In-House Virtual Planning and 3D Printed Surgical Guides for Reconstructive Rhinoplasty.

BACKGROUND: Performing rhinoplasty in patients with craniofacial malformations remains a challenge, even for experienced surgeons. Advances in 3D technology and its application in surgical planning and printing of cutting guides and splints have become important tools to improve aesthetic and functional results. OBJECTIVES: To describe an in-house workflow for surgical planning and printing of cutting guides and splints for complex rhinoplasty cases. METHODS: This article describes an in-house workflow for complex rhinoplasty, as used in the maxillofacial department of a children's hospital specialized in the treatment of cleft and craniofacial malformations. RESULTS: Customized surgical guides help the surgeon to harvest and mold potential septal and costochondral grafts more accurately, to reduce surgical time and to verify the dimensions of the sculpted nasal shape following surgical planning templates. Patient satisfaction degree according to Rhinoplasty Outcome Evaluation questionnaire was 18/24. CONCLUSIONS: The presented workflow represents a potential asset in obtaining more accurate and satisfactory results in complex rhinoplasties.

Clinical activity of CC-90011, an oral, potent, and reversible LSD1 inhibitor, in advanced malignancies.

BACKGROUND: CC-90011 is an oral, potent, selective, reversible inhibitor of lysine-specific demethylase 1 (LSD1) that was well tolerated, with encouraging activity in patients who had advanced solid tumors or relapsed/refractory marginal zone lymphoma. The authors present long-term safety and efficacy and novel pharmacodynamic and pharmacokinetic data from the first-in-human study of CC-90011. METHODS: CC-90011-ST-001 (ClincalTrials.gov identifier NCT02875223; Eudract number 2015-005243-13) is a phase 1, multicenter study in which patients received CC-90011 once per week in 28-day cycles. The objectives were to determine the safety, maximum tolerated dose, and/or recommended phase 2 dose (primary) and to evaluate preliminary efficacy and pharmacokinetics (secondary). RESULTS: Sixty-nine patients were enrolled, including 50 in the dose-escalation arm and 19 in the dose-expansion arm. Thrombocytopenia was the most common treatment-related adverse event and was successfully managed with dose modifications. Clinical activity with prolonged, durable responses were observed, particularly in patients who had neuroendocrine neoplasms. In the dose-escalation arm, one patient with relapsed/refractory marginal zone lymphoma achieved a complete response (ongoing in cycle 58). In the dose-expansion arm, three patients with neuroendocrine neoplasms had stable disease after nine or more cycles, including one patient who was in cycle 46 of ongoing treatment. CC-90011 decreased levels of secreted neuroendocrine peptides chromogranin A, progastrin-releasing peptide, and RNA expression of the blood pharmacodynamic marker monocyte-to-macrophage differentiation-associated. CONCLUSIONS: The safety profile of CC-90011 suggested that its reversible mechanism of action may provide an advantage over other irreversible LSD1 inhibitors. The favorable tolerability profile, clinical activity, durable responses, and once-per-week dosing support further exploration of CC-90011 as monotherapy and in combination with other treatments for patients with advanced solid tumors and other malignancies.

Auricular Reconstructive Surgery Improvement to the Firmin Technique for Placing an Earring.

Microtia has an incidence of 1 in 7000 to 8000 births. Ear reconstruction has 2 main aims: reconstructive and aesthetic, and a considerable number of patients ask for an earring at the end of their treatment. Herein, we explain our team's modification to the Firmin technique, perforating the lowest part of the autologous cartilage framework (Parri's modification). The orifice is cartilaginous and the skin covering both sides is easily perforable without contacting the rest of the framework. In conclusion, our modification for placing an earring is simple; it does not increase the surgical time and contributes to approach the perfection of auricular reconstructive surgery.

Imaging Evaluation of Pediatric Parotid Gland Abnormalities.

Parotid gland lesions in children can be divided into benign or malignant. The age of the patient helps narrow the differential diagnosis, with vascular and congenital lesions being more frequent in the 1st year of life, while solid tumors are more frequent in older children. Inflammatory disease usually has rapid onset in comparison with that of neoplastic or congenital processes, which have more gradual clinical evolution. Currently, multiple imaging techniques are available to study the parotid region, such as US, CT, and MRI. However, it is still a challenge to distinguish nonmalignant lesions from malignant ones. US is the first-line diagnostic approach in children to characterize the morphology and vascularity of these lesions. CT in children may be indicated for evaluation of abscesses or sialolithiasis. MRI is the imaging modality of choice for investigating the nature of the lesion and its extent. In addition to complete and detailed clinical information, knowledge of parotid gland anatomy and characteristic radiologic features of parotid disorders is essential for optimal radiologic evaluation and avoiding unnecessary interventional diagnostic procedures or treatment. This article illustrates a variety of entities (congenital, inflammatory, vascular, neoplastic) that can occur in the parotid gland, highlighting the most frequent radiologic patterns of manifestation and correlating them with clinical, surgical, and pathologic findings. ©RSNA, 2018.

Surgical Repositioning of the Premaxilla Using a Minimally Invasive Endonasal Approach.

OBJECTIVE: The aim of this study was to evaluate a technique for the surgical repositioning of the premaxilla using a minimally invasive endonasal approach. DESIGN: Retrospective review of clinical records. SETTING: Tertiary care, University Hospital, pediatric maxillofacial surgery unit. PATIENTS: Twenty-one patients (12 boys and 9 girls), ages ranging from 6 to 21 years, with BCLP+A and premaxillary malposition (PM). INTERVENTIONS: Surgical repositioning of the premaxilla (SRP) using a minimally invasive endonasal approach, from November 2007 to November 2015. MAIN OUTCOME MEASURES: Achieving maxillary arch alignment and premaxillary stability was defined as treatment success. Intraoperative and postoperative complications were also recorded. RESULTS: In all cases (100%), the treatment was successful either at first surgery or after reoperation. Two patients (9.5%) were reoperated-one due to premaxillary instability and one due to PM relapse. There were no perioperative complications. CONCLUSIONS: SRP using a minimally invasive endonasal approach is a safe and effective technique that levels and aligns the maxillary arch in preparation for SABG, which minimizes the risk of wound infection and premaxillary vascular compromise. The endonasal approach improves tissue quality of the mucoperiosteal flaps when performing the SABG procedure. Further prospective studies are needed to elucidate the best protocols and techniques for the management of PM in patients with BCLP+ A.

Isolation of N2 -fixing rhizobacteria from Lolium perenne and evaluating their plant growth promoting traits.

Twenty one dinitrogen (N2 )-fixing bacteria were isolated from the rhizosphere of Lolium perenne grown for more than 10 years without N-fertilization. The nearly complete sequence of the 16S rRNA gene of each strain and pairwise alignments among globally aligned sequences of the 16S rRNA genes clustered them into nine different groups. Out of the 21 strains, 11 were members of genus Bacillus, 3 belonged to each one of genera Paenibacillus and Pseudoxanthomonas, and the remaining 2 strains to each one of genera Burkholderia and Staphylococcus, respectively. A representative strain from each group contained the nifH gene and fixed atmospheric N2 as determined by the acetylene-dependent ethylene production assay (acetylene reduction activity, ARA). The nine selected strains were also examined to behave as plant growth promoting bacteria (PGPRs) including their ability to act as a biocontrol agent. The nine representative strains produced indol acetic acid (IAA) and solubilized calcium triphosphate, five of them, strains C2, C3, C12, C15, and C16, had ACC deaminase activity, and strains C2, C3, C4, C12, C16, and C17 produced siderophores. Strains C13, C16, and C17 had the capability to control growth of the pathogen Fusarium oxysporum mycelial growth in vitro. PCA analysis of determined PGPR properties showed that ARA, ACC deaminase activity, and siderophore production were the most valuable as they had the maximal contribution to the total variance.

Effect of intra-alveolar placement of 0.2% chlorhexidine bioadhesive gel on the incidence of alveolar osteitis following the extraction of mandibular third molars. A double-blind randomized clinical trial.

UNLABELLED: Alveolar osteitis (AO) is a common complication after third molar surgery. One of the most studied agents in its prevention is chlorhexidine (CHX), which has proved to be effective. OBJECTIVES: The aim of this randomized double-blind clinical trial was to evaluate the efficacy of 0.2% bioadhesive chlorhexidine gel placed intra-alveolar in the prevention of AO after the extraction of mandibular third molars and to analyze the impact of risk factors such as smoking and oral contraceptives in the development of AO. STUDY DESIGN: The study was a randomized, double-blind, clinical trial performed in the Ambulatory Surgery Unit of Hospital Vall d'Hebron and was approved by the Ethics Committee. A total of 160 patients randomly received 0.2% bioadhesive gel (80 patients) or bioadhesive placebo (80 patients). RESULTS: 0.2% bioadhesive chlorhexidine gel applied in the alveolus after third molar extraction reduced the incidence of dry socket by 22% compared to placebo with differences that were not statistically significant. Smoking and the use of oral contraceptives were not related to higher incidence of dry socket. Female patients and the difficulty of the surgery were associated with a higher incidence of AO with statistically significant differences. 0.2% bioadhesive chlorhexidine gel did not produce any of the side effects related to chlorhexidine rinses. CONCLUSIONS: A 22% reduction of the incidence of alveolar osteitis with the application of 0.2% bioadhesive chlorhexidine gel compared to placebo with differences that were not statistically significant was found in this clinical trial. The lack of adverse reactions and complications related to chlorhexidine gel supports its clinical use specially in simple extractions and adds some advantages compared to the rinses in terms of duration of the treatment and reduction of staining and taste disturbance.

Analysis of the implementation of a circuit for intra-operative superposition and comparison of the surgical outcomes using ICBCT in maxillofacial surgery.

PURPOSE: This paper describes a novel circuit for intraoperative analysis with ICBCT in maxillofacial surgery. The aim is to establish guidelines, define indications, and conduct an analysis of the implementation of the circuit for intraoperative comparison of surgical outcomes in relation to 3D virtual planning in maxillofacial surgery. METHODS: The study included 150 maxillofacial surgical procedures. Intraoperative actions involved fluoroscopy localization, intraoperative CBCT acquisition, segmentation, and superimposition, among other steps. Surgical times due to intraoperative superposition were measured, including time required for ICBCT positioning and acquisition, image segmentation, and comparison of 3D surfaces from the surgical planning. RESULTS: Successful intraoperative comparison was achieved in all 150 cases, enabling surgeons to detect and address modifications before concluding the surgery. Out of the total, 26 patients (17.33%) required intraoperative revisions, with 11 cases (7.33%) needing major surgical revisions. On average, the additional surgical time with this circuit implementation was 10.66 ± 3.03 min (n = 22). CONCLUSION: The results of our research demonstrate the potential for performing intraoperative surgical revision, allowing for immediate evaluation, enhancing surgical outcomes, and reducing the need for re-interventions.

Patient-Specific 3D Printed Soft Models for Liver Surgical Planning and Hands-On Training.

Background: Pre-surgical simulation-based training with three-dimensional (3D) models has been intensively developed in complex surgeries in recent years. This is also the case in liver surgery, although with fewer reported examples. The simulation-based training with 3D models represents an alternative to current surgical simulation methods based on animal or ex vivo models or virtual reality (VR), showing reported advantages, which makes the development of realistic 3D-printed models an option. This work presents an innovative, low-cost approach for producing patient-specific 3D anatomical models for hands-on simulation and training. Methods: The article reports three paediatric cases presenting complex liver tumours that were transferred to a major paediatric referral centre for treatment: hepatoblastoma, hepatic hamartoma and biliary tract rhabdomyosarcoma. The complete process of the additively manufactured liver tumour simulators is described, and the different steps for the correct development of each case are explained: (1) medical image acquisition; (2) segmentation; (3) 3D printing; (4) quality control/validation; and (5) cost. A digital workflow for liver cancer surgical planning is proposed. Results: Three hepatic surgeries were planned, with 3D simulators built using 3D printing and silicone moulding techniques. The 3D physical models showed highly accurate replications of the actual condition. Additionally, they proved to be more cost-effective in comparison with other models. Conclusions: It is demonstrated that it is possible to manufacture accurate and cost-effective 3D-printed soft surgical planning simulators for treating liver cancer. The 3D models allowed for proper pre-surgical planning and simulation training in the three cases reported, making it a valuable aid for surgeons.

A state-of-the-art guide about the effects of sterilization processes on 3D-printed materials for surgical planning and medical applications: A comparative study.

Surgeons use different medical devices in the surgery, such as patient-specific anatomical models, cutting and positioning guides, or implants. These devices must be sterilized before being used in the operation room. There are many sterilization processes available, with autoclave, hydrogen peroxide, and ethylene oxide being the most common in hospital settings. Each method has both advantages and disadvantages in terms of mechanics, chemical interaction, and post-treatment accuracy. The aim of the present study is to evaluate the dimensional and mechanical effect of the most commonly used sterilization techniques available in clinical settings, i.e., Autoclave 121, Autoclave 134, and hydrogen peroxide (HPO), on 11 of the most used 3D-printed materials fabricated using additive manufacturing technologies. The results showed that the temperature (depending on the sterilization method) and the exposure time to that temperature influence not only the mechanical behavior but also the original dimensioning planned on the 3D model. Therefore, HPO is a better overall option for most of the materials evaluated. Finally, based on the results of the study, a recommendation guide on sterilization methods per material, technology, and clinical application is presented.

Advanced Strategies for the Fabrication of Multi-Material Anatomical Models of Complex Pediatric Oncologic Cases.

The printing and manufacturing of anatomical 3D models has gained popularity in complex surgical cases for surgical planning, simulation and training, the evaluation of anatomical relations, medical device testing and patient-professional communication. 3D models provide the haptic feedback that Virtual or Augmented Reality (VR/AR) cannot provide. However, there are many technologies and strategies for the production of 3D models. Therefore, the aim of the present study is to show and compare eight different strategies for the manufacture of surgical planning and training prototypes. The eight strategies for creating complex abdominal oncological anatomical models, based on eight common pediatric oncological cases, were developed using four common technologies (stereolithography (SLA), selectie laser sinterning (SLS), fused filament fabrication (FFF) and material jetting (MJ)) along with indirect and hybrid 3D printing methods. Nine materials were selected for their properties, with the final models assessed for application suitability, production time, viscoelastic mechanical properties (shore hardness and elastic modulus) and cost. The manufacturing and post-processing of each strategy is assessed, with times ranging from 12 h (FFF) to 61 h (hybridization of FFF and SLS), as labor times differ significantly. Cost per model variation is also significant, ranging from EUR 80 (FFF) to EUR 600 (MJ). The main limitation is the mimicry of physiological properties. Viscoelastic properties and the combination of materials, colors and textures are also substantially different according to the strategy and the intended use. It was concluded that MJ is the best overall option, although its use in hospitals is limited due to its cost. Consequently, indirect 3D printing could be a solid and cheaper alternative.

Value of second-trimester uterine artery pulsatility index in pregnancies with systemic lupus erythematosus and/or antiphospholipid syndrome.

OBJECTIVE: To assess the value of the second trimester mean pulsatility index of the uterine arteries (MPI-UtA) to predict adverse perinatal outcome (APO) in women with systemic lupus erythematosus (SLE) and/or antiphospholipid syndrome (APS). METHODS: Pregnancies with either an SLE diagnosis or with primary APS controlled at our Hospital during a 10 years period were included. MPI-UtA was performed between 19-23 weeks' gestation. The MPI-UtA was defined as abnormal when it was >95th centile. APO was defined as the presence of: preeclampsia (PE), small for gestational age (SGA) newborn, preterm delivery, placental abruption and fetal or neonatal death. RESULTS: There were 39 ongoing pregnancies, 16 of them with SLE and 23 with primary APS. Nine patients had no previous pregnancy (23%). Globally, 35 live births were recorded, being the mean gestational age at delivery 38.1 ± 2.1 weeks and the mean birth weight 2835 ± 492 g. Abnormal MPI-UtA was found in 6 (15%) pregnancies, all of them (100%) had an APO: there were 4 fetal deaths and 2 further severe PE with live newborn. Normal MPI-UtA was shown in the remaining 33 (84.6%); of them, 6 (18%) had an APO: one late PE with a premature newborn, another one severe preterm baby and 4 SGA term newborns. No cases of perinatal death occurred in this group. Therefore, accuracy of MPI-UtA evaluation for APO was: sensitivity 50%, specificity 100%, PPV 100% and NPV 82%, respectively (p < .001). CONCLUSION: Abnormal second-trimester uterine artery Doppler evaluation is highly predictive for adverse perinatal outcome in pregnancies affected by SLE or APS.

Virtual planning in Le Fort III distraction osteogenesis: A case series.

The objective of this study is to determine the value of using 3D planning tools and 3D printed cutting guides in Le Fort III osteotomies with external frame distraction osteogenesis. The process of planning and transfer of the virtual planning to the operating room is illustrated with 5 case. The virtual planning is transferred to the operating room using a 3D-printed supra-orbital reference bar with puzzle connections for the planned osteotomy guides. Different systems are presented to transfer the vector of distraction and the position of the external midface distractor. Three-dimensional planning tools and cutting guides help to design the Le Fort III osteotomy and the distraction vector, to anticipate possible difficulties, and to avoid adverse events.

Accuracy of Virtually Planned Maxillary Distraction in Cleft Patients - An Evaluative Study.

INTRODUCTION: Maxillary distraction may be used to treat severe maxillary hypoplasia in cleft lip and palate (CLP) patients. Three-dimensional (3D) planning has been shown to increase the accuracy of distraction and reduce operative time and complications. The aim of the study was to measure the accuracy of internal maxillary distraction after 3D planning in CLP patients, to add evidence to validate the virtual osteotomy and distraction procedure. MATERIALS AND METHODS: Eleven CLP patients with severe maxillary hypoplasia underwent maxillary distraction using internal distractors. Virtual planning was used to design the osteotomies, the distractor position, and the distraction vector. Cutting and positioning guides transferred this information to the surgical procedure. Four to six month postoperative computed tomography-scan was done before distractor removal; anatomical reference points were compared to the virtual planning to determine accuracy. RESULTS: A high accuracy (point dislocation <1.5 mm) was found in 90% of the points of the surface of the maxilla; the majority of the zygomatic screws were placed within a distance of 0.8-1 mm from their planned position. DISCUSSION: The high accuracy achieved through virtual planning promotes optimal distractor placement; a customized distraction vector has a direct effect on the final position of the maxilla.

Phase I Study of Lysine-Specific Demethylase 1 Inhibitor, CC-90011, in Patients with Advanced Solid Tumors and Relapsed/Refractory Non-Hodgkin Lymphoma.

PURPOSE: Lysine-specific demethylase 1 (LSD1) is implicated in multiple tumor types, and its expression in cancer stem cells is associated with chemoresistance. CC-90011 is a potent, selective, and reversible oral LSD1 inhibitor. We examined CC-90011 in advanced solid tumors and relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL). PATIENTS AND METHODS: CC-90011-ST-001 (NCT02875223; 2015-005243-13) is a phase I, multicenter, first-in-human dose-escalation study. Nine dose levels of CC-90011 (1.25-120 mg) given once per week were explored. Primary objectives were to determine safety, maximum tolerated dose (MTD), and/or recommended phase II dose (RP2D). Secondary objectives were to evaluate preliminary efficacy and pharmacokinetics. RESULTS: Fifty patients were enrolled, 49 with solid tumors (27 neuroendocrine tumors/carcinomas) and 1 with R/R NHL. Median age was 61 years (range, 22-75). Patients received a median of three (range, 1-9) prior anticancer regimens. The RP2D was 60 mg once per week; the nontolerated dose (NTD) and MTD were 120 mg once per week and 80 mg once per week, respectively. Grade 3/4 treatment-related toxicities were thrombocytopenia (20%; an on-target effect unassociated with clinically significant bleeding), neutropenia (8%; in the context of thrombocytopenia at the highest doses), and fatigue (2%). The patient with R/R NHL had a complete response, currently ongoing in cycle 34, and 8 patients with neuroendocrine tumors/carcinomas had stable disease ≥6 months, including bronchial neuroendocrine tumors, kidney tumor, and paraganglioma. CONCLUSIONS: CC-90011 is well tolerated, with the RP2D established as 60 mg once per week. The MTD and NTD were determined to be 80 mg once per week and 120 mg once per week, respectively. Further evaluation of CC-90011 is warranted.

HER2 carboxyl-terminal fragments regulate cell migration and cortactin phosphorylation.

A group of breast cancer patients with a higher probability of developing metastasis expresses a series of carboxyl-terminal fragments (CTFs) of the tyrosine kinase receptor HER2. One of these fragments, 611-CTF, is a hyperactive form of HER2 that constitutively establishes homodimers maintained by disulfide bonds, making it an excellent model to study overactivation of HER2 during tumor progression and metastasis. Here we show that expression of 611-CTF increases cell motility in a variety of assays. Since cell motility is frequently regulated by phosphorylation/dephosphorylation, we looked for phosphoproteins mediating the effect of 611-CTF using two alternative proteomic approaches, stable isotope labeling with amino acids in cell culture and difference gel electrophoresis, and found that the latter is particularly well suited to detect changes in multiphosphorylated proteins. The difference gel electrophoresis screening identified cortactin, a cytoskeleton-binding protein involved in the regulation of cell migration, as a phosphoprotein probably regulated by 611-CTF. This result was validated by characterizing cortactin in cells expressing this HER2 fragment. Finally, we showed that the knockdown of cortactin impairs 611-CTF-induced cell migration. These results suggest that cortactin is a target of 611-CTF involved in the regulation of cell migration and, thus, in the metastatic behavior of breast tumors expressing this CTF.

Middle cerebral artery Doppler pulsatility index as a predictor of intrapartum meconium release in prolonged pregnancies.

OBJECTIVES: The aim of this study was to asses the correlation of middle cerebral artery pulsatility index (MCA-PI) and perinatal outcomes in prolonged pregnancies. STUDY DESIGN: This was a prospective study of all consecutive pregnant women beyond 41 weeks' gestation attending for obstetric surveillance during a two years period. We evaluated the predictive value of MCA-PI lower than the 5th percentile (

The Mnks: MAP kinase-interacting kinases (MAP kinase signal-integrating kinases).

The human MAP kinase-interacting kinases (or MAP kinase signal-integrating kinases), Mnks, comprise a group of four proteins derived from two genes (Gene symbols: MKNK1 and MKNK2) by alternative splicing. Mnk1a/b differ at their C-termini, as do Mnk2a/2b: in each case, the a-form possesses a longer C-terminal region than the b-form, which lacks the MAP kinase-binding region. The N-termini of all forms contain a polybasic region which binds importin a and the translation factor scaffold protein eukaryotic initiation factor (eIF) 4G. The catalytic domains of Mnk1a/b and Mnk2a/b share three unusual features: two short inserts and a DFD feature where other kinases have DFG. Mnk isoforms differ markedly in their activity and regulation, and in subcellular localization. The best-characterised Mnk substrate is eIF4E. The cellular role of eIF4E phosphorylation remains unclear: it may promote export of certain mRNAs from the nucleus. Other Mnk substrates bind to AU-rich elements that modulate the stability/translation of specific mRNAs. Mnks may also control production of inflammatory mediators and signaling from tyrosine kinase receptors, as well as cell proliferation or survival.

Maxillomandibular Syngnathia: 3D Planning and Review of the Literature.

Congenital maxillomandibular fusion or syngnathia is a rare craniofacial disorder with only 26 cases reported in the literature. We present a case of a congenital complex zygomatico-mandibular syngnathia associated with a palatal cleft, posterior maxilla and turbinate agenesia, mild hemifacial microsomia, and a disordered dental eruption. The patient has the highest age (15 years) at diagnosis described in the literature. 3D planning of the surgery was performed to study the patient's anatomy and design the necessary osteotomies to separate the jaws. En bloc removal of the fused fragment with bilateral coronoidectomy and aggressive long-term physiotherapy for 3 months led to a stable increase in mouth opening from 0 to 21 mm inter-incisor distance. The patient reported an improvement in speech, was able to eat without restriction regarding food consistency, and could maintain a good oral hygiene.

The Drosophila protein kinase LK6 is regulated by ERK and phosphorylates the eukaryotic initiation factor eIF4E in vivo.

In Drosophila cells, phosphorylation of eIF4E (eukaryotic initiation factor 4E) is required for growth and development. In Drosophila melanogaster, LK6 is the closest homologue of mammalian Mnk1 and Mnk2 [MAPK (mitogen-activated protein kinase) signal-integrating kinases 1 and 2 respectively] that phosphorylate mammalian eIF4E. Mnk1 is activated by both mitogen- and stress-activated signalling pathways [ERK (extracellular-signal-regulated kinase) and p38 MAPK], whereas Mnk2 contains a MAPK-binding motif that is selective for ERKs. LK6 possesses a binding motif similar to that in Mnk2. In the present study, we show that LK6 can phosphorylate eIF4E at the physiological site. LK6 activity is increased by the ERK signalling pathway and not by the stress-activated p38 MAPK signalling pathway. Consistent with this, LK6 binds ERK in mammalian cells, and this requires an intact binding motif. LK6 can bind to eIF4G in mammalian cells, and expression of LK6 increases the phosphorylation of the endogenous eIF4E. In Drosophila S2 Schneider cells, LK6 binds the ERK homologue Rolled, but not the p38 MAPK homologue. LK6 phosphorylates Drosophila eIF4E in vitro. The phosphorylation of endogenous eIF4E in Drosophila cells is increased by activation of the ERK pathway but not by arsenite, an activator of p38 MAPK. RNA interference directed against LK6 significantly decreases eIF4E phosphorylation in Drosophila cells. These results show that LK6 binds to ERK and is activated by ERK signalling and it is responsible for phosphorylating eIF4E in Drosophila.