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.

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.

Three-dimensional finite element analysis of stress in the periodontal ligament of the maxillary first molar with simulated bone loss.

The purpose of the study was to use the finite element method to simulate the effect of alveolar bone loss on orthodontically induced stress in the periodontal ligament of the maxillary first molar. A 3-dimensional finite element model of a tooth with different levels of bone height was constructed to estimate the reduction in force and the increase in moment to force (M/F) ratio necessary to obtain evenly distributed stress in the periodontal ligament of a tooth with horizontal bone loss. The 3-dimensional finite model comprised a maxillary first molar, the periodontal ligament, and alveolar bone and consisted of 3097 nodes and 2521 elements. An anterior force of 300 g was applied at the center of the buccal crown surfaces of teeth with normal bone height and with bone loss that ranged from 2.0 to 6.0 mm. The results showed that force magnitude required lowering from 80% (2-mm bone loss) and gradually to 37% (6-mm bone loss) of the initial load applied to the tooth without bone loss. The countertipping moment (gram-millimeters) to force (gram) ratio should increase from 9 (no bone loss) to nearly 13 (6-mm bone loss) to maintain the same range of stress in the periodontal ligament as was obtained without bone loss. A linear relationship was observed between the amount of bone loss, the desired reduction in force magnitude, and the increase in M/F ratio. The results of this study indicate that a combination of force reduction and increased M/F ratio is required to achieve uniform stress in the periodontal ligament of a tooth with bone loss.

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.

Pyrithiones as antifoulants: Environmental chemistry and preliminary risk assessment.

Pyrithiones are widely used as bactericides, fungicides, or algicides in a variety of products such as shampoos, metal working fluids, adhesives, sealants, and coatings. This broad antimicrobial activity, along with low water solubility and favorable environmental chemistry, makes zinc pyrithione and copper pyrithione potentially ideal replacements for TBT in marine antifouling paints. Several studies on the toxicity and environ- • mental fate of these pyrithiones have been conducted in freshwater and saltwater systems. Environmental fate studies show that pyrithiones rapidly degrade in the water column to less toxic compounds. Sediment accumulation is also prevented by the facile reduction of a critical functional group under anaerobic conditions. Modeling programs were used to calculate the predicted environmental concentration (PEC) for pyrithione. Comparison of PECs calculated for more persistent antifoulants with actual measured concentrations provided a measure of the bias inherent to the models. The results indicate a pyrithione risk quotient (PEC/PNEC) < 1. The findings are consistent with the absence of ecological effects during the long history of the use of zinc pyrithione as an antidandruff agent.

Cephalometric changes after the correction of class III malocclusion with maxillary expansion/facemask therapy.

The purpose of this study was to analyze the cephalometric changes that occurred during and after the correction of Class III malocclusion. The records of 24 Class III patients treated with a banded expansion appliance and custom facemask were compared with 24 Class I and 27 Class III untreated controls. Cephalometric means were calculated for the annualized data and compared univariately with unpaired t tests to determine significant differences. Treatment results showed more convexity of the facial profile from anterior displacement and downward and backward rotation of the maxilla and clockwise rotation of the mandible. The maxillary teeth moved forward while the lower incisors retruded. Postprotraction results showed the maxilla did not relapse after treatment but grew anteriorly similar to the Class III controls but less than the Class I controls. Mandibular growth was similar for the treatment and control groups. Dental changes compensated for decreasing overjet whereas the soft tissue profile showed no significant posttreatment changes. Results in the intercontrol comparison showed the Class III controls had significantly less forward movement of A-point and greater forward movement of the mandible than Class I controls. Because of these differences using a Class I control group to compare to a Class III treatment group will tend to underestimate the treatment effects and overestimate posttreatment changes. Overcorrection of the Class III malocclusion is recommended to compensate for postprotraction growth deficiency of the maxilla.

The female soft tissue profile as presented in fashion magazines during the 1900s: a photographic analysis.

Numerous studies have emphasized the importance of the facial profile in orthodontic treatment planning, with some arguing that the esthetic ideal has remained unchanged for thousands of years. To evaluate changes in the white female facial profile, we measured 14 soft tissue variables on profile photographs presented in fashion magazines during the 1900s. Five time frames were studied, with a sample of 25 photographs from each period corrected for size and orientation. Between-group differences were examined by use of analysis of variance, using a P value corrected for a multivariable analysis. Significant between-group differences (P < 0.0001) were found for anteroposterior lip position, amount of visible lip tissue, and interlabial angle, with the more recent groups displaying fuller and more anteriorly positioned lips. No significant differences were found for measurements calculated superior to subnasale (frontonasal angle, nasal tip angle, and nasolabial angle) or in the relationship of the chin to the upper face (total facial angle). The results of this study suggest that standards for the esthetic white female facial profile are not static and show a trend in this century toward fuller and more anteriorly positioned lips.

Analysis of stress in the periodontium of the maxillary first molar with a three-dimensional finite element model.

The aim of this study was to simulate the stress response in the periodontium of the maxillary first molar to different moment to force ratios, and to determine the moment to force ratio for translational movement of the tooth by means of the finite element method. The three-dimensional finite element model of the maxillary first molar consisted of 3097 nodes and 2521 isoparametric eight-node solid elements. The model was designed to dissect the periodontal ligament, root, and alveolar bone separately. The results demonstrate the sensitivity of the periodontium to load changes. The stress pattern in the periodontal ligament for a distalizing force without counterbalancing moments showed high concentration at the cervical level of the distobuccal root due to tipping and rotation of the tooth. After various counterrotation as well as countertipping moments were applied, an even distribution of low compression on the distal side of the periodontal ligament was obtained at a countertipping moment to force ratio of 9:1 and a counterrotation moment to force ratio of 5:1. This lower and uniform stress in the periodontal ligament implies that a translational tooth movement may be achieved. Furthermore, high stress concentration was observed on the root surface at the furcation level in contrast with anterior teeth reported to display high concentration at the apex. This result may suggest that the root morphology of the maxillary first molar makes it less susceptible to apical root resorption relative to anterior teeth during tooth movement. The stress patterns in the periodontal ligament corresponded with the load types; those on the root appeared to be highly affected by bending and the high stiffness of the root.

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.

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.

Changes in the Caucasian male facial profile as depicted in fashion magazines during the twentieth century.

The purposes of this study were to (1) measure changes in the young adult Caucasian male profile through time and (2) describe the male profile depicted in current fashion magazines. Profile photographs (n = 116) of male models collected from leading fashion magazines of the last 65 years were analyzed. They were reproduced as slides, and the images were scanned and projected onto a computer monitor. Soft tissue landmarks were digitized and the profiles were corrected for size differences. Six linear, nine angular, and three proportional parameters were measured. Anteroposterior lip position, lip curl, and vermilion area showed statistically significant correlations (r > or = 31, p < 0.01) with the progression of time. Other angular measurements and vertical facial proportions did not change significantly (r < or = 17, p > 0.05). The results showed that (1) the male profile depicted in fashion magazines has changed significantly with time and the changes were in the area of the lips; and (2) there was a trend of increasing lip protrusion, lip curl, and vermilion display. We conclude that similar to the female profile, the esthetic male profile has changed with time.

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.

Cephalometric effects of face mask/expansion therapy in Class III children: a comparison of three age groups.

The purpose of this investigation was to determine the skeletal, dental, and soft tissue effects of face mask/expansion therapy and to examine the effect of age on treatment response. Pretreatment and posttreatment cephalometric radiographs from 63 subjects (4 to 13 years) who had a Class III malocclusion were analyzed. Serial cephalometric tracings of 32 subjects with Class I occlusion made at 4, 6, 8, 10, 12, and 14 years were used as controls. Landmarks were digitized on each tracing and treatment effects were measured by using cranial base and maxillary superimposition techniques. Annual rate differences were compared with t tests for the combined treated group (N = 63) and between stratified treated groups (4 to 7 years N = 15, 7 to 10 years N = 32, 10 to 14 years N = 16). The treated group (N = 63) demonstrated significant (p < 0.001) hard and soft tissue changes that resulted from treatment. Skeletal change was primarily a result of anterior and vertical movement of the maxillae. Mandibular position was directed in a downward and backward vector. Orthodontic changes contributed to the correction, and soft tissue effects resulted in a more convex profile. Minimal significant differences were observed between age groups when comparing angular and linear measurements alone. However, when analyzing the algebraic sum of treatment effects (Johnston analysis), significantly (p < 0.01) greater differences were observed in apical base change (ABCH) and total molar correction (6/6) in the younger age groups. This study demonstrates that face mask/expansion therapy produces dentofacial changes that combine to improve the Class III malocclusion. Although early treatment may be most effective, face mask therapy can provide a viable option for older children as well.

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.

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--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.