Pancreatic CAF-Derived Autotaxin Drives Autocrine CTGF Expression to Modulate Protumorigenic Signaling.

Autotaxin (ATX), encoded by ENPP2, is a clinical target in pancreatic ductal adenocarcinoma (PDAC). ATX catalyzes the production of lysophosphatidic acid (LPA), an important regulator within the tumor microenvironment (TME), yet the protumorigenic action of the ATX/LPA axis in PDAC remains unclear. In this study, by interrogating patient samples and cell line datasets, we show that the PDAC TME, rather than cancer cells, is responsible for the majority of ENPP2 expression and highlight a key role for cancer-associated fibroblast (CAF)-derived ATX in autocrine and paracrine protumorigenic signaling.

IOA-244 is a Non-ATP-competitive, Highly Selective, Tolerable PI3K Delta Inhibitor That Targets Solid Tumors and Breaks Immune Tolerance.

Unlabelled: PI3K delta (PI3Kδ) inhibitors are used to treat lymphomas but safety concerns and limited target selectivity curbed their clinical usefulness. PI3Kδ inhibition in solid tumors has recently emerged as a potential novel anticancer therapy through the modulation of T-cell responses and direct antitumor activity. Here we report the exploration of IOA-244/MSC2360844, a first-in-class non-ATP-competitive PI3Kδ inhibitor, for the treatment of solid tumors.

In silico identification and synthesis of a multi-drug loaded MOF for treating tuberculosis.

Conventional drug delivery systems have been applied to a myriad of active ingredients but may be difficult to tailor for a given drug. Herein, we put forth a new strategy, which designs and selects the drug delivery material by considering the properties of encapsulated drugs (even multiple drugs, simultaneously). Specifically, through an in-silico screening process of 5109 MOFs using grand canonical Monte Carlo simulations, a customized MOF (referred as BIO-MOF-100) was selected and experimentally verified to be biologically stable, and capable of loading 3 anti-Tuberculosis drugs Rifampicin+Isoniazid+Pyrazinamide at 10% + 28% + 23% wt/wt (total > 50% by weight).

Granular Cell Tumor in a 13-Year-Old Girl.

Granular cell tumors are rare benign soft-tissue lesions that most commonly occur in the head and neck. They usually present in adulthood and are rarely seen in children. Here we present a 13-year-old girl who experienced symptoms of hoarseness of voice for most of her childhood and was unsuccessfully treated for asthma, acid reflux, allergies, and bronchitis before direct visualization revealed what was initially thought to be a vocal cord cyst.

iHear: Canadian medical student based hearing assessment program for grade school children using a tablet audiometer.

Purpose: To evaluate the progress and challenges of a hearing screening program as well as review the incidence of pediatric hearing loss in grade school children participating in this program.

Methods: Medical students from the University of Ottawa established iHear, a grade school hearing assessment program that uses novel tablet audiometry. Over 3 years, children in grades 1 and 2 were assessed and those found to have abnormal results on iHear assessment were then referred to audiology for formal testing, and to otolaryngology if needed.

Cerebrospinal Fluid Leaks From the Lateral Ventricle: A Case Series.

Objectives: Describe the diagnosis and management of lateral skull base (LSB) cerebrospinal fluid (CSF) leaks originating from the lateral ventricle.

Study Design: Retrospective case review.

Setting: Tertiary referral academic center.

Pedicled Cervical Lymphoadipose Tissue for Volume Reconstruction after Superficial Parotidectomy.

Volume restoration is often required after parotidectomy due to the resultant facial contour deformity. Common procedures include local pedicled flaps, such as the sternocleidomastoid muscle flap, fat grafting, and even autologous free flaps, for more extensive defects. Local pedicled flaps have the advantage of a single surgical site, which spares the patient the added morbidity of a separate fat graft donor site, while simultaneously reducing the operative time.

The transcriptional signature associated with human motile cilia.

Cilia are complex microtubule-based organelles essential to a range of processes associated with embryogenesis and tissue homeostasis. Mutations in components of these organelles or those involved in their assembly may result in a diverse set of diseases collectively known as ciliopathies. Accordingly, many cilia-associated proteins have been described, while those distinguishing cilia subtypes are poorly defined.

TALPID3 in Joubert syndrome and related ciliopathy disorders.

TALPID3 (KIAA0586) is a centrosomal protein which has specific functions during centriole maturation during the formation of the centrosomal-dependent organelle, the cilia, as well as less well understood roles in the cytoskeleton and during cell polarisation. Cilia are an essential component of signal transduction during embryonic development and the loss of TALPID3 function in humans can cause both severe lethal and mild cilia-related developmental disorders known as 'ciliopathies' the most common being Joubert syndrome. TALPID3 related ciliopathies affect the development of multiple organ systems including the brain, skeleton, eyes, lungs and liver.

East meets West: Shadow coaching to support online reflective practice.

Objectives: A structured, reflection-based electronic portfolio program (ePortfolio), with novel faculty development initiative, involving 'shadow coaches', was shared with the newly formed Ottawa-Shanghai Joint School of Medicine (OSJSM). OSJSM is a partnership between Shanghai Jiao Tong University and the University of Ottawa. As the world's first Sino-Canadian Joint Medical School, OSJSM introduced North American undergraduate medical curriculum to China.

The developmental and genetic basis of 'clubfoot' in the peroneal muscular atrophy mutant mouse.

Genetic factors underlying the human limb abnormality congenital talipes equinovarus ('clubfoot') remain incompletely understood. The spontaneous autosomal recessive mouse 'peroneal muscular atrophy' mutant (PMA) is a faithful morphological model of human clubfoot. In PMA mice, the dorsal (peroneal) branches of the sciatic nerves are absent.

Preparing anesthesiology faculty for competency-based medical education.

Purpose: Competency-based medical education (CBME) is quickly becoming the dominant organizing principle for medical residency programs. As CBME requires changes in the way medical education is delivered, faculty will need to acquire new skills in teaching and assessment in order to navigate the transition. In this paper, we examine the evidence supporting best practices in faculty development, propose strategies for faculty development for CBME-based residency programs, and discuss the results of faculty development initiatives at the pioneering anesthesia CBME residency program at the University of Ottawa.

Cognitive Aids for Role Definition (CARD) to improve interprofessional team crisis resource management: An exploratory study.

This study aimed to assess the perceived value of the Cognitive Aids for Role Definition (CARD) protocol for simulated intraoperative cardiac arrests. Sixteen interprofessional operating room teams completed three consecutive simulated intraoperative cardiac arrest scenarios: current standard, no CARD; CARD, no CARD teaching; and CARD, didactic teaching. Each team participated in a focus group interview immediately following the third scenario; data were transcribed verbatim and qualitatively analysed.

Curriculum reform for residency training: competence, change, and opportunities for leadership.

Purpose: Certain pressures stemming from within the medical community and from society in general, such as the need for increased accountability in resident training and restricted resident duty hours, have prompted a re-examination of methods for training physicians. Leaders in medical education in North America and around the world champion competency-based medical education (CBME) as a solution. The Department of Anesthesiology at the University of Ottawa launched Canada's first CBME program for anesthesiology residents on July 1, 2015.

TALPID3 controls centrosome and cell polarity and the human ortholog KIAA0586 is mutated in Joubert syndrome (JBTS23).

Joubert syndrome (JBTS) is a severe recessive neurodevelopmental ciliopathy which can affect several organ systems. Mutations in known JBTS genes account for approximately half of the cases. By homozygosity mapping and whole-exome sequencing, we identified a novel locus, JBTS23, with a homozygous splice site mutation in KIAA0586 (alias TALPID3), a known lethal ciliopathy locus in model organisms.