Cellular complexity captured in durable silica biocomposites

Tissue-derived cultured cells exhibit a remarkable range of morphological features in vitro, depending on phenotypic expression and environmental interactions. Translation of these cellular architectures into inorganic materials would provide routes to generate hierarchical nanomaterials with stabilized structures and functions. Here, we describe the fabrication of cell/silica composites (CSCs) and their conversion to silica replicas using mammalian cells as scaffolds to direct complex structure formation. Under mildly acidic solution conditions, silica deposition is restricted to the molecularly crowded cellular template. Inter- and intracellular heterogeneity from the nano- to macroscale is captured and dimensionally preserved in CSCs following drying and subjection to extreme temperatures allowing, for instance, size and shape preserving pyrolysis of cellular architectures to form conductive carbon replicas. The structural and behavioral malleability of the starting material (cultured cells) provides opportunities to develop robust and economical biocomposites with programmed structures and functions.     

Enhanced oncolysis mediated by Coxsackievirus A21 in combination with doxorubicin hydrochloride

Virotherapy is an emerging strategy for the treatment of cancer that utilizes both replication-competent and genetically modified viruses to selectively kill tumor cells. We have previously shown that Coxsackievirus A21 (CVA21), a common-cold producing enterovirus, is an effective oncolytic agent against human melanoma, prostate, and breast cancer xenografts in vivo. CVA21 specifically targets and lytically infects susceptible cells expressing the CVA21 cellular receptors, intercellular adhesion molecule-1 (ICAM-1) and decay-accelerating factor (DAF). Herein, the efficacy of CVA21 administered in combination with doxorubicin hydrochloride as a new therapeutic regimen for cancer was investigated. Flow cytometric analysis demonstrated that the human breast, colorectal, and pancreatic cancer cell lines examined expressed moderate levels of surface ICAM-1 and DAF, whilst a normal breast cell line expressed only minimal levels. When CVA21 was combined with doxorubicin hydrochloride, synergistically enhanced cell death was observed when CVA21 was administered both simultaneously or 24 h prior to doxorubicin hydrochloride exposure. Doxorubicin hydrochloride had no effect on CVA21 replication. Through the use of an orthotopic (MDA-MB-231-luc) xenograft SCID mouse model of human breast cancer we showed that a single intravenous injection of CVA21 in combination with an intraperitoneal injection of doxorubicin hydrochloride resulted in significantly greater tumor reduction compared to either agent alone. Overall, these findings highlight the exciting potential of CVA21, administered in combination with doxorubicin hydrochloride, as a new therapeutic regimen for cancer.     

Using Expert Panels to Determine the Level of Cancer Knowledge Required of Junior Doctors in Australia. Part 1: Methodology and Results

A number of curricula have been developed to address shortfalls in cancer education. However, no standardised means of assessing medical graduates against such curricula currently exist. This paper describes the use of expert panels to determine the level of cancer-related knowledge required by junior doctors. Participants individually reviewed knowledge items from the Ideal Oncology Curriculum for Medical Students and rated the level of understanding and specificity of each. On completion, panel sessions were convened to reach consensus. Fifty-two (17 %) items were considered irrelevant for junior doctors, whilst 164 items (54 %) and 85 items (28 %) were deemed appropriate at a moderate and high level of understanding, respectively. As a result, 249 (83 %) of the 301 items were deemed appropriate for junior doctors. Expert panels provide an important insight into the requirements of junior doctors, reduce ambiguity and facilitate discussion, resulting in higher quality data than that produced solely through individual reviews.     

Patterns of treatment utilization and methamphetamine use during first 10 years after methamphetamine initiation

The study examined joint trajectories of methamphetamine (MA) use and substance abuse treatment utilization and identified differences among pattern groups for a sample of 348 treated for MA use. Results from group-based trajectory modeling showed that treatment utilization during the first 10 years after initiation of MA use could be categorized into three distinctive patterns: about half the MA users have a pattern of low treatment utilization; one-fourth follow a quicker-to-treatment trajectory with higher probability of treatment during the first 5 years of MA use and less treatment in the next 5 years; and one-fourth have a slower-to-treatment trajectory with more treatment during the second half of the 10-year period. Four MA use patterns were identified: consistently low use, moderate, and high use, as well as a decreasing use pattern. Periods of greater likelihood of treatment participation were associated with periods of decreasing or lower frequency of MA use.     

Nicotinic Receptor Mutation in a Mildly Dysmorphic Girl with Duane Retraction Syndrome

Background: To evaluate possible monogenic and chromosomal anomalies in a patient with unilateral Duane retraction syndrome and modest dysmorphism.

Materials and Methods: Clinical evaluation, sequencing of candidate genes, and array comparative genomic hybridization (array CGH).

Results: The proband had unilateral Duane retraction syndrome (DRS) with low-set ears bilaterally, a high arched palate, and clinodactyly. Motor development and cognitive function were normal. Parents were first cousins, but no other family member was similarly affected. No mutations were detected in the HOXA1. KIF21A. SALL4, TUBB3, and CHN1 genes. Array CGH revealed a 16?Kb de novo deletion at chromosome 8p11.2 that encompassed a portion of only one gene, the Cholinergic Receptor, Nicotinic, Beta-3 (CHRNB3, Neuronal). This gene encodes a protein that is involved in the nicotinic acetylcholine receptor on neurons. It interacts functionally with other genes that code components of the acetylcholine receptor.

Conclusions: This patient’s chromosomal abnormality affected only one gene that is highly expressed in the brainstem and brain, involved in neurotransmission, and could be related to her Duane retraction syndrome.     

Initial Feasibility Study of a New Transcatheter Mitral Prosthesis: The First 100 Patients

Background

Transcatheter mitral valve replacement (TMVR) is a rapidly evolving therapy. Follow-up of TMVR patients remains limited in duration and number treated.

Infectious keratitis: an update on epidemiology,causative microorganisms,risk factors,and antimicrobial resistance

Corneal opacity is the 5th leading cause of blindness and visual impairment globally, affecting ~6 million of the world population. In addition, it is responsible for 1.5–2.0 million new cases of monocular blindness per year, highlighting an ongoing uncurbed burden on human health. Among all aetiologies such as infection, trauma, inflammation, degeneration and nutritional deficiency, infectious keratitis (IK) represents the leading cause of corneal blindness in both developed and developing countries, with an estimated incidence ranging from 2.5 to 799 per 100,000 population-year. IK can be caused by a wide range of microorganisms, including bacteria, fungi, virus, parasites and polymicrobial infection. Subject to the geographical and temporal variations, bacteria and fungi have been shown to be the most common causative microorganisms for corneal infection. Although viral and Acanthamoeba keratitis are less common, they represent important causes for corneal blindness in the developed countries. Contact lens wear, trauma, ocular surface diseases, lid diseases, and post-ocular surgery have been shown to be the major risk factors for IK. Broad-spectrum topical antimicrobial treatment is the current mainstay of treatment for IK, though its effectiveness is being challenged by the emergence of antimicrobial resistance, including multidrug resistance, in some parts of the world. In this review, we aim to provide an updated review on IK, encompassing the epidemiology, causative microorganisms, major risk factors and the impact of antimicrobial resistance.Subject terms: Corneal diseases, Epidemiology, Risk factors