The TSAR-osteotomy, a total subapical and ramus osteotomy: A technical note.

There are several treatment options to treat a class II dentofacial deformity with a pronounced chin. A total subapical osteotomy is one of these options. This type of osteotomy was refined to total subapical and ramus (TSAR) osteotomy. In this technical note, a detailed and schematic presentation of the TSAR osteotomy is presented step by step. The surgical approach to the TSAR osteotomy is divided into three parts. The first part consists of the horizontal osteotomy at the level of the ramus, the second part approaches the corticotomy to release and protect the mental nerve and the third part consists of connecting the horizontal ramus osteotomy and the local corticotomy around the mental nerve. In this third part, it is important that the inferior alveolar nerve (IAN) is actively sought and protected.

Growth/differentiation factor 15 controls ependymal and stem cell number in the V-SVZ.

The expression of growth/differentiation factor (GDF) 15 increases in the ganglionic eminence (GE) late in neural development, especially in neural stem cells (NSCs). However, GDF15 function in this region remains unknown. We report that GDF15 receptor is expressed apically in the GE and that GDF15 ablation promotes proliferation and cell division in the embryonic GE and in the adult ventricular-subventricular zone (V-SVZ). This causes a transient generation of additional neuronal progenitors, compensated by cell death, and a lasting increase in the number of ependymal cells and apical NSCs. Finally, both GDF15 receptor and the epidermal growth factor receptor (EGFR) were expressed in progenitors and mutation of GDF15 affected EGFR signaling. However, only exposure to exogenous GDF15, but not to EGF, normalized proliferation and the number of apical progenitors. Thus, GDF15 regulates proliferation of apical progenitors in the GE, thereby affecting the number of ependymal cells and NSCs.

Accuracy of mandibular anterior subapical osteotomy by virtual planning in orthognathic surgery using patient-specific implants.

INTRODUCTION: Mandibular anterior subapical osteotomy (MASO) is a complementary procedure during orthognathic surgery to correct proclination or extrusion of the anterior incisors when orthodontic movements fail. The increasing use of patient-specific implants (PSI, titanium plates) in orthognathic surgery has extended to this procedure. Digital orthognathic surgery planning involves manufacturing cutting/drilling guides and specific implants to provide better accuracy and allow complex movement with reduced surgical times compared to conventional planning. This study aimed to assess the accuracy of computer-aided surgery with patient-specific implants in mobilising the MASO segment according to planning. METHODS: Eleven consecutive patients with mean age 26.82 years (15-41, SD = 10.65) were treated with MASO in addition to other conventional orthognathic procedures incorporating digital planning and patient-specific implants. A three-dimensional "stl" format file of the mandibular dental arch was obtained using an intraoral scanner at the end of the surgical procedure. The accuracy of the MASO segment displacement imposed by PSI was assessed by comparing preoperative 3D-planned mandibular dental arch with the immediate postoperative 3D-measured arch, using surface superimposition and 7 standard dental landmarks. Deviations between the preoperative and postoperative landmarks were calculated and compared to determine whether MASO segment repositioning is sufficiently accurate to be safely used to reposition the incisor/canine axis. RESULTS: Quantitative analysis revealed an absolute linear difference of 0.66 mm (SD = 0.51) between preoperative 3D digital dental arch impression and postoperative planned 3D dental arch. Overall, the median absolute discrepancies in the x-axis (right-left direction), y-axis (antero-posterior direction), and z-axis (supero-inferior direction) were respectively 0.56 mm (SD = 0.42), 0.77 mm (SD = 0.45) and 0.65 mm (SD = 0.61). CONCLUSION: A high degree of accuracy between the virtual plan and the immediate postoperative result was observed. According to our results, PSI can be used safely with accuracy in MASO as an adjunct to other conventional orthognathic procedures.

Restriction of subapical proteins during cellularization depends on the onset of zygotic transcription and the formin Dia.

Cortical domains are characterized by spatially restricted polarity proteins. The pattern of cortical domains is dynamic and changes during cell differentiation and development. Although there is a good understanding for how the cortical pattern is maintained, e. g. by mutual antagonism, less is known about how the initial pattern is established, and its dynamics coordinated with developmental progression. Here we investigate the initial restriction of subapical marker proteins during the syncytial-cellular transition in Drosophila embryos. The subapical markers Canoe/Afadin, the complex ELMO-Sponge, Baz and Arm become initially restricted between apical and lateral domains during cellularization. We define the role of zygotic genome activation as a timer for subapical domain formation. Subapical markers remained widely spread in embryos treated with α-amanitin and became precociously restricted in mutant embryos with premature zygotic transcription. In contrast, remodeling of the nuclear division cycle without cytokinesis to a full cell cycle is not a prerequisite for subapical domain formation, since we observed timely subapical restriction in embryos undergoing an extra nuclear cycle. We provide evidence that earliest subapical markers ELMO-Sponge and Canoe are required for subapical accumulation of Baz. Supporting an important role of cortical F-actin in subapical restriction, we found that the formin Dia was required for Baz restriction, and its distribution depended on the onset of zygotic gene expression. In summary, we define zygotic transcription as a timer, to which subapical markers respond in a dia-dependent mechanism.

Vertebral column resection (VCR) at the subapical vertebra for correction of angular kyphosis associated with neurofibromatosis type 1(NF1): a case report.

PURPOSE: To describe the process and outcome of vertebral column resection (VCR) at the subapical vertebra for correction of angular kyphosis associated with neurofibromatosis type 1(NF1). METHODS: A review and summary of the medical history, radiographs, operative procedure, and complications of a 16-year-old male presenting with severe angular kyphosis associated with NF1 with dyspnea. RESULTS: A 16-year-old male presented with severe angular kyphosis associated with NF1 with dyspnea. Preoperative radiographs demonstrated multiple vertebrae were rotated in the vicinity of the apical vertebra, with a wedge-shaped deformity, dysplasia, T10-T12 kyphotic angle of 160°, and T2-L2 kyphotic angle of 95°. VCR at the L1 vertebra (distal end of the apical vertebra) with bone grafting and internal fixation was performed. Postoperative imaging revealed that the T2-L2 Cobb angle was 20°, denoting a correction rate of 79%. The patient's height increased from 130 to 150 cm. The position of internal fixation was not displaced, and the correction angle was maintained at 2-year follow-up. CONCLUSIONS: The novel strategy of performing VCR at the subapical vertebra, with posterior displacement of the distal end, and remodeling of the spinal canal is potentially a safe and efficacious option to correct sharp angular kyphosis.

Changes in Facial Profile after Modified Anterior Maxillary Subapical Osteotomy.

(1) Background: This study explored the effects of modified anterior maxillary subapical osteotomy (AMSO) on facial profile changes in patients with bimaxillary protrusion. (2) Methods: Cephalograms of patients were collected preoperatively and over 2 months postoperatively. The following landmarks were recorded: pronasale (Prn), subnasale (Sn), labrale superius (Ls), anterior nasal spine (ANS), and incisor superius (Is). The following distances and angles were measured: ANS-Prn, ANS-Sn, ANS-Ls, Is-Sn, Is-Ls, SNA angle, and nasolabial (NLA) angle. (3) Results: Is and ANS were significantly retracted by 7.3 and 2.3 mm, respectively. Soft tissue landmarks (Prn, Sn, and Ls) were significantly retracted (1.2, 1.6, 4.4 mm, respectively). Postoperative changes in soft/hard tissue ratios were 0.54, 0.72, 0.31, and 0.60 for Prn/ANS, Sn/ANS, ANS/Is, and Ls/Is, respectively. The NLA angle was increased significantly by 7.1°. (4) Conclusions: The horizontal soft/hard tissue ratios of Sn/Is, ANS/Is, and Ls/Is were 0.22, 0.31, and 0.60, respectively. The NLA angle was increased significantly by 7.1°. The modified AMSO provides an increased blood supply, allows for direct vision, and results in fewer complications than other AMSO methods.

Plasmolipin regulates basolateral-to-apical transcytosis of ICAM-1 and leukocyte adhesion in polarized hepatic epithelial cells.

Apical localization of Intercellular Adhesion Receptor (ICAM)-1 regulates the adhesion and guidance of leukocytes across polarized epithelial barriers. Here, we investigate the molecular mechanisms that determine ICAM-1 localization into apical membrane domains of polarized hepatic epithelial cells, and their effect on lymphocyte-hepatic epithelial cell interaction. We had previously shown that segregation of ICAM-1 into apical membrane domains, which form bile canaliculi and bile ducts in hepatic epithelial cells, requires basolateral-to-apical transcytosis. Searching for protein machinery potentially involved in ICAM-1 polarization we found that the SNARE-associated protein plasmolipin (PLLP) is expressed in the subapical compartment of hepatic epithelial cells in vitro and in vivo. BioID analysis of ICAM-1 revealed proximal interaction between this adhesion receptor and PLLP. ICAM-1 colocalized and interacted with PLLP during the transcytosis of the receptor. PLLP gene editing and silencing increased the basolateral localization and reduced the apical confinement of ICAM-1 without affecting apicobasal polarity of hepatic epithelial cells, indicating that ICAM-1 transcytosis is specifically impaired in the absence of PLLP. Importantly, PLLP depletion was sufficient to increase T-cell adhesion to hepatic epithelial cells. Such an increase depended on the epithelial cell polarity and ICAM-1 expression, showing that the epithelial transcytotic machinery regulates the adhesion of lymphocytes to polarized epithelial cells. Our findings strongly suggest that the polarized intracellular transport of adhesion receptors constitutes a new regulatory layer of the epithelial inflammatory response.

Evaluation of different fixation methods with finite element analysis in total mandibular subapical osteotomy.

PURPOSE: The purpose of the study was to evaluate the stress distribution in various miniplates that were used in cases that underwent advancement with total mandibular subapical osteotomy (TMSO) using finite element analysis (FEA). MATERIAL AND METHOD: Cone beam computed tomography (CBCT) images of a patient with appropriate bone tissues were used as a reference for the modeling of the mandible. In all mandibular models, horizontal TMSO was performed in a region 5 mm away from the apex of the teeth and vertical TMSO was performed in the retromolar region, 10 mm posterior to the second molar tooth. After TMSO, the dentoalveolar segment was advanced 3 mm and miniplates were placed symmetrically at four points for fixation. Four different miniplates with 2.0 mm thickness were used. Three different forces were applied to the models. Stress distribution on the models was evaluated using maximum von Mises stress values. RESULTS: The maximum von Mises stress occurred in Y + I and Y + L models following the application of 300 N force from the incisal. An evaluation of posterior unilateral force indicated that the stress was remarkably high in the models with a posterior I-plate. The stress in the Y + I model was higher under unilateral force compared to the stress in other models. Under posterior bilateral force, the maximum von Mises stress values ​​occurred in the I-plates of T + I, Y + I, and L + I models (1006, 1012, and 1004 MPa, respectively). CONCLUSION: Within the limitations of our study, we found that the ideal stress distribution was in the T + L and L + L plate combinations in the plates used for fixation after advancement with TMSO.

Dia- and Rok-dependent enrichment of capping proteins in a cortical region.

Rho signaling with its major targets the formin Dia, Rho kinase (Rok) and non-muscle myosin II (MyoII, encoded by zip in flies) control turnover, amount and contractility of actomyosin. Much less investigated has been a potential function for the distribution of F-actin plus and minus ends. In syncytial Drosophila embryos, Rho1 signaling is high between actin caps, i.e. the cortical intercap region. Capping protein binds to free plus ends of F-actin to prevent elongation of the filament. Capping protein has served as a marker to visualize the distribution of F-actin plus ends in cells and in vitro. In the present study, we probed the distribution of plus ends with capping protein in syncytial Drosophila embryos. We found that capping proteins are specifically enriched in the intercap region similar to Dia and MyoII but distinct from overall F-actin. The intercap enrichment of Capping protein was impaired in dia mutants and embryos, in which Rok and MyoII activation was inhibited. Our observations reveal that Dia and Rok-MyoII control Capping protein enrichment and support a model that Dia and Rok-MyoII control the organization of cortical actin cytoskeleton downstream of Rho1 signaling. This article has an associated First Person interview with the first authors of the paper.

The ESCRT-III molecules regulate the apical targeting of bile salt export pump.

BACKGROUND: The bile salt export pump (BSEP) is a pivotal apical/canalicular bile salt transporter in hepatocytes that drives the bile flow. Defects in BSEP function and canalicular expression could lead to a spectrum of cholestatic liver diseases. One prominent manifestation of BSEP-associated cholestasis is the defective canalicular localization and cytoplasmic retention of BSEP. However, the etiology of impaired BSEP targeting to the canalicular membrane is not fully understood. Our goal was to discover what molecule could interact with BSEP and affect its post-Golgi sorting. METHODS: The human BSEP amino acids (a.a.) 491-630 was used as bait to screen a human fetal liver cDNA library through yeast two-hybrid system. We identified a BSEP-interacting candidate and showed the interaction and colocalization in the co-immunoprecipitation in hepatoma cell lines and histological staining in human liver samples. Temperature shift assays were used to study the post-Golgi trafficking of BSEP. We further determine the functional impacts of the BSEP-interacting candidate on BSEP in vitro. A hydrodynamically injected mouse model was established for in vivo characterizing the long-term impacts on BSEP. RESULTS: We identified that charged multivesicular body protein 5 (CHMP5), a molecule of the endosomal protein complex required for transport subcomplex-III (ESCRT-III), interacted and co-localized with BSEP in the subapical compartments (SACs) in developing human livers. Cholestatic BSEP mutations in the CHMP5-interaction region have defects in canalicular targeting and aberrant retention at the SACs. Post-Golgi delivery of BSEP and bile acid secretion were impaired in ESCRT-III perturbation or CHMP5-knockdown hepatic cellular and mouse models. This ESCRT-III-mediated BSEP sorting preceded Rab11A-regulated apical cycling of BSEP. CONCLUSIONS: Our results showed the first example that ESCRT-III is essential for canalicular trafficking of apical membrane proteins, and provide new targets for therapeutic approaches in BSEP associated cholestasis.

Physical interactions between Gsx2 and Ascl1 balance progenitor expansion versus neurogenesis in the mouse lateral ganglionic eminence.

The Gsx2 homeodomain transcription factor promotes neural progenitor identity in the lateral ganglionic eminence (LGE), despite upregulating the neurogenic factor Ascl1. How this balance in maturation is maintained is unclear. Here, we show that Gsx2 and Ascl1 are co-expressed in subapical progenitors that have unique transcriptional signatures in LGE ventricular zone (VZ) cells. Moreover, whereas Ascl1 misexpression promotes neurogenesis in dorsal telencephalic progenitors, the co-expression of Gsx2 with Ascl1 inhibits neurogenesis. Using luciferase assays, we found that Gsx2 reduces the ability of Ascl1 to activate gene expression in a dose-dependent and DNA binding-independent manner. Furthermore, Gsx2 physically interacts with the basic helix-loop-helix (bHLH) domain of Ascl1, and DNA-binding assays demonstrated that this interaction interferes with the ability of Ascl1 to bind DNA. Finally, we modified a proximity ligation assay for tissue sections and found that Ascl1-Gsx2 interactions are enriched within LGE VZ progenitors, whereas Ascl1-Tcf3 (E-protein) interactions predominate in the subventricular zone. Thus, Gsx2 contributes to the balance between progenitor maintenance and neurogenesis by physically interacting with Ascl1, interfering with its DNA binding and limiting neurogenesis within LGE progenitors.

Current views on endocytosis in filamentous fungi.

Filamentous fungi grow by adding cell wall and membrane exclusively at the apex of tubular structures called hyphae. Growth was previously believed to occur only through exocytosis at the Spitzenkörper, an organised body of secretory macro- and microvesicles found only in growing hyphae. More recent work has indicated that an area deemed the sub-apical collar is enriched for endocytosis and is also required for hyphal growth. It is now generally believed that polarity of filamentous fungi is achieved through the balancing of the processes of endocytosis and exocytosis at these two areas. This review is an update on the current progress and understanding surrounding the occurrence of endocytosis and its spatial regulation as they pertain to growth and pathogenicity in filamentous fungi.

Three-dimensional treatment planning for maxillary and mandibular segmental surgery for an adult Class III: Where old meets new.

Class III open bite malocclusion can be among the most difficult case types to obtain an excellent occlusal, skeletal, and facial outcome. Treatment options include growth modification, extraction for orthodontic camouflage, and orthognathic surgery. For the most severely affected and non-growing patients, orthognathic surgery is often the most predictable and, in some situations, the only viable way of achieving an optimal result. The risks and benefits of surgical treatment options can occasionally be difficult to assess particularly for providers with limited experience. Two-dimensional surgical predictions can assist but do not permit the third dimension to be visualized. New techniques of computer-aided surgical simulation can enable the surgeon, orthodontist, and patient to better visualize and understand the treatment approach and enable them to make the most effective and efficient treatment related decisions. This case merges knowledge of the full spectrum of historical surgical techniques with the new approach of computer-aided surgical simulation (CASS) to perform complex segmental maxillary and mandibular surgery to obtain an excellent functional and esthetic result.

ELMO and Sponge specify subapical restriction of Canoe and formation of the subapical domain in early Drosophila embryos.

Canoe/Afadin and the GTPase Rap1 specify the subapical domain during cellularization in Drosophila embryos. The timing of domain formation is unclear. The subapical domain might gradually mature or emerge synchronously with the basal and lateral domains. The potential mechanism for activation of Rap1 by guanyl nucleotide exchange factors (GEFs) or GTPase activating proteins (GAPs) is unknown. Here, we retraced the emergence of the subapical domain at the onset of cellularization by in vivo imaging with CanoeYFP in comparison to the lateral and basal markers ScribbledGFP and CherrySlam. CanoeYFP accumulates at a subapical position at about the same time as the lateral marker ScribbledGFP but a few minutes prior to basal CherrySlam. Furthermore, we show that the unconventional GEF complex ELMO-Sponge is subapically enriched and is required for subapical restriction of Canoe. The localization dynamics of ELMO-Sponge suggests a patterning mechanism for positioning the subapical region adjacent to the apical region. While marking the disc-like apical regions before cellularization, ELMO-Sponge redistributes to a ring-like pattern surrounding the apical region at the onset of cellularization.

Inferior subapical osteotomy for dentoalveolar decompensation of class III malocclusion in 'surgery-first' and 'surgery-early' orthognathic treatment.

Increasing experience with alternative timing protocols in orthognathic surgery has given way to new surgical and orthodontic techniques to shorten treatment times, reduce biological costs, and improve the final outcome. A prospective evaluation of class III patients who received an inferior segmental osteotomy (ISO) for decompensation of significantly retroclined lower incisors in the context of 'surgery-first' (SF) or 'surgery-early' (SE) timing protocols was performed. Treatment was planned virtually. A thorough periodontal assessment was performed at baseline and periodically until debonding. A minimally invasive surgical technique including selective interdental corticotomies and elective bone augmentation was used. Patient and orthodontist satisfaction with the treatment was evaluated. Eight patients (mean age 26.3 years) underwent surgery. One had isolated maxillary surgery and seven had bimaxillary surgery in combination or not with additional cosmetic procedures. The periodontal status of all patients remained stable throughout the observation period. The mean duration of orthodontic treatment was 8.7 months in the SF group and 10.5 months in the SE group. Satisfaction with treatment was extremely high. The ISO is a safe, reliable technique for dentoalveolar decompensation in timing protocols with a short or no orthodontic preparatory phase. This methodology may represent a reasonable approach in selected class III patients.

Live Cell Imaging of Actin Dynamics in the Filamentous Fungus Aspergillus nidulans.

Hyphal cells of filamentous fungi grow at their tips in a method analogous to pollen tube and root hair elongation. This process, generally referred to as tip growth, requires precise regulation of the actin cytoskeleton, and characterizing the various actin structures in these cell types is currently an active area of research. Here, the actin marker Lifeact was used to document actin dynamics in the filamentous fungus Aspergillus nidulans. Contractile double rings were observed at septa, and annular clusters of puncta were seen subtending growing hyphal tips, corresponding to the well-characterized subapical endocytic collar. However, Lifeact also revealed two additional structures. One, an apical array, was dynamic on the face opposite the tip, while a subapical web was dynamic on the apical face and was located several microns behind the growth site. Each was observed turning into the other over time, implying that they could represent different localizations of the same structure, although hyphae with a subapical web grew faster than those exhibiting an apical array. The subapical web has not been documented in any filamentous fungus to date, and is separate from the networks of F-actin seen in other tip-growing organisms surrounding septa or stationary along the plasmalemma.

Surgery preceding orthodontics in bimaxillary cases.

Orthognathic surgery is performed to alter the shape of the jaws to increase the facial esthetic and improve the occlusions. Surgery prior orthodontics reduces the total length of the treatment of the patients, followed by orthodontics treatment. Advantages is positive outcome in short period of time. Surgical procedure includes Anterior Maxillary osteotomy and Anterior subapical mandibular osteotomy. Complication includes haemorrhage, paraesthesia, malunion of bone, etc.

Innovative use of anterior subapical setback combined with bilateral sagittal split osteotomy in patients with obstructive sleep apnoea.

We describe the use of anterior mandibular subapical setback osteotomy combined with bilateral sagittal split osteotomy in the treatment of selected patients with obstructive sleep apnoea (OSA). The technique enables maximal mandibular advancement, it alleviates pharyngeal narrowing, and minimises the alteration to the mid facial profile that is associated with traditional maxillomandibular advancement.

Evaluation of transverse maxillary expansion after a segmental posterior subapical maxillary osteotomy in cleft lip and palate patients with severe collapse of the lateral maxillary segments.

Objective : The purpose of this longitudinal retrospective study was to evaluate transverse maxillary expansion after a Schuchardt or segmental posterior subapical maxillary osteotomy (SPSMO) in patients with cleft lip and palate (CLP). A second aim was to compare these data with data for adult patients without CLP who were receiving a surgical assisted rapid palatal expansion (SARPE). Method : The study group comprised 19 patients with CLP and a severe transversally collapsed maxilla who were treated with SPSMO followed by hyrax expansion at the University Hospitals Leuven. Dental casts of the 19 patients were analyzed before treatment, at maximum expansion, during orthodontic treatment, at the completion of orthodontic treatment. and 2 years after orthodontic treatment and were measured at the canine, premolar, and molar levels. Adult patients without CLP who were enrolled in a prospective study served as the control group. Results : Maxillary expansion within the study group was significantly greater (P < .05) at all measured levels compared with the maxillary arch before treatment. No significant relapse was measured in the study group 2 years after orthodontic treatment. When comparing the study and control groups, the only statistical difference was that canine expansion was significantly greater in the study group. Conclusion : SPSMO followed by maxillary expansion and orthodontic treatment is an appropriate treatment option to correct a severe transversally collapsed maxilla in patients with CLP. The overall treatment effect of SPSMO expansion is comparable with the effects of SARPE, although canine expansion was greater in the SPSMO group.

Evaluation of Transverse Maxillary Expansion After a Segmental Posterior Subapical Maxillary Osteotomy in Cleft Lip and Palate Patients With Severe Collapse of the Lateral Maxillary Segments.

Objective : The purpose of this longitudinal retrospective study was to evaluate transverse maxillary expansion after a Schuchardt or segmental posterior subapical maxillary osteotomy (SPSMO) in patients with cleft lip and palate (CLP). A second aim was to compare these data with data for adult patients without CLP who were receiving a surgical assisted rapid palatal expansion (SARPE). Method : The study group comprised 19 patients with CLP and a severe transversally collapsed maxilla who were treated with SPSMO followed by hyrax expansion at the University Hospitals Leuven. Dental casts of the 19 patients were analyzed before treatment, at maximum expansion, during orthodontic treatment, at the completion of orthodontic treatment. and 2 years after orthodontic treatment and were measured at the canine, premolar, and molar levels. Adult patients without CLP who were enrolled in a prospective study served as the control group. Results : Maxillary expansion within the study group was significantly greater (P < .05) at all measured levels compared with the maxillary arch before treatment. No significant relapse was measured in the study group 2 years after orthodontic treatment. When comparing the study and control groups, the only statistical difference was that canine expansion was significantly greater in the study group. Conclusion : SPSMO followed by maxillary expansion and orthodontic treatment is an appropriate treatment option to correct a severe transversally collapsed maxilla in patients with CLP. The overall treatment effect of SPSMO expansion is comparable with the effects of SARPE, although canine expansion was greater in the SPSMO group.