Epoxytiglianes induce keratinocyte wound healing responses via classical protein kinase C activation to promote skin re-epithelialization.

Epoxytiglianes are a novel class of diterpene esters. The prototype epoxytigliane, EBC-46 (tigilanol tiglate), is a potent anti-cancer agent in clinical development for local treatment of a range of human and animal tumors. EBC-46 also consistently promotes wound re-epithelialization at the treatment sites, mediated via activation of classical protein kinase C (PKC) isoforms.

Tigilanol tiglate is an oncolytic small molecule that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade.

Background: Tigilanol tiglate (TT) is a protein kinase C (PKC)/C1 domain activator currently being developed as an intralesional agent for the treatment of various (sub)cutaneous malignancies. Previous work has shown that intratumoral (I.T.

Use of angled-tip aspiration catheters is associated with a lower cost of thrombectomy in patients with acute ischemic stroke secondary to large and medium vessel occlusions.

Background: Recently, the angled-tip Zoom aspiration catheters were introduced. The tip is designed to improve suction force for clot retrieval. We evaluated the possibility of reducing procedure costs when using angled-tip catheters and compared the safety and angiographic effectiveness of angled-tip versus straight-tip catheters.

One bite or two? A comparison of single bite and double bite opsy echniques in gastrointetinal endocopy (BITES).

Background And Aim: Endoscopic biopsies can be taken using either single or double bite technique. In the single bite method, intubation time may be proportionately prolonged depending upon the number of biopsies taken. In contrast to this, double bite, though a greater number of biopsies may be taken per unit time, it may influence the quality of the biopsy specimen.

Videoconference based training on diabetes technology for school nurses and staff: Pilot study.

Purpose: Children with diabetes spend a significant portion of time at school and in school-related activities and rely on school nurses for diabetes management support. Diabetes technologies are rapidly evolving, and there are no standardized competencies or training programs for school personnel providing diabetes care.

Design And Methods: A virtual diabetes education program was provided to school nurses and staff in 3 Florida school districts.

Effects of Leg Length, Sex, Laterality, and the Intermediate Femoral Cutaneous Nerve on Infrapatellar Innervation.

Background: An iatrogenic injury to the infrapatellar branch of the saphenous nerve (IPBSN) is a common precipitant of postoperative knee pain and hypoesthesia.

Purpose: To locate potential safe zones for incision by observing the patterns and pathway of the IPBSN while examining the relationship of its location to sex, laterality, and leg length.

Study Design: Descriptive laboratory study.

Provision and standards of care for treatment and follow-up of patients with Autoimmune Hepatitis (AIH).

Background: Autoimmune hepatitis (AIH) is a substantial UK health burden, but there is variation in care, facilities and in opinion regarding management. We conducted an audit of service provision and care of patients with AIH in 28 UK hospitals.

Methods: Centres provided information about staffing, infrastructure and patient management (measured against predefined guideline-based standards) via a web-based data collection tool.

Treatment and Outcome of Autoimmune Hepatitis (AIH): Audit of 28 UK centres.

Background: With few data regarding treatment and outcome of patients with AIH outside of large centres we present such a study of patients with AIH in 28 UK hospitals of varying size and facilities.

Methods: Patients with AIH were identified in 14 University and 14 District General hospitals; incident cases during 2007-2015 and prevalent cases, presenting 2000-2015. Treatment and outcomes were analysed.

Mapping a Danger Zone of the Dorsal Nerve of the Clitoris: Implications in Female Cosmetic Genital Surgery.

Background: The literature regarding the route of the dorsal nerve of the clitoris is sparse and lacks surgical focus. With an increasing number of procedures being performed on the labia, it is important to elucidate the route and note any variation from normal of the nerve.

Methods: Fifty-one cadavers were dissected to yield 97 dorsal nerve of the clitoris samples.

Activation of PKC supports the anticancer activity of tigilanol tiglate and related epoxytiglianes.

The long-standing perception of Protein Kinase C (PKC) as a family of oncoproteins has increasingly been challenged by evidence that some PKC isoforms may act as tumor suppressors. To explore the hypothesis that activation, rather than inhibition, of these isoforms is critical for anticancer activity, we isolated and characterized a family of 16 novel phorboids closely-related to tigilanol tiglate (EBC-46), a PKC-activating epoxytigliane showing promising clinical safety and efficacy for intratumoral treatment of cancers. While alkyl branching features of the C12-ester influenced potency, the 6,7-epoxide structural motif and position was critical to PKC activation in vitro.

Key Anatomical Clarifications for the Marginal Mandibular Branch of the Facial Nerve: Clinical Significance for the Plastic Surgeon.

Background: The marginal mandibular branch (MMBr) of the facial nerve is the least likely to recover from injury due to infrequent anastomosis with other branches. The MMBr has been described as coursing superior to the inferior border of the mandible. However, studies have reported variations in its location in embalmed and fresh specimens.

Etiology and Comorbidity Diagnoses Effect on Outcomes for Patients Undergoing Endoscopic Retrograde Cholangiopancreatography.

Introduction Endoscopic retrograde cholangiopancreatography (ERCP) is now the first-line approach to treating choledocholithiasis. As a minimally invasive procedure, it is considered relatively safe but still entails a higher risk than other routine endoscopic procedures. This study aims to look at possible patient etiologies and comorbidities that may affect patient outcomes.

EBC-232 and 323: A Structural Conundrum Necessitating Unification of Five In Silico Prediction and Elucidation Methods.

Structurally unique halimanes EBC-232 and EBC-323, isolated from the Australian rainforest plant Croton insularis, proved considerably difficult to elucidate. The two diastereomers, which consist an unusual oxo-6,7-spiro ring system fused to a dihydrofuran, were solved by unification and consultation of five in silico NMR elucidation and prediction methods [i.e.

Anatomic Variations From 120 Mental Nerve Dissections: Lessons for Transoral Thyroidectomy.

Background: Transoral endoscopic thyroidectomy vestibular approach (TOETVA) is a promising technique for eliminating a neck incision. A new risk of TOETVA is the potential for injury to the mental nerves during placement of three oral endoscopic ports. A better understanding of the variations in mental nerve anatomy is needed to inform safer TOETVA technique.

Randomized controlled clinical study evaluating the efficacy and safety of intratumoral treatment of canine mast cell tumors with tigilanol tiglate (EBC-46).

Objective: To evaluate the efficacy and safety of tigilanol tiglate (TT) for local intratumoral treatment of mast cell tumors (MCTs) in dogs.

Methods: A randomized controlled clinical study in 2 phases involving 123 dogs with cytologically diagnosed MCT. Phase 1 compared 81 TT-treated dogs with 42 control dogs; phase 2 allowed TT treatment of control dogs and retreatment of dogs that failed to achieve tumor resolution after TT treatment in phase 1.

Novel epoxy-tiglianes stimulate skin keratinocyte wound healing responses and re-epithelialization via protein kinase C activation.

Epoxy-tiglianes are a novel class of diterpene esters. The prototype epoxy-tigliane, EBC-46 (tigilanol tiglate), possesses potent anti-cancer properties and is currently in clinical development as a local treatment for human and veterinary cutaneous tumors. EBC-46 rapidly destroys treated tumors and consistently promotes wound re-epithelialization at sites of tumor destruction.

Dose Characterization of the Investigational Anticancer Drug Tigilanol Tiglate (EBC-46) in the Local Treatment of Canine Mast Cell Tumors.

Mast cell tumor (MCT) is the most common cutaneous neoplasm in dogs and wide surgical resection is the current first-line treatment. However, recurrence is common and often requires more specialist and expensive therapies. Tigilanol tiglate is a novel small molecule drug delivered by intratumoral injection that is currently under development to provide a new option for treating MCT.

New Casbanes and the First trans-Cyclopropane seco-Casbane from the Australian Rainforest Plant Croton insularis.

Investigation of the Australian rainforest plant Croton insularis revealed seven new cis-, two new trans-cyclopropane casbanes, and the first trans-cyclopropane seco-casbane. The relative configuration of the cyclopropane moiety for all compounds (EBC-182, 217, 218, 220, 343, 357, 358, 361, 365, 373; EBC=EcoBiotics Compound) was assigned using C NMR data. Comparison of the experimental electronic circular dichroism (ECD) spectra with the theoretical curves, calculated by TD-DFT at the B3LYP/6-31+G**//B3LYP/6-31+G** level, in conjunction with NOE data afforded the absolute configuration.

Diagnosis, presentation and initial severity of Autoimmune Hepatitis (AIH) in patients attending 28 hospitals in the UK.

Background & Aims: There is limited information regarding patients with AIH outside relatively few large centres. We describe here the presenting features of patients with AIH, collected as part of an audit involving 28 UK hospitals.

Methods: Patients (incident since 1/1/2007 or prevalent since 1/1/2000) were ≥18 years and either met 1999 International AIH Group (IAIHG) diagnostic criteria (n = 1164), or received immunosuppressive therapy for clinically diagnosed AIH (n = 103).

The First Casbane Hydroperoxides EBC-304 and EBC-320 from the Australian Rainforest.

Investigation of the Australian rainforest plant Croton insularis led to isolation of the first casbane hydroperoxide diterpenes EBC-304 and EBC-320. Extensive DFT and electronic circular dichroism (ECD) calculations in combination with 2D NMR spectroscopy determined the absolute configurations. EBC-304 and EBC-320 both display significant cytotoxicity.

Using Plate Osteosynthesis to Treat Isolated Greater Tuberosity Fractures.

Isolated greater tuberosity fractures make up a small subset of proximal humerus fractures. We conducted a study to evaluate the radiologic and clinical outcomes of patients who underwent a novel use of plate osteosynthesis in the treatment of displaced greater tuberosity fractures. Eleven consecutive patients with a displaced greater tuberosity fracture were treated.

Use of reverse total shoulder arthroplasty in the Medicare population.

Background: Reverse shoulder arthroplasty (RSA) has been Food and Drug Administration approved in the United States since 2004 but did not obtain a unique code until 2010. Therefore, the use of this popular procedure has yet to be reported. The purpose of this study was to examine the use and reimbursement of RSA compared with total shoulder arthroplasty (TSA) and shoulder hemiarthroplasty (SHA).

Intra-lesional injection of the novel PKC activator EBC-46 rapidly ablates tumors in mouse models.

Intra-lesional chemotherapy for treatment of cutaneous malignancies has been used for many decades, allowing higher local drug concentrations and less toxicity than systemic agents. Here we describe a novel diterpene ester, EBC-46, and provide preclinical data supporting its use as an intra-lesional treatment. A single injection of EBC-46 caused rapid inflammation and influx of blood, followed by eschar formation and rapid tumor ablation in a range of syngeneic and xenograft models.

Unprecedented 1,14-seco-crotofolanes from Croton insularis: oxidative cleavage of crotofolin C by a putative homo-Baeyer-Villiger rearrangement.

EBC-162 isolated from Croton insularis, obtained from the northern rainforest of Australia, was structurally affirmed as crotofolin C (4). Novel oxidative degradation products, EBC-233 and EBC-300, which are the first crotofolane endoperoxides, were also isolated. Both endoperoxides were found to be stable intermediates, which are proposed to undergo an unprecedented homo-Baeyer-Villiger biosynthetic rearrangement to give a new class of 1,14-seco-crotofolane diterpenes.