Novel interferon-beta-induced gene expression in peripheral blood cells

Type I IFNs are used for treating viral, neoplastic, and inflammatory disorders. The protein products encoded by IFN-stimulated genes (ISGs) likely mediate clinical effects of IFN in patients. Macroarray assays, used for studying ISG induction in IFN-treated patients, comprise genes identified predominantly through analysis of long-term cell lines. To discover genes induced selectively by IFN-beta in PBMC, we exposed whole blood to physiological concentrations of IFN-beta. PBMC were prepared, and RNA was extracted, reverse-transcribed, and hybridized to cDNA microarrays, and microarray analysis identified 39 ISGs and 20 IFN-repressed genes (IRGs). Thirty-three ISGs were known previously, and six ISGs were novel. New ISGs included GTP cyclohydrolase 1; hypothetical protein LOC129607; hypothetical protein FLJ38348; leucine aminopeptidase 3; squalene epoxidase; and GTP-binding protein overexpressed in skeletal muscle. Twenty IRGs included IL-1beta and CXCL8, which had been identified earlier. CXCL1 was a novel IRG identified in the current study. PCR analysis demonstrated the regulation of six novel ISGs and CXCL1 as an IRG in PBMC and astrocytoma cells. Results were validated using RNA obtained ex vivo from blood of patients after injection with IFN-beta. Identification of new ISGs and IRGs in primary PBMC will enhance macroarray assays for monitoring IFN responsiveness.     

Phase I Study Assessing the Pharmacokinetic Profile,Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (C_max), and area under the concentration-time curve from time zero to infinity (AUC_0–∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. {"type":"clinical-trial","attrs":{"text":"NCT01893346","term_id":"NCT01893346"}}NCT01893346.)     

Smaller Counter Cation for Higher Transconductance in Anionic Conjugated Polyelectrolytes

Conjugated polyelectrolytes (CPEs) are a focus of research because combine their inherent electrical conductivity and the ability to interact with ions in aqueous solutions or biological systems. However, it is still not understood to what degree the counter ion in CPEs influences the properties of the CPE itself and the performance of electronic transducers. In order to investigate this, three different conjugated polyelectrolytes, poly(6‐(thiophen‐3‐yl)hexane‐1‐sulfonate)s (PTHS^?X⁺), are synthesized, which have the same polythiophene backbone but different X⁺ counter ions: the bulky tetrabutylammonium (TBA⁺), tetraethylammonium (TEA⁺), and the smallest tetramethylammonium (TMA⁺). At the interface with biological systems, thin CPE films have to be stable in an aqueous environment and should allow the inward and outward flow of ions from the electrolyte. Since the studied PTHS^?X⁺ have different solubilities in water, the optical properties of pristine PTHS^?X⁺ as well as of crosslinked PTHS^?X⁺ via UV–vis absorption spectroscopy are investigated additionally. PTHS^?TMA⁺ exhibits better aggregation, fast interdiffusion of ions, and fast recovery from the oxidized state. Additionally, spectroelectrochemical and cyclic voltammetric as well as electrochemical capacitance investigations show that PTHS^?TMA⁺ can be oxidized to a higher degree. This leads to a better performance of PTHS^?TMA⁺‐based organic electrochemical transistors.     

Human chondrocyte migration behaviour to guide the development of engineered cartilage

Tissue‐engineering techniques have been successful in developing cartilage‐like tissues in vitro using cells from animal sources. The successful translation of these strategies to the clinic will likely require cell expansion to achieve sufficient cell numbers. Using a two‐dimensional (2D) cell migration assay to first identify the passage at which chondrocytes exhibited their greatest chondrogenic potential, the objective of this study was to determine a more optimal culture medium for developing three‐dimensional (3D) cartilage‐like tissues using human cells. We evaluated combinations of commonly used growth factors that have been shown to promote chondrogenic growth and development. Human articular chondrocytes (AC) from osteoarthritic (OA) joints were cultured in 3D environments, either in pellets or encapsulated in agarose. The effect of growth factor supplementation was dependent on the environment, such that matrix deposition differed between the two culture systems. ACs in pellet culture were more responsive to bone morphogenetic protein (BMP2) alone or combinations containing BMP2 (i.e. BMP2 with PDGF or FGF). However, engineered cartilage development within agarose was better for constructs cultured with TGFβ3. These results with agarose and pellet culture studies set the stage for the development of conditions appropriate for culturing 3D functional engineered cartilage for eventual use in human therapies. Copyright © 2015 John Wiley & Sons, Ltd.     

Steps Per Day Among Persons With Multiple Sclerosis: Variation by Demographic,Clinical, and Device Characteristics

Objectives

To identify steps per day in a large sample of persons with multiple sclerosis (MS) and to describe variation by demographic and clinical characteristics and device type.

Design

Cross-sectional design.

Setting

General community.

Participants

Convenience sample of persons with multiple sclerosis (N=645) recruited from the general community who were ambulatory and relapse free for 30 days. Mean age ± SD of the participants was 46.3±10.6 years old. Participants were mostly women (85%), white (93%), and employed (64%).

Interventions

Not applicable.

Main Outcome Measure

Step counts measured by a motion sensor during a 7-day period.

Results

The average value for the entire sample was 5903±3185 steps per day. This value varied by demographic and clinical characteristics, but not device type, and indicated that men, participants who were unemployed, had a high school education or less, progressive MS, a longer disease duration, and higher disability were less physically active based on the metric of steps per day.

Conclusions

This study provides an expected value for average steps per day among persons with MS. Such an expected value for this population is an important first step to help researchers and clinicians interested in improving the overall health of persons with MS through physical activity promotion.     

Animal models in retinoblastoma research

Advances in animal models of retinoblastoma have accelerated research in this field, aiding in understanding tumor progression and assessing therapeutic modalities. The distinct pattern of mutations and specific location of this unique intraocular tumor have paved the way for two types of models- those based on genetic mutations, and xenograft models. Retinoblastoma gene knockouts with an additional loss of p107, p130, p53 and using promoters of Nestin, Chx10, and Pax6 genes show histological phenotypic changes close to the human form of retinoblastoma. Conditional knockout in specific layers of the developing retina has thrown light on the origin of this tumor. The use of xenograft models has overcome the obstacle of time delay in the presentation of symptoms, which remains a crucial drawback of genetic models. With the advances in molecular and imaging technologies, the current research aims to develop models that mimic all the features of retinoblastoma inclusive of its initiation, progression and metastasis. The combination of genetic and xenograft models in retinoblastoma research has and will help to pave way for better understanding of retinoblastoma tumor biology and also in designing and testing effective diagnostic and treatment modalities.     

Quality of Life Measures Following Laser Assisted Uvulopalatopharyngoplasty (LAUP) in Obstructive Sleep Apnoea Syndrome (OSAS)

The objective of this study is to assess the efficacy of laser assisted uvulopalatopharyngoplasty in the treatment of Obstructive Sleep Apnoea Syndrome. This study was conducted over a period of 2 years and comprised of a total of 18 patients of both sexes, from a pool of 64 patients who presented with clinical features of OSAS. All the surgeries were done by the same surgeon and standardised criteria for diagnosis was followed. Only those Patients who were diagnosed to have moderate to severe OSAS of the obstructive type with single level retro palatal obstruction were treated surgically with LAUP, and followed up for a period of 6 months. Of the 18 patients 16 reported of improvement in quality of life, as assessed by Functional Outcomes of Sleep Questionnaire (FOSQ), accounting for 88.8%. The results support the surgical treatment for OSAS of moderate to severe single level retro palatal type, as evidenced by the FOSQ scoring. LAUP is a very good surgical option in alleviating the symptoms of moderate to severe single level retro palatal OSAS.     

Performance measures, efficiency, productivity

The paradox of the increased use of imaging without obvious evidence of improved health outcomes has led to calls for payment based on value rather than volume. Measurement of radiologists' performance is a key component of the measurement of value. The paradigm shift occurring in radiology and health care as a whole may seem daunting to the radiologist with the clamor for increasing accountability from payers and patients alike. However, it is through powerful tools such as performance measures in radiology and their accompanying incentive-based payment systems that practices can be improved and confidence of patients restored.