exposed and contaminated by biofilm, subsequent surface debridement / decontamination becomes considerably more complex than with that of a natural tooth, which is usually debrided using a metal curette or ultrasonic device. The micro/nano-textured surface of a dental implant is easily damaged by instrumentation using a metal curette. If an efficient method of dental implant surface decontamination could be established, then clinical protocols may be developed that effectively clean the implant surface to achieve peri-implant tissue health. To this end, lasers have been introduced; however, directly applied laser energy may also affect implant surface characteristics, including micro/nano-structure and composition, essential to osseointegration. Therefore, lasers may have disadvantageous clinical effects, in turn compromising peri-implant tissue consolidation and health: the very aspects its use is attempting to provide. Commercially available Er,Cr:YSGG lasers have been used to remove such implant-attached deposits, however the efficacy in removal of bacteria and the safety to the implant surface integrity have yet to be demonstrated quantitatively.

Within the medical field, the demand to store and analyze small sample, large variable data has become ever-abundant. Several two-sample tests for equality of means, including the revered Hotelling’s T2 test, have already been established when the combined sample size of both populations exceeds the dimension of the variables. However, tests such as Hotelling’s T2 become either unusable or output small power when the number of variables is greater than the combined sample size. We propose a test using both prepivoting and Edgeworth expansion that maintains high power in this higher dimensional scenario, known as the “large p small n ” problem. Our test’s finite sample performance is compared with other recently proposed tests designed to also handle the “large p small n ” situation. We apply our test to a microarray gene expression data set and report competitive rates for both power and Type-I error.

A current paradigm-shift in implant dentistry places restorative factors associated with esthetics and function in front of implant site selection based on bone quantity and quality. Marginal bone loss after implant placement, resorption of the edentulous alveolar ridge, bone defects from periodontal disease, and ridge aberrations due to trauma all challenge implant treatment driven by esthetics and function. Clinicians compensate for bone loss using bone augmentation procedures including bone grafts, bone materials, biologic mediators, barrier devices, or combinations thereof. The search for treatment modalities to address implant placement into compromised sites has lead to the development of a variety of products designed to replace or induce bone formation. Some believe an ideal material could be coated onto implants, to promote osseointegration, induce local bone formation, while not requiring adjunctive biomaterials, or procedures including placement of allogeneic and xenogeneic biomaterials, or autograft bone.

The discovery and subsequent characterization of endogenous signaling peptides known as bone morphogenetic proteins (BMPs) capable of inducing de novo bone formation in postfetal life represents a critical advancement in the understanding of tissue morphogenesis and has become an incentive to develop additional growth factor based tissue engineering strategies (Wozney & Seeherman 2004). Because BMPs act locally, a suitable carrier system must be used to ensure effective presentation of an adequate dose to a target site (Mont et al. 2004). A number of candidate biomaterials have thus been tested as potential carrier technologies (Huang et al. 2008). Currently, recombinant human BMP-2 (rhBMP-2) coupled with an absorbable collagen sponge (ACS) manufactured from bovine Achilles tendon Type 1 collagen is the only FDA approved device for orthopedic and craniofacial indications. Although the rhBMP-2/ACS construct has demonstrated clinical efficacy for indications including spine fusion, long bone fracture healing, sinus and alveolar augmentation, the ACS’s inability to resist tissue compression limits its use for onlay indications (Wikesjö et al. 2007).

The use of implant-retained and supported prostheses has become a very successful treatment for completely edentulous patients. One of the most common fixed solutions involving implants consists of 5 to 7 implants supporting a framework upon which either porcelain or prefabricated acrylic resin denture teeth are added. A screw is utilized to attach the framework/prosthesis to the implants. Screw loosening is the second most common clinical complication in the implant-prosthesis system. If clinicians fail to detect worn or loose retaining screws, prosthetic fracture could occur, leading to more complicated, time consuming, and expensive repairs. Unfortunately, there is no established parameter that indicates when to expect these complications, and there is no proven recall-maintenance protocol to prevent them. The aim of this study is to examine and compare differences among de-torque values and prosthetic retention screws, using a simulated 5 implant-supported, mandibular complete fixed prosthesis. Material and Methods: Nine groups, each with its respective control, using five Nobel Biocare implants and a milled titanium framework were fabricated, assembled and tested. Dynamic loading was p on the performed tested groups through a custom made loading device for anterior, posterior, and distal cantilevered segments of the prosthesis, calculated to simulate clinical usage time. Removal of screws after 2 years of simulated oral function was performed. Before and after testing, screws were evaluated with a Scanning Electronic Microscope (SEM), for presence of debris, thread striations and homogeneity. Control groups remained unloaded for the same time the loaded groups were tested. Results: Comparisons of the difference between initial tightening torque and de-torque screw values were performed between loaded/unloaded groups and with respect to implant position. The interaction between loaded and position was significant (p=0.002). The comparison between loaded/unloaded groups was not statistically significant (p=0.518). Loaded and unloaded groups were compared separately at each of the 5 implants position, which showed a significant difference (p=0.0002, α=0.001). The sequencing effect was only seen in the control groups and thus would only be relative to framework insertion. The sequence effect was found to be overcome by from loading and resulted in a totally different position related to screw tightness. Within the limitations of this in vitro study, it was concluded that sequence of torque application could play a role in the preload of screws even with a passive fit, regardless the load applied.