Orthodontic correction of anterior open bite using skeletal anchorage: systematic review and meta-analysis.

The purpose of this study was to investigate the scientific evidence on the short- and long-term effects of orthodontic correction of anterior open bite (AOB) using skeletal anchorage (SA). Clinical studies on the use of SA for AOB in patients with permanent dentition, or at least 12 years of age, were searched. Short- and long-term (≥2 years) outcomes were collected. Mean differences were calculated from pooled data. Twenty-four eligible articles with a total of 362 subjects were selected for inclusion in the meta-analysis. There was a significant increase in overbite (3.88 mm, P < 0.001) and maxillary molar intrusion (-2.15 mm, P < 0.001). The mandible showed counterclockwise rotation with anterosuperior chin movement (all P < 0.001). Long term, the decrease in overbite was 19.9% and decrease in molar intrusion was 22.9%. The decrease in the mandibular projection was 14.6% for ANB (A-point-nasion-B-point angle) and 46.2% for mandibular anteroposterior position. The overall risk of bias in the included studies was rated as moderate to high, and publication bias existed for several key variables. SA for maxillary molar intrusion effectively improved dental and skeletal outcomes, but there was a long-term decrease in overbite and maxillary molar position. The variable data quality, heterogeneity, and publication bias in investigated outcomes are limitations in interpreting the findings.

Outbreak of hemolytic uremic syndrome with unusually severe clinical presentation caused by Shiga toxin-producing Escherichia coli O26:H11 in France.

BACKGROUND: In spring 2019, an outbreak of Shiga toxin-producing Escherichia coli-associated hemolytic uremic syndrome (STEC HUS) occurred in France. Epidemiological investigations made by Santé publique France in connection with microbiological investigations at the national reference center for STEC promptly identified a common exposure to consumption of raw cow's milk cheese, and confirmed a cluster affiliation of the E. coli O26:H11 outbreak strain. Here, we report the clinical characteristics of the patients, the treatment used, as well as the outcome at 1 month. METHOD: Patients with STEC HUS linked to the E. coli O26:H11 outbreak strain were identified from the national surveillance network of pediatric STEC HUS cases coordinated by Santé publique France. Clinical data were analyzed from the patients' hospital records obtained from the treating physicians. RESULTS: Overall, 20 pediatric cases of STEC HUS linked to the outbreak strain were identified. Their median age of the patients was 16 months (range: 5-60). Most of them presented with diarrhea but none had received prior antibiotherapy. A total of 13 patients required dialysis; 10 patients and four patients had central nervous system (CNS) and cardiac involvement, respectively. No deaths occurred. At the 1-month follow-up, only two patients had a decreased glomerular filtration rate, below 80 mL /min/1.73m2 and four had hypertension. One patient had neurological sequelae. CONCLUSION: The E. coli O26:H11 strain identified as the cause of an STEC HUS outbreak in France in spring 2019 is notable for the initial severe clinical presentation of the patients, with a particularly high frequency of CNS and cardiac involvement similar to the German E. coli O104:H4 outbreak described in 2011. However, despite the initial severity, the 1-month outcome was favorable in most cases. The patients' young age in this outbreak highlights the need to improve information and caregiver awareness regarding consumption of at-risk foods by young children as key preventive measures against STEC infections.

Carotid Plaque Composition Assessed by CT Predicts Subsequent Cardiovascular Events among Subjects with Carotid Stenosis.

BACKGROUND AND PURPOSE: Currently, the characteristics of carotid plaques are considered important factors for identifying subjects at high risk of stroke. This study aimed to test the hypothesis that carotid plaque composition assessed by CTA is associated with an increased risk of future major adverse cardiovascular events among asymptomatic subjects with moderate-to-severe carotid artery stenosis. MATERIALS AND METHODS: This single-center, retrospective cohort study included 194 carotid plaques from 176 asymptomatic subjects with moderate-to-severe carotid artery stenosis. The association of CTA-determined plaque composition with the risk of subsequent adverse cardiovascular events was analyzed. RESULTS: During a median follow-up of 41 months, the adverse cardiovascular event incidence among 194 carotid plaques was 19.6%. There were significant differences in plaque Hounsfield units (P < .001) and spotty calcium presence (P < .001) between carotid plaques from subjects with and without subsequent adverse cardiovascular events. Multivariable analysis revealed carotid plaque Hounsfield unit density (P < .001) and spotty calcium (P < .001) as independent predictors of subsequent adverse cardiovascular events. In association with moderate carotid artery stenosis, the plaque Hounsfield unit values were significantly lower among carotid plaques from subjects who experienced subsequent adverse cardiovascular events (P = .002), strokes (P = .01), and cardiovascular deaths (P = .04); the presence of spotty calcium was significantly associated with the occurrence of adverse cardiovascular events (P = .001), acute coronary syndrome (P = .01), and cardiovascular death (P = .04). CONCLUSIONS: Carotid plaque Hounsfield unit density and spotty calcium were independent predictors of a greater risk of adverse cardiovascular event occurrence.

ATLAS trial of adjuvant axitinib in patients with renal cell carcinoma: subgroup analyses with focus on axitinib dosing and racial groups.

BACKGROUND: The ATLAS trial, investigating adjuvant axitinib versus placebo in renal cell carcinoma (RCC), was stopped for futility at a preplanned interim analysis. We report subgroup outcome analyses by ethnicity, time on treatment, dose modification and toxicity. PATIENTS AND METHODS: Patient demographics, baseline characteristics, treatment duration and exposure and safety were analysed for Asian versus non-Asian patients treated with axitinib versus placebo. Disease-free survival (DFS) was analysed by ethnicity, treatment duration (≥1 versus <1 year), dose modification and adverse event (AE) grade. RESULTS: No DFS benefit was observed for Asian {hazard ratio (HR) 0.883 [95% confidence interval (CI) 0.638-1.220]} or non-Asian [HR 0.828 (95% CI 0.490-1.400)] patients treated with axitinib or placebo. Fewer Asian versus non-Asian patients were in the highest-risk group in axitinib (51.9% versus 72.3%) or placebo (51.5% versus 66.0%) arm. Highest-risk patients in both subgroups had no DFS benefit with either treatment. More axitinib-treated Asian versus non-Asian patients had dose reductions due to AEs (58.8% versus 46.0%; P = 0.028). Asian patients experienced more nasopharyngitis but less fatigue or asthenia than non-Asians. Among Asian patients, proteinuria, hypothyroidism, nasopharyngitis, and hypertension were more common in Japanese patients than Korean patients and more common in Korean patients than Chinese patients. Patients receiving axitinib >1 year versus ≤1 year did not have different DFS: HR 0.572 (95% CI 0.247-1.327); P = 0.1874. Compared with patients on stable axitinib dose, DFS was longer in patients with dose reduction [HR 0.458 (95% CI 0.305-0.687); P = 0.0001], whereas DFS was not different in those with dose escalation [HR 1.936 (95% CI 0.937-3.997); P = 0.0685]. DFS was not different in patients experiencing grade ≥2 versus <2 AEs within 6 months of initiating axitinib: HR 0.885 (95% CI 0.419-1.869); P = 0.7488. CONCLUSIONS: Asian versus non-Asian subgroup analysis revealed differences in AE experience and drug exposure. There were no DFS differences based on ethnicity or treatment duration, but axitinib dose reduction led to longer DFS.

[Enoxaparin and tinzaparin in pediatrics: Impact of recommendation on prescription quality and anti-Xa levels]. / Énoxaparine et tinzaparine en pédiatrie : impact de recommandations sur la qualité des prescriptions et l'activité anti-Xa.

OBJECTIVES: A protocol has been written and distributed in May 2017 to all prescribers in a pediatric hospital to standardize and to secure the prescriptions of enoxaparin and tinzaparin considered as two high risk medications. The aim of this study is to evaluate the impact of the protocol on those prescriptions in a pediatric population. METHODS: This is a monocentric retrospective study comparing prescriptions of this two low-molecular-weight heparins for patients under 18 years old in 2016 and 2018, thus before and after the protocol redaction. RESULTS: In 2016, 2246 prescriptions of enoxaparin and tinzaparin were analyzed for 627 patients. Among them, 142 (22.6%) patients have had at least one anti-Xa level dosed. On the other hand, in 2018, 2061 prescriptions were written for 628 patients including 96 (15.3%) who have had at least one anti-Xa level dosed. The conformity rate of the first dose in IU/kg/administration of the first enoxaparin prescription goes from 36.3% before protocol to 52.1% after (P=0.03*). Concerning tinzaparin, the conformity rate goes from 69.2% to 83.3%. (P=0.19). The rate of first anti-Xa level in the range 0.4 to 1.2 IU/ml increase between 2016 and 2018 from 27.7% to 43.8% (P<0.001*). CONCLUSION: This protocol enabled to improve the quality of prescriptions in terms of: dosage written in IU/kg/administration, frequency of administration, dilution conformity, and result of the first anti-Xa level. Some efforts must be made in writing the dose in IU not in mg or ml.

Prenylflavonoids isolated from Macaranga tanarius stimulate odontoblast differentiation of human dental pulp stem cells and tooth root formation via the mitogen-activated protein kinase and protein kinase B pathways.

AIM: To identify odontogenesis-promoting compounds and examine the molecular mechanism underlying enhanced odontoblast differentiation and tooth formation. METHODOLOGY: Five different nymphaeols, nymphaeol B (NB), isonymphaeol B (INB), nymphaeol A (NA), 3'-geranyl-naringenin (GN) and nymphaeol C (NC) were isolated from the fruit of Macaranga tanarius. The cytotoxic effect of nymphaeols on human DPSCs was observed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effect of nymphaeols on odontoblast differentiation was analysed with Alizarin Red S staining and odontoblast marker expression was assessed using real-time polymerase chain reaction and Western blot analysis. The molecular mechanism was investigated with Western blot analysis. In order to examine the effect of INB on dentine formation in the developing tooth germ, INB-soaked beads were placed under the tooth bud explants in the collagen gel; thereafter, the tooth bud explant-bead complexes were implanted into the sub-renal capsules for 3 weeks. Tooth root formation was analysed using micro-computed tomography and histological analysis. Data are presented as mean ± standard error (SEM) values of three independent experiments, and results are compared using a two-tailed Student's t-test. The data were considered to have statistical significance when the P-value was less than 0.05. RESULTS: Three of the compounds, NB, INB, and GN, did not exert a cytotoxic effect on human DPSCs. However, INB was most effective in promoting the deposition of calcium minerals in vitro (P < 0.001) and induced the expression of odontogenic marker genes (P < 0.05). Moreover, this compound strongly induced the phosphorylation of mitogen-activated protein (MAP) kinases and protein kinase B (AKT) (P < 0.05). The inhibition of p38 MAP, c-Jun N-terminal kinase (JNK), and AKT substantially suppressed the INB-induced odontoblast differentiation (P < 0.001). In addition, isonymphaeol B significantly induced the formation of dentine and elongation of the tooth root in vivo (P < 0.05). CONCLUSIONS: Prenylflavonoids, including INB, exerted stimulatory effects on odontoblast differentiation and tooth root and dentine formation via the MAP kinase and AKT signalling pathways. These results suggest that nymphaeols could stimulate the repair processes for dentine defects or injuries.

Influence of mandibular setback surgery on three-dimensional pharyngeal airway changes.

The aim of this study was to investigate the factors influencing three-dimensional changes in pharyngeal airway space after mandibular setback surgery. Airway changes in 48 skeletal class III patients who had undergone mandibular setback surgery alone (n=25, group 1) or with maxillary surgery (n=23, group 2) were analyzed. Linear parameters, cross-sectional area, and volumes of the pharyngeal airway were evaluated before (T0), immediately after (T1), and 1year after surgery (T2) by cone beam computed tomography. Although the reduced airway volume and cross-sectional area recovered slightly in the long term after surgery, the total pharyngeal airway volume (TPV) was significantly reduced compared to baseline, by 15% in group 1 and 12% in group 2. Regression analysis showed that maxillary posterior impaction in two-jaw surgery had a protective effect on preserving TPV. A change in body mass index from T0 to T2 was an important predictor of decreased TPV in one-jaw surgery patients. Maxillary posterior impaction can be a reliable option for compensating the pharyngeal airway reduction after mandibular setback surgery. Postoperative weight gain can increase the risk of postoperative pharyngeal airway reduction. Therefore, these factors need to be considered before and after mandibular setback surgery.

Axitinib versus placebo as an adjuvant treatment of renal cell carcinoma: results from the phase III, randomized ATLAS trial.

Background: The ATLAS trial compared axitinib versus placebo in patients with locoregional renal cell carcinoma (RCC) at risk of recurrence after nephrectomy. Patients and methods: In a phase III, randomized, double-blind trial, patients had >50% clear-cell RCC, had undergone nephrectomy, and had no evidence of macroscopic residual or metastatic disease [independent review committee (IRC) confirmed]. The intent-to-treat population included all randomized patients [≥pT2 and/or N+, any Fuhrman grade (FG), Eastern Cooperative Oncology Group status 0/1]. Patients (stratified by risk group/country) received (1 : 1) oral twice-daily axitinib 5 mg or placebo for ≤3 years, with a 1-year minimum unless recurrence, occurrence of second primary malignancy, significant toxicity, or consent withdrawal. The primary end point was disease-free survival (DFS) per IRC. A prespecified DFS analysis in the highest-risk subpopulation (pT3, FG ≥ 3 or pT4 and/or N+, any T, any FG) was conducted. Results: A total of 724 patients (363 versus 361, axitinib versus placebo) were randomized from 8 May 2012, to 1 July 2016. The trial was stopped due to futility at a preplanned interim analysis at 203 DFS events. There was no significant difference in DFS per IRC [hazard ratio (HR) = 0.870; 95% confidence interval (CI) : 0.660-1.147; P = 0.3211). In the highest-risk subpopulation, a 36% and 27% reduction in risk of a DFS event (HR; 95% CI) was observed per investigator (0.641; 0.468-0.879; P = 0.0051), and by IRC (0.735; 0.525-1.028; P = 0.0704), respectively. Overall survival data were not mature. Similar adverse events (AEs; 99% versus 92%) and serious AEs (19% versus 14%), but more grade 3/4 AEs (61% versus 30%) were reported for axitinib versus placebo. Conclusions: ATLAS did not meet its primary end point; however, improvement in DFS per investigator was seen in the highest-risk subpopulation. No new safety signals were reported. Trial registration number: NCT01599754.

Genetic evolution of classical swine fever virus under immune environments conditioned by genotype 1-based modified live virus vaccine.

Modified live vaccines (MLVs) based on genotype 1 strains, particularly C-strain, have been used to prevent and control classical swine fever virus (CSFV) worldwide. Nevertheless, a shift in the predominant CSFV strains circulating in the field from genotype 1 or 3 to genotype 2 is seen. Genotype 2 is genetically distant from the vaccine strains and was recently reported during outbreaks after vaccine failure; this has raised concerns that vaccination has influenced viral evolution. In Korea in 2016, there was an unexpected CSF outbreak in a MLV-vaccinated commercial pig herd. The causative CSFV strain was genetically distinct from previously isolated Korean strains but similar to recent Chinese strains exhibiting enhanced capacity to escape neutralization; this suggests the need for global cooperative research on the evolution of CSFV. We analysed global E2 sequences, using bioinformatics tools, revealing the evolutionary pathways of CSFV. Classical swine fever virus genotypes 1 and 2 experienced different degrees and patterns of evolutionary growth. Whereas genotype 1 stayed relatively conserved over time, the genetic diversity of genotype 2 has progressively expanded, with few fluctuations. It was determined that genotype 2 evolved under lower immune pressures and at a higher evolutionary rate than genotype 1. Further, several selected codons, under diversifying selection in genotype 1 but under purifying selection in genotype 2, correspond to antigenic determinants, which could lead to evasion of vaccine-induced immunity. Our findings provide evidence that evolutionary changes in CSFV are the result of the disproportionate usage of the CSF MLVs in endemic areas; this underscores the need to develop mitigation strategies to minimize the substantial risk associated with the emergence of vaccine-escaping mutants.

Role of the histone deacetylase inhibitor valproic acid in high-fat diet-induced hypertension via inhibition of HDAC1/angiotensin II axis.

BACKGROUND: Obesity is known as an epidemic worldwide because of consumption of westernized high-fat diets and one of the major risk factors of hypertension. Histone deacetylases (HDACs) control gene expression by regulating histone/non-histone protein deacetylation. HDAC inhibitors exert anti-cancer and anti-inflammatory effects and play a protective role in cardiovascular diseases. In the present study, we tested the effect of an FDA-approved pan-HDAC inhibitor valproic acid (VPA) on high-fat diet (HFD)-induced hypertension in mice. Furthermore, we examined the mechanism of VPA-induced prevention of hypertension. METHODS: Nine-week-old male C57BL/6 mice were fed either a normal diet (ND) or HFD. When the HFD group reached a pre-hypertensive phase (130-140 mm Hg systolic blood pressure), VPA was administered for 6 days (300 mg kg-1 per day). Body weights and blood pressure (BP), expression of renin-angiotensin system (RAS) components and HDAC1 were determined. The direct role of HDAC1 in the expression of RAS components was investigated using gene silencing. RESULTS: HFD accelerated the increase in body weight from 22.4±1.3 to 31.9±3.0 compared to in the ND group from 22.7±0.9 to 26.0±1.7 (P=0.0134 ND vs HFD), systolic BP from 118.5±5.7 to 145.0±3.0 (P<0.001), and diastolic BP from 91.0±13.6 to 121.0±5.0 (P=0.006); BP was not altered in the ND group. HFD increased RAS components and HDAC1 in the kidneys as well as leptin in the plasma. VPA administration prevented the progression of hypertension and inhibited the increase in expression of HDAC1 and RAS components. VPA did not affect plasma leptin level. Knockdown of HDAC1 in MDCK cells decreased the expression of angiotensinogen and type 1 angiotensin II receptor. CONCLUSIONS: VPA prevented HFD-induced hypertension by downregulating angiotensin II and its receptor via inhibition of HDAC1, offering a novel therapeutic option for HFD-induced hypertension.

Evaluation of the 3dMDface system as a tool for soft tissue analysis.

OBJECTIVES: To evaluate the accuracy of three-dimensional stereophotogrammetry by comparing values obtained from direct anthropometry and the 3dMDface system. To achieve a more comprehensive evaluation of the reliability of 3dMD, both linear and surface measurements were examined. SETTING AND SAMPLE POPULATION: UCLA Section of Orthodontics. Mannequin head as model for anthropometric measurements. MATERIAL AND METHODS: Image acquisition and analysis were carried out on a mannequin head using 16 anthropometric landmarks and 21 measured parameters for linear and surface distances. 3D images using 3dMDface system were made at 0, 1 and 24 hours; 1, 2, 3 and 4 weeks. Error magnitude statistics used include mean absolute difference, standard deviation of error, relative error magnitude and root mean square error. Intra-observer agreement for all measurements was attained. RESULTS: Overall mean errors were lower than 1.00 mm for both linear and surface parameter measurements, except in 5 of the 21 measurements. The three longest parameter distances showed increased variation compared to shorter distances. No systematic errors were observed for all performed paired t tests (P<.05). Agreement values between two observers ranged from 0.91 to 0.99. CONCLUSIONS: Measurements on a mannequin confirmed the accuracy of all landmarks and parameters analysed in this study using the 3dMDface system. Results indicated that 3dMDface system is an accurate tool for linear and surface measurements, with potentially broad-reaching applications in orthodontics, surgical treatment planning and treatment evaluation.

Influence of rabbit notochordal cells on symptomatic intervertebral disc degeneration: anti-angiogenic capacity on human endothelial cell proliferation under hypoxia.

OBJECTIVES: Symptomatic degenerative disc disease (DDD) is associated with neovascularization and nerve ingrowth into intervertebral discs (IVDs). Notochordal cells (NCs) are key cells that may lead to regeneration of IVDs. However, their activities under conditions of hypoxia, the real environment of IVD, are not well known. We hypothesized that NCs may inhibit neovascularization by interacting with endothelial cells (ECs) under hypoxia. DESIGN: Human IVDs were isolated and cultured to produce nucleus pulposus (NP) cell conditioned medium (NPCM). Immortalized human microvascular ECs were cultured in NPCM with notochordal cell-rich rabbit nucleus pulposus cells (rNC) under hypoxia. Vascular endothelial growth factor (VEGF), vascular cell adhesion molecule (VCAM), and interleukin-8 (IL-8) were analyzed by ELISA. Focal adhesion kinase (FAK), filamentous actin (F-actin), and platelet-derived growth factor (PDGF) were evaluated to investigate EC activity. Wound-healing migration assays were performed to examine EC migration. RESULTS: The VEGF level of EC cells cultured in NPCM was significantly higher under hypoxia compared to normoxia. VEGF expression was significantly decreased, and FAK, F-actin, PDGF expression were inhibited when ECs were cocultured with rNCs under hypoxia. ECs cocultured with rNC in NPCM showed significantly decreased migratory activity compared to those without rNC under hypoxia. CONCLUSIONS: The angiogenic capacity of ECs was significantly inhibited by NCs under hypoxia via a VEGF-related pathway. Our results suggest that NCs may play a key role in the development of IVDs by inhibiting vascular growth within the disc, and this may be a promising novel therapeutic strategy for targeting vascular ingrowth in symptomatic DDD.

Rectus femoris muscle atrophy and recovery caused by preoperative pretibial traction in femoral shaft fractures-comparison between traction period.

BACKGROUND: Skeletal traction is performed to temporarily stabilize fracture sites before surgery in patients with femoral fracture. To date, however, there is no study evaluating the difference in the degree of the recovery, of the muscle strength, as well as muscle atrophy following skeletal traction. The purpose of this study was to compare the degree of recovery of rectus femoris muscle strength after surgery in association with muscle atrophy by analyzing the duration of preoperative tibial traction, age and sex in patients with femoral fracture. HYPOTHESIS: Rectus femoris muscle atrophy will progress depending on the duration of preoperative tibial traction, age and sex in patients with femoral fracture. PATIENTS AND METHOD: Thirty-one patients who underwent preoperative pretibial skeletal traction and intramedullary nailing were divided into two groups according to the traction period: group A (n=12) with a duration of traction of <7 days (mean: 4.08±1.78 days) and group B (n=19) ≥7 days (mean: 13.63±7.17 days). The degree of muscle atrophy and recovery were compared between the two groups, according to age and gender. The degree of muscle atrophy was measured by the difference in thickness of the rectus femoris between pre- and post-traction using ultrasound. The degree of muscle recovery was evaluated by the Q-setting and heel off time. Clinical outcome was evaluated by the non-union rate and Lysholm score. RESULTS: The degree of muscle atrophy was 0.99±0.14mm in group A and 2.22±0.11mm in group B (P<0.001). The Q-setting time was 4.83±0.94 days in group A and 6.56±1.38 days in group B (P=0.001). Heel off time was also shorter in group A at 2.58±0.90 days, taking 3.72±1.27 days in group B (P=0.012). The recovery rate in the rectus femoris was significantly higher in group A than in group B (P<0.001). There was no significant difference in non-union rate between group A and B (P=0.672) but the mean Lysholm score at the last follow-up was significantly higher in group A than in group B (P=0.006). However, no significant differences were detected in the mean thickness of the rectus femoris, Q-setting, and heel off time between the different age and gender groups (P<0.05). CONCLUSIONS: The prolonged duration of preoperative skeletal traction indicates not only that the resulting disuse atrophy would progress further but also that the muscle atrophy would be accelerated more rapidly for shorter periods of time, based on a cut-off value of 7 days. In addition, the rate of rectus femoris muscle recovery and clinical outcomes were lower in patients undergoing traction for longer periods of time. This indicates that it would be effective for increasing the rate of the recovery and minimizing the occurrence of post surgical complications if surgeons could perform surgery at the earliest possible opportunity following traction, within seven days after the onset of trauma. LEVEL OF EVIDENCE: IV, retrospective cohort study.

Efficacy and safety of non-invasive body tightening with high-intensity focused ultrasound (HIFU).

BACKGROUND: Noninvasive skin-tightening devices have become increasingly popular in response to increasing demand for improvements in skin laxity and tightening with minimal risk and recovery time. OBJECTIVE: We evaluated the efficacy and safety of HIFU for skin tightening in the face and body. METHODS: A total of 32 Korean subjects enrolled in this prospective clinical trial. The subjects were treated with HIFU to both cheeks, lower abdomen, and thigh. Skin elasticity was measured before and after treatment using a Cutometer (CT575, Courage and Khazaka® , Cologne, Germany). Three blinded, experienced dermatologists evaluated paired pre- and post-treatment (week 4 and 12) photographs according to the Global Aesthetic Improvement Scale (GAIS). Participants also completed self-assessments using GAIS. Subjects rated their pain on a numeric rating scale (NRS) immediately, 7 days, 4 weeks, and 12 weeks after treatment. RESULTS: Skin elasticity measured via a Cutometer was significantly improved 12 weeks after treatment at all treated sites (P<.05). Both IGAIS and SGAIS showed significant improvements 12 weeks after treatment. Immediately after treatment the mean NRS score was 3.00±1.586, but no pain was reported at 4 and 12 weeks post-treatment. No serious adverse effects were observed during the follow-up period. CONCLUSION: HIFU safely and effectively improves skin elasticity and clinical contouring of the face and body.

Three-dimensional analysis of mandibular condyle position in patients with deviated mandibular prognathism.

The purpose of this study was to evaluate the bilateral difference in condyle position in patients with deviated mandibular prognathism. Patients with asymmetrical (n=28) and symmetrical mandibular prognathism (n=23) were compared using the three-dimensional (3D) reformatted image from cone beam computed tomography. Significant positional differences in the condyle and subcondyle region (sigmoid notch) were found between the deviated and contralateral sides in the group with asymmetrical mandibular prognathism, but not in the control group. The lateral condyle was more laterally and inferiorly positioned on the contralateral side than on the deviated side (P<0.05). The sigmoid notch was more laterally, superiorly, and posteriorly positioned on the deviated side (P<0.01). Interestingly, condyle width and height on the deviated side was narrower and shorter than on the contralateral side and in the control group. Menton deviation was closely correlated with the bilateral difference in condyle height and 3D position of the sigmoid notch (P<0.01). The degree of asymmetry was more highly correlated with condyle height than with the spatial orientation of the condyle head. The results demonstrated that mandibular prognathism with asymmetry is associated with bilateral differences in 3D morphology and orientation of the condyle. Therefore, clinicians should consider these variations during surgical planning.

Histopathological and scanning electron microscopy findings of retrieved porous polyethylene implants.

Porous polyethylene (PPE) implants are biocompatible alloplastic materials commonly used for facial augmentation. However, the effect of sub-periosteal PPE application on the surrounding tissues has not been analyzed clearly. This report documents the case of a 22-year-old woman who underwent peri-alar augmentation with PPE to improve midface retrusion. Although no infection or inflammation occurred at the surgical site, the patient requested removal of the PPE implant for aesthetic reasons alone at 1 year after the surgery. The removed implant was subjected to histological and morphological evaluation using conventional histological staining and scanning electron microscopy (SEM). Histopathological staining revealed bone ingrowth into the pores of the implant near the boundary with the host bone. Little evidence of a foreign body reaction was observed. SEM revealed densely arranged collagen fibres and osteoblastic cells in the pores. Moreover, the outer surface of the PPE implant in contact with the periosteum showed fibrous tissue ingrowth, leading to tissue adhesion. These findings confirm bone ingrowth into the PPE pore structure in humans.

Hematological adverse effects and pharmacokinetics of ribavirin in pigs following intramuscular administration.

Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double-oil emulsion (RBV-DOE) and gel (RBV-Gel), which were injected into the pigs as single-dose IM injections. After injection of RBV, all of the pigs were monitored. The collected serum and whole blood samples were analyzed by liquid chromatography-tandem mass spectrometry and complete blood count analysis, respectively. All of the ribavirin-treated pigs showed significant decreases in body weight compared to the control groups. Severe clinical signs including dyspnea, anorexia, weakness, and depression were present in ribavirin-treated pigs until 5 days postinjection (dpi). The ribavirin-treated groups showed significant decrease in the number of red blood cells and hemoglobin concentration until 8 dpi. The mean half-life of the RBV-DOE and RBV-Gel was 27.949 ± 2.783 h and 37.374 ± 3.502 h, respectively. The mean peak serum concentration (Cmax ) and area under the serum concentration-time curve from time zero to infinity (AUCinf ) of RBV-DOE were 8340.000 ± 2562.577 ng/mL and 16 0095.430 ± 61 253.400 h·ng/mL, respectively. The Cmax and AUCinf of RBV-Gel were 15 300.000 ± 3764.306 ng/mL and 207526.260 ± 63656.390 h·ng/mL, respectively. The results of this study provided the index of side effect and pharmacokinetics of ribavirin in pigs, which should be considered before clinical application.

Improved methods for evaluating pre-clinical and histological effects of subcutaneous fat reduction using high-intensity focused ultrasound in a porcine model.

BACKGROUND: Non-invasive body sculpting procedures are becoming increasingly popular. High-intensity focused ultrasound (HIFU) treatment is a non-surgical fat reduction procedure that permanently destroys unwanted abdominal fat. Despite its increasing popularity, evaluation methods for the procedure have not yet been fully developed. AIMS: The objective of this study was to develop evaluation methods for HIFU for non-surgical, permanent fat reduction in the anterior abdomen using a porcine model. METHODS: The abdomens of female pigs (Sus scrofa, n = 7) were treated with a HIFU device (SCIZER™ , Classys Inc, Seoul, Korea). We examined treatment effects using photography, ultrasound, gross and microscopic pathology, and serum lipid and liver function level analysis, carbon tracer test, and histological examination in order to determine the mechanism of action, efficacy, and safety of the procedure. RESULTS: HIFU treatment effectively reduced abdominal fat in a porcine model; it accurately treated the target subcutaneous fat layer and the subcutaneous fat was reduced effectively via ultrasonic measurement after HIFU treatment. On histological staining (H&E, toluidine blue, oil red O and immunohistochemistry), we found that subcutaneous fat reduction occurred effectively via accurate treatment of the targeted subcutaneous fat layer. On hematological assay, there were changes within normal range, and values remained stable after 48 h. Via carbon tracer test, the migration of activated macrophages was identified within the axillary lymph node (LN). PPAR-delta, a protein defined by immunohistochemistry staining, was overexpressed in the early stage on days 1 and 7, but a gradual decreasing pattern was confirmed. CONCLUSION: We successfully used a HIFU device for body contouring and fat reduction in a pre-clinical study. These results provide that the essential clues toward the effective evaluation, guiding selection of the appropriate diagnostic investigations.