Distinct and shared genetic architectures of Gestational diabetes mellitus and Type 2 Diabetes Mellitus.

Gestational diabetes mellitus (GDM) affects more than 16 million pregnancies annually worldwide and is related to an increased lifetime risk of Type 2 diabetes (T2D). The diseases are hypothesized to share a genetic predisposition, but there are few GWAS studies of GDM and none of them is sufficiently powered to assess whether any variants or biological pathways are specific to GDM. We conducted the largest genome-wide association study of GDM to date in 12,332 cases and 131,109 parous female controls in the FinnGen Study and identified 13 GDM-associated loci including 8 novel loci. Genetic features distinct from T2D were identified both at the locus and genomic scale. Our results suggest that the genetics of GDM risk falls into two distinct categories - one part conventional T2D polygenic risk and one part predominantly influencing mechanisms disrupted in pregnancy. Loci with GDM-predominant effects map to genes related to islet cells, central glucose homeostasis, steroidogenesis, and placental expression. These results pave the way for an improved biological understanding of GDM pathophysiology and its role in the development and course of T2D.

Suppression of behavioural and physiological oestrus in the mare by vaccination against GnRH.

OBJECTIVE: To examine the immunogenicity of an equine immunocontraceptive vaccine and its efficacy in controlling hormone-related behaviour. DESIGN: A total of 24 mares at two sites in Australia were vaccinated with an immunocontraceptive vaccine comprising gonadotrophin releasing hormone (GnRH) conjugated to a carrier protein in immunostimulating complex as an adjuvant. Twelve animals at each site received a placebo of adjuvant alone and served as controls for seasonal oestrus, hormonal and behaviour patterns. Animals were observed for injection site reactions, ovarian and follicular activity, and serum levels of antibody, 17beta-oestradiol and progesterone in the weeks following vaccination. Mares were also examined for oestrous behaviour by teasing with a stallion. RESULTS: All mares responded to vaccination. Two weeks following the second vaccination there was a peak in antibody response to GnRH that declined gradually over the following weeks. Commensurate with the elevated anti-GnRH antibody there was a marked effect on ovarian activity with a reduction in 17beta-oestradiol and progesterone levels in the 24 vaccinated mares. There was also a reduction of oestrus-related behaviour as determined by a teaser stallion. This effect lasted a minimum of 3 months and correlated with the initial level of antibody response. CONCLUSION: Following a conventional two-dose immunisation regime this commercially available equine immunocontraceptive vaccine was effective at inhibiting oestrous behaviour for at least 3 months. This vaccine has a high level of safety since there were no significant local reactions nor were there any adverse systemic responses to vaccination.

Genetic stability among temporally and geographically diverse isolates of Barmah Forest virus.

An increase in the incidence of polyarthritis caused by Barmah Forest (BF) virus, and its recent emergence into Western Australia, prompted a study of the molecular epidemiology of this Australian mosquito-borne alphavirus. The nucleotide sequence of a 500-basepair region of the 3' end of the envelope (E2) gene of the prototype BF virus strain (BH2193) was compared with other members of the alphavirus genus, and to a panel of isolates of BF virus collected more for than 20 years from different geographic regions of Australia. The BF virus was shown to be genetically distinct from other members of the alphavirus genus. A high degree of sequence homology (98-100%) was found between the BF isolates, with no evidence of geographic or temporal divergence. This nucleotide homogeneity was similar to that observed with other Australian mosquito-borne viruses with avian vertebrate hosts, such as Sindbis, Murray Valley, and Kunjin viruses, but it contrasts to the heterogeneity reported for Ross River virus, an alphavirus with mammalian vertebrate hosts.

Positive screening tests for barbiturates in urine samples in the York area over a 1-year period.

Following the screening of urine samples for a panel of drugs over a period of 1 year, a peak was observed during December 1999 and January 2000 in the numbers of samples testing positive for both morphine and barbiturates. This increase may be due to the adulteration of street heroin with barbiturate during this period.

Surgical-orthodontic management of persistent closed lock of the TM joints.

Surgical management of internal derangement in the temporomandibular joint traditionally involves disk repair or removal. Disks are often replaced with various types of autogenous, allogenic or alloplastic materials. The failure rates for such replacements are estimated at 10% to 20%. Current thinking suggests that permanent alloplastic interpositional grafts should be avoided. The following report describes the orthodontic/orthognathic surgical management of a patient with bilateral Silastic fossa implants.

Cephalometric effects of combined palatal expansion and facemask therapy on Class III malocclusion.

The purpose of this study was to examine the cephalometric changes that occur with palatal expansion/facemask therapy for Class III malocclusion. Pretreatment and posttreatment lateral cephalograms from 21 patients were traced and analyzed by traditional cephalometric measures, an x-y coordinate system, and along the functional occlusal plane. Differences between T1 and T2 values were analyzed with paired t-tests. Mean ages were 7.26 years (T1) and 8.18 years (T2). Average treatment time was 11.05 months. Statistically significant anterior movement of the maxilla occurred with increases in SNA (+2.35), maxillary depth (+2.22), and ANB (+3.66), and anterior movement of A-point (+3.34 mm) and ANS (+3.17 mm). The maxilla rotated counterclockwise, with PNS moving down more than ANS (-2.21 mm and -0.82, respectively). The mandible rotated clockwise with mild decreases in SNB (-1.32) and facial depth, (-1.2) but significant downward movement at menton (-4.34 mm). Occlusal plane analysis demonstrated that the correction was due more to the maxilla than the mandible (+2.35 and -1.88 mm, respectively). The maxillary molars moved forward (+1.70 mm) as did the incisors (+1.75 mm). Soft tissue changes included the nose and upper lip moving forward (3.43 and 3.67 mm, respectively), and menton moving downward (-3.49 mm). The results indicate that facemask/palatal expansion therapy improves Class III malocclusion by a combination of skeletal and dental changes that occur the anteroposterior dimension and in the vertical plane of space.

Force magnitude effects upon osteoprogenitor cells during premaxillary expansion in rats.

To study the effects of force magnitude on osteoprogenitor cell activity during premaxillary expansion, stainless steel helical springs were attached to the maxillary central incisors of 45 3-month-old male rats. The animals were randomly divided into force levels (0, 50, 100, 150, 200 gm) and were injected intraperitoneally with tritiated thymidine (1.0 uc/g wt.) 1 hour prior to sacrifice which occurred at 27, 40, and 60 hours. In order to examine cell activity within different regions of the suture, each premaxilla was divided into three geographic areas. Quantitative results were obtained by comparing the percent of labeled cells observed at different force levels, geographic areas, and observation times. The greatest number of labeled cells at each force level was found at 27 hours. Increased forces were correlated with increased numbers of labeled cells up to 100 gm, with decreased cell numbers at higher forces. The numbers of labeled cells at 200 gm were not significantly different from the controls. Histological observations of early bone formation at 60 hours supported the quantitative labeling results at 27 hours. The results also demonstrate a significant correlation between the geographic location of the labeled cells and force magnitude, with maximal cell stimulation occurring more superiorly in the suture as forces increased. The results suggest that early bone formation within the expanded suture can be maximized by varying force magnitude and distance from the point of force application.

Soft tissue evaluation of contemporary Caucasian and African American female facial profiles.

Previous studies suggest that esthetic Caucasian profiles exhibit fuller lips than the norm for their race, while esthetic African American profiles are similar to those of esthetic Caucasians. The present study was undertaken to compare the profiles of female Caucasian and African American models and their nonmodel counterparts. Four groups of 30 subjects were evaluated: Caucasian models [CM], Caucasian controls [CC], African American models [AM], and African American controls [AC]. The models' profiles were photographed from current fashion magazines, the photos were scanned, and 17 landmarks were digitized. Each profile was standardized for size and oriented along the N'-Sn' line on a Macintosh 6115CD computer. Control photographs were processed in a similar manner. Twenty-six variables were measured for each profile. Means, ranges, and standard deviations were computed along with unpaired, two-tailed Student's t-tests (p<0.05) to evaluate group differences. The results showed that for the AM and AC profiles, all but two of the 26 variable were similar. For the CM and CC profiles, eight variables demonstrated significant differences. Between-race comparisons demonstrated greater numbers of parameters that were significantly different: CM/AM with 18 and CM/AC, CC/AC, and CC/AM with 22 each. Most of the differences involved the lips. Vertical soft tissue proportions for the four groups did not follow a 40/20/40 ratio. Caucasian and African American models displayed significantly different profile characteristics. The African American models and controls showed similar profile features, whereas greater differences were observed between Caucasian models and controls. Based on our study, the African American profile currently presented in the mass media is not "Caucasian-like." In fact, it appears that Caucasian models display more ethnic features than African American models do Caucasian features, suggesting that previously held concepts of facial beauty may no longer apply.

Traumatically intruded teeth.

Various combinations of orthodontic force, luxation, and observation are applied to 12 teeth traumatically intruded in 3 large dogs. All showed root resorption to some degree. Early orthodontic repositioning, with luxation if immobile, produced the best recovery.

Characteristics of headgear release mechanisms: safety implications.

The risk of serious eye injury caused by a headgear appliance is a significant concern. Various safety release mechanisms have been developed in order to help prevent this type of injury, but little testing has been done. The purpose of this study was to test 18 headgear release mechanisms. Four characteristics were evaluated: force at release, extension at release, consistency of release, and performance at different rates of pull. At the point of release, mean force values ranged from 5.33 pounds to 32.83 pounds, and mean extension values ranged from 0.84 inches to 2.93 inches. Consistency was based on the percent standard deviation, and the appliances were ranked relative to each other. Nine of the 18 appliances had statistically significant differences in the two pull rates for either variable or both, but the clinical significance is uncertain. The results show a wide range of performance among the 18 appliances tested and indicate that some perform better than others.

Response of headgear release mechanisms to nonaxial force application.

Safety products have been developed to help reduce the incidence of trauma caused by headgear. Previous studies have reported the characteristics of breakaway-type headgear release mechanisms with axial force application. Not all accidental releases are triggered by an axial force and it is necessary to understand the characteristics of these mechanisms with nonaxial force application. Thirteen headgear release mechanisms were tested as part of a complete headgear system. With the system attached to a plaster head and neck model a tensile force was applied to the system at 30 degrees to the sagittal plane at 2 rates. The force of activation at release and the distance traveled were determined and analyzed statistically. Force values ranged from 4.6 to 36.7 pounds and face bow travel before release ranged from 0.97 to 3.42 inches. No consistent pattern of rate dependence was observed. Several devices demonstrated the desirable combination of low force and face bow travel at release.

Orthodontic force application to titanium endosseous implants.

Endosseous implants in dogs are used successfully to apply orthodontic and orthopedic forces. Not all experimental implants remained firm enough through the initial healing period to be used for anchorage.

Orthodontic management of the short face patient.

A short lower face may accompany various types of malocclusions depending on the structural etiology. Because most cephalometric analyses focus on the anteroposterior plane of space, they are often insufficient in diagnosing a significant vertical dysplasia. This article describes a cephalometric analysis that examines not only the vertical proportions of the face, but the various anatomical features that contribute to the dysplasia. Diagnosis is further enhanced by evaluating the facial profile with the mandible postured at various amounts of opening, suggesting the degree of vertical discrepancy. Traditional orthodontic therapy corrects the associated malocclusion but is usually ineffective in changing inherent facial proportions. However, several orthopedic methods have shown the ability to increase lower facial height when used in combination with nonextraction orthodontic mechanotherapy. Adults with short faces require a combination of orthodontics and orthognathic surgery. The Class II malocclusion can usually be managed by surgically advancing the mandible with the curve of Spee maintained. In cases of vertical maxillary deficiency, the LeFort I osteotomy with inferior repositioning provides the spatial correction that is needed. Two cases are presented to illustrate the cephalometric and facial analyses used in diagnosis, as well as the common surgical procedures to manage the short face patient.

The Don Spring Memorial Oration: orthodontic management of the short face patient.

In September 1992, the Australian Foundation for Orthodontic Research and Education held its biennial meeting at Hamilton Island, Queensland. The guest lecturer was Dr Patrick Turley. The first of Dr Turley's presentations was the The Don Spring Memorial Oration, the content of which is included in the following article. The article has been reprinted with the permission of the Editor of the Pacific Coast Society of Orthodontists' Bulletin. The second article will appear in the October 1993 edition of this Journal.

The Don Spring Memorial Oration--Part II: early management of the developing Class III malocclusion.

It was apparent from Dr Turley's presentation that many cases, previously thought to be untreatable by conventional orthodontic means, can be managed with a high degree of success using the techniques described. It is hoped that this overview of management of the developing Class III malocclusion will provide a rationale, a means and a reason for all of us to feel comfortable in treating these interesting and sometimes difficult cases.

The clinical management of ectopically erupting first permanent molars.

The literature on ectopically erupting first permanent molars is reviewed. The progression of the ectopic condition is discussed along with factors that will affect the practitioner's decision on a mode of treatment. The optimal treatment approach depends on the clinical eruption status of /6/, the change in position of /6/, the amount of enamel ledge of /E/ entrapping /6/, the mobility of /E/, and the presence of pain or infection. A variety of treatment approaches together with diagnostic rationale and clinical guidelines are presented. Overall aspects of the malocclusion must be considered when planning the management of ectopically erupting first permanent molars.