Polymeric delivery systems for nucleic acid therapeutics: Approaching the clinic.

Gene therapy using nucleic acids has many clinical applications for the treatment of diseases with a genetic origin as well as for the development of innovative vaccine formulations. Since nucleic acids in their free form are rapidly degraded by nucleases present in extracellular matrices, have poor pharmacokinetics and hardly pass cellular membranes, carrier systems are required. Suitable carriers that protect the nucleic acid payload against enzymatic attack, prolong circulation time after systemic administration and assist in cellular binding and internalization are needed to develop nucleic acid based drug products.

Utility of Serum miR-371a-3p in Predicting Relapse on Surveillance in Patients with Clinical Stage I Testicular Germ Cell Cancer.

Background: Optimal management of clinical stage I (CSI) testicular cancer is controversial due to lack of robust prognostic factors; miRNA-371a-3p holds promise as a biomarker, although its clinical utility for identifying patients at risk of relapse is unknown.

Objective: To explore the association between serum miR-371a-3p and CSI surveillance relapse.

Design, Setting, And Participants: Serial banked sera from 151 CSI (101 seminomas and 50 nonseminomatous germ cell tumors [NSGCTs]) samples from our Princess Margaret active surveillance cohort were tested.

Prediction of relapse in stage I testicular germ cell tumor patients on surveillance: investigation of biomarkers.

Background: Better biomarkers for assessing risk of relapse in stage I testicular germ cell tumor patients are needed, to complement classical histopathological variables. We aimed to assess the prognostic value of previously suggested biomarkers, related to proliferation (MIB-1 and TEX19) and to immune microenvironment (CXCL12, CXCR4, beta-catenin and MECA-79) in a surveillance cohort of stage I testicular germ cell tumor patients.

Methods: A total of 70 patients were included.

NOTCH inhibition promotes bronchial stem cell renewal and epithelial barrier integrity after irradiation.

Hyperactivity of the NOTCH pathway is associated with tumor growth and radiotherapy resistance in lung cancer, and NOTCH/γ-secretase inhibitors (GSIs) are a potential therapeutic target. The therapeutic outcome, however, is often restricted by the dose-limiting toxicity of combined treatments on the surrounding healthy tissue. The NOTCH signaling pathway is also crucial for homeostasis and repair of the normal airway epithelium.

-Promoter Demethylation as Tissue Biomarker for Testicular Germ Cell Tumors and Spermatogenesis Quality.

Background: The event of X chromosome inactivation induced by , which is physiologically observed in females, is retained in testicular germ cell tumors (TGCTs), as a result of a supernumerary X chromosome constitution. X chromosome inactivation also occurs in male germline, specifically during spermatogenesis. We aimed to analyze the promoter methylation status of in a series of TGCT tissues, representative cell lines, and testicular parenchyma.

Parameters of glucose metabolism and the aging brain: a magnetization transfer imaging study of brain macro- and micro-structure in older adults without diabetes.

Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain MRI was used to detect macro-structural damage (atrophy, white matter hyper-intensities, infarcts and/or micro-bleeds) and magnetization transfer imaging (MTI) to detect loss of micro-structural homogeneity that remains otherwise invisible on conventional MRI.

Associations between insulin action and integrity of brain microstructure differ with familial longevity and with age.

Impaired glucose metabolism and type 2 diabetes have been associated with cognitive decline, dementia, and with structural and functional brain features. However, it is unclear whether these associations differ in individuals that differ in familial longevity or age. Here, we investigated the association between parameters of glucose metabolism and microstructural brain integrity in offspring of long-lived families ("offspring") and controls; and age categories thereof.

Microstructural brain tissue damage in metabolic syndrome.

Objective: We investigated the association between metabolic syndrome risk factors and brain tissue integrity, as assessed by magnetic resonance imaging.

Research Design And Methods: From the Leiden Longevity Study, which is a community-based study of long-lived subjects, their offspring, and partners thereof, 130 subjects (61 men; mean age 66 years) were included. A metabolic syndrome score was computed by summing the individual number of components according to the Adult Treatment Panel III criteria.

Effectiveness of percutaneous laser disc decompression versus conventional open discectomy in the treatment of lumbar disc herniation; design of a prospective randomized controlled trial.

Background: The usual surgical treatment of refractory sciatica caused by lumbar disc herniation, is open discectomy. Minimally invasive procedures, including percutaneous therapies under local anesthesia, are increasingly gaining attention. One of these treatments is Percutaneous Laser Disc Decompression (PLDD).