Thyroid Hormone Levels Correlate With the Maturation of Implanted Pancreatic Endoderm Cells in Patients With Type 1 Diabetes.

Background: Macroencapsulated pancreatic endoderm cells (PECs) can reverse diabetes in rodents and preclinical studies revealed that thyroid hormones in vitro and in vivo bias PECs to differentiate into insulin-producing cells. In an ongoing clinical trial, PECs implanted in macroencapsulation devices into patients with type 1 diabetes were safe but yielded heterogeneous outcomes. Though most patients developed meal responsive C-peptide, levels were heterogeneous and explanted grafts had variable numbers of surviving cells with variable distribution of endocrine cells.

The role of mitochondrial apoptotic pathway in islet amyloid-induced β-cell death.

Islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to β-cell death in type 2 diabetes. We previously showed that extracellular hIAPP aggregates promote Fas-mediated β-cell apoptosis. Here, we tested if hIAPP aggregates can trigger the mitochondrial apoptotic pathway (MAP).

The Teacher-Learner Contract (TLC): An Objectives-Based Checklist for Surgical Shadowing.

Objective: A lack of structure and communication in physician shadowing experiences may prevent medical students from accruing its potential benefits. In this study, we evaluated the use of an objectives-based surgical shadowing teacher-learner contract (TLC) on the outcomes of shadowing experiences.

Design: Cross-sectional study with 30 unique student-surgeon pairs who participated in a 1-time shadowing experience between December 2016 and May 2017.

Devil's Club Falcarinol-Type Polyacetylenes Inhibit Pancreatic Cancer Cell Proliferation.

Natural falcarinol-type (FC-type) polyacetylenes are known to show anticancer activities. We studied the bioactivity of synthetic FC, 1,2-dihydrofalcarinol (FCH) and 3-acetoxyfalcarinol (FCA) and compared them with the natural bioactive polyacetylene [9,17-octadecadiene-12,14-diyne-1,11,16-triol,1-acetate] (DCA) isolated from Devil's club (DC) Oplopanax horridus. Antiproliferation activity of these polyacetylenes, along with DC inner stem bark 70% ethanol and water extracts, was tested on human pancreatic ductal adenocarcinoma cell lines PANC-1 and BxPC-3.

Enhanced recovery after surgery in colorectal surgery: Impact of protocol adherence on patient outcomes.

Study Objectives: There is growing evidence internationally to support Enhanced Recovery After Surgery (ERAS) pathways. The impact of pathway compliance and the relative importance of individual components, however, remains less clear. Our institution implemented a multimodal ERAS protocol for elective colorectal surgery in November 2013.

Amyloid formation reduces protein kinase B phosphorylation in primary islet β-cells which is improved by blocking IL-1β signaling.

Amyloid formation in the pancreatic islets due to aggregation of human islet amyloid polypeptide (hIAPP) contributes to reduced β-cell mass and function in type 2 diabetes (T2D) and islet transplantation. Protein kinase B (PKB) signaling plays a key role in the regulation of β-cell survival, function and proliferation. In this study, we used human and hIAPP-expressing transgenic mouse islets in culture as two ex vivo models of human islet amyloid formation to: 1.

Amyloid formation disrupts the balance between interleukin-1β and interleukin-1 receptor antagonist in human islets.

Objectives: β-cell dysfunction and apoptosis associated with islet inflammation play a key role in the pathogenesis of type 2 diabetes (T2D). Growing evidence suggests that islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to islet inflammation and β-cell death in T2D. We recently showed the role of interleukin-1β (IL-1β)/Fas/caspase-8 apoptotic pathway in amyloid-induced β-cell death.

Measurement of Pro-Islet Amyloid Polypeptide (1-48) in Diabetes and Islet Transplants.

Context: Islet amyloid is a feature of β-cell failure in type 2 diabetes (T2D) and type 1 diabetes (T1D) recipients of islet transplants. Islet amyloid contains islet amyloid polypeptide (IAPP; amylin), a circulating peptide that is produced in β cells by processing of its precursor, proIAPP1-67, via an intermediate form, proIAPP1-48. Elevated proinsulin to C-peptide ratios in the plasma of persons with diabetes suggest defects in β-cell prohormone processing.

Dual role of interleukin-1β in islet amyloid formation and its β-cell toxicity: Implications for type 2 diabetes and islet transplantation.

Aims: Islet amyloid, formed by aggregation of human islet amyloid polypeptide (hIAPP), contributes to β-cell failure in type 2 diabetes, cultured and transplanted islets. We previously showed that biosynthetic hIAPP aggregates induce β-cell Fas upregulation and activation of the Fas apoptotic pathway. We used cultured human and hIAPP-expressing mouse islets to investigate: (1) the role of interleukin-1β (IL-1β) in amyloid-induced Fas upregulation; and (2) the effects of IL-1β-induced β-cell dysfunction on pro-islet amyloid polypeptide (proIAPP) processing and amyloid formation.

The application of mRNA-based gene transfer in mesenchymal stem cell-mediated cytotoxicity of glioma cells.

Since the tumor-oriented homing capacity of mesenchymal stem cells (MSCs) was discovered, MSCs have attracted great interest in the research field of cancer therapy mainly focused on their use as carries for anticancer agents. Differing from DNA-based vectors, the use of mRNA-based antituor gene delivery benefits from readily transfection and mutagenesis-free. However, it is essential to verify if mRNA transfection interferes with MSCs' tropism and their antitumor properties.

Fluorescent cholangiography in laparoscopic cholecystectomy: the initial Canadian experience.

Background: Bile duct injury remains a worrisome complication of laparoscopic cholecystectomy. Indocyanine Green (ICG) fluorescent cholangiography (FC) is a new approach that facilitates real-time intraoperative identification of biliary anatomy. This technology is hoped to improve the safety of dissection within Calot's triangle.

Statistical approaches and software for clustering islet cell functional heterogeneity.

Worldwide efforts are underway to replace or repair lost or dysfunctional pancreatic β-cells to cure diabetes. However, it is unclear what the final product of these efforts should be, as β-cells are thought to be heterogeneous. To enable the analysis of β-cell heterogeneity in an unbiased and quantitative way, we developed model-free and model-based statistical clustering approaches, and created new software called TraceCluster.

Fibroblast Cell-Based Therapy for Experimental Autoimmune Diabetes.

Type 1 diabetes (T1D) results from autoimmune destruction of insulin producing β cells of the pancreatic islets. Curbing autoimmunity at the initiation of T1D can result in recovery of residual β cells and consequently remission of diabetes. Here we report a cell-based therapy for autoimmune diabetes in non-obese diabetic (NOD) mice using dermal fibroblasts.

IDO-Expressing Fibroblasts Protect Islet Beta Cells From Immunological Attack and Reverse Hyperglycemia in Non-Obese Diabetic Mice.

Indoleamine 2,3-dioxygenase (IDO) induces immunological tolerance in physiological and pathological conditions. Therefore, we used dermal fibroblasts with stable IDO expression as a cell therapy to: (i) Investigate the factors determining the efficacy of this cell therapy for autoimmune diabetes in non-obese diabetic (NOD) mice; (ii) Scrutinize the potential immunological mechanisms. Newly diabetic NOD mice were randomly injected with either 10 × 10(6) (10M) or 15 × 10(6) (15M) IDO-expressing dermal fibroblasts.

Why Canada needs networks to provide rural surgical care, including family doctors with essential surgical skills.

Time is long overdue for action to improve rural surgical services in Canada. In this issue of CJS, a proposed curriculum for the provision of enhanced surgical skills (ESS) to rural family physicians offers an opportunity to fortify a seamless network of high-quality surgical care for rural Canada. It is supported and enhanced by the best available evidence and measured advice from specialists and generalists alike.

Therapeutic potential of CAR-T cell-derived exosomes: a cell-free modality for targeted cancer therapy.

Chimeric antigen receptor (CAR)-based T-cell adoptive immunotherapy is a distinctively promising therapy for cancer. The engineering of CARs into T cells provides T cells with tumor-targeting capabilities and intensifies their cytotoxic activity through stimulated cell expansion and enhanced cytokine production. As a novel and potent therapeutic modality, there exists some uncontrollable processes which are the potential sources of adverse events.

Joint position paper on rural surgery and operative delivery.

Our professional organizations have prepared this paper as part of an integrated, multidisciplinary plan to ensure the availability of well-trained practitioner teams to sustain safe, effective and high-quality rural surgical and operative delivery services. Without these robust local (or nearby) surgical services, sustaining rural maternity care is much more difficult. This paper describes the "network model" as a health human resources solution to meet the surgical needs, including operative delivery, of rural residents; outlines necessary policy directions for achieving this solution; and poses a series of enabling recommendations.

Inhibition of Human Pancreatic Cancer Cell Proliferation by Devil's Club Oplopanax horridus and Its Polyacetylene Bioactive Compound.

Devil's club Oplopanax horridus (DC) is a close relative of ginseng; its inner root and stem bark extract showed antiproliferation activity on human leukemia, ovarian, breast and colon cancer cells. We study here the effects of DC 70% ethanol extract alone, or in combination with cisplatin, gemcitabine, and paclitaxel on pancreatic endocrine HP62 and pancreatic ductal carcinoma PANC-1 and BxPC-3 cells. Antiproliferation activity assay, cell cycle analysis by flow cytometry, apoptosis-related markers by antibody array, and RT-PCR assay were used for this study.

Hair follicle dermal sheath derived cells improve islet allograft survival without systemic immunosuppression.

Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants.

Human islet function following 20 years of cryogenic biobanking.

Aims/hypothesis: There are potential advantages to the low-temperature (-196 °C) banking of isolated islets, including the maintenance of viable islets for future research. We therefore assessed the in vitro and in vivo function of islets cryopreserved for nearly 20 years.

Methods: Human islets were cryopreserved from 1991 to 2001 and thawed between 2012 and 2014.

Human fetal skin fibroblasts: Extremely potent and allogenic candidates for treatment of diabetic wounds.

The number of patients with diabetes has been expected around 300 million by 2025 and 366 million by 2030 by WHO. On the other hand, diabetic wounds as one of the common complications of diabetes represent major health challenges. Recently, wound care biological products have been proposed for treatment of chronic wounds such as the diabetic wound.

Percutaneous autologous pancreatic islet cell transplantation for traumatic pancreatic injury.

Context: Traumatic pancreatic injury with pancreatic duct disruption is surgically managed with at least a partial pancreatectomy, often leading to poor blood glucose control and the subsequent development of diabetes mellitus. Autologous β-islet cell transplantation may therefore help to preserve pancreatic endocrine function.

Case Description: We describe 3 patients with pancreatic duct disruption from traumatic pancreatic injury who were treated with a partial pancreatectomy followed by autologous β-islet cell transplantation via a percutaneous transhepatic approach.

B7-H4 as a protective shield for pancreatic islet beta cells.

Auto- and alloreactive T cells are major culprits that damage β-cells in type 1 diabetes (T1D) and islet transplantation. Current immunosuppressive drugs can alleviate immune-mediated attacks on islets. T cell co-stimulation blockade has shown great promise in autoimmunity and transplantation as it solely targets activated T cells, and therefore avoids toxicity of current immunosuppressive drugs.