Three-dimensional digital assessment of typodont activations.

OBJECTIVES: Wax typodonts are widely used as pre-clinical teaching tools to test and research the complex force systems created by archwire activations, however, a limitation is the inability to quantify the resultant statically indeterminate tooth movements. The aim of this study was to develop an analogue-to-digital typodont system to quantify the effects of archwire activations on individual typodont teeth in three dimensions. METHODS: The typodont system was developed using CAD/CAM technology. Posterior expansion, squared, tapered, asymmetrical arch forms and reversed curve of Spee activations were tested with three repeats. The resulting three-dimensional movements of individual typodont teeth were assessed with six degrees of freedom (df). Cartesian coordinate systems were set for each tooth. Mesio-distal, bucco-lingual and intrusive-extrusive movements were assessed as changes in the location of the geometrically estimated centre of resistance in the x, y and z axes, respectively. Torque, tip and rotation movements were assessed as the rotations around the mesio-distal, bucco-lingual and intrusive-extrusive axes, respectively. RESULTS: Individual typodont tooth displacements from each activation could reliably be described with six df. The transversal-to-sagittal movement ratio ranged from 2:1 to 7:1, depending on the activation. Asymmetrical arch form activations caused a midline shift and affected the lateral overjet. Reversing the curve of Spee led to intrusion of incisors and second molars, extrusion of premolars and first molars and pronounced first and third order effects. CONCLUSION: The digital typodont system is a promising teaching tool. The tested activations have implications in three dimensions, which should be considered when planning tooth movements.

Biomechanical properties of the lips in a pre-orthodontic sample of adolescents and young adults.

OBJECTIVES: To assess biomechanical properties of the lip muscles and to investigate their relationship with sex, age, body mass index (BMI), and cephalometric variables. MATERIALS AND METHODS: Demographic information and BMI were collected from 83 study participants seeking orthodontic treatment at the University of Otago. Tone, stiffness, and elasticity of the lip muscles were measured thrice at four different anatomical sites using a digital palpation device. To estimate method error, a duplicate set of measurements in a subsample of 20 participants was taken a week later. Sagittal and vertical cephalometric classifications were based on ANB and FMPA angles, respectively. Data were analysed using mixed models. RESULTS: Biomechanical properties of lip muscles were remarkably consistent both within and between different recording sessions. The lower lip had higher tone and stiffness than the upper lip. Both the upper and lower lip stiffness and tone were higher in females than in males, whereas upper lip elasticity was higher in males. Thinner upper lips had higher tone and were stiffer than thicker upper lips, whereas thinner lower lips were less elastic than thicker lower lips. Muscle tone and stiffness of both the upper and lower lips were lower in Class III than in Class I and Class II individuals. The upper lip of hyperdivergent individuals was less elastic than that of normodivergent and hypodivergent individuals, and stiffer than that of hypodivergent individuals. CONCLUSIONS: The biomechanical properties of perioral soft tissues can be reliably measured and vary with anatomical site, sex, and cephalometric measurements.

Common variants of EDA are associated with non-syndromic hypodontia.

OBJECTIVE: The aim of this case-control study was to investigate the association between non-syndromic hypodontia and nineteen common variants of candidate genes ectodysplasin A (EDA), paired box 9 (PAX9), msh homeobox 1 (MSX1) and axis inhibition protein 2 (AXIN2). SETTINGS AND SAMPLE POPULATION: Sixty-one hypodontia cases were frequency-matched to 253 controls with no missing teeth (excluding the third molars). MATERIAL AND METHODS: Self-report data and DNA samples were collected from each participant. RESULTS: The sample had a mean age of 16.6 years (SD = 7.3), with most participants being female (59.6%), and of New Zealand European origin (75.4%). Using multiple logistic regression analysis, it was found that the T-allele of rs12853659 (EDA) and the G-allele of rs2428151 (EDA) were both associated with a higher risk of hypodontia (odds ratio, OR = 2.79, 95% CI = 1.11-7.01; and OR = 2.87, 95% CI = 1.04-7.94, respectively). The G-allele of rs2520378 (EDA) showed a protective effect with an OR of 0.61 (95% CI = 0.38-0.99). The EDA SNP findings were consistent with previous reports included in a meta-analysis. No associations were found with the PAX9, AXIN2 and MSX1 genes, after adjusting for sex and ethnicity. CONCLUSIONS: Common variants of the EDA genes are associated with specific phenotypes of non-syndromic hypodontia, thus confirming their role in the regulatory pathways of normal tooth development. However, larger samples are needed to investigate the association further.

Factors associated with orthodontic pain.

BACKGROUND: Pain experienced at teeth during orthodontic treatment varies largely over time, with the reasons for its interindividual variability being largely unknown: age, sex, clinical activations, psychosocial factors and genetic polymorphisms of candidate genes are putative factors that may account to explain this variability. We aimed to investigate the effect of clinical, demographic, psychological and genetic factors on pain levels experienced during fixed orthodontic treatment. METHODS: A convenience sample of 183 patients undergoing full-fixed orthodontic treatment were recruited. Participant's pain levels were assessed seven times over a three-day period via a smartphone app. Clinical, demographic and psychological data were collected via questionnaires. This included the Pain Catastrophising Scale (Child version), the Corah Dental Anxiety Scale and the State and Trait Anxiety Inventory. Participants provided a DNA sample either in the form of blood or saliva, which were used for genotyping COMT gene rs6269, rs4680, rs4646310, NR3C1 gene rs2963155 and the HTR2A gene rs9316233. RESULTS: Bond ups had the greatest influence on perceived levels of pain experienced on teeth during orthodontic treatment, accounting for over 20% of total variance in pain response. High-pain responders had higher scores on pain catastrophising (magnification subscale). Self-reported pain during fixed orthodontic treatment was not influenced by sex, age, time into treatment, anxiety, nor by polymorphisms of COMT, HTR2A or NR3C1 genes. CONCLUSIONS: Pain on teeth resulting from orthodontic fixed appliances is stronger during bonds-up and in patients with high catastrophising scores. Demographics, type of clinical activations and the genetic polymorphisms investigated in this research had little or no impact on perceived pain levels.

Role of Bile Acids and GLP-1 in Mediating the Metabolic Improvements of Bariatric Surgery.

BACKGROUND & AIMS: Bile diversion to the ileum (GB-IL) has strikingly similar metabolic and satiating effects to Roux-en-Y gastric bypass (RYGB) in rodent obesity models. The metabolic benefits of these procedures are thought to be mediated by increased bile acids, although parallel changes in body weight and other confounding variables limit this interpretation. METHODS: Global G protein-coupled bile acid receptor-1 null (Tgr5-/-) and intestinal-specific farnesoid X receptor null (FxrΔ/E) mice on high-fat diet as well as wild-type C57BL/6 and glucagon-like polypeptide 1 receptor deficient (Glp-1r-/-) mice on chow diet were characterized following GB-IL. RESULTS: GB-IL induced weight loss and improved oral glucose tolerance in Tgr5-/-, but not FxrΔ/E mice fed a high-fat diet, suggesting a role for intestinal Fxr. GB-IL in wild-type, chow-fed mice prompted weight-independent improvements in glycemia and glucose tolerance secondary to augmented insulin responsiveness. Improvements were concomitant with increased levels of lymphatic GLP-1 in the fasted state and increased levels of intestinal Akkermansia muciniphila. Improvements in fasting glycemia after GB-IL were mitigated with exendin-9, a GLP-1 receptor antagonist, or cholestyramine, a bile acid sequestrant. The glucoregulatory effects of GB-IL were lost in whole-body Glp-1r-/- mice. CONCLUSIONS: Bile diversion to the ileum improves glucose homeostasis via an intestinal Fxr-Glp-1 axis. Altered intestinal bile acid availability, independent of weight loss, and intestinal Akkermansia muciniphila appear to mediate the metabolic changes observed after bariatric surgery and might be manipulated for treatment of obesity and diabetes.

Some orthodontists' experiences of volunteering for a community orthodontic initiative.

INTRODUCTION: In society, dental professionals, including orthodontists, are often viewed as being solely motivated by money. Nevertheless, numerous orthodontists volunteer for community initiatives where they provide free or heavily subsidized treatment for underserved populations. This study explores the motivations of a group of New Zealand orthodontists who volunteered for one of these initiatives, Wish For A Smile (WFAS), as well as the high and low points of this work. METHODS: Qualitative telephone interviews were conducted with 11 orthodontists who volunteer for WFAS. An inductive data analysis of the data was undertaken and a descriptive qualitative method was chosen. RESULTS: Most participants volunteered for WFAS because they desired to give back to the community. High points of their voluntary work were seeing patients' self-esteem, happiness, and future life chances increase as a result of treatment. Low points included seeing the challenging life circumstances of some WFAS patients and treating some adolescents who appeared not to qualify. A number of participants said WFAS patients were more grateful and cooperative than fee-paying patients, whereas others reported the opposite. CONCLUSIONS: There are many reasons why orthodontists volunteer for orthodontic community initiatives, although many may be motivated by a sense of social responsibility to give back to the community.

Long-term changes in oral health-related quality of life of standard, cleft, and surgery patients after orthodontic treatment: A longitudinal study.

INTRODUCTION: The aim of this study was to assess long-term changes and describe the trajectories of oral health-related quality of life (OHRQoL) in a cohort of cleft, surgery, and standard patients who received orthodontic treatment. METHODS: Standard (n = 16), cleft (n = 19), and orthognathic surgery (n = 22) patients completed the short-form of the Oral Health Impact Profile (OHIP-14) before treatment, immediately posttreatment, and approximately 5 years posttreatment. RESULTS: An overall reduction in OHIP-14 scores (improvement in OHRQoL) occurred after orthodontic treatment; however, this was only significant for the surgery and standard groups (P <0.05). The total OHIP-14 score increased significantly from posttreatment to 5 years follow-up for all 3 study groups (P <0.05). Relative to pretreatment, however, there were significant reductions in total OHIP-14 scores at 5 years posttreatment in the surgery group (-57.4%; P <0.05), but not in the standard sample (-24.2%; P >0.05). By contrast, the OHIP-14 score in the cleft group increased but not significantly (40.2%; P >0.05). Using a mixed model analysis, a significant interaction was detected between patient group and time (ie, study time point) (F = 6.0; P <0.0001), after adjusting for age and sex. CONCLUSIONS: Distinct patient groups showed different OHRQoL trajectories after orthodontic treatment. Treatment-related improvements in OHRQoL are maintained over time for surgery patients, but not for those with standard malocclusions and orofacial clefts.

Metabolic responses to exogenous ghrelin in obesity and early after Roux-en-Y gastric bypass in humans.

AIMS: Ghrelin is a gastric-derived hormone that stimulates growth hormone (GH) secretion and has a multi-faceted role in the regulation of energy homeostasis, including glucose metabolism. Circulating ghrelin concentrations are modulated in response to nutritional status, but responses to ghrelin in altered metabolic states are poorly understood. We investigated the metabolic effects of ghrelin in obesity and early after Roux-en-Y gastric bypass (RYGB). MATERIALS AND METHODS: We assessed central and peripheral metabolic responses to acyl ghrelin infusion (1 pmol kg-1 min-1 ) in healthy, lean subjects (n = 9) and non-diabetic, obese subjects (n = 9) before and 2 weeks after RYGB. Central responses were assessed by GH and pancreatic polypeptide (surrogate for vagal activity) secretion. Peripheral responses were assessed by hepatic and skeletal muscle insulin sensitivity during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Ghrelin-stimulated GH secretion was attenuated in obese subjects, but was restored by RYGB to a response similar to that of lean subjects. The heightened pancreatic polypeptide response to ghrelin infusion in the obese was attenuated after RYGB. Hepatic glucose production and hepatic insulin sensitivity were not altered by ghrelin infusion in RYGB subjects. Skeletal muscle insulin sensitivity was impaired to a similar degree in lean, obese and post-RYGB individuals in response to ghrelin infusion. CONCLUSIONS: These data suggest that obesity is characterized by abnormal central, but not peripheral, responsiveness to ghrelin that can be restored early after RYGB before significant weight loss. Further work is necessary to fully elucidate the role of ghrelin in the metabolic changes that occur in obesity and following RYGB.

Effect of orthodontic treatment on the periodontal tissues.

Reduced periodontal support is a challenge that clinicians often face during rehabilitation of compromised dentition. The close and intricate relationship between the periodontal tissues and the processes of tooth movement suggest that adjunct orthodontic therapy may play an important role in overcoming these problems. On the other hand, excessive movement of teeth beyond the anatomic boundaries of the alveolar process is commonly believed to contribute to further destruction of the periodontal tissues. This review evaluates the clinical effects of various orthodontic tooth movements on the surrounding periodontal soft tissues and alveolar bone. Another objective was to identify possible patient and treatment-related factors that may influence the response of periodontal tissue to specific orthodontic treatments. Particular emphasis is placed on specific tooth movements, such as extrusion, intrusion, space closure and arch expansion. Limitations of current research are also highlighted and discussed.

Management of missing mandibular second premolars: a review.

Tooth agenesis is the most common developmental dental anomaly and it is frequently associated with other dento-skeletal disturbances, such as structural variations of other teeth, late dental eruption, transpositions and crowding. Except for the third molars, the mandibular second premolars are the most commonly missing teeth. Oral rehabilitation of patients with missing mandibular premolars often requires a multi-disciplinary approach, and usually results in prolonged treatment time and a greater burden of care. An understanding of the aetiology and clinical features of hypodlontia is essential for the planning phase and the outcome of treatment. The purpose of the present review is, therefore, to discuss the aetiology of hypodlontia as well as to evaluate the clinical options available for the treatment of missing mandibular second premolars. An insight into future research directions and their clinical applications will also be discussed.

Jejunal administration of glucose enhances acyl ghrelin suppression in obese humans.

Ghrelin is a gastric hormone that stimulates hunger and worsens glucose metabolism. Circulating ghrelin is decreased after Roux-en-Y gastric bypass (RYGB) surgery; however, the mechanism(s) underlying this change is unknown. We tested the hypothesis that jejunal nutrient exposure plays a significant role in ghrelin suppression after RYGB. Feeding tubes were placed in the stomach or jejunum in 13 obese subjects to simulate pre-RYGB or post-RYGB glucose exposure to the gastrointestinal (GI) tract, respectively, without the confounding effects of caloric restriction, weight loss, and surgical stress. On separate study days, the plasma glucose curves obtained with either gastric or jejunal administration of glucose were replicated with intravenous (iv) infusions of glucose. These "isoglycemic clamps" enabled us to determine the contribution of the GI tract and postabsorptive plasma glucose to acyl ghrelin suppression. Plasma acyl ghrelin levels were suppressed to a greater degree with jejunal glucose administration compared with gastric glucose administration (P < 0.05). Jejunal administration of glucose also resulted in a greater suppression of acyl ghrelin than the corresponding isoglycemic glucose infusion (P ≤ 0.01). However, gastric and isoglycemic iv glucose infusions resulted in similar degrees of acyl ghrelin suppression (P > 0.05). Direct exposure of the proximal jejunum to glucose increases acyl ghrelin suppression independent of circulating glucose levels. The enhanced suppression of acyl ghrelin after RYGB may be due to a nutrient-initiated signal in the jejunum that regulates ghrelin secretion.

Morphometric growth changes of the nasopharyngeal space in subjects with different vertical craniofacial features.

INTRODUCTION: The purpose of this study was to morphometrically investigate the growth pattern of the adenoids in growing subjects with hyperdivergent and hypodivergent vertical craniofacial features. METHODS: In this retrospective study, we used a longitudinal sample of lateral cephalometric radiographs of 28 hyperdivergent and 30 hypodivergent subjects from 4 to 13 years of age. The radiographs were obtained from the American Association of Orthodontists Foundation Craniofacial Growth Legacy Collection. Measurements were made using digital tracings of the lateral cephalograms and point distribution models. Mixed-model analyses were used for statistical analysis. RESULTS: The mean distance between the sphenoid bone and the posterior nasal spine increased up to 5.3 mm over a 9-year span (95% CI, 4.1-6.5 mm; P <0.001). Furthermore, the mean distance between the sphenoid bone and the posterior nasal spine differed significantly (P = 0.029) between facial types; it was consistently greater (1.8 mm; 95% CI, 0.2-3.3 mm) in the hyperdivergent group. The nasopharyngeal airway area showed a trend to increase with age up to 12-fold (P <0.001). A significant interaction (P = 0.004) was found between age and facial type. Assessment of the adenoid shapes showed greater convexities in the hyperdivergent group, which were observable from an earlier age and for a longer duration. CONCLUSIONS: Clear differences in the morphometric growth pattern of the adenoids were found between facial types. Evaluation of adenoid shapes showed more prominent convexities that lasted longer in the long facial types than in the short facial types.

Hepatic TLR4 signaling in obese NAFLD.

Nonalcoholic fatty liver disease occurs frequently in the setting of metabolic syndrome, but the factors leading to nonalcoholic steatohepatitis (NASH) are not fully understood. This study investigated Toll-like receptor 4 (TLR4) signaling in human liver with the goal of delineating whether activation of this pathway segregates those with nonalcoholic fatty liver from those with NASH. Experiments were performed using liver biopsy tissue obtained from class III obese subjects undergoing bariatric surgery, and extended to an immortalized human hepatocyte HepaRG cell line and primary human hepatocytes. The bacterial endotoxin lipopolysaccharide (LPS) and total free fatty acid levels were significantly increased in plasma of NASH patients. TLR4 mRNA levels were significantly increased in subjects with NASH compared with NAFL as was interferon regulatory factor (IRF) 3 in the myeloid differentiation factor 88-independent signaling pathway. In HepaRG cells, nuclear factor-κB (NF-κB) nuclear translocation and functional activity increased following treatment with the fatty acid, palmitate, and following exposure to LPS compared with hepatocytes stimulated with a lipogenic treatment that induced de novo lipogenesis. Palmitate and LPS induction of NF-κB activity was partially attenuated by chemical- or small-interfering RNA-mediated inhibition of TLR4. Expression of TLR4 and its downstream mediators was upregulated with palmitate and LPS. Similar results were observed using primary human hepatocytes from a lean donor. Interestingly, NF-κB activity assays showed obese donor hepatocytes were resistant to chemical TLR4 inhibition. In conclusion, TLR4 expression is upregulated in a large cohort of NASH patients, compared with those with NAFL, and this occurs within the setting of increased LPS and fatty acids.

Oral health-related quality of life changes in standard, cleft, and surgery patients after orthodontic treatment.

INTRODUCTION: The purpose of this study was to investigate the effect of orthodontic treatment on oral health-related quality of life (OHRQoL) in groups of standard patients with severe malocclusions; cleft lip, cleft palate, or cleft lip and palate patients; and orthognathic surgery patients. METHODS: The study sample consisted of 83 consecutive patients undergoing treatment at the orthodontic unit of Christchurch Hospital, Christchurch, New Zealand, divided into 3 groups: 30 adolescents with severe malocclusions; 24 adolescents with cleft lip, cleft palate, or cleft lip and palate; and 29 adults with severe skeletal discrepancies requiring both orthognathic surgery and orthodontic treatment. Each patient completed the Short Form of the Oral Health Impact Profile (OHIP-14) questionnaire before and after orthodontic treatment. RESULTS: The baseline OHIP-14 subscale scores among the 3 study groups were significantly different, with the surgery patients having nearly twice the OHIP-14 scores of the other 2 groups for nearly half of the items (P <0.05). The surgery patients experienced the greatest reduction in OHIP-14 scores (ie, improvement in OHRQoL), with the largest effect sizes reported for the psychological discomfort (+2.73) and disability (+2.65) domains. The group with clefts experienced the smallest changes in OHIP-14 scores across all 7 domains (-0.03 to +0.63). After adjusting for age and sex, the surgical patients had a significantly greater reduction in pretreatment OHIP-14 scores than did the standard and the cleft patients (P <0.01). CONCLUSIONS: The effect of orthodontic treatment on OHRQoL varies for different patient groups even after adjusting for age and sex. The greatest improvement in OHRQoL occurred in adults with a need for orthognathic surgery, whereas the least improvement seemed to occur in adolescents with cleft lip, cleft palate, or cleft lip and palate.

Evidence of secular trends in a collection of historical craniofacial growth studies.

BACKGROUND/OBJECTIVES: Although secular trends have been well documented in the craniofacial region, there is no evidence to suggest that these temporal changes exist in samples used for orthodontic research. The aim of this study is to determine the effect of secular trends on craniofacial growth in a series of longitudinal birth cohorts that are frequently used in orthodontic research. MATERIALS/METHODS: Cephalometric data from serial lateral headfilms of 138 adolescents (total of 1252 cephalograms) were collected from the Craniofacial Growth Legacy Collection, which includes nine historical growth studies that were mostly conducted throughout the past century. Mixed-effects linear models were used to test the effect of 'year of birth (yob)', 'age', and their interaction on six sagittal (SNA, SNB, ANB, S-N, Co-A, Co-Po) and two vertical (N-Me, ANS-Me) cephalometric measurements. RESULTS: Five of the eight cephalometric variables showed a significant (P ≤ 0.017) 'yob' effect, with four of these indicating an increase over time (SNA, ANB, S-N, Co-A) and one indicating a decrease (SNB). Highly significant (P < 0.001) interactions between 'age' and 'yob' were found for the measurements SNA, ANB, Co-A, and S-N. LIMITATIONS: Some of the limitations of the present study include the use of a small, non-random sample of the original large-scale growth studies. CONCLUSIONS/IMPLICATIONS: Secular trends were found in the craniofacial growth records of the 138 participants derived from the longitudinal growth studies. These secular trends are likely to have important clinical implications for the findings of controlled clinical trials in orthodontics. More research is needed to establish the presence of secular trends in other historical collections.

Pharmaceutical policy reform in the Russian Federation.

Of Russia's 142 million citizens, fewer than 20 million are enrolled in outpatient drug coverage plans. The current government aims to establish universal health insurance including outpatient medicines. Based on the current political and regulatory environment, this report explores pharmaceutical pricing options for Russia that balance greater access to medicines with achieving government plans of boosting local pharmaceutical production. To match innovative medicine prices with their health benefits, in the long run, we suggest that Russia consider adopting value-based pricing, and in the short term, that it introduce direct price negotiations and price drugs according to reference countries that use health technology assessment. Although generic market shares are high, generic medicine prices are higher than they should be. We propose tenders at the manufacturer level for the pricing of high-selling generics, and free pricing for products with sufficient market competition. These policy recommendations are a jumping-off point for further discussion about how pharmaceutical policy could aid this major economy to achieve its population health and health service goals.

The effect of incremental lower lip advancement on oral pressure and EMG activity of the lower lip.

OBJECTIVES: During orthodontic arch expansion, the teeth are displaced against the perioral soft tissues. This can affect the equilibrium of forces that are thought to act on teeth, with consequent implications for long-term stability. The aim of this study was to investigate the effect of incremental lower lip advancement on intraoral pressure and electromyographic (EMG) activity of the lower lip. MATERIALS AND METHODS: Intraoral pressure and EMG activity was measured in 10 participants (2 males, 8 females; 22 years ± 7 months) as the lower lip was incrementally advanced using three custom-made vacuum-formed stents of differing labial thicknesses (0.5, 2.5, and 4.5 mm). A task paradigm including at rest recordings and maximal voluntary contraction was completed for each tray. RESULTS: Resting lip pressure generated increased as the lower lip was advanced (P < 0.001). The EMG activity of the lower lip increased significantly (P < 0.001) only once the lip was advanced from 2.5 to 4.5 mm. For the pressure recordings, the response to incremental lip advancement showed considerable individual variation. CONCLUSIONS: These findings suggest that the initial pressure increase on the lower incisors was mostly likely due to the inherent viscoelastic properties of the lower lip, while the pressure increase between the 2.5 and 4.5 mm advancement was due to increased muscle activity. Each individual also responded to lower lip advancement in a different yet subject-specific manner.

A three-dimensional evaluation of Maori and New Zealand European faces.

OBJECTIVE: Maori patients are often inappropriately treated using Caucasian norms, despite obvious differences in facial morphology. There is currently very little data concerning the nature and/or magnitude of these differences in facial features. The objective of the present study was therefore to evaluate the facial features of Maori and New Zealand (NZ) Europeans. METHODS: Two convenience samples of 30 Maori and 30 NZ Europeans, evenly matched for age and gender, were recruited from amongst students of the University of Otago, New Zealand. Using a 3D white-light scanner, 12 facial scans were taken of each participant, which were then merged to form a single 3D image of the face. Prior to scanning, round markers were fixed to the skin in order to facilitate the localisation of facial anthropometric points and from which vertical, sagittal, and transverse measurements were assessed from the 3D facial image. Univariate and multivariate analyses of variance were used to test for differences between the two groups before and after adjusting for body mass index (BMI). RESULTS: Significant differences were found in vertical, sagittal, and transverse facial dimensions, before and after adjusting for BMI. The overall face of Maori was significantly larger than that of NZ Europeans, although the facial proportions were generally similar. However, Maori had a broader face, more anterior position of the chin and reduced facial convexity in comparison with NZ Europeans (p < 0.01). CONCLUSION: Maori have markedly different sagittal facial features compared with NZ Europeans. These distinctive features may reflect important differences in environmental and genetic influences between the two populations. The findings from the present study may assist the clinician in the treatment planning and assessment of facial dysmorphology in these ethnic groups.

Intraduodenal nutrient infusion differentially alters intestinal nutrient sensing, appetite, and satiety responses in lean and obese subjects.

BACKGROUND: Intestinal nutrient sensing regulates food intake and energy metabolism by acting locally and relaying nutritional status to the brain. It is unclear whether these mechanisms are altered in obese humans. OBJECTIVES: We aimed to investigate differences in duodenal nutrient sensing in humans with or without obesity and the effects of transiently blocking vagal transmission on nutrient sensing, hunger, and appetite. METHODS: In a single-blinded, randomized, cross-over design, subjects with or without obesity (n = 14 and n = 11, respectively) were infused intraduodenally with saline or a combination of glucose and oleic acid for 90 min (glucose load: 22.5 g, 1 kcal/min; oleic acid load: 10 g, 1 kcal/min) in the presence or absence of local anesthetic (benzocaine). Blood was sampled at 10-min intervals (120-240 min) and 15-min intervals until termination of the study for measurements of gut hormones, insulin, leptin, and C-peptide. Hunger and satiety sensations were scored using the visual analog scale, and hepatic glucose production and glucose oxidation rates were measured. RESULTS: Duodenal nutrient infusion in lean subjects led to a 65% drop in acyl ghrelin release and robustly increased cholecystokinin 8 (CCK-8) release (65%; P = 0.023); benzocaine infusion delayed this response (2-factor repeated-measures analysis of variance, P = 0.0065). In contrast, subjects with obesity had significantly blunted response to nutrient infusion, and no further effects were observed with benzocaine. Additionally, significant delays were observed in peptide YY (3-36), pancreatic polypeptide, glucose inhibitory peptide, and glucagon-like peptide 1 (7-36) response. No significant interactions were found between body mass index (BMI) or baseline hormone levels and areas under the curve for hormones except CCK-8 (BMI, P = 0.018; baseline CCK, P = 0.013). Nutrient-induced hunger and satiety sensations were impeded by benzocaine only in the lean cohort. Hunger and satiety sensations in subjects with obesity were not responsive to nutrient entry into the duodenum, and no additional effects were observed by blocking neural signaling. CONCLUSION: Nutrient-induced gut hormone release and response to transient vagal blockade are significantly blunted in subjects with obesity. This trial was registered at clinicaltrials.org as NCT02537314.

Botulinum Injection Into the Proximal Intestinal Wall of Diet-Induced Obese Mice Leads to Weight Loss and Improves Glucose and Fat Tolerance.

Botulinum neurotoxin (available commercially as BOTOX) has been used successfully for treatment of several neuromuscular disorders, including blepharospasm, dystonia, spasticity, and cerebral palsy in children. Our data demonstrate that injection of Botox into the proximal intestinal wall of diet-induced obese (DIO) mice induces weight loss and reduces food intake. This was associated with amelioration of hyperglycemia, hyperlipidemia, and significant improvement of glucose tolerance without alteration of energy expenditure. We also observed accelerated gastrointestinal transit and significant reductions in glucose and lipid absorption, which may account, at least in part, for the observed weight loss and robust metabolic benefits, although possible systemic effects occurring as a consequence of central and/or peripheral signaling cannot be ignored. The observed metabolic benefits were found to be largely independent of weight loss, as demonstrated by pair-feeding experiments. Effects lasted ∼8 weeks, for as long as the half-life of Botox as reported in prior rodent studies. These results have valuable clinical implications. If the observed effects are translatable in humans, this approach could lay the foundation for therapeutic approaches geared toward robust and sustained weight loss, mimicking some of the benefits of bariatric operations without its cost and complications.