Examining an internet-delivered intervention for anxiety and depression when delivered as a part of routine care for university students: A phase IV trial.

BACKGROUND: There has been growing interest in the potential of emerging internet-delivered psychological treatments for supporting the mental health needs of university students. However, no large-scale prospective effectiveness trials examining their real-world potential have been reported. OBJECTIVE: The aim of the current study was to evaluate the acceptability and effectiveness of a brief, 5-week, internet-delivered and therapist-guided intervention for anxiety and depression, when delivered as part of routine care by a university counselling service. DESIGN: A large, prospective, single-group Phase-IV clinical trial. Students (n = 1326) engaging with the university counselling service were provided the opportunity to receive the intervention based on their preferences and identified needs. Students completed standardised measures of anxiety and depression at pre-treatment, each week of the intervention, post-treatment and 3-month follow-up. RESULTS: Over a 4 year period, 1081 students (10% of those presenting to the counselling service) participated in the intervention. Large clinical reductions in symptoms of both anxiety (% reduction = 41%; Cohen's d = 0.94) and depression (% reduction = 36%; Cohen's d = 0.81) were observed alongside high levels of acceptability. The intervention required relatively little counsellor time (M = 36.28 mins; SD = 20.56) per student, and symptom deterioration was observed in less than 5% of students. CONCLUSION: The findings of the current study are supportive of internet-delivered interventions provided as routine care to university students. Further research is needed to carefully explore whether these interventions could be used with a larger proportion of students presenting to counselling services, paying close attention to acceptability, engagement and clinical outcomes.

The epidemiology of injury for an elite junior Australian Football cohort.

OBJECTIVES: To implement an injury recording protocol in a junior elite Australian Football competition and determine the injury profile of this population. DESIGN: Longitudinal cohort study. METHODS: Players from an elite Under 18 Australian Football competition were tracked throughout one football season in terms of participation or non-participation in the football competition. Injury reporting forms were collected for all players who were not available for selection as a result of injury. RESULTS: The cohort consisted of 532 players who provided consent for inclusion in the study (100% of players in the competition). There were 256 injuries sustained during the season. Results were standardised to a 40 man team to allow comparison with results from the Australian Football League. The injury incidence was 17.1 new injuries per club (95% CI 14.1-19.4), and prevalence 63.3 missed matches per club (95% CI 59.1-67.1). The category "Ankle joint injuries" was the most commonly reported (n=34) and "Collision with another player" was the main injury mechanism (n=75). CONCLUSIONS: The most commonly injured region in junior elite Australian Football was the ankle and collision with another player was the most common injury mechanism. As with previous reports on junior Australian Football, injury incidence was low in comparison to the senior elite competition. Defining the injury profile guides injury prevention strategies. Analysis of injury in junior elite football may provide a unique opportunity to affect both junior and senior injury rates.

Microarrays of lentiviruses for gene function screens in immortalized and primary cells.

Here we describe lentivirus-infected cell microarrays for the high-throughput screening of gene function in mammalian cells. To create these arrays, we cultured mammalian cells on glass slides 'printed' with lentiviruses pseudotyped as vesicular stomatitis virus glycoprotein, which encode short hairpin RNA or cDNA. Cells that land on the printed 'features' become infected with lentivirus, creating a living array of stably transduced cell clusters within a monolayer of uninfected cells. The small size of the features of the microarrays (300 microm in diameter) allows high-density spotting of lentivirus, permitting thousands of distinct parallel infections on a single glass slide. Because lentiviruses have a wide cellular tropism, including primary cells, lentivirus-infected cell microarrays can be used as a platform for high-throughput screening in a variety of cell types.

Towards molecular spintronics.

The ability to manipulate electron spin in organic molecular materials offers a new and extremely tantalizing route towards spin electronics, both from fundamental and technological points of view. This is mainly due to the unquestionable advantage of weak spin-orbit and hyperfine interactions in organic molecules, which leads to the possibility of preserving spin-coherence over times and distances much longer than in conventional metals or semiconductors. Here we demonstrate theoretically that organic spin valves, obtained by sandwiching an organic molecule between magnetic contacts, can show a large bias-dependent magnetoresistance and that this can be engineered by an appropriate choice of molecules and anchoring groups. Our results, obtained through a combination of state-of-the-art non-equilibrium transport methods and density functional theory, show that although the magnitude of the effect varies with the details of the molecule, large magnetoresistance can be found both in the tunnelling and the metallic limit.

Microarrays of small molecules embedded in biodegradable polymers for use in mammalian cell-based screens.

We developed a microarray-based system for screening small molecules in mammalian cells. This system is compatible with image-based screens and requires fewer than 100 cells per compound. Each compound is impregnated in a 200-microm-diameter disc composed of biodegradable poly-(D),(L)-lactide/glycolide copolymer. Cells are seeded on top of these discs, and compounds slowly diffuse out, affecting proximal cells. In contrast with microtiter-based screening, this system does not involve the use of wells or walls between each compound-treated group of cells. We demonstrate detection of the effects of a single compound in a large microarray, that diverse compounds can be released in this format, and that extended release over several days is feasible. We performed a small synthetic lethal screen and identified a compound (macbecin II) that has reduced activity in cells with RNA interference-mediated decrease in the expression of tuberous sclerosis 2. Thus, we have developed a microarray-based screening system for testing the effects of small molecules on mammalian cells by using an imaging-based readout. This method will be useful to those performing small-molecule screens to discover new chemical tools and potential therapeutic agents.

RNAi living-cell microarrays for loss-of-function screens in Drosophila melanogaster cells.

RNA interference (RNAi)-mediated loss-of-function screening in Drosophila melanogaster tissue culture cells is a powerful method for identifying the genes underlying cell biological functions and for annotating the fly genome. Here we describe the development of living-cell microarrays for screening large collections of RNAi-inducing double-stranded RNAs (dsRNAs) in Drosophila cells. The features of the microarrays consist of clusters of cells 200 mum in diameter, each with an RNAi-mediated depletion of a specific gene product. Because of the small size of the features, thousands of distinct dsRNAs can be screened on a single chip. The microarrays are suitable for quantitative and high-content cellular phenotyping and, in combination screens, for the identification of genetic suppressors, enhancers and synthetic lethal interactions. We used a prototype cell microarray with 384 different dsRNAs to identify previously unknown genes that affect cell proliferation and morphology, and, in a combination screen, that regulate dAkt/dPKB phosphorylation in the absence of dPTEN expression.

Distal filter protection during saphenous vein graft stenting: technical and clinical correlates of efficacy.

OBJECTIVES: The aim of this study was to evaluate the clinical, angiographic, and technical factors related to successful stenting of diseased saphenous vein grafts (SVGs) using a novel filter-based distal protection device. BACKGROUND: Protection of the distal microvasculature with a balloon occlusion and aspiration system has been shown to reduce atherothrombotic embolization and peri-procedural myocardial infarction (MI) after percutaneous coronary intervention (PCI) in SVGs. The safety, efficacy, and technical factors relating to procedural success with filter-based distal protection devices are unknown. METHODS: Percutaneous coronary intervention was performed in 60 lesions in 48 patients undergoing SVG intervention with the FilterWire EX distal protection system in a phase I experience at six sites. A larger phase II study was then performed in 248 lesions in 230 SVGs at 65 U.S. centers. RESULTS: Cumulative adverse events to 30 days occurred in 21.3% of patients in phase I, including a 19.1% rate of MI. Numerous anatomic, device-specific, and operator-related contributors to these adverse events were identified, resulting in significant changes to the protocol and instructions for use. Subsequently, despite similar clinical and angiographic characteristics to the phase I patients, the 30-day adverse event rate in phase II was reduced to 11.3% (p = 0.09), due primarily to a lower incidence of peri-procedural Q-wave and non-Q-wave MI. CONCLUSIONS: Distal protection during SVG PCI with the FilterWire EX is associated with a low rate of peri-procedural adverse events compared to historical controls. A unique set of anatomic, technical, and operator-related issues exist with distal filters which, if ignored, may reduce their effectiveness.

Cell-biological applications of transfected-cell microarrays.

Cell microarrays are a recent addition to the set of tools available for functional genomic studies. Each cell microarray is a slide with thousands of cell clusters that are each transfected with a defined DNA, which directs either the overproduction or the inhibition of a particular gene product. By using a range of detection assays, the phenotypic consequences of perturbing each gene in mammalian cells can be probed in a systematic, high-throughput fashion. Combining well-established methods for cellular investigation with the miniaturization and multiplexing capabilities of microarrays, cell arrays are a versatile tool that can be useful in many cell-biological applications.

Methods for predicting sexual maturity in male cynomolgus macaques on the basis of age, body weight, and histologic evaluation of the testes.

In pharmaceutical drug safety testing, sexual maturity is an important experimental parameter. Histologic immaturity of the tissues of the reproductive system can interfere with the interpretation of compound-related effects on the reproductive organs. In female cynomolgus macaques, determination of sexual maturity is simplified by the presence of a menstrual cycle. For male cynomolgus macaques, predicting maturity is much more difficult. In this study, we evaluated methods that would reliably predict sexual maturity in male cynomolgus macaques. The results of histologic examination of testes of control male cynomolgus macaques used for drug safety studies were examined retrospectively for evidence of sexual maturity. These data were compared with age and body weight determinations to establish statistical models for determining the probability that a male cynomolgus macaque is sexually mature. This model presents a simple prospective method of predicting sexual maturity in male cynomolgus macaques.

Applications of transfected cell microarrays in high-throughput drug discovery.

DNA microarrays and, more recently, protein microarrays, have become important tools for high-throughput genomic and proteomic studies. Transfected cell microarrays are a complementary technique in which array features comprise clusters of cells overexpressing defined cDNAs. Complementary DNAs cloned in expression vectors are printed on microscope slides, which become living arrays after the addition of a lipid transfection reagent and adherent mammalian cells. This article discusses two potential uses of cell microarrays in drug discovery: as a method of screening for gene products involved in biological processes of pharmaceutical interest and as in situ protein microarrays for the development and assessment of leads.

Angiogenic bFGF expression from gas-plasma treated scaffolds.

PURPOSE: In vivo experiments indicate that gas-plasma-treated D,L-polylactide polymers expressing basic fibroblast growth factor (bFGF) exhibit enhanced angiogenesis. bFGF is not a single entity, but it is instead a family of isoforms. Consequently, we sought to determine which bFGF isoforms and levels initiate angiogenesis in nude mice peritoneums. METHODS: Cytoplasmic and nuclear bFGF were characterized for nude mice peritoneums incubated with nontreated scaffolds containing HAEC (CW), its respective polymer-only scaffolds (Cp) and gas-plasma treated scaffolds with HAEC (TW) and without cells (Tp). NuPAGE electrophoresis and WesternBreeze Chemiluminescent kits were used to analyze relative bFGF densities and molecular weights. VEGF was quantified using ImageJ. RESULTS: bFGF bands were located at molecular weights of 24, 48, 58, 72 and 80 kDa, depending on whether they were from cytoplasms or nuclei. At 12, 24 and 72 days, 58-kDa bFGF bands were observed from nuclei of TW and Tp, 80-kDa bFGF bands were only observed in cytoplasmic fractions < or = 24 days. Total cytoplasmic and nuclear bFGF intensities increased from 12 to 24 days, then declined by 72 days. CONCLUSIONS: (1) Gas-plasma treated scaffolds up-regulate bFGF isoforms. (2) bFGF was expressed in the nuclei; however, 80-kDa bFGF was seen only in cytoplasms.

VEGF analysis induced by endothelialized gas-plasma treated D,L-PLA scaffolds.

PURPOSE: Vascular endothelial growth factor (VEGF) isoforms play different roles in the temporal sprouting of endothelial-lined vessels in a nude mouse peritoneal model as cells respond to nontreated control and gas-plasma-treated bioresorbable poly-D,L-lactide acid 3D scaffolds with human aortic endothelial cells (HAEC). METHODS AND MATERIALS: Nude mice peritoneums were incubated with HAEC (CW = control; TW = gas-plasma treated) or polymer scaffolds (Cp = control; Tp = treated) for 12, 24 and 72 days. Cytoplasmic and nuclear protein fractions were isolated using NER, electrophoresized using NuPAGE-MES and analyzed by WesternBreeze Chemiluminescent. RESULTS: Prominent VEGF bands included 28, 45 and 62 kDa; 52-kDa VEGF observed in cytoplasmic TW fractions contributed about 18.6% at 12 days, 20.0% at 24 days and 13.1% at 72 days of the total VEGF signal. Yet, it was only noted in CW at 72 days where it accounted for 6.9%. A unique 32-kDa band appeared in both Cp (24.6%) and Tp (18.3%). Significant differences between band densities occurred for cytoplasmic nuclear CW24- TW24 (P = .022), CW72-TW72 (P = .011) and, also, cytoplasmic Cp24-Tp24 (P = .038). CONCLUSIONS: The temporal and spatial organization of the TW isoforms results in more angiogenesis.