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Chang Heng Hsieh,1 Li-Ching Lee,1 Wai-Yin Leong,1 Tsai-Chen Yang,1 Ching-Fa Yao,2 Kang Fang1 1Department of Life Science, 2Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan Abstract: Trinucleotide CAG repeat expansion in the coding region of genes has a propensity to form polyglutamine (polyQ) aggregates that contribute to neuronal disorders. Strategies in elevating autophagy to disintegrate the insoluble aggregates without injuring cells have become a major goal for therapy. In this work, a triazole derivative, OC-13, was found accelerating autophagic clearance of polyQ aggregation in human neuroblastoma cells following induction of the enhanced green fluorescence-conjugated chimeric protein that enclosed 79 polyQ repeats (Q79-EGFP). OC-13 accelerated autophagy development and removed nuclear Q79-EGFP aggregates. The increase of Beclin-1, turnover of LC3-I to LC3-II and degradation of p62 supported autophagy activation. Pretreatment of autophagy inhibitor, bafilomycin A1, not only suppressed autophagolysome fusion, but also impeded aggregate eradication. The study also showed that c-Jun N-terminal kinase/Beclin-1 pathway was activated during OC-13 treatment and c-Jun N-terminal kinase inhibitor impaired autophagy and final breakdown. Autophagic clearance of the insoluble aggregates demonstrated the feasibility of OC-13 in alleviating neuronal disorders because of expanded glutamine stretches. Keywords: autophagic flux, polyglutamine, aggregates clearance, triazole, JNK pathway, neuronal disorders, green fluorescence protein

Pin-Jui Kung,1,* Yu-Chen Tao,1,* Ho-Chiang Hsu,1 Wan-Ling Chen,1 Te-Hsien Lin,1 Donala Janreddy,2 Ching-Fa Yao,2 Kuo-Hsuan Chang,3 Jung-Yaw Lin,1 Ming-Tsan Su,1 Chung-Hsin Wu,1 Guey-Jen Lee-Chen,1 Hsiu-Mei Hsieh-Li1 1Department of Life Science, 2Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan *These authors contributed equally to this work Abstract: In spinocerebellar ataxia type 17 (SCA17), the expansion of a translated CAG repeat in the TATA box binding protein (TBP) gene results in a long polyglutamine (polyQ) tract in the TBP protein, leading to intracellular accumulation of aggregated TBP and cell death. The molecular chaperones act in preventing protein aggregation to ameliorate downstream harmful events. In this study, we used Tet-On SH-SY5Y cells with inducible SCA17 TBP/Q79-green fluorescent protein (GFP) expression to test indole and synthetic derivative NC001-8 for neuroprotection. We found that indole and NC001-8 up-regulated chaperone expression to reduce polyQ aggregation in neuronal differentiated TBP/Q79 cells. The effects on promoting neurite outgrowth and on reduction of aggregation on Purkinje cells were also confirmed with cerebellar primary and slice cultures of SCA17 transgenic mice. Our results demonstrate how indole and derivative NC001-8 reduce polyQ aggregation to support their therapeutic potentials in SCA17 treatment. Keywords: spinocerebellar ataxia type 17, TATA box binding protein, polyQ aggregation, indole and derivative, therapeutics

The Michael addition of anilines to β-chloroenones gives enaminones by the elimination of hydrochloric acid (HCl). These enaminones are transformed into α-chloroenaminones via in situ sp 2 C-H functionalization. Anilines that are attached to an electron-donating group react more readily with β-chloroenone to give the corresponding products in excellent yields. A highly atom-economical method has been developed using dimethyl sulfoxide (DMSO) as a green oxidant and solvent. The desired α-functionalized enaminones are formed in good yields with excellent Z -selectivity. We have established the generality of this reaction with many substrates, and scaled-up reactions have been performed to showcase the practical applications. A catalyst-free double annulation of β-chloroenones with o -phenylenediamine has also been demonstrated for the synthesis of 1,4-benzodiazepine derivatives in moderate yields under mild reaction conditions.

Polyglutamine (polyQ)-mediated spinocerebellar ataxia (SCA), including SCA1, 2, 3, 6, 7, and 17, are caused by mutant genes with expanded CAG repeats, leading to the intracellular accumulation of aggregated proteins, the production of reactive oxygen species, and cell death. Among SCA, SCA3 is caused by a mutation in the ATXN3 (ataxin-3) gene. In a circumstance of polyQ aggregation, the autophagic pathway is induced to degrade the aggregated proteins, thereby suppressing downstream deleterious effects and promoting neuronal survival. In this study, we tested the effects of synthetic indole (NC009-1, -2, -3, -6) and coumarin (LM-022, -031) derivatives as chemical chaperones to assist mutant ATXN3-Q 75 folding, as well as autophagy inducers to clear aggregated protein. Among the tested compounds, NC009-1, -2, and -6 and LM-031 interfered with Escherichia coli -derived ATXN3-Q 75 aggregation in thioflavin T binding and filter trap assays. In SH-SY5Y cells expressing GFP-fused ATXN3-Q 75 , these compounds displayed aggregation-inhibitory and neurite growth-promoting potentials compared to untreated cells. Furthermore, these compounds activated autophagy by increasing the phosphatidylethanolamine-conjugated LC3 (microtubule associated protein 1 light chain 3)-II:cytosolic LC3-I ratio in these cells. A biochemical co-immunoprecipitation assay by using a mixture of HEK 293T cell lysates containing recombinant ATXN3-Q 75 -Venus-C-terminus (VC) or Venus-N-terminus (VN)-LC3 protein indicated that NC009-1 and -2 and LM-031 served as an autophagosome-tethering compound (ATTEC) to interact with ATXN3-Q 75 and LC3, and the interaction was further confirmed by bimolecular fluorescence complementation analysis in cells co-expressing both ATXN3-Q 75 -VC and VN-LC3 proteins. The study results suggest the potential of NC009-1 and -2 and LM-031 as an ATTEC in treating SCA3 and, probably, other polyQ diseases.

Objectives: The study aimed (1) to evaluate the site and severity of facial asymmetry in Class III patients before and after bimaxillary surgery, and (2) to identify the influence of initial severity and positional jaw asymmetry on residual facial asymmetry., Materials and Methods: Preoperative and postoperative cone-beam computed tomography of 65 patients with Class III facial asymmetry who underwent bimaxillary surgery were evaluated. Five midline and 14 paramedian facial soft tissue landmarks were identified to assess facial asymmetry. The outcomes were compared to a control group consisting of 30 age- and gender-matched Class I subjects. The postoperative positional jaw asymmetry (i.e., shift, roll, yaw) of each osteotomy segment (maxilla, mandible, chin, ramus) was also measured., Results: Before surgery, the asymmetry was more severe at the chin, middle and lower contour. Bimaxillary surgery effectively corrected facial asymmetry, particularly in achieving normalization of chin deviation. However, significant asymmetry persisted postoperatively in the middle and lower contour (p < 0.001 and p < 0.01, respectively), which was affected by the positional ramus asymmetry in the roll and shift., Conclusions: Deviation of the chin, middle and lower contour contributed significantly to overall facial asymmetry in Class III asymmetry. Despite normalization of the chin deviation after bimaxillary surgery, asymmetry persisted at the middle and lower contour, primarily as the result of insufficient correction of the positional ramus asymmetry., Clinical Relevance: Understanding the residual asymmetry after bimaxillary surgery is important for minimizing deviation and optimizing the surgical planning for its correction., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

A Pd-catalyzed regioselective hydroarylation of terminal alkynes containing a heteroatom has been developed via carbopalladation for the synthesis of allylic ethers, amines, and homoallylic alcohols. Moreover, hydroalkenylation of alkynes produces a variety of stereodefined 1,4-dienes with high regioselectivity. The important features of the present protocol are that it is highly regioselective, operationally rapid, and scalable with a huge substrate scope using only 3 mol% of PdCl 2 (PPh 3 ) 2 catalyst in the presence of a mild base KOAc.

Objectives: Successful orthognathic surgery requires accurate transfer of the intraoperative surgical plan. This study aimed to (1) evaluate the surgical error of a novel intermediate splint in positioning the maxilla during maxilla-first orthognathic surgery and (2) determine factors influencing surgical error., Materials and Methods: This prospective study examined 83 patients who consecutively underwent Le Fort I osteotomy for correction of skeletal class III deformity using a novel intermediate splint and a bilateral sagittal split osteotomy. Surgical error was the outcome variable, measured as the difference in postoperative translational and rotational maxillary position from the virtual plan. Measures included asymmetry, need and amount for mandibular opening during fabrication of intermediate splints, and planned and achieved skeletal movement., Results: Mean errors in translation for vertical, sagittal, and transversal dimensions were 1.0 ± 0.7 mm, 1.0 ± 0.6 mm, and 0.7 ± 0.6 mm, respectively; degrees in rotation for yaw, roll, and pitch were 0.8 ± 0.6, 0.6 ± 0.4, and 1.6 ± 1.1, respectively. The transverse error was smaller than sagittal and vertical errors; error for pitch was larger than roll and yaw (both p < 0.001). Error for sagittal, transverse, and roll positioning was affected by the achieved skeletal movement (roll, p < 0.05; pitch and yaw, p < 0.001). Surgical error of pitch positioning was affected by planned and achieved skeletal movement (both p < 0.001)., Conclusions: Using the novel intermediate splint when performing Le Fort I osteotomy allowed for accurate positioning of the maxilla., Clinical Relevance: The novel intermediate splint for maxillary positioning can be reliably used in clinical routines., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: The Chang Gung Forum has been dedicated to the care of craniofacial anomalies since 2000. This annual continuing medical education program focuses on orofacial cleft and surgery-first orthognathic surgery by providing up-to-date information and management guidelines. This study explored how the Chang Gung Forum has influenced medical perspectives, decisions, and practices in a multidisciplinary craniofacial team., Methods: Between 2000 and 2022, 20 Chang Gung Forums have been held. A questionnaire was distributed among 170 attendees who had participated in the forum more than once. The questionnaire collected information on the participants' experiences and levels of satisfaction with the educational program and whether or how it had influenced their clinical practice., Results: Valid responses from 86 attendees (response rate, 50.6%) who had participated more than once were collected and analyzed. The overall satisfaction rate of the Chang Gung Forum based on the respondents' most recent visits was 4.28 ± 0.63 out of 5. Of the respondents, 90.9% acknowledged changes in their clinical practice, with modifications in surgery plans and decisions being the most notable (48.5%). In addition, comprehension increased throughout years of attending the annual forum (P < 0.001)., Conclusion: The Chang Gung Forum has contributed markedly to the community of congenital craniofacial anomalies. The program will continue providing updated information and influencing the clinical decision-making of health care professionals., Competing Interests: Conflicts of interest and sources of funding: This work was supported in part by a grant from the Craniofacial Research Center, Taoyuan Chang Gung Memorial Hospital (CMRPG3J0823, CMRPG3L0361, CORPG3M0211)., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background/purpose: Skeletal stability after orthognathic surgery is essential for positive treatment outcome. This study evaluated the stability of osteotomy segments after surgery-first bimaxillary surgery for class III asymmetry., Materials and Methods: Seventy adults with class III asymmetry consecutively corrected through surgery-first Le Fort I and bilateral sagittal split osteotomies were investigated. Cone-beam computed tomography before treatment (T0), 1-week after surgery (T1), and after all treatment (T2, ≥1-year after surgery) was used to assess surgical movement (T0 to T1) and skeletal stability (T1 to T2) regarding the translation and rotation of the maxillary, mandibular distal, and proximal segments., Results: At T1, the maxillary segment had moved forward and upward, turned to the deviated side, and rotated downward (all P  < 0.01). The distal segment of mandible had moved forward and upward and rotated upward (all P  < 0.001). The deviated proximal segment had moved upward, tilted to the opposite side, and rotated upward (all P  < 0.001). The opposite proximal segment had moved upward and tilted to the deviated side (both P  < 0.01). At T2, significant relapse occurred in the mandible. The distal segment moved forward and upward and rotated upward (all P  < 0.001). The deviated proximal segment moved upward, tilted to the opposite side, and rotated upward (all P  < 0.001). The opposite proximal segment moved upward and tilted to the deviated side (both P  < 0.01)., Conclusion: Clinically significant relapse of class III asymmetry was discovered on the mandibular distal and opposite proximal segments., (© 2023 Association for Dental Sciences of the Republic of China. Publishing services by Elsevier B.V.)

Background: Although several studies have reported the advantages of the surgery-first approach for orthognathic correction of class III deformity, there is no report of the success of this approach for patients with cleft lip and palate. Therefore, the purpose of this study was to evaluate the stability and outcome of bimaxillary surgery for cleft-related dentofacial deformity using a surgery-first approach., Methods: Forty-one patients with unilateral cleft lip and palate who consecutively underwent Le Fort I and bilateral sagittal split osteotomies for skeletal class III deformity were included. Cone-beam computed tomographic scans before surgery, 1 week after surgery, and after orthodontic treatment were used to measure the surgical and postsurgical changes in jaw position by landmarks, and outcomes of jaw protrusion and relation, incisor angle and occlusion, and menton deviation after treatment. Self-report questionnaires regarding satisfaction with overall appearance of the face and seven facial regions were administered after treatment., Results: A clinically insignificant relapse was found in the maxilla (<1 mm) and mandible (<2 mm). There was a significant improvement in the jaw protrusion and relation, incisor angle and occlusion, and menton deviation. Responses from the self-report questionnaires completed after treatment indicated that patient satisfaction was high., Conclusion: These findings demonstrate surgical-orthodontic treatment with a surgery-first approach can successfully improve cleft-related dentofacial deformity in patients with unilateral cleft lip and palate., Clinical Question/level of Evidence: Therapeutic, IV., (Copyright © 2023 by the American Society of Plastic Surgeons.)

The [4 + 2] annulation of β-formyl ketones with an indole has been developed for the regioselective synthesis of diphenyl-substituted carbazoles in the presence of a catalytic amount of iodine. The 1,4-dicarbonyl compound containing a phenyl group at the α-position of an aldehyde group reacts more readily with indoles to form carbazole derivatives. Using this method, a variety of carbazole derivatives can be readily accessed under mild reaction conditions.

Background: This prospective study aimed to compare regional soft tissue changes between patients with class III overbite and open bite deformities treated with bimaxillary surgery involving clockwise and counter-clockwise mandibular setback, respectively., Material and Methods: Class III deformity adults receiving Le Fort I and bilateral sagittal split osteotomies were grouped according to the incisal occlusion: overbite (n = 30) and open bite (n = 30). Combined cone-beam CT scans and 3D facial photographs preoperative and at least 1-year postoperative were taken to assess the soft tissue changes., Results: Postoperative changes for the overbite and open bite groups included anterior repositioning of nose (-0.8 ± 1.2 mm and -1.1 ± 1.1 mm, respectively) and cheek (-1.9 ± 1.3 mm and -1.7 ± 2.6 mm, respectively), posterior repositioning of chin (5.2 ± 4.0 mm and 4.9 ± 3.2 mm, respectively), and medial (-1.7 ± 2.0 mm and -1.9 ± 2.1 mm, respectively) and posterior (2.7 ± 1.4 mm and 2.8 ± 2.3 mm, respectively) repositioning of bilateral angles. Posterior (1.2 ± 2.0 mm and 5.1 ± 3.3 mm) and inferior (-1.4 ± 2.2 mm and -2.4 ± 2.7 mm) repositioning of upper lip and lower lip occurred in overbite group. Inferior (-2.3 ± 2.4 mm) and superior (3.7 ± 3.4 mm) repositioning of chin occurred in the overbite and open bite groups, respectively., Conclusions: Treatment of class III overbite and open bite deformities with bimaxillary rotational surgery resulted in comparable regional soft tissue changes, except for upper lip, lower lip and chin., Competing Interests: Conflicts of interest All authors declare that they have no conflicts of interest., (Copyright © 2022 Chang Gung University. Published by Elsevier B.V. All rights reserved.)

This Letter outlines palladium-catalyzed regioselective (Markovnikov's) addition of aryl boronic acids to propargyl 1,3-dicarbonyl alkyne to accomplish olefinic/diene 1,3-dicarbonyl compounds without the need for water workup. This methodology showcases remarkable performance with wide-ranging substrate diversity, achieving high yields while employing merely 3 mol % [Pd] alongside a mild KOAc base. Moreover, the utility of dicarbonyl olefins is exemplified through their application in intramolecular cyclization and debenzoylation reactions to access valuable trisubstituted pyran building blocks and ( E )-4-methylene-1,6-diphenylhex-5-en-1-one synthesis.

Parkinson's disease (PD) is featured mainly by the loss of dopaminergic neurons and the presence of α-synuclein-containing aggregates in the substantia nigra of brain. The α-synuclein fibrils and aggregates lead to increased oxidative stress and neural toxicity in PD. Chronic inflammation mediated by microglia is one of the hallmarks of PD pathophysiology. In this report, we showed that coumarin-chalcone hybrid LM-021 and indole derivative NC009-1 reduced the expression of major histocompatibility complex-II, NLR family pyrin domain containing (NLRP) 3, caspase-1, inducible nitric oxide synthase, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in α-synuclein-activated mouse BV-2 microglia. Release of pro-inflammatory mediators including nitric oxide, IL-1β, IL-6 and TNF-α was also mitigated. In BE(2)-M17 cells expressing A53T α-synuclein aggregates, LM-021 and NC009-1 reduced α-synuclein aggregation, neuroinflammation, oxidative stress and apoptosis, and promoted neurite outgrowth. These protective effects were mediated by downregulating NLRP1, IL-1β and IL-6, and their downstream pathways including nuclear factor (NF)-κB inhibitor alpha (IκBα)/NF-κB P65 subunit (P65), c-Jun N-terminal kinase (JNK)/proto-oncogene c-Jun (JUN), mitogen-activated protein kinase 14 (P38)/signal transducer and activator of transcription (STAT) 1, and Janus kinase 2 (JAK2)/STAT3. The study results indicate LM-021 and NC009-1 as potential new drug candidates for PD.

We report on a copper-catalyzed three-component reaction for the synthesis of disubstituted nicotinonitriles using 3-bromopropenals, benzoylacetonitriles, and ammonium acetate (NH 4 OAc). The Knoevenagel-type condensation of 3-bromopropenals with benzoylacetonitriles gives δ-bromo-2,4-dienones that contain strategically placed functional groups that react with the ammonia generated in situ to give the corresponding azatrienes. These azatrienes can then be transformed into trisubstituted pyridines under the reaction conditions via a reaction sequence involving 6π-azaelectrocyclization and aromatization.

The iodine-catalyzed cascade reaction of ortho -formylarylketones with indoles for the synthesis of indolylbenzo[ b ]carbazoles is reported. The reaction is initiated in the presence of iodine by two successive nucleophilic additions of indoles with an aldehyde group of ortho -formylarylketones, and the ketone does not undergo a nucleophilic addition and only involves in the Friedel-Crafts-type cyclization. A variety of substrates are tested, and the efficiency of this reaction is demonstrated with gram-scale reactions.

Neuroinflammation and oxidative stress have been emerging as important pathways contributing to Parkinson's disease (PD) pathogenesis. In PD brains, the activated microglia release inflammatory factors such as interleukin (IL)-β, IL-6, tumor necrosis factor (TNF)-α, and nitric oxide (NO), which increase oxidative stress and mediate neurodegeneration. Using 1-methyl-4-phenylpyridinium (MPP + )-activated human microglial HMC3 cells and the sub-chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, we found the potential of indole derivative NC009-1 against neuroinflammation, oxidative stress, and neurodegeneration for PD. In vitro, NC009-1 alleviated MPP + -induced cytotoxicity, reduced NO, IL-1β, IL-6, and TNF-α production, and suppressed NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in MPP + -activated HMC3 cells. In vivo, NC009-1 ameliorated motor deficits and non-motor depression, increased dopamine and dopamine transporter levels in the striatum, and reduced oxidative stress as well as microglia and astrocyte reactivity in the ventral midbrain of MPTP-treated mice. These protective effects were achieved by down-regulating NLRP3, CASP1, iNOS, IL-1β, IL-6, and TNF-α, and up-regulating SOD2, NRF2, and NQO1. These results strengthen the involvement of neuroinflammation and oxidative stress in PD pathogenic mechanism, and indicate NC009-1 as a potential drug candidate for PD treatment.

Minimal persistent inflammation (MPI), the local inflammation that occurs after an acute type II immune response in patients with allergic rhinitis (AR), is responsible for airway hyperreactivity and the recurrence of AR. Innate lymphoid cells (ILCs) play a crucial role in mucosal immune homeostasis, but the changes of ILC subsets in the MPI stage remain unclear. In this study, the levels of ILC-secreting cytokines in nasal lavages were analyzed from 19 AR patients and 8 healthy volunteers. AR and MPI model mice were established to study the ILC subsets. The results showed that IL-17A was significantly increased in nasal lavage of AR patients in the MPI stage by MSD technology. When compared with the AR model mice, the frequency of IL-13 + ILC2 in the nasal mucosa and lungs decreased, while IL-5 + ILC2 remain high in MPI model mice. A part of the IL-5 + ILC2 subset displayed ILC3-like characteristics with elevated RORγt, IL-17A and IL-23R expression. Especially, these ILC3-like ILC2 exhibited up-regulation of GATA3 + RORγt + were increased in MPI model mice. After the treatment of Biminkang, the frequencies of IL-5 + ILC2, IL-17A + ILC3, and GATA3 + RORγt + ILC3-like ILC2 were significantly reduced, and IL-23R expression was also decreased on ILC3-like-ILC2 subset. These results suggested that the elevated IL-17A in the MPI stage has been related to or at least partly due to the increased of ILC3-like ILC2. Biminkang could effectively decrease IL-17A + ILC3 and inhibit ILC3-like ILC2 subset in the MPI stage. Biminkang is effective in administrating MPI by regulating airway ILC homeostasis., (© 2022 Society for Leukocyte Biology.)

(1) Background: This study aimed to determine the postoperative vermillion symmetry between the cleft and non-cleft sides of patients with unilateral cleft lip during the early and late postoperative periods. (2) Methods: 57 patients with complete and 38 with incomplete unilateral cleft lips operated on between 2010 and 2014 were retrospectively evaluated within 1 month (T1), 9 months to 1 ½ years (T2), and more than 4 years (T3). Vermilion heights of the cleft and non-cleft sides were measured from frontal photographs. The Cleft Lip Component Symmetry Index (CLCSI) was used to determine the symmetry of the cleft and non-cleft sides and was then analyzed. (3) Results: Among the 95 patients studied, vermilion height was excessive on the cleft side throughout the three time periods. There was a significant increase in CLCSI from T1 to T2 for both complete and incomplete types, and a significant increase from T1 to T3 only in the incomplete group and no difference from T2 to T3 for both the groups. (4) Conclusions: Even with efforts to obtain a symmetric vermilion height during the primary cheiloplasty, vermilion height excess was noted with time in complete and incomplete cleft types. Secondary revisional vermilion surgery may be performed to achieve symmetry.

The synthesis of unsymmetrical urea generally requires toxic reagent, solvent and harsh reaction condition. Herein, we introduce Cu-catalyzed greener and safer unsymmetrical urea derivatives synthesis in ethyl acetate. This method minimized utilization of toxic reagent. A variety of indole, amines, and azides with bis-indole successfully employed leading to high yields and gram scale synthesis of isolated urea., (© 2022 Wiley-VHCA AG, Zurich, Switzerland.)

Objectives: Surgery-first orthognathic surgery is rarely used in class III asymmetry due to concerns of reduced skeletal stability from unstable surgical occlusion. This study aimed to evaluate if skeletal stability after surgery-first orthognathic surgery is related to virtual surgical occlusal contact or surgical change., Materials and Methods: We studied 58 adults with class III asymmetry, consecutively corrected by Le Fort I osteotomy and bilateral sagittal split osteotomy using a surgery-first approach. Dental casts were manually set to measure virtual surgical occlusal contact including contact distribution, contact number, and contact area. Cone-beam computed tomography taken before treatment, 1-week post-surgery, and after treatment was used to measure surgical change and post-surgical stability of the maxilla and mandible in translation (left/right, posterior/anterior, superior/inferior) and rotation (pitch, roll, yaw). The relationship between skeletal stability and surgical occlusal contact or surgical change was evaluated with correlation analysis., Results: Significant instability was found in the mandible but not in the maxilla. No correlation was found between the maxillary or mandibular stability and surgical occlusal contact (all p > 0.01). However, a significant correlation was found between the maxillary (roll and yaw) or mandibular (shift, roll and pitch) stability and its surgical change (all p < 0.001)., Conclusions: In correction of class III asymmetry with surgery-first bimaxillary surgery, the skeletal stability is not related to the virtual surgical occlusal contact, but surgical skeletal change., Clinical Relevance: Planned over-correction is a reasonable option for correction of severe shift or roll mandibular asymmetry in bimaxillary surgery for class III deformity., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Botulinum toxin type A (BTA) injections into the subjacent orbicularis oris muscle have been shown to improve appearance and produce narrower cheiloplasty scars. This study was performed to determine the effect of BTA injected at different sites on the unilateral cleft lip scar and cleft side nostril width. A double-blind, randomized prospective trial was conducted involving 64 consecutive patients with unilateral cleft lip undergoing primary cheiloplasty between September 2016 and January 2019. The patients were randomized to receive BTA injections either into the subjacent orbicularis oris muscle (4 points group) or into the bilateral nasolabial fold region (6 points group) during cheiloplasty. The scars were assessed by photographic scar width measurements and Vancouver scar scale assessment tool. The cleft side nostril width was compared to the non-cleft side width. Fifty-six patients completed the trial, 24 in the 4 points group and 31 in the 6 points group. There was no significant difference in scar width or nostril width measurements between the groups at the end of follow-up. The Vancouver scar scale assessment was also similar between the groups. There was no significant difference in scar width or nostril width measurements after cleft lip repair between patients treated with botulinum toxin injections to the subjacent orbicularis oris muscle and patients treated with injections in the nasolabial region., (Copyright © 2021 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: In this study, we aim to present a single institution’s 25-year experience of employing a comprehensive multidisciplinary team-based surgical approach for treating patients with NF-1. Summary Background Data: All patients (n = 106) with a confirmed diagnosis of NF-1 who were treated using a multidisciplinary surgical treatment algorithm at Chang Gung Memorial Hospital between 1994 and 2019 were retrospectively enrolled. Patients were categorized into groups according to the anatomy involved (craniofacial and noncraniofacial groups) and the type of clinical presentation (plexiform and cutaneous neurofibromas groups) for comparative analysis. Methods: The number of surgical interventions and number of specialists involved in surgical care were assessed. Results: Most of the patients exhibited craniofacial involvement (69.8%) and a plexiform type of NF-1 (58.5%), as confirmed through histology. A total of 332 surgical interventions (3.1 ± 3.1 procedures per patient) were performed. The number of specialists involved in surgical care of the included patients was 11 (1.6 ± 0.8 specialists per patient). Most of the patients (62.3%) underwent two or more surgical interventions, and 40.6% of the patients received treatment from two or more specialists. No significant differences were observed between the craniofacial and noncraniofacial groups in terms of the average number of surgical interventions (3.3 ± 3.2 vs. 2.7 ± 2.7, respectively) and number of specialists involved (1.7 ± 0.9 vs. 1.4 ± 0.6). Patients with plexiform craniofacial involvement underwent a significantly higher average number of surgical interventions (4.3 ± 3.6 vs. 1.6 ± 1.1; p < 0.001) and received treatment by more specialists (1.9 ± 0.9 vs. 1.2 ± 0.5; p < 0.001) compared with those having cutaneous craniofacial involvement. Conclusions: In light of the potential benefits of employing the multidisciplinary team-based surgical approach demonstrated in this study, such an approach should be adopted to provide comprehensive individualized care to patients with NF-1.

Objectives: Some adults with cleft lip and palate (CLP) require orthognathic surgery due to skeletal deformity. This prospective study aimed to (1) compare skeletal stability following bimaxillary surgery for correction of class III deformity between patients with unilateral CLP (UCLP) and bilateral CLP (BCLP), and (2) identify risk factors of stability., Materials and Methods: Adults with CLP and skeletal class III deformities who underwent surgery-first bimaxillary surgery were divided into two groups according to cleft type: UCLP (n = 30) and BCLP (n = 30). Skeletal stability was assessed with measures from cone beam computed tomography images of the maxilla and mandible taken before treatment, 1-week and ≥ 1 year postsurgery for translation (left/right, posterior/anterior, superior/inferior) and rotation (yaw, roll, pitch); multiple regression analysis examined risk factors., Results: At follow-up, the maxilla moved upwards in both groups, and backwards in the UCLP group. The mandible moved forward and upward, shifted to the cleft (deviated) side, and rotated upward in both groups. The amount of surgical advancement was a risk factor for sagittal stability in the maxilla (ß = -0.14, p < 0.05). The mandible had three risk factors for sagittal stability: age (ß = -0.23, p < 0.05), surgical team (ß = -1.83, p < 0.05), and amount of surgical setback (ß = -0.32, p = 0.001)., Conclusions: Two years after bimaxillary surgery, patients with UCLP had a higher sagittal relapse of the maxilla compared with patients with BCLP, which was due to a greater surgical advancement in the patients with UCLP., Clinical Relevance: Surgery-first bimaxillary surgery results in favorable treatment outcomes for correction of cleft-related class III deformity. Severity of jaw discrepancy and surgeons should be considered in the surgical design of overcorrection., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Maxillomandibular advancement (MMA) is an effective short-term treatment for obstructive sleep apnea (OSA). This study aimed to evaluate the long-term stability of the facial skeleton, upper airway, and its surrounding structures, as well as improvement in OSA following MMA., Materials and Methods: Thirty-one adults with moderate-to-severe OSA underwent surgery-first modified MMA as primary surgery. Polysomnography and cone-beam computed tomography were obtained pre-surgery, early post-surgery, and at follow-up (i.e., ≥ 2 years post-surgery). Image analysis software assessed the facial skeleton, upper airway, and its surrounding structures., Results: Early post-surgery, apnea-hypopnea index (AHI) had decreased significantly (p < 0.001) and the minimum oxygen saturation (MSAT) increased (p = 0.001), indicating significant improvement in OSA. At follow-up, the AHI and MSAT remained stable. However, the anterior maxilla, soft palate, and tongue moved backward while the hyoid moved downward. There was also a significant decrease in the minimal cross-sectional area of the oropharynx. The reduction in AHI was significantly related to the anterior movement of the anterior maxilla and tongue, inferior movement of the posterior maxilla, and superior movement of the soft palate tip., Conclusions: The improvement of OSA after modified MMA remained stable for at least 2 years following treatment, despite the relapse of the facial skeleton, upper airway, and its surrounding structures. The reduction of AHI was not related to changes in the caliber of the upper airway but to the movement of the maxilla, soft palate, and tongue. Clinical relevance Modified MMA is clinically effective for long-term treatment of patients with moderate-to-severe OSA., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The concept of gingivoperiosteoplasty (GPP) in the mixed dentition stage as compared with secondary alveolar bone grafting (ABG) in management of alveolar cleft has not been much discussed upon. The authors present the experience with extensive GPP and ABG in the mixed dentition stage in complete bilateral alveolar cleft cases., Methods: A retrospective review of nonsyndromic patients with complete bilateral alveolar cleft operated on with either GPP or ABG (iliac crest) in the mixed dentition stage with at least 1-year follow-up was performed. Dental occlusal radiographs were evaluated for level of bone gain using Bergland and Witherow scales. Statistical evaluation of clinical success and procedure-related complications was conducted using χ2 test and odds ratio., Results: Twenty-four patients in the GPP group and 20 in the ABG group were comparatively studied. Clinical success rate as indicated by Bergland scales I and II (87.5% in GPP vs 82.5% in ABG; P = 0.731), complication rate (20.83% in GPP vs 30% in ABG; P = 0.484), and status of canine eruption showed no significant differences in clinical outcomes in both groups., Conclusions: The technique of extensive GPP as described by authors shows equal efficacy to secondary ABG for management of bilateral alveolar clefts during the mixed dentition period., Competing Interests: Conflicts of interest and sources of funding: Supported by research project 109-TMUH-SP-04 of Taipei Medical University Hospital, Taipei, Taiwan. The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Various methods have been used to classify class III asymmetry. There is little information on the use of an asymmetry index to examine soft tissue changes and outcomes for patients with class III asymmetry. This study aimed to (1) evaluate soft tissue changes and outcomes for three types of mandibular asymmetry and (2) determine if measures are associated with type of asymmetry., Materials and Methods: Adults who consecutively underwent bimaxillary surgery using surgery-first approach for correction of class III asymmetry were divided into three groups based on type of mandibular asymmetry. This previously reported classification system is simple and mutually independent, categorizing mandibular asymmetry according to the amount and direction of ramus asymmetry relative to menton deviation: patients with a larger transverse ramus distance on the menton deviation side were divided into group 1 and group 2; group 1 (n = 45) exhibited a menton deviation larger than ramus discrepancy; group 2 (n = 11) exhibited a menton deviation less than ramus discrepancy; group 3 (n = 22) had larger transverse ramus distance contralateral to the side of the menton deviation. Soft tissue facial asymmetry indices, calculated from cone beam computed tomography images, assessed midline and contour asymmetry presurgery, changes postsurgery, and outcomes., Results: Compared with groups 1 and 2, the presurgery index for contour and midline asymmetry was smallest for group 3. All the three groups had significant improvement in midline asymmetry postsurgery, and outcome measures were good; there were no differences between groups. However, contour asymmetry only improved significantly for groups 1 and 2. The outcome for contour asymmetry was fair for groups 1 and 3 and poor for group 2., Conclusions: Bimaxillary surgery significantly improved facial midline asymmetry. The type of mandibular asymmetry was associated with postsurgical changes and outcomes for contour asymmetry., Clinical Relevance: Understanding the types of mandibular asymmetry could help clinicians to develop treatment plans and predict treatment changes and outcomes., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To investigate the repair effect and JNK/NF-κB,SOX9 mechanisms of vibration exercise with different frequencies on articular cartilage in rats with early knee osteoarthritis. Methods: Forty-eight adult male SD rats were randomly divided into six groups( n =8):model control group(MC),high frequency vibration group 1 (GP 1 ,60 Hz),high frequency vibration 2 group (GP 2 ,40 Hz),medium frequency vibration group (ZP,20 Hz),minor frequency group(DP,10 Hz)and normal control group(NC). Except for NC group,the rats in each group were made into early knee osteoarthritis model after six weeks of knee joint cavity injection of papain solution and 2% mixture l-cysteine on the 1 st ,4 th and 7 th day. Each exercise group was subjected vibration to 40 minutes a day with amplitude of 2～5 mm and 5 days a week. Four weeks later, the articular cartilage of the lateral femoral condyle of the both back leg knee joints were detected by HE staining,serine O staining and Mankin scores for morphological observation. The expression levels of JNK,NF-κB p65 and Sox9 mRNA in articular cartilage of the medial femoral condyle were detected by RT-qPCR,and the protein expressions of JNK,NF-κB p65 and Sox9 were detected by Western blot. Results: Compared with the NC group,the Mankin score in other groups was significantly higher ( P ＜0.01). Compared with the MC group,the Mankin score of each vibration group was significantly lower( P ＜0.05),the mRNA and protein expressions of JNK and NF-κB p65 in each vibration training group were significantly lower ( P ＜0.01),the expressions of Sox9 mRNA and protein in vibration training group were increased significantly ( P ＜0.01). Compared with the higher frequency group,the Mankin score,the mRNA and protein expressions of JNK and NF-κB p65 of lower frequency group were significantly lower ( P ＜0.05 or P ＜0.01). But the expressions of Sox9 mRNA and protein were significantly higher ( P ＜ 0.05 or P ＜0.01). Conclusion: Vibration exercise of different frequencies may present varying degrees of cartilage repair impact in rats with early knee osteoarthritis,and the cartilage repair by low-frequency vibration training is better than that by high-frequency vibration. This can be one of the mechanisms on controlling collagen synthesis by down-regulating JNK/NF-κB expression and increasing SOX9 activity of OA articular cartilage.

Objectives: Two-jaw orthognathic surgery (OGS) is done using either the one-splint technique with free-hand positioning of the maxillomandibular complex or the two-splint technique with intermediate splints to position the maxilla. It is uncertain which technique achieves better outcomes. This study compares frontal soft tissue symmetry and subjective patient QoL between one-splint and two-splint techniques in skeletal Class III asymmetry patients undergoing OGS with three-dimensional surgical planning., Materials and Methods: This retrospective case-control study comprised 34 one-splint and 46 two-splint OGS patients. Frontal photographs and Orthognathic Quality of Life Questionnaire (OQLQ) were done pre- and post-treatment. Frontal soft tissue symmetry was analysed with the anthropometric Facial Symmetry Index. Measurements were compared with t-tests and chi-squared tests with p-value set at 0.05., Results: The groups differed in pre-treatment ANB and OQLQ scores. The two-splint group showed significant improvement in all symmetry measures. The one-splint group showed significant improvement in all symmetry measures except midface deviation, upper contour deviation and the Facial Contour Symmetry Index. Both groups showed significant improvement in OQLQ scores. There were no significant differences in post-treatment symmetry measurements and OQLQ scores between groups., Conclusions: Although two-splint technique may better improve contour symmetry, there were no significant differences in frontal soft tissue symmetry and QoL after OGS in skeletal Class III asymmetry with either one-splint or two-splint technique, with both techniques resulting in significant improvement., Clinical Relevance: One-splint and two-splint surgical techniques produce similar patient-centred outcomes in Class III asymmetry patients., (© 2021. The Author(s).)

Background: In this study, we aimed to identify factors correlating with satisfaction with orthognathic surgery in order to improve its outcome., Methods: We recruited 77 participants who had received orthognathic surgery and 32 age- and gender-matched normal-controls. Questionnaires that included devised questions for family support, Big Five Inventory, Derriford Appearance Score, Pittsburgh Sleep Quality Index, Hospital Anxiety and Depression Scale, 36-Item Short-Form Health Survey, and a visual analogy scale for satisfaction, were completed before and one month and nine months after the surgery. The statistical analysis methods included descriptive statistics, t -test, and Pearson correlation., Results: All participants received the preoperative and one-month follow-up, while 28 also completed the nine-month follow-up. Satisfaction was not significantly related to demographic data, but long-term satisfaction was related to an extraverted personality. The preoperative and postoperative results of the Derriford Appearance Scale were related to short-term and long-term satisfaction. Furthermore, both the preoperative and one-month postoperative Pittsburgh Sleep Quality Index findings were significantly related to short-term satisfaction. The postoperative 36-Item Short-Form Health Survey was significantly related to short-term and long-term satisfaction., Conclusions: Not only subjective distress and dysfunction of appearance but also sleep problems and quality of life were correlated to satisfaction with orthognathic surgery. In the future, relevant interventions can be developed to further improve patient's satisfaction and their physical and mental health.

Objectives: To assess and compare the stability and outcomes of the two surgical approaches for patients with roll asymmetry., Materials and Methods: A total of 50 adult patients were consecutively recruited for this prospective study. Patients with class III asymmetry and lip or occlusal cant who underwent bimaxillary surgery were grouped according to surgical approach: asymmetric posterior impaction on both sides (API, n = 31) and posterior impaction on one side and posterior extrusion on the other side (PIE, n = 19). Postsurgical stability and outcomes between groups were determined with cone-beam computed tomography for facial midline, lip, and occlusal cant at 1 week (T1), and at least 12-month postsurgery (T2, completion of orthodontic treatment)., Results: Presurgery, the upper anterior occlusal cant and lip cant were significantly greater for the PIE group (p < 0.05). Postsurgery (T2), the mandible moved upward and rotated upward in both groups. However, the upward rotation was significantly greater in the PIE group compared with the API group. Although the two approaches resulted in significant improvements in facial symmetry, the deviation in the facial midline remained under-corrected for most API patients., Conclusions: Patient outcomes for mandibular stability and facial symmetry differed between the two surgical approaches for correction of class III asymmetry with lip or occlusal cant., Clinical Relevance: The findings of this study suggest that planned over-correction is a reasonable option for the approach of asymmetric posterior impaction on both sides., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To detect and analyze coagulation related indexes and genotypes of a patient with congenital fibrinogen deficiency and his family members, and to investigate the possible molecular pathogenesis., Methods: Four peripheral blood samples (proband and 3 family members) were collected and the prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fg), D-Dimer and eight coagulation factor indicators were detected. All exons and flanking sequences of the FGA, FGB, and FGG genes encoding the three peptide chains of fibrinogen were sequenced and analyzed by bioinformatics., Results: Among the eight coagulation factors of the proband and the elder sister, F Ⅴ and F Ⅷ were slightly higher, TT was significantly prolonged, and Fg was significantly reduced. Sequencing results showed that c.901C>T heterozygous mutation existed in the FGG gene. Bioinformatics analysis showed that the mutation changed the original protein structure and reduced the number of hydrogen bonds., Conclusion: The fibrinogen gamma chain c.901C>T heterozygous mutation is the main cause of congenital fibrinogen deficiency in this family. This mutation is reported for the first time at home and abroad.

Background: Le Fort I maxillary repositioning influences nasal morphology. In Asian cultures, upward nasal tip rotation with increased nostril exposure is considered aesthetically unpleasant and can have psychosocial consequences. This three-dimensional imaging-based study evaluated the effect of different Le Fort I maxillary movements on nasal tip rotation., Methods: Consecutive patients who underwent two-jaw orthognathic surgery (n = 107) were enrolled. To achieve a standard head orientation, preoperative and 1-week and 12-month postoperative cone-beam computed tomography-derived three-dimensional craniofacial models were superimposed. Tip rotation angle was calculated according to the Frankfort horizontal plane for all three-dimensional digital models. The final tip rotation angle change was defined as 12-month postoperative value minus preoperative value. Translational maxillary movement types (advancement versus setback and intrusion versus extrusion), postoperative maxillary segment locations (anterosuperior, anteroinferior, posterosuperior, or posteroinferior), and actual linear maxillary changes were noted., Results: Advancement (1.79 ± 5.20 degrees) and intrusion (2.23 ± 4.96 degrees) movements demonstrated significantly larger final tip rotation angle changes than setback (-0.88 ± 5.15 degrees) and extrusion (0.09 ± 5.44 degrees) movements (all p < 0.05). Postoperative anterosuperior location (2.95 ± 4.52 degrees) of the maxillary segment demonstrated a significantly larger final tip rotation angle change than anteroinferior (0.48 ± 5.65 degrees), posterosuperior (-1.08 ± 4.77 degrees), and posteroinferior (-0.64 ± 5.80 degrees) locations (all p < 0.05). Translational maxillary movement and actual linear maxillary change were not correlated with final tip rotation angle change., Conclusion: Effects of Le Fort I maxillary repositioning on nasal tip rotation depend on movement types and maxillary segment location., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2021 by the American Society of Plastic Surgeons.)

A water-soluble and low-valent rhenium(I) catalyst for the C2 alkenylation of N -pyridyl/ N -pyrimidylindole derivatives with ynamides under mild conditions using water as the solvent has been described. The reaction of N -pyridyl/ N -pyrimidyl indole with the ynamide afforded the C2- Z -selective alkenylation derivative as the sole product, and the reactions of N -pyrimidylanilines delivered the corresponding N -alkenylated product rather than the expected C-H alkenylation products in high yields under the same conditions.

Background: Surgical mobilization of the maxillary segment affects nasal morphology. This study assessed the impact of the type of maxillary mobilization on the three-dimensional (3D) nasal morphometry., Methods: Pre- and postsurgery cone beam computed tomography-derived facial image datasets of consecutive patients who underwent two-jaw orthognathic surgery were reviewed. Using preoperative 3D facial models as the positional reference of the skeletal framework, 12-month postoperative 3D facial models were classified into four types of maxillary mobilizations (advancement [n = 83], setback [n = 24], intrusion [n = 55], and extrusion [n = 52]) and four types of final maxillary positions (anterosuperior [n = 44], anteroinferior [n = 39], posterosuperior [n = 11], and posteroinferior [n = 13]). Six 3D soft tissue nasal morphometric parameters were measured, with excellent intra- and interexaminer reliability scores (ICC>0.897) for all the measurements. The 3D nasal change for each nasal parameter was computed as the difference between postoperative and preoperative measurement values., Results: The intrusion maxillary mobilization resulted in a significantly (all p<0.05) larger 3D nasal change in terms of alar width, alar base width, and nostril angle parameters, and a smaller change in terms of the nasal tip height parameter than the extrusion maxillary mobilization; however, no significant (all p>0.05) difference was observed between advancement and setback maxillary mobilizations. The anterosuperior and posterosuperior maxillary positions had a significantly (all p<0.05) larger 3D nasal change in terms of the alar base width and nostril angle than the anteroinferior and posteroinferior maxillary positions., Conclusion: The type of maxillary mobilization affects the 3D nasal morphometry., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Midface retrusion is a common problem in patients with cleft lip and palate owing to the lack of adequate growth of the maxilla. Midface advancement surgery is a definite treatment for midface retrusion; however, the subsequent oropharyngeal airway changes might result in velopharyngeal insufficiency (VPI) in affected patients. Determining the predictors of VPI beforehand and modifying the surgical procedure would be beneficial., Materials and Methods: A retrospective review of 42 patients with cleft lip and palate who underwent orthognathic surgery from 2013 to 2014 was performed. A total of 25 patients met the inclusion criteria and had undergone complete pre- and postsurgery videofluoroscopy, nasopharyngoscopy (NPS), and speech assessment. We compared 2 groups of patients, those who showed NPS finding changes of more than 0.1 (8 patients) and those without changes (17 patients), by measuring the distances of the contact point to the tip of the velum, gap size at maximum closure (MC) and rest, contact area length, lateral wall closure rate, closure velocity, and 2 angles (from the velum to the hard palate and genu) at MC and rest. The amount of maxillary advancement was also recorded., Results: Among the 8 patients with NPS finding changes, 3 underwent Furlow palatoplasty for VPI. No significant difference was found in the amount of maxillary advancement between the groups (5.8 vs 5.7 mm). Significant differences were found in the preoperative gap size at MC and angle at the genu at MC (P = 0.035 and .012). These could be considered as the predictors before surgery. After surgery, a significant difference was found in the contact area, lateral wall closure rate, and gap size at MC (P = 0.005, 0.018, and 0.01)., Conclusion: Videofluoroscopy is a relatively applicable method of determining dynamic changes in the velum function. By performing videofluoroscopy before midface advancement surgery in patients with cleft lip and palate, we may predict the risk of VPI and consider alternative surgical strategies., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Le Fort I maxillary movements affect nasal width, but nasal width changes with specific movement types have not been formally addressed to date., Objectives: The purpose of this study was to analyze and compare the changes in nasal width with different maxillary movements., Methods: A retrospective study was performed among consecutive patients who underwent bimaxillary orthognathic surgery (n = 138) and who were grouped based on the type of maxillary movement (ie, maxillary advancement with intrusion [MAI], maxillary advancement with extrusion [MAE], and maxillary setback with intrusion [MSI]). Preoperative and 12-month postoperative nasal widths were analyzed photogrammetrically by 2 blinded evaluators., Results: Maxillary advancement with intrusion and MAE presented a significantly (P < 0.05) higher alar base widening than MSI did, with no significant (P > 0.05) differences between MAI and MAE. Maxillary advancement movements (MAI and MAE) showed significantly (P < 0.05) higher alar base widening than maxillary setback movement (MSI). However, no significant (P > 0.05) difference was observed between maxillary intrusion (MAI and MSI) and maxillary extrusion (MAE) movements., Conclusions: This study shows that the nasal width varies distinctly depending on the type of Le Fort I maxillary surgical movement., Competing Interests: Conflicts of interest and sources of funding: Part of this study was supported by grants from the Craniofacial Research Center, Taoyuan Chang Gung Memorial Hospital (CMRPG3J0821, CMRPG3K0391, and NRRPG3K0031). The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This retrospective study analyzed the outcomes of patients undergoing complete or incomplete unilateral cleft lip repair using the Chang Gung technique. The goal was to compare the symmetry and change of the technique through the measurement of anthropometric points on digital photographs., Methods: From 2010 to 2016, a total of 274 complete and incomplete cleft lip patients without other craniofacial deformities were included in the study. All included patients had a minimum 1-year follow-up with frontal view photographs taken. The vermilion area, lip width, vermilion height, lateral lip length, lip height, and Cupid's bow width of both cleft and noncleft sides were measured for all patients. The Cleft Lip Component Symmetry Index was used to determine the symmetry of the cleft and noncleft sides in both incomplete and complete cleft groups., Results: A total of 152 complete and 122 incomplete cleft lip patients were included in the study. The mean Cleft Lip Component Symmetry Index values showed that the vermilion area, lip height, and Cupid's bow width were symmetric on both cleft and noncleft sides. Lip width and lateral lip length were noted to be shorter, whereas the vermilion height was thicker on the cleft side than on the noncleft side. Significant differences between the complete and incomplete cleft group measurements were found for lateral lip length and lip height, and complete cleft measurements were shorter than those for incomplete clefts. There were no significant differences in vermilion area, lip width, vermilion height, and Cupid's bow width., Conclusions: The outcome analysis showed that vermilion height reduction and modifications could be made for both complete and incomplete groups. The complete cleft lip has been found to have a significantly shorter lateral lip length and lip height, reflecting a more severe anatomical soft tissue deficiency in this group. A long-term outcome anthropometric point study may further verify the results of this surgical technique., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: Several studies have investigated risk factors of unfavorable splits associated with sagittal split osteotomies but yielded conflicting information. The purpose of this study is to estimate the frequency of and identify factors associated with unfavorable splits during sagittal split osteotomies (SSOs)., Material and Methods: A retrospective cohort study was conducted on patients who underwent orthognathic surgery, including SSOs at our institution from January 2010 to October 2016. The independent variables were mandibular third molar (M3) status, age, gender, and preoperative dentofacial diagnosis. The outcome variable was the effectiveness of the sagittal split resulting in either favorable or an unfavorable split. Data analyses were performed using logistic regression models except in the case of small sample sizes of preoperative dentofacial diagnoses for which the Fisher's exact test was used., Results: A total of 888 patients with an average age of 24.97 ± 5.09 years underwent 1,776 SSOs. Sixteen (0.90%) unilateral unfavorable splits occurred. Unfavorable splits were less common in patients with an M3 present than in patients with the M3 absent. Having an M3 present reduced the chance of an unfavorable split by 69%, adjusted for age and gender; OR (95% CI) = 0.308 (0.103, 0.919); P = .035. The odds of having an unfavorable split were increased by 8.8% for every year of age increase; adjusted OR (95% CI) = 1.088 (1.004, 1.178); P = .038. Based on this estimation, a 45-year-old is 2.3 times more likely to have an unfavorable split compared to a 35-year-old (95% CI:1.041, 5.146), and is 5.4 times more likely to have an unfavorable split compared to a 25-year-old (95% CI:1.083, 26.48)., Conclusions: The presence of a mandibular third molar (M3) was associated with a decreased risk of an unfavorable split, independent of age and gender. There was a significant association between increased age and the incidence of an unfavorable split., (Copyright © 2020 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Polyglutamine (polyQ)-mediated spinocerebellar ataxias (SCA) are caused by mutant genes with expanded CAG repeats encoding polyQ tracts. The misfolding and aggregation of polyQ proteins result in increased reactive oxygen species (ROS) and cellular toxicity. Inflammation is a common manifestation of oxidative stress and inflammatory process further reduces cellular antioxidant capacity. Increase of activated microglia in the pons of SCA type 3 (SCA3) patients suggests the involvement of neuroinflammation in the disease pathogenesis. In this study, we evaluated the anti-inflammatory potentials of indole compound NC009-1, 4-aminophenol-arachidonic acid derivative AM404, quinoline compound VB-037 and chalcone-coumarin derivative LM-031 using human HMC3 microglia and SCA3 ATXN3/Q 75 -GFP SH-SY5Y cells. The four tested compounds displayed anti-inflammatory activity by suppressing NO, IL-1β, TNF-α and IL-6 production and CD68 expression of IFN-γ-activated HMC3 microglia. In retinoic acid-differentiated ATXN3/Q 75 -GFP SH-SY5Y cells inflamed with IFN-γ-primed HMC3 conditioned medium, treatment with the tested compounds mitigated the increased caspase 1 activity and lactate dehydrogenase release, reduced polyQ aggregation and ROS and/or promoted neurite outgrowth. Examination of IL-1β- and TNF-α-mediated signaling pathways revealed that the tested compounds decreased IκBα/P65, JNK/JUN and/or P38/STAT1 signaling. The study results suggest the potential of NC009-1, AM404, VB-037 and LM-031 in treating SCA3 and probable other polyQ diseases.

Objectives: We aimed to quantify the displacement of the proximal segment after bilateral sagittal split osteotomy in patients with class III asymmetry and evaluate if the displacement was related to the movement of the distal segment., Material and Methods: Forty adults with class III asymmetry corrected by bimaxillary surgery were studied. Cone-beam computed tomography taken before and 1 week after surgery was used to measure the displacement of proximal segments and movement of the distal segment in terms of translation and rotation. The relationship between the displacemnt of the proximal segment and the movement of the distal segment was evaluated., Results: After surgery, the deviated proximal segment was displaced forward and to the deviated side, rotated downward, tilted, and turned to the opposite side. The opposite proximal segment was displaced forward and rotated downward. The roll rotation of the proximal segment was correlated with the left/right movement and roll rotation of the distal segment., Conclusion: Early after orthognathic correction for class III asymmetry, the deviated proximal segment was displaced in a direction favorable for correction of asymmetry. The roll rotation of the proximal segment was affected by the transverse movement and roll rotation of the distal segment., Clinical Relevance: Knowledge of the ability and limitation of the proximal segment rotation improves the virtual simulation.

Background: Since 2012, the authors have adopted the medial subcoronoid process bone interpositional grafting in OGS and genioplasty procedures. The purpose of this study was to present the technical details and clinical outcomes of this alternative bone interpositional grafting for LeFort I and chin osteotomies., Methods: Consecutive patients (n = 50) who underwent single-splint bimaxillary OGS with or without genioplasty and received medial subcoronoid bone interpositional grafting were included. Standardized facial and intraoral photographs at early and late postoperative periods (12.2 ± 3.3 and 44.8 ± 8.4 months postsurgery, respectively) were blindly rated to assess facial symmetry, chin, and occlusion status based on qualitative rating scales. Complication and reoperation rates were also reviewed., Results: The medial subcoronoid bone interpositional grafts were adopted to stabilize different LeFort I maxillary movement types or lengthening/advancing genioplasty (36 and 14 patients, respectively). Overall, the early facial symmetry, chin, and occlusion status were maintained at late evolutions. None of the patients had donor-site or bone graft-related complications (i.e., bad split, undesired mandible fracture, infection, fibrous union, nonunion, and/or permanent neurosensory deficit) or revisionary surgery during follow-up., Conclusion: The medial subcoronoid process bone grafting was a feasible alternative for bone interpositional defects of LeFort I and chin osteotomies with no significant morbidity and avoiding secondary donor sites.

An efficient one-pot two-step sequential reaction for the synthesis of biologically active 3-hydroxyisoindolin-1-one derivatives from 2-iodobenzamide derivatives and various substituted benzyl cyanides in the presence of CuCl and cesium carbonate in DMSO is reported. Furthermore, 3-hydroxyisoindolinone derivatives possessing bromo substituents were obtained from 2-iodobenzamide and 2-bromobenzyl cyanide substrates in two steps. Benzyl cyanide has been successfully used for the first time as a benzoyl synthon for the synthesis of 3-hydroxyisoindolin-1-ones. Interestingly, the mechanism of formation of 3-hydroxyisoindolin-1-ones is a novel pathway that involves carbon degradation followed by ring contraction.

Background: Modern orthognathic surgery (OGS) was established on the basis of contributions from multidisciplinary centers worldwide. This study reports the history and evolution of OGS at the Chang Gung Craniofacial Center (CGCC) and identifies the lessons learned from 35 years of experience., Methods: The total number of OGS procedures managed by the CGCC multidisciplinary team between 1981 and 2016 was determined. The database of the senior author (Y.-R.C.) was reviewed for consecutive OGS procedures performed between 2003 and 2016. A literature review was also performed to retrieve the contributions from the total CGCC team., Results: The 35 years of experience at a single center and 13-year experience of a single surgeon corresponded to 8073 and 2883 OGS procedures, respectively. Moreover, 53 peer-reviewed articles were reviewed. Teamwork (plastic surgeons, orthodontists, and anesthetists) ensured an optimal balance between occlusion functional and facial aesthetic outcomes, with patient safety ensured and a minimum of OGS-related complications. Progression from the conventional orthodontics-first approach to the surgery-first OGS approach decreased the overall treatment time. Transition from 1-jaw to 2-jaw surgery enabled more consistent aesthetic outcomes to be achieved. Conversion from the 2-splint to the single-splint technique enabled development of a more precise tridimensional simulation plan and surgical execution, including in challenging scenarios such as malocclusion associated with facial asymmetry. Clockwise pitch rotation of the maxillomandibular complex has been designed for facial aesthetic purposes in class III malocclusion, whereas counterclockwise pitch rotation of the maxillomandibular complex improves airway function in those with sleep apnea., Conclusions: The lessons learned from experience and outcome-based articles reveal that OGS has successfully evolved at the CGCC, with a balance being achieved between functional and aesthetic outcomes and effective decreases in the burden of care (ie, morbidity, complications, and treatment time).

Parkinson's disease (PD) is a common neurodegenerative disease accompanied by a loss of dopaminergic (DAergic) neurons. The development of therapies to prevent disease progression is the main goal of drug discovery. There is increasing evidence that oxidative stress and antioxidants may contribute to the pathogenesis and treatment of PD, respectively. In the present study, we investigated the antioxidative protective effects of the indole-derivative compound NC001-8 in DAergic neurons derived from SH-SY5Y cells and PD-specific induced pluripotent stem cells (PD-iPSCs) carrying a PARKIN ex5del mutation. In SH-SY5Y-differentiated DAergic neurons under 1-methyl-4-phenylpyridinium (MPP + ) treatment, NC001-8 remarkably reduced the levels of reactive oxygen species (ROS) and cleaved caspase 3; upregulated nuclear factor erythroid 2-related factor 2 (NRF2) and NAD(P)H dehydrogenase, quinone 1 (NQO1); and promoted neuronal viability. In contrast, NRF2 knockdown abolished the effect of NC001-8 on the reduction of ROS and improvement of neuronal viability. In H 2 O 2 -treated DAergic neurons differentiated from PD-iPSCs, NC001-8 rescued the aberrant increase in ROS and cleaved caspase 3 by upregulating NRF2 and NQO1. Our results demonstrated the protective effect of NC001-8 in DAergic neurons via promoting the NRF2 antioxidative pathway and reducing ROS levels. We anticipate that our present in vitro assays may be a starting point for more sophisticated in vivo models or clinical trials that evaluate the potential of NC001-8 as a disease modifier for PD., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2019 Pei-Cih Wei et al.)

A stable occlusion at the time of surgery is considered important for post-surgical stability after orthognathic surgery. The aim of this study was to determine whether skeletal stability after bimaxillary surgery using a surgery-first approach for skeletal class III deformity is related to the surgical occlusal contact or surgical change. Forty-two adult patients with a skeletal class III deformity corrected by Le Fort I osteotomy and bilateral sagittal split osteotomy with a surgery-first approach were studied. Dental models were set and used to measure the surgical occlusal contact, including contact distribution, contact number, and contact area. Cone beam computed tomography was used to measure the surgical change (amount and rotation) and post-surgical skeletal stability. The relationship between skeletal stability and surgical occlusal contact or surgical change was evaluated. No relationship was found between maxillary or mandibular stability and surgical occlusal contact. However, a significant relationship was found between maxillary and mandibular stability and the amount and rotation of surgical change. The results suggest that in the surgical-orthodontic correction of skeletal class III deformity with a surgery-first approach, the post-surgical skeletal stability is not related to the surgical occlusal contact but is related to the surgical change., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Accumulation of nucleotide building blocks prior to and during S phase facilitates DNA duplication. Herein, we find that the anaphase-promoting complex/cyclosome (APC/C) synchronizes ribose-5-phosphate levels and DNA synthesis during the cell cycle. In late G 1 and S phases, transketolase-like 1 (TKTL1) is overexpressed and forms stable TKTL1-transketolase heterodimers that accumulate ribose-5-phosphate. This accumulation occurs by asymmetric production of ribose-5-phosphate from the non-oxidative pentose phosphate pathway and prevention of ribose-5-phosphate removal by depleting transketolase homodimers. In the G 2 and M phases after DNA synthesis, expression of the APC/C adaptor CDH1 allows APC/C CDH1 to degrade D-box-containing TKTL1, abrogating ribose-5-phosphate accumulation by TKTL1. TKTL1-overexpressing cancer cells exhibit elevated ribose-5-phosphate levels. The low CDH1 or high TKTL1-induced accumulation of ribose-5-phosphate facilitates nucleotide and DNA synthesis as well as cell cycle progression in a ribose-5-phosphate-saturable manner. Here we reveal that the cell cycle control machinery regulates DNA synthesis by mediating ribose-5-phosphate sufficiency.

Alzheimer's disease (AD), probably caused by abnormal accumulation of β-amyloid (Aβ) and aberrant phosphorylation of tau, is the most common cause of dementia among older people. Generation of patient-specific neurons by induced pluripotent stem cell (iPSC) technology facilitates exploration of the disease features in live human neurons from AD patients. In this study, we generated iPSCs from two familial AD patients carrying a heterozygous D678H mutation in the APP gene (AD-iPSCs). The neurons derived from our AD-iPSCs demonstrated aberrant accumulation of intracellular and secreted Aβ42 and Aβ40, reduction of serine 9 phosphorylation in glycogen synthase kinase 3β (GSK3β) hyperphosphorylation of threonine 181 and serine 396 in tau protein, impaired neurite outgrowth, downregulation of synaptophysin, and increased caspase 1 activity. The comparison between neurons derived from a sibling pair of wild-type and mutated iPSCs successfully recapitulated these AD phenotypes. Treatment with indole compound NC009-1 (3-((1H-Indole-3-yl)methyl)-4-(2-nitrophenyl)but-3-en-2-one), a potential Aβ aggregation reducer, normalized the Aβ levels and GSK3β and tau phosphorylation, attenuated caspase 1 activity, and improved neurite outgrowth in AD-iPSC-derived neurons. Thus, APP D678H iPSCs-derived neurons recapitulate the cellular characteristics relevant to AD and enable exploration of the underlying pathogenesis and therapeutic strategies for AD.

Neonicotinoid insecticide pollution in soil and water poses serious environmental risks. Microbial biodegradation is an important neonicotinoid insecticide degradation pathway in the environment. In this study, 70.0% of the acetamiprid in a 200 mg/L solution was degraded by actinomycetes Streptomyces canus CGMCC 13662 (isolated from soil) in 48 h, and the acetamiprid degradation half-life was 27.7 h. Acetamiprid was degraded to IM-1-2 (( E)-1-(1-(((6-chloropyridin-3-yl)methyl)(methyl) amino)ethylidene)urea) through hydrolysis of the cyanoimine moiety. Gene cloning and overexpression indicated that a novel nitrile hydratase with three unusual subunits (AnhD, AnhE, and AnhA) without accessory protein mediated IM-1-2 formation. The purified nitrile hydratase responsible for degrading acetamiprid had a K m of 5.85 mmol/L and a V max of 15.99 U/mg. A homology model suggested that AnhD-Glu56 and AnhE-His21 play important roles in the catalytic efficiency of the nitrile hydratase. S. canus CGMCC 13662 could be used to remediate environments contaminated with acetamiprid.