Molecular imaging allows clinicians to visualize the progression of tumours and obtain relevant information for patient diagnosis and treatment1. Owing to their intrinsic optical, electrical and magnetic properties, nanoparticles are promising contrast agents for imaging dynamic molecular and cellular processes such as protein-protein interactions, enzyme activity or gene expression2. Until now, nanoparticles have been engineered with targeting ligands such as antibodies and peptides to improve tumour specificity and uptake. However, excessive loading of ligands can reduce the targeting capabilities of the ligand3,4,5 and reduce the ability of the nanoparticle to bind to a finite number of receptors on cells6. Increasing the number of nanoparticles delivered to cells by each targeting molecule would lead to higher signal-to-noise ratios and improve image contrast. Here, we show that M13 filamentous bacteriophage can be used as a scaffold to display targeting ligands and multiple nanoparticles for magnetic resonance imaging of cancer cells and tumours in mice. Monodisperse iron oxide magnetic nanoparticles assemble along the M13 coat, and its distal end is engineered to display a peptide that targets SPARC glycoprotein, which is overexpressed in various cancers. Compared with nanoparticles that are directly functionalized with targeting peptides, our approach improves contrast because each SPARC-targeting molecule delivers a large number of nanoparticles into the cells. Moreover, the targeting ligand and nanoparticles could be easily exchanged for others, making this platform attractive for in vivo high-throughput screening and molecular detection.

Purpose: We are in great need of specific biomarkers to detect pancreatic ductal adenocarcinoma (PDAC) at an early stage, ideally before invasion. Plectin-1 (Plec1) was recently identified as one such biomarker. However, its suitability as a specific biomarker for human pancreatic cancer, and its usability as an imaging target, remain to be assessed.Experimental Design: Specimens of human PDAC, chronic pancreatitis, and normal pancreata were evaluated by immunohistochemistry and Western blot analysis. To validate Plec1 as an imaging target, Plec1-targeting peptides (tPTP) were used as a contrast agent for single photon emission computed tomography in an orthotopic and liver metastasis murine model of PDAC.Results: Plec1 expression was noted to be positive in all PDACs but negative in benign tissues. Plec1 expression increases during pancreatic carcinogenesis. It was found to be misexpressed in only 0% to 3.85% of early PDAC precursor lesions (PanIN I/II) but in 60% of PanIN III lesions. Plec1 expression was further noted to be retained in all metastatic foci assayed and clearly highlighted these metastatic deposits in lymph nodes, liver, and peritoneum. In vivo imaging using tPTP specifically highlighted the primary and metastatic tumors. Biodistribution studies performed after imaging show that the primary pancreatic tumors and liver metastases retained 1.9-to 2.9-fold of tPTP over normal pancreas and 1.7-fold over normal liver.Conclusions: Plec1 is the first biomarker to identify primary and metastatic PDAC by imaging and may also detect preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore improve detection and staging. Clin Cancer Res; 17(2); 302-9. Ó2010 AACR.

From 1996 to 2003, four 12-month population-based surveys were performed in FoodNet sites to determine the burden of diarrhoeal disease in the population. Acute diarrhoeal illness (ADI) was defined as > or =3 loose stools in 24 hours with impairment of daily activities or duration of diarrhoea >1 day. A total of 52840 interviews were completed. The overall weighted prevalence of ADI in the previous month was 5.1% (95% CI+/-0.3%), corresponding to 0.6 episodes of ADI per person per year. The average monthly prevalence of ADI was similar in each of the four survey cycles (range 4.5-5.2%). Rates of ADI were highest in those age <5 years. Of those with ADI, 33.8% (95% CI+/-2.7%) reported vomiting, 19.5% (95% CI+/-2.1%) visited a medical provider, and 7.8% (95% CI+/-1.4%) took antibiotics. Rates of ADI were remarkably consistent over time, and demonstrate the substantial burden placed on the health-care system.

We identified low but escalating risk of severe M. chimaera infection associated with heater-coolers with cases in a quarter of cardiothoracic centers. Our investigations strengthen etiological evidence for the role of heater-coolers in transmission and raise the possibility of an ongoing, international point-source outbreak. Active management of heater-coolers and heightened clinical awareness are imperative given the consequences of infection.

Many studies have evaluated the role of Cryptosporidium spp. in outbreaks of enteric illness, but few studies have evaluated sporadic cryptosporidiosis in the United States. To assess the risk factors for sporadic cryptosporidiosis among immunocompetent persons, a matched case-control study was conducted in seven sites of the Foodborne Diseases Active Surveillance Network (FoodNet) involving 282 persons with laboratoryidentified cryptosporidiosis and 490 age-matched and geographically matched controls. Risk factors included international travel (odds ratio [OR] ‫؍‬ 7.7; 95% confidence interval [95% CI] ‫؍‬ 2.7 to 22.0), contact with cattle (OR ‫؍‬ 3.5; 95% CI ‫؍‬ 1.8 to 6.8), contact with persons >2 to 11 years of age with diarrhea (OR ‫؍‬ 3.0; 95% CI ‫؍‬ 1.5 to 6.2), and freshwater swimming (OR ‫؍‬ 1.9; 95% CI ‫؍‬ 1.049 to 3.5). Eating raw vegetables was protective (OR ‫؍‬ 0.5; 95% CI ‫؍‬ 0.3 to 0.7). This study underscores the need for ongoing public health education to prevent cryptosporidiosis, particularly among travelers, animal handlers, child caregivers, and swimmers, and the need for further assessment of the role of raw vegetables in cryptosporidiosis.