Development of a clinically relevant chemoresistant mantle cell lymphoma cell culture model.

Unlabelled: Mantle cell lymphoma is an aggressive subtype of non-Hodgkin’s lymphoma that claims the lives of tens of thousands of people every year. Although combination chemotherapy treatments such as CHOP have yielded promising outcomes in the clinic, the development of chemoresistance in patients has limited their long-term success. The lack of chemoresistance models has limited our ability to understand the mechanisms by which cells develop resistance, and thus our ability to develop novel therapeutics to overcome this issue.

Branched-Tail Lipid Nanoparticles Potently Deliver mRNA In Vivo due to Enhanced Ionization at Endosomal pH.

The potential of mRNA therapeutics will be realized only once safe and effective delivery systems are established. Unfortunately, delivery vehicle development is stymied by an inadequate understanding of how the molecular properties of a vehicle confer efficacy. Here, a small library of lipidoid materials is used to elucidate structure-function relationships and identify a previously unappreciated parameter-lipid nanoparticle surface ionization-that correlates with mRNA delivery efficacy.

Lipid nanoparticle siRNA cocktails for the treatment of mantle cell lymphoma.

Mantle cell lymphoma is an aggressive and incurable subtype of non-Hodgkin B cell lymphoma. Patients typically present with advanced disease, and most patients succumb within a decade of diagnosis. There is a clear and urgent need for novel therapeutic approaches that will affect mantle cell lymphoma through a unique mechanism compared to current therapies.

Lipidoid nanoparticle mediated silencing of Mcl-1 induces apoptosis in mantle cell lymphoma.

Conventional chemo-immunotherapy fails to cure the majority of mantle cell lymphoma patients and causes substantial toxicity. Resistant mantle cell lymphoma cells commonly overexpress and are dependent on the anti-apoptotic protein, Mcl-1, for survival. In this study, we use potent lipidoid nanoparticles to deliver siRNA to silence Mcl-1 expression.

Lipidoid Nanoparticles for siRNA Delivery to the Intestinal Epithelium: In Vitro Investigations in a Caco-2 Model.

Short interfering ribonucleic acid (siRNA) therapeutics show promise for the treatment of intestinal diseases by specifically suppressing the expression of disease relevant proteins. Recently, a class of lipid-like materials termed "lipidoids" have been shown to potently deliver siRNA to the liver and immune cells. Here, we seek to establish the utility of lipidoid nanoparticles (LNPs) in the context of siRNA delivery to the intestinal epithelium.

Introduction of a fresh cadaver laboratory during the surgery clerkship improves emergency technical skills.

Background: Student acquisition of technical skills during the clinical years of medical school has been steadily declining. To address this issue, the authors instituted a fresh cadaver-based Emergency Surgical Skills Laboratory (ESSL).

Methods: Sixty-three medical students rotating through the third-year surgery clerkship participated in a 2-hour, fresh cadaver-based ESSL conducted during the first 2 days of the clerkship.

In pursuit of a moving target: nanotherapeutics for the treatment of non-Hodgkin B-cell lymphoma.

Introduction: Non-Hodgkin lymphoma (NHL) is diagnosed in 70,000 Americans annually. Chemotherapy was the standard course of treatment until the addition of the monoclonal antibody (mAb) drug, rituximab, to therapy regimens in 1997. Although disease prognosis has improved dramatically since that time, nearly 20,000 patients succumb annually to the disease, with an average life expectancy beyond diagnosis of only 12 years.

OKN asymmetry in human subjects: a literature review.

Optokinetic nystagmus (OKN) is a reflex eye movement induced by motion of the whole or a large proportion of the visual field. It can be horizontal, vertical, and torsional in direction and consists of two basic components, a slow tracking movement and a rapid recovery saccade. Two forms of OKN exist: "look" and "stare" OKN.

Effect of distance upon horizontal and vertical look and stare OKN.

Previous reports suggest that distance influences horizontal stare OKN gains; however, the effect of distance on vertical OKN and look OKN is unknown. Horizontal and vertical look and stare OKN gains were recorded in 16 healthy volunteers (velocity 38.4 degrees /s) at three distances (0.

Vertical optokinetic nystagmus in Parkinson's disease.

Parkinson's disease (PD) is associated with a number of oculomotor deficits; however, little is known about changes in vertical optokinetic nystagmus (OKN) associated with PD. We recorded eye movements in 14 PD patients and 14 age-matched controls in response to large field OKN stimulation using stimulus velocities of 20 degrees /second and 40 degrees /second. We compared asymmetry of horizontal and vertical responses in the two groups.

Horizontal and vertical look and stare optokinetic nystagmus symmetry in healthy adult volunteers.

Purpose: Look optokinetic nystagmus (OKN) consists of voluntary tracking of details in a moving visual field, whereas stare OKN is reflexive and consists of shorter slow phases of lower gain. Horizontal OKN is symmetrical in healthy adults, whereas symmetry of vertical OKN is controversial. Horizontal and vertical look and stare OKN symmetry was measured, and the consistency of individual asymmetries and the effect of varying stimulus conditions were investigated.

The VF-14 and psychological impact of amblyopia and strabismus.

Purpose: To assess the impact of amblyopia, strabismus and glasses on subjective visual and psychological function among amblyopes.

Methods: Questionnaires were administered to 120 teenagers with amblyopia (cases), with residual amblyopia after treatment, or with or without strabismus and 120 control subjects (controls) Cases underwent ophthalmic examination including cycloplegic refraction. Two questionnaires (visual function 14 [VF-14] and a newly designed eight-item questionnaire) were administered to assess the psychological impact score of general daily life, having a weaker eye, glasses wear, and current noticeable strabismus.

Benign recurrent abducens (6th) nerve palsy in two children.

Benign recurrent abducens (6th) nerve palsy is rare. We found 23 cases in children reported in the literature; however, many of these cases followed immunization or were associated with viral illness. Here we report two cases of recurrent abducens nerve palsy with no obvious etiology.