Comparison of three-dimensional soft tissue changes according to the split pattern after sagittal split osteotomy in patients with skeletal class III malocclusion.

OBJECTIVES: This study aimed to analyse the changes in soft tissue and hard tissue stability associated with the split pattern, i.e. long split (LS) or short split (SS), after sagittal split osteotomy. MATERIALS AND METHODS: Patients who underwent sagittal split ramus osteotomy were classified into LS or SS groups according to postoperative computed tomography images. They were examined via lateral cephalography and three-dimensional (3D) optical scanning before surgery (T0) and 1 (T1), 3 (T2), and 12 (T3) months after surgery. Six standard angles (SNA, SNB, ANB, FMA, FMIA, and IMPA) were used as measures of hard tissue change. The two sets of 3D data were superimposed, and the volumetric differences were calculated as the soft tissue change. The areas evaluated were delimited by 10 × 20-mm rectangles in the frontal aspect and a 25 × 25-mm square in the lateral aspect. RESULTS: A total of 42 sides (26 patients) were analysed, including 20 (16 patients) in the SS group and 22 (16 patients) in the LS group. We found no significant differences in cephalographic angle or soft tissue changes in the frontal aspect between the SS and LS groups. We found significant differences in the subauricular region from T0-T1 (p = 0.02), T0-T2 (p = 0.03), and T0-T3 (p = 0.037) in terms of soft tissue changes in the lateral aspect. The volume increase associated with posterior mandibular movement was greater in the LS group. CONCLUSIONS: We found that LS patients with mandibular prognathism exhibited increased subauricular volumes following mandibular setback. CLINICAL RELEVANCE: It is essential to predict the postoperative facial profile before surgery. The split pattern after sagittal split osteotomy affects the postoperative profile of patients with mandibular prognathism.

Behavioral change stage might moderate the impact of multifaceted interventions on non-attendance from medical care among patients with type 2 diabetes: The Japan Diabetes Outcome Intervention Trial-2 Large-Scale Trial 007 (J-DOIT2-LT007).

AIMS/INTRODUCTION: Non-attendance from regular medical care is a major problem in diabetes patients. This study aimed to examine the impact of a multifaceted lifestyle intervention by face-to-face approach (FFA) on non-attendance from regular medical care in comparison with that by telephone from the technical support center (TSC). MATERIALS AND METHODS: This was secondary analysis from a 1-year, prospective, cluster randomized, intervention study. Patients with type 2 diabetes, who were regularly visiting primary care physicians cluster-randomized into the control or intervention (TSC or FFA according to resource availability of the district medical associations) groups, were consecutively recruited. The primary end-point was non-attendance from regular medical care. The interaction between the type of intervention (TSC vs FFA) and behavioral change stage (pre- vs post-action stage) in diet and exercise for the dropout rate was assessed. RESULTS: Among the 1,915 participants (mean age 56 ± 6 years; 36% women) enrolled, 828, 564 and 264 patients belonged to the control, TSC and FFA groups, respectively. We found evidence suggestive of an interaction between the intervention type and behavioral change stage in diet (P = 0.042) and exercise (P = 0.038) after adjusting for covariates. The hazard ratios (95% confidence interval) of FFA to TSC were 0.21 (0.05-0.93) and 7.69 (0.50-117.78) in the pre-action and post-action stages for diet, respectively, whereas they were 0.20 (0.05-0.92) and 4.75 (0.29-73.70) in the pre-action and post-action stages for exercise. CONCLUSIONS: Among diabetes patients, the impact of multifaceted intervention on non-attendance from medical care might differ by the behavioral change stage.

Dispersion Effect of Molecular Crowding on Ligand-Protein Surface Binding Sites of Escherichia coli RNase HI.

The molecular crowding effect on ligand-protein interactions, which plays several crucial roles in life processes, has been investigated using various models by adding crowding agents to mimic the intracellular environment. Several studies evaluating this effect have focused on the ligand-protein binding reaction of well-structured binding sites with rigid conformations. However, the crowding effect on flexible binding sites is not well-understood, especially in terms of the conformations. In this work, to elucidate the detailed molecular mechanism underlying the ligand-protein interactions with flexible binding sites on a protein surface, we studied the interaction between the basic protrusion of Escherichia coli ribonuclease HI (RNase HI) and 8-anilinonaphthalene-1-sulfonic acid (ANS). The RNase HI concentration-dependent measurement of ANS fluorescence combined with the multivariate analysis and the fluorescence vibronic structure analysis revealed an increase in the heterogeneous species with an increase in the protein concentration, which is a different behavior from that of proteins with rigid binding sites. This result indicates that ANS molecules bind to the additional binding sites because of the destabilization of the main sites by the excluded volume effect in a crowded environment. The fluorescence vibronic structure analysis yields a detailed molecular picture, indicating that the main species of ANS can have a distorted structure. On the other hand, some ANS molecules move to the minor binding sites of a different microenvironment to secure a stabilized structure. These spectroscopic analyses may show a hypothesis, suggesting that the decrease in the ΔG difference between the main and minor sites due to destabilization of the main binding site could lower the potential barrier between them, inducing the dispersion of binding pathways.

Psychological and Situational Factors Affecting Dropout from Regular Visits in Diabetes Practice: The Japan Diabetes Outcome Intervention Trial-2 Large Scale Trial 004 (J-DOIT2-LT004).

Introduction: This study explored the psychological and situational factors affecting dropout from regular visits to diabetes care using data obtained from the Japan Diabetes Outcome Intervention Trial 2 (J-DOIT2) Large-scale Trial (LT). Methods: A total of 2,031 patients with type 2 diabetes who participated in the J-DOIT2-LT were included in the analysis. Responses to a baseline questionnaire with 17 items asking about the experience of dropout from regular visits in diabetes care and its reasons were analyzed using principal component analysis, and factors related to dropout were extracted. Using Cox regression analysis, the association of these factors with the incidence of dropout was investigated. Results: The mean age of the 2,031 patients was 56.4 ± 5.9 years and 742 (36.5%) were women. They were followed for a median of 392 days, and 125 patients dropped out from regular visits during the follow-up period. In the principal component analysis of the questionnaire, there were four latent factors with eigenvalues of >1.0, which were labeled as "negative perceptions for regular visits," "social pressure," "lack of perceived necessity," and "environmental obstacles" based on the retained items. The Cox regression analysis demonstrated that patients with high scores of "lack of perceived necessity" and "environmental obstacles" had a significantly increased risk of dropout from regular visits. Conclusions: The present study revealed psychological and situational factors related to dropout, which may be useful for detecting patients at high risk of dropout. Effective measures focusing on such patients to prevent dropouts should be investigated in future studies (The trial registration number: UMIN000002186, registered at the University Hospital Medical Information Network-Clinical Trials Registry).

Employment status and diabetic outpatient appointment non-attendance in middle to senior working generation with type 2 diabetes: the Japan diabetes outcome intervention trial-2 large­scale trial 005 (J-DOIT2-LT005).

AIMS: Workplace demands, support, and relationships differ according to employment status (e.g., employment that is full-time, part-time, or self-employed) and may lead to unequal opportunities to keep diabetic appointments. We investigated the association between employment status and outpatient diabetic appointment non-attendance among working-age adults with type 2 diabetes. METHODS: This was a secondary analysis of a cluster-randomized trial (the Japan diabetes outcome intervention trial 2 large-scale trial). The analysis included 2010 trial participants (40-65 years old) with type 2 diabetes who were regularly followed by primary care physicians (PCPs). The outcome measure was the first non-attendance (defined as a failure to visit a PCP within 2 months of the original appointment) during the one-year follow-up. The association between baseline employment status and non-attendance was examined using Cox proportional hazard model in men and women. RESULTS: During the 1279 and 789 person-year follow-up periods, 90 men and 34 women, respectively, experienced their first appointment non-attendance. Among men, self-employed participants had a higher risk of non-attendance compared with full-time employees (adjusted HR, 1.84; 95% CI, 1.15, 2.95). The trial intervention (attendance promotion) was associated with a significantly reduced risk of non-attendance among self-employed participants (HR, 0.51; 95% CI, 0.26, 0.99). Among women, a significant association between employment status and non-attendance was not observed. CONCLUSIONS: Self-employed men with type 2 diabetes had a twofold increased risk of non-attendance than did full-time employees. Our study suggests that self-employed men with type 2 diabetes should be targeted for interventions promoting appointment adherence.

Radiologic Risk Factors for Persistent Mandibular Nerve Neurosensory Disturbance Following Sagittal Split Osteotomy.

PURPOSE: Neurosensory disturbance (NSD) occurring in the lower lips and chin is a major postoperative complication related to bilateral sagittal split osteotomy (SSO). The purpose of this study is to identify preoperative radiographic findings following SSO procedure associated with persistent NSD. METHODS: This retrospective cohort study analyzed data for consecutive patients who underwent SSO. Primary predictor variables, including ramus width, mandibular body height, mandibular angle length, gonial angle, distance from mental foramen to distal aspect of mandibular second molar (MFD), and measurement of bone marrow space (BMS), were examined in a series of radiographic images. The primary outcome variable was NSD. Patients with NSD were divided into 2 groups based on findings obtained 1 year postoperatively: persistent, for those with NSD remaining after 1 year, and transient, when NSD occurred for less than 1 year. Covariates included sex and age. Comparisons were analyzed by use of Mann-Whitney U test or χ2 test. Multivariate analysis was performed using step-wise logistic regression to determine significant factors related to persistent NSD. A P value .005 or less was considered statistically significant. RESULTS: Of the 349 sides investigated, the persistent NSD group consisted of 59 sides (16.9%), while the transient NSD group consisted of 290 sides (83.1%). The occurrence of persistent NSD was correlated with age (P < .05), MFD (P < .001), mandibular body height (P < .05), and BMS (P < .001). Multivariate logistic analysis also showed a significant association of MFD (P < .001) and BMS (P < .001). CONCLUSIONS: Preoperative MFD and BMS are radiographic findings that are associated with an increased risk for persistent NSD following SSO procedure.

A comparison of postoperative, three-dimensional soft tissue changes in patients with skeletal class III malocclusions treated via orthodontics-first and surgery-first approaches.

The aim of this retrospective study was to compare three-dimensional (3D) soft tissue and hard tissue changes between orthodontics-first approach (OFA) and surgery-first approach (SFA) after mandibular setback surgery. All patients underwent bilateral sagittal split osteotomy, and were examined by lateral cephalograms and 3D optical scanner before surgery (T0) and 1 (T1), 3 (T2), and 12 (T3) months after surgery. Three standard angles (FMA, U1 to FH, IMPA) were measured as hard tissue change and the 2 sets of 3D data were superimposed, and volumetric differences were calculated as soft tissue change. Statistical analyses were performed by using unpaired t-tests. Differences with P < 0.05 were considered significant. A total of 39 patients with mandibular prognathism were included in this study. The OFA group consisted of 24 patients and the SFA group of 15 patients. The SFA group exhibited more labial inclination from T1 to T2 (p = 0.008) and T2 to T3 (p = 0.003) than did the OFA group. There were no significant changes at maxilla and mandible at each term of T0, T1, T2 and T3 (p > 0.05), but compared to before surgery, mandibular volume in SFA group significant increased at 1year (p = 0.049) after surgery. We found that the soft tissue changes after the SFA differed significantly from those after the OFA; thus, soft tissue predictions require more care. An analysis of our data compared with OFA and SFA for the patient with mandibular prognathism confirm that the mandibular soft tissue changes by postoperative orthodontic treatment and occlusal relationship in SFA.

AMPK is indispensable for overload-induced muscle glucose uptake and glycogenesis but dispensable for inducing hypertrophy in mice.

Chronic muscle loading (overload) induces skeletal muscles to undergo hypertrophy and to increase glucose uptake. Although AMP-activated protein kinase (AMPK) reportedly serves as a negative regulator of hypertrophy and a positive regulator of glucose uptake, its role in overload-induced skeletal muscle hypertrophy and glucose uptake is unclear. This study aimed to determine whether AMPK regulates overload-induced hypertrophy and glucose uptake in skeletal muscles. To this end, skeletal muscle overload was induced through unilateral synergist ablations in wild-type (WT) and transgenic mice, expressing the dominant-negative mutation of AMPK (AMPK-DN). After 14 days, parameters, including muscle fiber cross-sectional area (CSA), glycogen level, and in vivo [3 H]-2-deoxy-D-glucose uptake, were assessed. No significant difference was observed in body weight or blood glucose level between the WT and AMPK-DN mice. However, the 14-day muscle overload activated the AMPK pathway in WT mice skeletal muscle, whereas this response was impaired in the AMPK-DN mice. Despite a normal CSA gain in each fiber type, the AMPK-DN mice demonstrated a significant impairment of overload-induced muscle glucose uptake and glycogenesis, compared to WT mice. Moreover, 14-day overload-induced changes in GLUT4 and HKII expression levels were reduced in AMPK-DN mice, compared to WT mice. This study demonstrated that AMPK activation is indispensable for overload-induced muscle glucose uptake and glycogenesis; however, it is dispensable for the induction of hypertrophy in AMPK-DN mice. Furthermore, the AMPK/GLUT4 and HKII axes may regulate overload-induced muscle glucose uptake and glycogenesis.

Author Correction: A cluster-randomized trial of the effectiveness of a triple-faceted intervention promoting adherence to primary care physician visits by diabetes patients: J-DOIT2 large-scale trial (J-DOIT2-LT).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

The relationship between neurosensory disturbance of the inferior alveolar nerve and the lingual split pattern after sagittal split osteotomy.

OBJECTIVE: The aim of this study was to evaluate the relationship between neurosensory disturbance (NSD) and the different types of bilateral sagittal split osteotomy (BSSO) lingual fracture created. STUDY DESIGN: The study group consisted of 45 patients with mandibular deformities (90 sides; 14 males and 31 females). Computed tomography (CT) scans were obtained preoperatively and 1 week postoperatively. All patients were divided into lingual fracture line groups on the basis of their postoperative scans. NSD was tested preoperatively and 1, 3, and 12 months postoperatively by using a sensory touch Semmes-Weinstein (SW) test and the 2-point discrimination (TPD) test. RESULTS: Patients were divided into 2 groups on the basis of their lingual fracture lines after mandibular BSSO; among the 45 patients, 39 sides (43.3%) had short-splits, and 51 sides (56.7%) had long-splits. The short-split group was less affected at all tested times, and the difference between the 2 groups was significant 1 month postoperatively on TPD test but not at other times on the both tests. CONCLUSIONS: The split type did not affect the NSD incidence at 3 and 12 months postoperatively.

The Accuracy of Maxillary Position Using a Computer-Aided Design/Computer-Aided Manufacturing Intermediate Splint Derived Via Surgical Simulation in Bimaxillary Orthognathic Surgery.

PURPOSE: The purpose of this study was to assess the clinical interventions and the accuracy of maxillary reposition using a computer-aided design/computer-aided manufacturing (CAD/CAM) splint derived via surgical simulation. MATERIALS AND METHODS: The retrospective study comprised 24 patients who underwent bimaxillary surgery. The patients were assigned to 1 of 2 groups by a way of maxillary repositioning. One group received conventional intermediate wafers and the other CAD/CAM wafers during Le Fort I osteotomy. We recorded operation time, blood loss, the operative accuracy. Accuracy was analyzed by 3-dimensional computed tomography images before and immediately after the operation. The evaluation points were the right maxillary first incisor (U1), the right maxillary second molar (M2-right), and the left maxillary second molar (M2-left). RESULTS: The 2 groups did not differ significantly in operation time and blood losses. The vertical axis of U1 data differed significantly between the 2 groups (P = 0.008). None of the horizontal, vertical, or anteroposterior axis of M2-right data differed significantly, and anteroposterior axis of M2-left data differed significantly (P = 0.0296). The CAD/CAM group 3-dimensional distance errors were less than those of the conventional group for all points. CONCLUSION: Placement of CAD/CAM splint allowed highly accurate repositioning; the accuracy exceeded that afforded by conventional model surgery using a facebow and articulator.

A cluster-randomized trial of the effectiveness of a triple-faceted intervention promoting adherence to primary care physician visits by diabetes patients.

We aimed to assess whether a triple-faceted intervention program administered in the primary care setting could decrease the risk of insufficient adherence to primary care physician (PCP) appointments among this patient population. We conducted a cluster-randomized controlled study to assess the effects of a 1-year intervention. The primary outcome was insufficient adherence to regular PCP attendance for diabetes treatment, defined as failure to visit a PCP within 2 months of an original appointment date. The intervention consisted of mailing patient reminders of their PCP appointments, providing patients with health education aimed at lifestyle modification and benchmarking PCP procedures. Eleven municipal level district medical associations employing 192 PCPs were divided into two subregions for assignment to intervention and control clusters, with 971 and 1,265 patients assigned to the intervention and control groups, respectively. Primary outcome data were available for 2,200 patients. The intervention reduced insufficient adherence to regular PCP appointments by 63% (hazard ratio, 0.37; 95% confidence interval [CI], 0.23-0.58). In conclusion, a triple-faceted intervention program consisting of health education, appointment reminders, and physician benchmarking may decrease the risk of incomplete adherence to regular PCP appointments by diabetes patients.

Pyramidal and posterior osseous release for maxillary superior/posterior mobilization using an ultrasonic bone-cutting device after Le Fort I osteotomy.

AIM: The purpose of this study was to evaluate the efficiency of pyramidal and posterior osseous release (PPOR) for maxillary impaction using an ultrasonic bone-cutting device after Le Fort I (LFI) osteotomy. MATERIALS AND METHODS: In total, 31 Japanese adults with jaw deformities, diagnosed as having maxillary excess with mandibular prognathism or deficiency, underwent LFI osteotomy and bilateral sagittal split osteotomy. The patients were divided into two groups: a trimming group (15 patients, four men and 11 women; mean age 24.8 years) and a PPOR group (16 patients, seven men and nine women; mean age 22.8 years). In the trimming group, osseous interference around the descending palatine artery (DPA) was removed using forceps, rounding bur, and reciprocating rasp. The PPOR technique was used to remove osseous fragments created by V-shaped osteotomy around the DPA following vertical osteotomy behind the DPA using an ultrasonic bone-cutting device (Variosurg 3; NSK, Tochigi, Japan). The operative times for maxillary osteotomy, total operative times (including bilateral sagittal split osteotomy), and total blood loss were assessed. RESULTS: The mean planned amounts of maxillary impaction were 4.37 ± 1.27 mm in the trimming group and 4.38 ± 1.36 mm in the PPOR group (p = 0.98). The mean maxillary operative time for the PPOR group was significantly shorter, by 25.5% (p < 0.001). Total operative time for the PPOR group was also significantly shorter, by 24.3% (p < 0.001). Mean blood loss was significantly lower in the PPOR group than in the trimming group (p = 0.003). CONCLUSION: The PPOR technique for maxillary impaction after LFI osteotomy shortened the operative time and enabled secure reduction of the maxilla in patients who required the treatment of maxillary impaction with preservation of the DPA bundle.

[Basic Studies on the Mechanism, Prevention, and Treatment of Osteonecrosis of the Jaw Induced by Bisphosphonates].

Since the first report in 2003, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been increasing, without effective clinical strategies. Osteoporosis is common in elderly women, and bisphosphonates (BPs) are typical and widely used anti-osteoporotic or anti-bone-resorptive drugs. BRONJ is now a serious concern in dentistry. As BPs are pyrophosphate analogues and bind strongly to bone hydroxyapatite, and the P-C-P structure of BPs is non-hydrolysable, they accumulate in bones upon repeated administration. During bone-resorption, BPs are taken into osteoclasts and exhibit cytotoxicity, producing a long-lasting anti-bone-resorptive effect. BPs are divided into nitrogen-containing BPs (N-BPs) and non-nitrogen-containing BPs (non-N-BPs). N-BPs have far stronger anti-bone-resorptive effects than non-N-BPs, and BRONJ is caused by N-BPs. Our murine experiments have revealed the following. N-BPs, but not non-N-BPs, exhibit direct and potent inflammatory/necrotic effects on soft-tissues. These effects are augmented by lipopolysaccharide (the inflammatory component of bacterial cell-walls) and the accumulation of N-BPs in jawbones is augmented by inflammation. N-BPs are taken into soft-tissue cells via phosphate-transporters, while the non-N-BPs etidronate and clodronate inhibit this transportation. Etidronate, but not clodronate, has the effect of expelling N-BPs that have accumulated in bones. Moreover, etidronate and clodronate each have an analgesic effect, while clodronate has an anti-inflammatory effect via inhibition of phosphate-transporters. These findings suggest that BRONJ may be induced by phosphate-transporter-mediated and infection-promoted mechanisms, and that etidronate and clodronate may be useful for preventing and treating BRONJ. Our clinical trials support etidronate being useful for treating BRONJ, although additional clinical trials of etidronate and clodronate are needed.

Spectroscopic Signature of the Steric Strains in an Escherichia coli RNase HI Cavity-Filling Destabilized Mutant Protein.

A cavity-filling mutation at a hydrophobic cavity is a useful method for increasing protein stability. This method, however, sometimes destabilizes the protein because of the accompanying structural changes by the steric hindrance around the cavity. Thus, detailed knowledge of unfavorable structural changes is important for a comprehensive understanding of the cavity-filling mutation. In the present study, by employing the cavity-filling mutant of Escherichia coli RNase HI as a case study, the structural change induced by the substitution of Phe for Ala52 (Ala52Phe) was analyzed in detail using Raman spectroscopy. In previous studies, the thermodynamic result apparently indicated a small decrease in ΔG (destabilization) by the mutation. In the present study, Raman differential spectra show a clear structural difference between wild-type E. coli RNase HI and Ala52Phe. Consequently, the direct signature of the conformational strains around the protein cavity is readily acquired, leading to further understanding of the trade-off relationship between the cavity-filling and incidental steric hindrance.

Increase in bone metabolic markers and circulating osteoblast-lineage cells after orthognathic surgery.

Increased mineralisation rate and bone formation after surgery or fracture is the regional acceleratory phenomenon (RAP), and its systemic impact is the systemic acceleratory phenomenon (SAP). The proportion of circulating osteoblast lineage cells, including osteocalcin-positive (OCN+) cells, in the peripheral blood is markedly higher during pubertal growth and in patients with bone fractures. This study aimed to elucidate the dynamic changes in bone metabolic activity after orthognathic surgery by longitudinal prospective observation. Peripheral venous blood samples were collected from patients who had undergone orthognathic surgery, and serum bone metabolic markers and the proportion of OCN+ cells were measured. Orthognathic surgery induces systemic dynamic changes in bone metabolic activity by targeting steps in the bone healing process and related proteins, such as surgical stress/inflammation (C-reactive protein), bone resorption (type I collagen C-telopeptide), and bone formation (alkaline phosphatase and bone-specific alkaline phosphatase). During the early post-operative period, the population of OCN+ cells significantly increased. Confocal microscopy revealed that OCN proteins were localised in the cytoplasm in Triton X-100-treated OCN+ cells. Furthermore, OCN, ALP, and COL1A1 gene expression was detected in OCN+ cells, suggesting the contribution of the local maturation of bone marrow-derived OCN+ cells at the site of bone healing.

Effect of "surgery first" orthognathic approach on temporomandibular symptoms and function: a comparison with "orthodontic first" approach.

OBJECTIVE: The aim of this study was to comparatively evaluate the effects of the surgery-first approach (SFA) and the orthodontics-first approach (OFA) on temporomandibular joint (TMJ) function and maximum mouth opening. STUDY DESIGN: This retrospective study investigated the outcomes of patients with diagnosed skeletal class III dentofacial deformities. Twenty-four patients were enrolled in the OFA group, and 23 patients were enrolled in the SFA group. All patients were examined in the same manner 4 times: before surgery and at 1, 3, 6, and 12 months after surgery. Range of mouth opening (ROM) was measured between the maxillary and mandibular central incisors. Symptoms were evaluated subjectively by using a questionnaire with items pertaining to pain on mandibular movements, TMJ sounds, and pain in masticatory muscles region. RESULTS: No severe complications or relapse occurred in either group during the 12-month follow-up period. Postoperative changes in ROM showed similar tendencies, but there was no significant difference in ROM during the follow-up period between the OFA and SFA groups (P < .05). The percentage reduction was nearly 45% at 1 month postoperatively and 20% at 3 months postoperatively compared with the preoperative situation. After 6 months postoperatively, the ROM was almost the same as before surgery. The number of patients with such sounds increased with time until 12-month postoperative examinations in the OFA group but increased slightly during this period in the SFA group. During the first 3 months postoperatively, less than 10% of patients in both groups had newly detected pain of TMJ and/or muscles. At 6 and 12 months postoperatively, only 1 patient in the SFA group had pain. CONCLUSIONS: No significant differences in TMJ symptoms or function were observed during a 12-month follow-up period between patients with skeletal class III malocclusion treated with the SFA and those treated with the OFA.

Augmentation of Lipopolysaccharide-Induced Production of IL-1α and IL-1ß in Mice Given Intravenous Zoledronate (a Nitrogen-Containing Bisphosphonate) and Its Prevention by Clodronate (a Non-nitrogen-containing Bisphosphonate).

Bisphosphonates (BPs) bind strongly to bone and exhibit long-acting anti-bone-resorptive effects. Among BPs, nitrogen-containing BPs (N-BPs) have far stronger anti-bone-resorptive effects than non-N-BPs. However, N-BPs induce acute inflammatory reactions (fever, arthralgia and myalgia, etc.) after their first injection. The mechanisms underlying these side effects remain unclear. Zoledronate (one of the most potent N-BPs) is given intravenously to patients, and the side-effect incidence is reportedly the highest among N-BPs. Our murine experiments have clarified that (a) intraperitoneally injected N-BPs induce various inflammatory reactions, including a production of interleukin-1 (IL-1) (a typical inflammatory cytokine), and these inflammatory reactions are weak in IL-1-deficient mice, (b) subcutaneously injected N-BPs induce inflammation/necrosis at the injection site, (c) lipopolysaccharide (LPS; a cell-wall component of Gram-negative bacteria) and N-BPs mutually augment their inflammatory/necrotic effects, (d) the non-N-BP clodronate can reduce N-BPs' inflammatory/necrotic effects. However, there are few animal studies on the side effects of intravenously injected N-BPs. Here, we found in mice that (i) intravenous zoledronate exhibited weaker inflammatory effects than intraperitoneal zoledronate, (ii) in mice given intravenous zoledronate, LPS-induced production of IL-1α and IL-1ß was augmented in various tissues, including bone, resulting in them increasing in serum, and (iii) clodronate (given together with zoledronate) prevented such augmentation and enhanced, slightly but significantly, zoledronate's anti-bone-resorptive effect. These results suggest that infection may be a factor promoting the acute inflammatory side effects of N-BPs via augmented production of IL-1 in various tissues (including bone), and that clodronate may be useful to reduce or prevent such side effects.

Volumetric comparison of maxillofacial soft tissue morphology: computed tomography in the supine position versus three-dimensional optical scanning in the sitting position.

OBJECTIVE: Three-dimensional (3-D) surgical simulation has become popular, but the accuracy of such simulation is difficult to assess. Because maxillofacial soft tissue profiles vary with posture, we compared such profiles obtained in the supine and sitting positions. STUDY DESIGN: In total, 28 patients with skeletal Class III jaw deformities underwent computed tomography in the supine position and 3-D optical scanning in the sitting position. The 2 sets of 3-D data were superimposed, and linear and volumetric differences were calculated. We evaluated the cheeks, the subauricular and infraorbital regions, the nose, the lips, and the chin. Statistical analyses were performed by using paired Student's t tests. Differences with P < .05 were considered significant. RESULTS: Patients were divided into 3 groups based on body mass index. The facial profiles of the cheeks and subauricular areas differed significantly between the sitting and supine positions. The extent of variation increased with body mass index. CONCLUSIONS: When a patient moves from the sitting position to the supine position, maxillofacial soft tissue migrates from the cheeks to the subauricular regions. Thus, simulations for surgery based on supine computed tomography alone do not accurately model the cheeks and subauricular areas.

Secretory units of islets in transplantation index is a useful predictor of insulin requirement in Japanese type 2 diabetic patients.

AIMS/INTRODUCTION: The objective of the present study was to clarify the validity of ß-cell function-related parameters for predicting the insulin requirement of Japanese type 2 diabetic patients. MATERIALS AND METHODS: In 188 patients with type 2 diabetes who had been admitted to the University of Toyama Hospital (Toyama, Japan) without receiving insulin therapy, we carried out a cross-sectional study examining the relationship between the homeostasis model assessment of ß-cell function (HOMA-ß) and C-peptide-based indices, and also carried out a retrospective study to examine the utility for predicting insulin requirement of several ß -cell function-related indices using a receiver operating characteristic (ROC) curve analysis. RESULTS: The secretory units of islets in transplantation index (SUIT) had the strongest correlation with HOMA-ß, followed by the fasting serum C-peptide immunoreactivity index (CPI); the fasting serum C-peptide immunoreactivity itself (F-CPR) had the least correlation. The CPI, HOMA-ß and SUIT were significantly lower in the insulin-requiring group than in the non-insulin-requiring group, even after adjustments for confounding factors (P < 0.01). The areas under the ROC curve for insulin requirement were 0.622, 0.774, 0.808, and 0.759 for F-CPR, CPI, SUIT, and HOMA-ß, respectively. The cut-off values of SUIT, CPI, and HOMA-ß for an over 80% specificity for the prediction of insulin therapy were 23.5, 1.00, and 14.9, respectively. CONCLUSIONS: The present study shows that SUIT is the best predictor of insulin requirement among these ß-cell function-related markers.