Unilateral drainage and chemotherapy prolong the patency of a plastic stent placed above the sphincter of Oddi in patients with malignant hilar biliary obstruction.

Objectives: To evaluate the results of inside stent therapy for unresectable malignant hilar biliary obstruction and identify factors related to stent patency duration. Methods: Of 44 patients who underwent initial inside-stent placement above the sphincter of Oddi from April 2017 to December 2022, 42 with the resolution of jaundice (clinical success rate, 95.5%) were retrospectively analyzed. Univariate and multivariate logistic regression analysis identified factors associated with stent patency duration. Results: Univariate analysis revealed significant differences in the drainage method (406 days for unilateral drainage vs. 305 days for bilateral drainage of the right and left liver lobes, p = 0.022) with or without chemotherapy (406 days with vs. 154 days without, p = 0.038). Multivariate analysis (Cox proportional hazards analysis) revealed similar results, with unilateral drainage (p = 0.031) and chemotherapy (p = 0.048) identified as independent factors associated with prolonged stent patency. Early adverse events were observed in two patients (4.8%; one cholangitis, one pancreatitis). Conclusions: Inside-stent therapy was safely performed in patients with malignant hilar biliary obstruction. Simple unilateral drainage and chemotherapy may prolong stent patency.

Extracorporeal membrane oxygenation-facilitated palliative radiotherapy for severe airway obstruction due to lung cancer: A case report.

Background: The use of venovenous extracorporeal membrane oxygenation (VV-ECMO), particularly during radiotherapy, for severe malignant central airway obstruction has rarely been reported. Case Presentation: A 47-year-old female presented to our emergency department with severe respiratory distress. Given her medical history, she was initially diagnosed with asthma. Despite initial treatment, which included intubation, her condition deteriorated, necessitating VV-ECMO. Computed tomography performed following the initiation of VV-ECMO revealed extensive lung cancer involving both bronchial types. Radiotherapy while on VV-ECMO led to a significant reduction in tumor size, allowing for the weaning of ECMO support and successful extubation. Conclusion: Malignant central airway obstruction is life-threatening. Our case demonstrates the efficacy of combining VV-ECMO with radiotherapy when conventional therapies fail. Further research is necessary to validate and explore this novel approach's implications.

Risk of stricture after endoscopic submucosal dissection in the cervical esophagus and efficacy of local steroid injection for stricture prevention (with video).

BACKGROUND AND AIMS: There is a high incidence of stricture after endoscopic submucosal dissection (ESD) for cervical esophageal cancer. We aimed to elucidate the risk factors for stricture and to evaluate the efficacy of steroid injection for stricture prevention in the cervical esophagus. METHODS: We retrospectively analyzed 100 patients who underwent ESD for cervical esophageal cancer to (1) identify the factors associated with stricture among patients who did not receive steroid injection, and (2) compare the incidence of stricture between patients with and without steroid injection. RESULTS: Among 48 patients who did not receive steroid injection, there were significant differences in tumor size (P = .026), resection time (P = .028), and circumferential extent of the mucosal defect (P = .005) between patients with stricture (n = 5) and without stricture (n = 43). Compared with patients without steroid injection, patients with steroid injection had a significantly lower incidence of stricture when the post-ESD mucosal defect was <3/4 and ≥1/2 (40% versus 8%; P = .039). For the patients with a post-ESD mucosal defect of ≥3/4 (n = 13), local steroid injection was performed for all of them, and 6 (46%) developed stricture. CONCLUSIONS: Patients who underwent ≥1/2 circumferential resection were at high risk of cervical esophageal stricture. Steroid injection had a stricture prevention effect in patients with <3/4 and ≥1/2 circumferential resection, but seemed to be insufficient in preventing stricture in patients with ≥3/4 circumferential resection.

Postoperative intravenous patient-controlled analgesia improves pain management after subcutaneous implantable defibrillator implantation.

Objective: Postoperative pain is a major issue with subcutaneous implantable cardioverter defibrillators (S-ICD). In 2020, we introduced intravenous patient-controlled analgesia (IV-PCA) in addition to the conventional, request-based analgesia for postoperative pain control in S-ICD. To determine the effect and safety, we quantitatively assessed the effect of IV-PCA after S-ICD surgery over conventional methods. Methods: During the study period, a total of 113 consecutive patients (age, 50.1 ± 15.5 years: males, 101) underwent a de novo S-ICD implantation under general anesthesia. While the postoperative pain was addressed with either request-based analgesia (by nonsteroid anti-inflammatory drugs, N = 68, dubbed as "PCA absent") or fentanyl-based IV-PCA in addition to the standard care (N = 45, dubbed as "PCA present"). The degree of postoperative pain from immediately after surgery to 1 week were retrospectively investigated by the numerical rating scale (NRS) divided into four groups at rest and during activity (0: no pain, 1-3: mild pain, 4-6: moderate pain, 7-10: severe pain). Results: Although IV-PCA was removed on Day 1, it was associated with continued better pain control compared to PCA absent group. At rest, the proportion of patients expressing pain (mild or more) was significantly lower in the PCA present group from Day 0 to Day 4. In contrast to at rest, a better pain control continued through the entire study period of 7 days. No serious adverse events were observed. A few patients experienced nausea in both groups and the inter-group difference was not found significant. Conclusion: IV-PCA suppresses postoperative pain in S-ICD without major safety concerns.

A Small Compound, HYGIC, Promotes Hypocotyl Growth Through Ectopic Ethylene Response.

Plant seedlings adjust the growth of the hypocotyl in response to surrounding environmental changes. Genetic studies have revealed key players and pathways in hypocotyl growth, such as phytohormones and light signaling. However, because of genetic redundancy in the genome, it is expected that not-yet-revealed mechanisms can be elucidated through approaches different from genetic ones. Here, we identified a small compound, HYGIC (HG), that simultaneously induces hypocotyl elongation and thickening, accompanied by increased nuclear size and enlargement of cortex cells. HG-induced hypocotyl growth required the ethylene signaling pathway activated by endogenous ethylene, involving CONSTITUTIVE PHOTOMORPHOGENIC 1, ETHYLENE INSENSITIVE 2 (EIN2) and redundant transcription factors for ethylene responses, ETHYLENE INSENSITIVE 3 (EIN3) and EIN3 LIKE 1. By using EBS:GUS, a transcriptional reporter of ethylene responses based on an EIN3-binding-cis-element, we found that HG treatment ectopically activates ethylene responses at the epidermis and cortex of the hypocotyl. RNA-seq and subsequent gene ontology analysis revealed that a significant number of HG-induced genes are related to responses to hypoxia. Indeed, submergence, a representative environment where the hypoxia response is induced in nature, promoted ethylene-signaling-dependent hypocotyl elongation and thickening accompanied by ethylene responses at the epidermis and cortex, which resembled the HG treatment. Collectively, the identification and analysis of HG revealed that ectopic responsiveness to ethylene promotes hypocotyl growth, and this mechanism is activated under submergence.

Analysis of IGHA1 and other salivary proteins post half marathon in female participants.

Background: High-intensity exercise (HIE), such as that in marathons and triathlons, suppresses transient local and systemic immunity. Serum and salivary immunoglobulin heavy constant alpha 1 (IGHA1) are major markers of immunosuppression by HIE. Although much is known about the systemic immunosuppressive response, little is known about its local response in the oral cavity, lungs, bronchial tubes, and skin. The oral cavity allows bacteria or viruses to enter the body. Saliva covers the epidermis of the oral cavity and plays an important role in the local stress response by preventing infection. In this study, we examined the properties of saliva secreted during the local stress response for half-marathon (HM) induced IGHA1 protein expression using quantitative proteomics. Methods: The Exercise Group (ExG) (19 healthy female university students) participated in a HM race. The Non-Exercise Group (NExG) (16 healthy female university students) did not participate in the ExG. The ExG saliva samples were collected 1 h pre and 2 h and 4 h post-HM. The NExG saliva samples were collected at the same time intervals. The saliva volume, protein concentration, and relative IGHA1 expression were analyzed. In addition, 1 h pre and 2 h post- HM saliva samples were analyzed by iTRAQ. The identified factors in iTRAQ were analyzed for the ExG and the NExG using western blotting. Results: We identified kallikrein 1 (KLK1), immunoglobulin kappa chain (IgK), and cystatin S (CST4) as suppression factors, as well as IGHA1, which has been reported to be an immunological stress marker. IGHA1 (p = 0.003), KLK1 (p = 0.011), IGK (p = 0.002), and CST4 (p = 0.003) were suppressed 2 h post-HM compared with their levels pre HM, and IGHA1 (p < 0.001), KLK1 (p = 0.004), and CST4 (p = 0.006) were suppressed 4 h post-HM. There was also a positive correlation between IGHA1, IGK, and CST4 levels at 2 and 4 h post-HM. In addition, KLK1 and IGK levels at 2 h post-HM were positively correlated. Conclusion: Our study demonstrated that the salivary proteome is regulated, and antimicrobial proteins are suppressed post-HM. These results suggest that oral immunity was transiently suppressed post-HM. The positive correlation of each protein at 2 and 4 h post-HM suggests that the suppressed state was similarly regulated up to 4 h after a HM. The proteins identified in this study may have applications as stress markers for recreational runners and individuals who perform moderate to HIE on a regular basis.

Serial assessment of multimodality imaging in anti-leucine-rich glioma-inactivated 1 antibody encephalitis: A case report.

In autoimmune encephalitis, abnormalities of diffusion-weighted imaging (DWI), fluid-attenuated inversion recovery (FLAIR), arterial spin labeling (ASL) in magnetic resonance imaging (MRI), single-photon emission computed tomography (SPECT) and 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) have been reported. However, there are few studies of long-term follow-up of imaging. We report a case of anti-leucine-rich glioma-inactivated 1 antibody encephalitis whose MRI (DWI, FLAIR and ASL), 99mTcHM-PAO SPECT (PAO-SPECT) and 18F-FDG-PET were evaluated through the clinical course. ASL, PAO-SPECT and 18F-FDG-PET consistently showed abnormalities in almost the same area. Serial assessment of these imaging modalities is useful in evaluating disease activity and efficacy of treatment.

Heteromeric interactions of ripening-related ethylene receptors in tomato fruit.

Ripening of climacteric fruits is initiated when the gaseous plant hormone ethylene is perceived by the cell. Ethylene binding to membrane-associated ethylene receptors (ETRs) triggers a series of biochemical events through multiple components, resulting in the induction of numerous ripening-related genes. In tomato (Solanum lycopersicum L.), there are seven members of the ETR family, which each contribute to the regulation of fruit ripening. However, the relative contribution of each individual receptor to ethylene signaling remains unknown. Here, we demonstrated the formation of heteromeric receptor complexes across the two ETR subfamilies in tomato fruit. Immunoprecipitation of subfamily II SlETR4 resulted in co-purification of subfamily I (SlETR1, SlETR2, and SlETR3), but not subfamily II members (SlETR5, SlETR6, and SlETR7). Such biased interactions were verified in yeast two-hybrid assays, and in transgenic Arabidopsis plants, in which heterologous SlETR4 interacts with subfamily I ETRs. Our analysis also revealed that the receptor complexes engage the Raf-like protein kinases SlCTR1 and SlCTR3, which are potential regulators of signaling. Here, we suggest that tomato receptor members form heteromeric complexes to fine-tune signal output to the downstream pathway, which is similar to that of the Arabidopsis system but appears to be partially diverged.

Suppression of MYC transcription activators by the immune cofactor NPR1 fine-tunes plant immune responses.

Plants tailor immune responses to defend against pathogens with different lifestyles. In this process, antagonism between the immune hormones salicylic acid (SA) and jasmonic acid (JA) optimizes transcriptional signatures specifically to the attacker encountered. Antagonism is controlled by the transcription cofactor NPR1. The indispensable role of NPR1 in activating SA-responsive genes is well understood, but how it functions as a repressor of JA-responsive genes remains unclear. Here, we demonstrate that SA-induced NPR1 is recruited to JA-responsive promoter regions that are co-occupied by a JA-induced transcription complex consisting of the MYC2 activator and MED25 Mediator subunit. In the presence of SA, NPR1 physically associates with JA-induced MYC2 and inhibits transcriptional activation by disrupting its interaction with MED25. Importantly, NPR1-mediated inhibition of MYC2 is a major immune mechanism for suppressing pathogen virulence. Thus, NPR1 orchestrates the immune transcriptome not only by activating SA-responsive genes but also by acting as a corepressor of JA-responsive MYC2.

Ultrahigh density atrio-ventricular dual-chamber mapping as a next generation tool for ablation of accessory pathways.

INTRODUCTION: Detailed three-dimensional (3D) mapping has been useful for effective radiofrequency catheter ablation. The Rhythmia system can create atrio-ventricular dual-chamber mapping, which reveals the atrial and ventricular potentials all at once in the same map. The aim of this study was to investigate the utility of mapping the atrium and ventricle simultaneously with a high-density 3D mapping system for the ablation of accessory pathways (AP). METHODS: From July 2015 to August 2020, 111 patients underwent ablation of APs. Dual-chamber maps were created in 50 patients (median age 15 [10-54], 32 male [64.0%]), while 61 patients underwent radiofrequency (RF) ablation with conventional single-chamber 3D maps. The background characteristics and procedural details were compared between the dual-chamber mapping group and the conventional single-chamber mapping group. RESULTS: The number of RF applications (median [IQR]; 1.0 [1.0-3.0] vs. 3.0 [1.0-6.0], p = .0023), RF time (median [IQR], s; 9.2 [2.0-95.7] vs. 95.6 [4.1-248.7], p = .0107), and RF energy (median [IQR], J; 248.4 [58.7-3328.2] vs. 2867.6 [134.2-7728.4], p = .0115) were significantly lower in the dual-chamber group. The fluoroscopy time (median [IQR], min; 19.9 [14.2-26.1] vs. 26.5 [17.7-43.4], p = .0025) and fluoroscopy dose (median [IQR], mGy; 52.5 [31.3-146.0] vs. 119.0 [43.7-213.5], p = .0249) were also significantly lower in the dual-chamber than single-chamber mapping group. CONCLUSION: The dual-chamber mapping was useful for ablating accessory pathways and reducing the number of RF applications, total RF energy, and radiation exposure as compared with traditional mapping techniques.

AP2/ERF Transcription Factor NbERF-IX-33 Is Involved in the Regulation of Phytoalexin Production for the Resistance of Nicotiana benthamiana to Phytophthora infestans.

Plants recognize molecular patterns unique to a certain group of microbes to induce effective resistance mechanisms. Elicitins are secretory proteins produced by plant pathogenic oomycete genera including Phytophthora and Pythium. Treatment of INF1 (an elicitin produced by P. infestans) induces a series of defense responses in Nicotiana species, including reactive oxygen species (ROS) production, transient induction of ethylene production, hypersensitive cell death and accumulation of the sesquiterpenoid phytoalexin capsidiol. In this study, we analyzed the expression profiles of N. benthamiana genes after INF1 treatment by RNAseq analysis. Based on their expression patterns, N. benthamiana genes were categorized into 20 clusters and 4,761 (8.3%) out of 57,140 genes were assigned to the clusters for INF1-induced genes. All genes encoding enzymes dedicated to capsidiol production, 5-epi-aristolochene (EA) synthase (NbEAS, 10 copies) and EA dehydrogenase (NbEAH, 6 copies), and some genes for ethylene production, such as 1-aminocyclopropane 1-carboxylate (ACC) synthase (NbACS) and ACC oxidase (NbACO), were significantly upregulated by INF1 treatment. Analysis of NbEAS1 and NbEAS4 promoters revealed that AGACGCC (GCC box-like motif) is the essential cis-element required for INF1-induced expression of NbEAS genes. Given that the GCC box is known to be targeted by ERF (ethylene-responsive factor) transcription factors, we created a complete list of N. benthamiana genes encoding AP2/ERF family transcription factors, and identified 45 out of 337 AP2/ERF genes in the clusters for INF1-induced genes. Among INF1-induced NbERF genes, silencing of NbERF-IX-33 compromised resistance against P. infestans and INF1-induced production of capsidiol. Recombinant NbERF-IX-33 protein can bind to the promoter sequence of NbEAS4, suggesting that NbERF-IX-33 is a transcription factor directly regulating the expression of genes for phytoalexin production.

A Case of Coexistence of Severe Coronary and Carotid Artery Stenosis Treated with Carotid Artery Stenting Using Intra-Aortic Balloon Pumping and a Temporary Pacemaker.

The risk factors of carotid stenosis and coronary stenosis are similar, and therefore, certain patients with carotid stenosis may have coronary heart disease. Coronary artery bypass graft (CABG) is the major therapy for ischemic heart disease with three-vessel and left main coronary artery (LMCA) disease. However, CABG can induce cerebral infarctions in cases with carotid stenosis. Carotid endarterectomy (CEA) was used to be the standard therapy for carotid stenosis; however, CEA requires general anesthesia and has a high risk of cardiovascular events in patients with ischemic heart disease. In recent times, carotid artery stenting (CAS), which does not need general anesthesia, is the new strategy for carotid stenosis. However, CAS induces hypotension and bradycardia because of a carotid node reflex, which is dangerous in patients with ischemic heart disease. We reported a case of the coexistence of severe coronary stenosis including the LMCA and three vessels and carotid stenosis. CAS before CABG under local anesthesia was successful with the use of intra-aortic balloon pumping (IABP) and a temporary pacemaker.

Artificial intelligence for the detection of COVID-19 pneumonia on chest CT using multinational datasets.

Chest CT is emerging as a valuable diagnostic tool for clinical management of COVID-19 associated lung disease. Artificial intelligence (AI) has the potential to aid in rapid evaluation of CT scans for differentiation of COVID-19 findings from other clinical entities. Here we show that a series of deep learning algorithms, trained in a diverse multinational cohort of 1280 patients to localize parietal pleura/lung parenchyma followed by classification of COVID-19 pneumonia, can achieve up to 90.8% accuracy, with 84% sensitivity and 93% specificity, as evaluated in an independent test set (not included in training and validation) of 1337 patients. Normal controls included chest CTs from oncology, emergency, and pneumonia-related indications. The false positive rate in 140 patients with laboratory confirmed other (non COVID-19) pneumonias was 10%. AI-based algorithms can readily identify CT scans with COVID-19 associated pneumonia, as well as distinguish non-COVID related pneumonias with high specificity in diverse patient populations.

Influence of various energy settings and overlap ratios on size and continuity of lesions in a laser balloon ablation in vitro model.

INTRODUCTION: The influence of power (Watt [W]) and total energy (Joule [J]) on lesion size and the optimal overlap ratio remain unclear in laser balloon (LB) ablation for atrial fibrillation. We aimed to evaluate lesion size and visible gaps after LB ablation with various energy settings and different overlap ratios in vitro model. METHODS AND RESULTS: Chicken muscles were cauterized using the first-generation LB with single applications of full and a half duration of six energy settings (5.5 W/30 seconds [165 J] to 12 W/20 seconds [240 J]) and varying power (5.5-12 W) at the constant total energy (160 J). Three overlapped ablations with different ratios (25% and 50%) for each energy setting were also performed to evaluate the visible gap degree categorized from 1 (perfect) to 3 (poor). Twenty lesions were evaluated for each energy setting. In single applications of full duration, lesion depth, lesion volume, and maximum lesion diameter increased according to the total energy (all, P < .001) and were greater than in those of half duration in each energy setting (all, P < .05). However, applications with larger power created larger lesion volume and maximum lesion diameter at constant total energy (P < .05). The visible gap degree was better in all energy settings with 50% overlapped ablation than in those with 25% (all, P < .001). CONCLUSION: Lesion size depends not only on power but also on total energy in the LB ablation. Sufficiently overlapped ablations allow continuous lesion formation.

Calcified mucinous adenocarcinoma of the stomach metastatic to the iris: a case report.

BACKGROUND: Gastric cancer has a wide spectrum of clinical features, imaging manifestations, and pathology. Punctate calcifications in gastric cancer are infrequent but are usually found in mucinous adenocarcinoma. However, there have only been a few autopsy case reports describing the correlation between the radiology and pathology findings of calcified mucinous adenocarcinoma of the stomach. We present an autopsy case of mucinous gastric adenocarcinoma with iris metastases as the initial symptom. CASE PRESENTATION: A 74-year-old Japanese woman presented with blurred vision. Her treating ophthalmologist diagnosed acute iritis with secondary glaucoma. The histopathological and immunohistochemical features of a trabeculectomy specimen favored metastatic carcinoma, most likely of gastrointestinal tract origin. Esophagogastroduodenoscopy revealed multiple irregularly shaped ulcerative lesions, multiple erosions, and thickened folds in the corpus of her stomach. Histologic examination of a gastric tissue specimen obtained by endoscopic biopsy revealed poorly differentiated carcinoma with signet ring cell features. Computed tomography revealed a tumor with multiple punctate calcifications in the thickened gastric wall with diffuse low attenuation and multiple lymph node metastases, including the para-aortic lymph nodes, and peritoneal dissemination. She was diagnosed with stage IV gastric cancer (T4N3M1) and underwent seven cycles of 5-weekly TS-1, a novel oral fluoropyrimidine derivative, plus cisplatin therapy. Serial follow-up computed tomography revealed successive increases in the gastric wall calcifications. Her disease stabilized, but she died of aspiration pneumonia 8 months after the first visit. Autopsy tissue specimens had miliary, punctate calcifications present in abundant extracellular mucin pools in the submucosa, corresponding to the thickened low-attenuating middle layer on computed tomography. The final diagnosis was mucinous gastric adenocarcinoma because mucinous adenocarcinoma is diagnosed when more than half of the tumor area contains extracellular mucin pools. CONCLUSIONS: We report the pathology and computed tomography imaging characteristics of a case of calcified mucinous adenocarcinoma of the stomach metastatic to the iris, including findings at autopsy. Metastatic carcinomas in the iris originating in the stomach are exceedingly rare. Multiple punctate calcifications were present in pools of extracellular mucin, a diagnostic clue for mucinous adenocarcinoma. Possible mechanisms underlying scattered punctuate calcifications in gastric mucinous adenocarcinoma warrant further investigation.

Nicotiana benthamiana RanBP1-1 Is Involved in the Induction of Disease Resistance via Regulation of Nuclear-Cytoplasmic Transport of Small GTPase Ran.

Plant cells enhance the tolerances to abiotic and biotic stresses via recognition of the stress, activation and nuclear import of signaling factors, up-regulation of defense genes, nuclear export of mRNA and translation of defense proteins. Nuclear pore-mediated transports should play critical roles in these processes, however, the regulatory mechanisms of nuclear-cytoplasmic transport during stress responses are largely unknown. In this study, a regulator of nuclear export of RNA and proteins, NbRanBP1-1 (Ran-binding protein1-1), was identified as an essential gene for the resistance of Nicotiana benthamiana to potato blight pathogen Phytophthora infestans. NbRanBP1-1-silenced plants showed delayed accumulation of capsidiol, a sesquiterpenoid phytoalexin, in response to elicitor treatment, and reduced resistance to P. infestans. Abnormal accumulation of mRNA was observed in NbRanBP1-1-silenced plants, indicating that NbRanBP1-1 is involved in the nuclear export of mRNA. In NbRanBP1-1-silenced plants, elicitor-induced expression of defense genes, NbEAS and NbWIPK, was not affected in the early stage of defense induction, but the accumulation of NbWIPK protein was reduced. Nuclear export of the small G-protein NbRan1a was activated during the induction of plant defense, whereas this process was compromised in NbRanBP1-1-silenced plants. Silencing of genes encoding the nuclear pore proteins, Nup75 and Nup160, also caused abnormal nuclear accumulation of mRNA, defects in the nuclear export of NbRan1a, and reduced production of capsidiol, resulting in decreased resistance to P. infestans. These results suggest that nuclear export of NbRan is a key event for defense induction in N. benthamiana, and both RanBP1-1 and nucleoporins play important roles in the process.

Skeletal open bite with amelogenesis imperfecta treated with compression osteogenesis: a case report.

BACKGROUND: We successfully treated a 37-year-old male who had skeletal open bite with severe amelogenesis imperfecta (AI) with orthodontics, compression osteogenesis, and prosthodontics. CASE PRESENTATION: The patient was diagnosed with severe anterior open bite caused by severe AI. Corticotomy was performed on both buccal and palatal sides of the molar regions, and anchor plates were placed onto the bilateral zygomatic buttress and the center of the hard palate. After corticotomy, posterior maxillary segments were moved 3.5 mm superiorly to correct skeletal open bite with elastic chains. After 8-month, overbite had decreased by 2.0 mm. After further 5 months of prosthodontic preparation, orthodontic appliances were removed, and provisional crowns were set on all teeth. The anterior open bite was corrected, and ideal occlusion with a Class I molar relationship was achieved. The upper first molars were intruded 3.5 mm, resulting in 3.0o counter-clockwise rotation of the mandible. The total active treatment period was 16 months. Acceptable occlusion with a good facial profile was well maintained throughout the 8-year retention period. CONCLUSIONS: Our results indicate long-term stability after interdisciplinary treatment combining orthodontics, oral surgery, and prosthodontics in a patient with severe anterior open bite and AI.

A Ycf2-FtsHi Heteromeric AAA-ATPase Complex Is Required for Chloroplast Protein Import.

Chloroplasts import thousands of nucleus-encoded preproteins synthesized in the cytosol through the TOC and TIC translocons on the outer and inner envelope membranes, respectively. Preprotein translocation across the inner membrane requires ATP; however, the import motor has remained unclear. Here, we report that a 2-MD heteromeric AAA-ATPase complex associates with the TIC complex and functions as the import motor, directly interacting with various translocating preproteins. This 2-MD complex consists of a protein encoded by the previously enigmatic chloroplast gene ycf2 and five related nuclear-encoded FtsH-like proteins, namely, FtsHi1, FtsHi2, FtsHi4, FtsHi5, and FtsH12. These components are each essential for plant viability and retain the AAA-type ATPase domain, but only FtsH12 contains the zinc binding active site generally conserved among FtsH-type metalloproteases. Furthermore, even the FtsH12 zinc binding site is dispensable for its essential function. Phylogenetic analyses suggest that all AAA-type members of the Ycf2/FtsHi complex including Ycf2 evolved from the chloroplast-encoded membrane-bound AAA-protease FtsH of the ancestral endosymbiont. The Ycf2/FtsHi complex also contains an NAD-malate dehydrogenase, a proposed key enzyme for ATP production in chloroplasts in darkness or in nonphotosynthetic plastids. These findings advance our understanding of this ATP-driven protein translocation system that is unique to the green lineage of photosynthetic eukaryotes.