Genomic and clinical profiling of a national nephrotic syndrome cohort advocates a precision medicine approach to disease management.

Steroid Resistant Nephrotic Syndrome (SRNS) in children and young adults has differing etiologies with monogenic disease accounting for 2.9-30% in selected series. Using whole exome sequencing we sought to stratify a national population of children with SRNS into monogenic and non-monogenic forms, and further define those groups by detailed phenotypic analysis.

Eradication of minimal residual disease improves overall and progression-free survival in patients with chronic lymphocytic leukaemia, evidence from NCRN CLL207: a phase II trial assessing alemtuzumab consolidation.

With immunochemotherapy, remission duration and survival in patients with chronic lymphocytic leukaemia is dependent on the level of minimal residual disease (MRD) after treatment. This phase II trial assessed alemtuzumab consolidation post-chemotherapy in patients who responded with persistent low levels of detectable disease. Blood was screened for MRD using multi-parameter flow cytometry, 6-24 months post-chemotherapy.

DNA vaccination for cervical cancer; a novel technology platform of RALA mediated gene delivery via polymeric microneedles.

HPV subtypes (16, 18) are associated with the development of cervical cancer, with oncoproteins E6 and E7 responsible for pathogenesis. The goal of this study was to evaluate our 'smart system' technology platform for DNA vaccination against cervical cancer. The vaccination platform brings together two main components; a peptide RALA which condenses DNA into cationic nanoparticles (NPs), and a polymeric polyvinylpyrrolidone (PVP) microneedle (MN) patch for cutaneous delivery of the loaded NPs.

Mutations Cause Congenital Nephrotic Syndrome.

Steroid-resistant nephrotic syndrome (SRNS), a heterogeneous disorder of the renal glomerular filtration barrier, results in impairment of glomerular permselectivity. Inheritance of genetic SRNS may be autosomal dominant or recessive, with a subset of autosomal recessive SRNS presenting as congenital nephrotic syndrome (CNS). Mutations in 53 genes are associated with human SRNS, but these mutations explain ≤30% of patients with hereditary cases and only 20% of patients with sporadic cases.

Further evidence of alerted default network connectivity and association with theory of mind ability in schizophrenia.

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) has repeatedly shown evidence of altered functional connectivity of large-scale networks in schizophrenia. The relationship between these connectivity changes and behaviour (e.g.

A Developmental and Molecular View of Formation of Auxin-Induced Nodule-Like Structures in Land Plants.

Several studies have shown that plant hormones play important roles during legume-rhizobia symbiosis. For instance, auxins induce the formation of nodule-like structures (NLSs) on legume roots in the absence of rhizobia. Furthermore, these NLS can be colonized by nitrogen-fixing bacteria, which favor nitrogen fixation compared to regular roots and subsequently increase plant yield.

Dissolving microneedles for DNA vaccination: Improving functionality via polymer characterization and RALA complexation.

DNA vaccination holds the potential to treat or prevent nearly any immunogenic disease, including cancer. To date, these vaccines have demonstrated limited immunogenicity in vivo due to the absence of a suitable delivery system which can protect DNA from degradation and improve transfection efficiencies in vivo. Recently, microneedles have been described as a novel physical delivery technology to enhance DNA vaccine immunogenicity.

Critical review: Injectability of calcium phosphate pastes and cements.

Unlabelled: Calcium phosphate cements (CPC) have seen clinical success in many dental and orthopaedic applications in recent years. The properties of CPC essential for clinical success are reviewed in this article, which includes properties of the set cement (e.g.

Mesenchymal stromal cells derived from whole human umbilical cord exhibit similar properties to those derived from Wharton's jelly and bone marrow.

Mesenchymal stromal cells (MSC) can be isolated from several regions of human umbilical cords, including Wharton's jelly (WJ), artery, vein or cord lining. These MSC appear to be immune privileged and are promising candidates for cell therapy. However, isolating MSC from WJ, artery, vein or cord lining requires time-consuming tissue dissection.

Chondrogenic Potency Analyses of Donor-Matched Chondrocytes and Mesenchymal Stem Cells Derived from Bone Marrow, Infrapatellar Fat Pad, and Subcutaneous Fat.

Autologous chondrocyte implantation (ACI) is a cell-based therapy that has been used clinically for over 20 years to treat cartilage injuries more efficiently in order to negate or delay the need for joint replacement surgery. In this time, very little has changed in the ACI procedure, but now many centres are considering or using alternative cell sources for cartilage repair, in particular mesenchymal stem cells (MSCs). In this study, we have tested the chondrogenic potential of donor-matched MSCs derived from bone marrow (BM), infrapatellar fat pad (FP), and subcutaneous fat (SCF), compared to chondrocytes.

Responses to altered oxygen tension are distinct between human stem cells of high and low chondrogenic capacity.

Background: Lowering oxygen from atmospheric level (hyperoxia) to the physiological level (physioxia) of articular cartilage promotes mesenchymal stem cell (MSC) chondrogenesis. However, the literature is equivocal regarding the benefits of physioxic culture on preventing hypertrophy of MSC-derived chondrocytes. Articular cartilage progenitors (ACPs) undergo chondrogenic differentiation with reduced hypertrophy marker expression in hyperoxia but have not been studied in physioxia.

Hydraulic Balance of a Plantation in Response to Periodic Drought in Low Subtropical China.

A clear understanding of hydraulic regulation in cultivated plants is crucial for addressing challenges to forest water cycling due to climate changes in low subtropical China. Experiments were conducted to determine the hydrologic balance of a plantation in response to periodic drought. Trees displayed lower stomatal conductance (G) and leaf water potentials (Ψ) during the dry periods.

Rapidly dissolving polymeric microneedles for minimally invasive intraocular drug delivery.

In this study, dissolving microneedles (MNs) were used to enhance ocular drug delivery of macromolecules. MNs were fabricated using polyvinylpyrrolidone (PVP) polymer of various molecular weights (MWs) containing three model molecules of increasing MW, namely fluorescein sodium and fluorescein isothiocyanate-dextrans (with MW of 70 k and 150 k Da). Arrays (3 × 3) of PVP MNs with conical shape measuring about 800 μm in height with a 300 μm base diameter, containing the model drugs, were fabricated and characterized for their fracture forces, insertion forces (in the sclera and cornea), depth of penetration (using OCT and confocal imaging), dissolution time and in vitro permeation.

Delivery of nucleic acids for cancer gene therapy: overcoming extra- and intra-cellular barriers.

The therapeutic potential of cancer gene therapy has been limited by the difficulty of delivering genetic material to target sites. Various biological and molecular barriers exist which need to be overcome before effective nonviral delivery systems can be applied successfully in oncology. Herein, various barriers are described and strategies to circumvent such obstacles are discussed, considering both the extracellular and intracellular setting.

Childhood-Diagnosed ADHD, Symptom Progression, and Reversal Learning in Adulthood.

Objective: ADHD persists in up to 60% into adulthood, and the reasons for persistence are not fully understood. The objective of this study was to characterize the neurofunctional basis of decision making in those with a childhood diagnosis of ADHD with either persistent or remitted symptoms in adulthood versus healthy control participants.

Method: Thirty-two adults diagnosed with ADHD as children were split into persistent ( n = 18) or remitted ( n = 14) ADHD groups.

Preclinical evaluation of gold-DTDTPA nanoparticles as theranostic agents in prostate cancer radiotherapy.

Aim: Gold nanoparticles have attracted significant interest in cancer diagnosis and treatment. Herein, we evaluated the theranostic potential of dithiolated diethylenetriamine pentaacetic acid (DTDTPA) conjugated AuNPs (Au@DTDTPA) for CT-contrast enhancement and radiosensitization in prostate cancer.

Materials & Methods: In vitro assays determined Au@DTDTPA uptake, cytotoxicity, radiosensitizing potential and DNA damage profiles.

Expert Facilitated Development of an Objective Assessment Tool for Point-of-Care Ultrasound Performance in Undergraduate Medical Education.

Background: With the various applications of point-of-care ultrasound (PoCUS) steadily increasing, many medical schools across North America are incorporating PoCUS training into their undergraduate curricula. The Faculty of Medicine at Memorial University also intends to introduce PoCUS training into its own undergraduate medical program. The proposed approach is to introduce a PoCUS curriculum focusing on anatomy and physiology while developing cognitive and psychomotor skills that are later transferred into clinical applications.

Objective Assessment of Adherence to Inhalers by Patients with Chronic Obstructive Pulmonary Disease.

Rationale: Objective adherence to inhaled therapy by patients with chronic obstructive pulmonary disease (COPD) has not been reported.

Objectives: To objectively quantify adherence to preventer Diskus inhaler therapy by patients with COPD with an electronic audio recording device (INCA).

Methods: This was a prospective observational study.

An Outbreak of Ebola Virus Disease in the Lassa Fever Zone.

Background: Kenema Government Hospital (KGH) has developed an advanced clinical and laboratory research capacity to manage the threat of Lassa fever, a viral hemorrhagic fever (VHF). The 2013-2016 Ebola virus (EBOV) disease (EVD) outbreak is the first to have occurred in an area close to a facility with established clinical and laboratory capacity for study of VHFs.

Methods: Because of its proximity to the epicenter of the EVD outbreak, which began in Guinea in March 2014, the KGH Lassa fever Team mobilized to establish EBOV surveillance and diagnostic capabilities.

NCRI phase II study of CHOP in combination with ofatumumab in induction and maintenance in newly diagnosed Richter syndrome.

Richter syndrome (RS) is associated with chemotherapy resistance and a poor historical median overall survival (OS) of 8-10 months. We conducted a phase II trial of standard CHOP-21 (cyclophosphamide, doxorubicin, vincristine, prednisolone every 21 d) with ofatumumab induction (Cycle 1: 300 mg day 1, 1000 mg day 8, 1000 mg day 15; Cycles 2-6: 1000 mg day 1) (CHOP-O) followed by 12 months ofatumumab maintenance (1000 mg given 8-weekly for up to six cycles). Forty-three patients were recruited of whom 37 were evaluable.

Effects of poly (ε-caprolactone) coating on the properties of three-dimensional printed porous structures.

Powder-based inkjet three-dimensional printing (3DP) to fabricate pre-designed 3D structures has drawn increasing attention. However there are intrinsic limitations associated with 3DP technology due to the weak bonding within the printed structure, which significantly compromises its mechanical integrity. In this study, calcium sulphate ceramic structures demonstrating a porous architecture were manufactured using 3DP technology and subsequently post-processed with a poly (ε-caprolactone) (PCL) coating.

A Comparison of a New Ultrasound-Based Whole Blood Viscoelastic Test (SEER Sonorheometry) Versus Thromboelastography in Cardiac Surgery.

Background: Viscoelastic thromboelastography tests such as TEG™ are now routine for assessing the coagulation status of cardiac surgery patients. We compared TEG™ with a new technology, sonic estimation of elasticity via resonance (SEER) sonorheometry, to compare measures of coagulation dynamics of whole blood and assess its potential for rapid, near-point-of-care monitoring of hemostasis during cardiac surgery.

Methods: Whole blood coagulation assessment of a prospective cohort of 50 cardiac surgery patients was performed using SEER sonorheometry and blood samples collected at 4 time points during cardiac surgery: baseline before anesthetic induction, during cardiopulmonary bypass on rewarming, 10 minutes after heparin reversal by protamine, and on patient transfer to the intensive care unit.

A Rare Case of an Early Postoperative Obstructive Ileus in a Young Female Patient due to a Residual Trichobezoar Mass.

Trichobezoar is a rare cause of small bowel obstruction, whereby a mass forms most commonly in the stomach and duodenum of young females, from ingestion of hair, a condition known as trichophagia. We present a case of recurrent small bowel obstruction due to a residual hair mass that was removed surgically in a young female patient who had a laparotomy and gastrotomy for removal of a large gastric trichobezoar just two weeks prior to the current admission. This case illustrates the importance of a thorough inspection of the whole bowel to ensure that no residual bezoars remain after surgery.