Targeted care navigation to reduce hospital readmissions in 'at-risk' patients.

Background: Care navigation is commonly used to reduce preventable hospitalisation. The use of Electronic Health Record-derived algorithms may enable better targeting of this intervention for greater impact.

Aims: To evaluate if community-based Targeted Care Navigation, supported by an Electronic Health Record-derived readmission risk algorithm, is associated with reduced rehospitalisation.

Impact of COVID-19 lockdowns on hospital presentations and admissions in the context of low community transmission: evidence from time series analysis in Melbourne, Australia.

Background: Melbourne, Australia, successfully halted exponential transmission of COVID-19 via two strict lockdowns during 2020. The impact of such restrictions on healthcare-seeking behaviour is not comprehensively understood, but is of global importance. We explore the impact of the COVID-19 pandemic on acute, subacute and emergency department (ED) presentations/admissions within a tertiary, metropolitan health service in Melbourne, Australia, over two waves of community transmission (1 March to 20 September 2020).

Tumor-penetrating therapy for β5 integrin-rich pancreas cancer.

Pancreatic ductal adenocarcinoma (PDAC) is characterized by marked desmoplasia and drug resistance due, in part, to poor drug delivery to extravascular tumor tissue. Here, we report that carcinoma-associated fibroblasts (CAFs) induce β5 integrin expression in tumor cells in a TGF-β dependent manner, making them an efficient drug delivery target for the tumor-penetrating peptide iRGD. The capacity of iRGD to deliver conjugated and co-injected payloads is markedly suppressed when β5 integrins are knocked out in the tumor cells.

Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy.

Bacterial resistance to antibiotics has made it necessary to resort to antibiotics that have considerable toxicities. Here, we show that the cyclic 9-amino acid peptide CARGGLKSC (CARG), identified via phage display on () bacteria and through screening in mice with -induced lung infections, increases the antibacterial activity of CARG-conjugated vancomycin-loaded nanoparticles in -infected tissues and reduces the needed overall systemic dose, minimizing side effects. CARG binds specifically to bacteria but not Pseudomonas bacteria , selectively accumulates in -infected lungs and skin of mice but not in non-infected tissue and Pseudomonas-infected tissue, and significantly enhances the accumulation of intravenously injected vancomycin-loaded porous silicon nanoparticles bearing the peptide in -infected mouse lung tissue.

Graphene biointerfaces for optical stimulation of cells.

Noninvasive stimulation of cells is crucial for the accurate examination and control of their function both at the cellular and the system levels. To address this need, we present a pioneering optical stimulation platform that does not require genetic modification of cells but instead capitalizes on unique optoelectronic properties of graphene, including its ability to efficiently convert light into electricity. We report the first studies of optical stimulation of cardiomyocytes via graphene-based biointerfaces (G-biointerfaces) in substrate-based and dispersible configurations.

Screening for canine transitional cell carcinoma (TCC) by SERS-based quantitative urine cytology.

Canine lower urinary tract neoplasia is a clinically important disease process that has high mortality due to late stage diagnosis and poorly durable response to treatment. Non-invasive diagnostic techniques (e.g.

Publisher Correction: Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease.

The original version of the Supplementary Information associated with this Article inadvertently omitted Supplementary Table 1. The HTML has now been updated to include a corrected version of the Supplementary Information.

Identification of a peptide recognizing cerebrovascular changes in mouse models of Alzheimer's disease.

Cerebrovascular changes occur in Alzheimer's disease (AD). Using in vivo phage display, we searched for molecular markers of the neurovascular unit, including endothelial cells and astrocytes, in mouse models of AD. We identified a cyclic peptide, CDAGRKQKC (DAG), that accumulates in the hippocampus of hAPP-J20 mice at different ages.

In vivo cation exchange in quantum dots for tumor-specific imaging.

In vivo tumor imaging with nanoprobes suffers from poor tumor specificity. Here, we introduce a nanosystem, which allows selective background quenching to gain exceptionally tumor-specific signals. The system uses near-infrared quantum dots and a membrane-impermeable etchant, which serves as a cation donor.

Porous Silicon Nanoparticle Delivery of Tandem Peptide Anti-Infectives for the Treatment of Pseudomonas aeruginosa Lung Infections.

There is an urgent need for new materials to treat bacterial infections. In order to improve antibacterial delivery, an anti-infective nanomaterial is developed that utilizes two strategies for localization: i) a biodegradable nanoparticle carrier to localize therapeutics within the tissue, and ii) a novel tandem peptide cargo to localize payload to bacterial membranes. First, a library of antibacterial peptides is screened that combines a membrane-localizing peptide with a toxic peptide cargo and discovers a tandem peptide that displays synergy between the two domains and is able to kill Pseudomonas aeruginosa at sub-micromolar concentrations.

Ratiometric in vivo auditioning of targeted silver nanoparticles.

Attaching affinity ligands to nanoparticles (NPs) increases selectivity for targeting cells and tissues, and can result in improved sensitivity and reduced off-target toxicity in diagnostic and therapeutic systems. The decision over key features - NP size, shape, coating strategies and targeting ligands for clinical translation is often hampered by a lack of quantitative in vivo NP homing assays. Sensitive, internally controlled assays are needed which allow for quantitative comparisons (auditions) among various formulations of targeted NPs.

Early experience of a new extracorporeal carbon dioxide removal device for acute hypercapnic respiratory failure.

Background: Recent advances in the technology of extracorporeal respiratory assist systems have led to a renewed interest in extracorporeal carbon dioxide removal (ECCOR). The Hemolung is a new, low-flow, venovenous, minimally invasive, partial ECCOR device that has recently been introduced to clinical practice to aid in avoiding invasive ventilation or to facilitate lung-protective ventilation.

Objective: We report our early experience on use, efficacy and safety of the Hemolung in three Australian intensive care units.

Composite Porous Silicon-Silver Nanoparticles as Theranostic Antibacterial Agents.

A theranostic nanoparticle with biochemically triggered antibacterial activity is demonstrated. Metallic silver is deposited onto porous silicon nanoparticles (pSiNPs) by galvanic displacement. When aqueous diaminesilver ([Ag(NH)]) is used as a silver source, the pSiNPs template the crystalline silver as small (mean diameter 13 nm) and well-dispersed nanoparticles embedded within and on the larger (100 nm) pSiNPs.

Nanostructured Antagonist of Extrasynaptic NMDA Receptors.

Glutamatergic cytotoxicity mediated by overactivation of N-methyl-d-aspartate receptors (NMDARs) is implicated in numerous neurological disorders. To be therapeutically viable, NMDAR antagonists must preserve physiological role of synaptic NMDARs (sNMDARs) in synaptic transmission and block only excessive pathological activation of NMDARs. Here we present a novel NMDAR antagonist that satisfies this two-fold requirement by exploiting spatial differences in NMDAR subcellular locations.

Tumor-Targeted Multimodal Optical Imaging with Versatile Cadmium-Free Quantum Dots.

The rapid development of fluorescence imaging technologies requires concurrent improvements in the performance of fluorescent probes. Quantum dots have been extensively used as an imaging probe in various research areas because of their inherent advantages based on unique optical and electronic properties. However, their clinical translation has been limited by the potential toxicity especially from cadmium.

A peptide for targeted, systemic delivery of imaging and therapeutic compounds into acute brain injuries.

Traumatic brain injury (TBI) is a major health and socio-economic problem, but no pharmacological agent is currently approved for the treatment of acute TBI. Thus, there is a great need for advances in this field. Here, we describe a short peptide (sequence CAQK) identified by in vivo phage display screening in mice with acute brain injury.

Urokinase-controlled tumor penetrating peptide.

Tumor penetrating peptides contain a cryptic (R/K)XX(R/K) CendR element that must be C-terminally exposed to trigger neuropilin-1 (NRP-1) binding, cellular internalization and malignant tissue penetration. The specific proteases that are involved in processing of tumor penetrating peptides identified using phage display are not known. Here we design de novo a tumor-penetrating peptide based on consensus cleavage motif of urokinase-type plasminogen activator (uPA).

New p32/gC1qR Ligands for Targeted Tumor Drug Delivery.

Cell surface p32, the target of LyP-1 homing peptide, is upregulated in tumors and atherosclerotic plaques and has been widely used as a receptor for systemic delivery of payloads. Here, we identified an improved LyP-1-mimicking peptide (TT1, CKRGARSTC). We used this peptide in a fluorescence polarization-based high-throughput screening of a 50,000-compound chemical library and identified a panel of compounds that bind p32 with low micromolar affinity.

Paclitaxel-Loaded Polymersomes for Enhanced Intraperitoneal Chemotherapy.

Peritoneal carcinomatosis is present in more than 60% of gastric cancer, 40% of ovarian cancer, and 35% of colon cancer patients. It is the second most common cause of cancer-related mortality, with a median survival of 1 to 3 months. Cytoreductive surgery combined with intraperitoneal chemotherapy is the current clinical treatment, but achieving curative drug accumulation and penetration in peritoneal carcinomatosis lesions remains an unresolved challenge.

Targeted silver nanoparticles for ratiometric cell phenotyping.

Affinity targeting is used to deliver nanoparticles to cells and tissues. For efficient targeting, it is critical to consider the expression and accessibility of the relevant receptors in the target cells. Here, we describe isotopically barcoded silver nanoparticles (AgNPs) as a tool for auditing affinity ligand receptors in cells.

Neuropilin-1 and heparan sulfate proteoglycans cooperate in cellular uptake of nanoparticles functionalized by cationic cell-penetrating peptides.

Cell-penetrating peptides (CPPs) have been widely used to deliver nanomaterials and other types of macromolecules into mammalian cells for therapeutic and diagnostic use. Cationic CPPs that bind to heparan sulfate (HS) proteoglycans on the cell surface induce potent endocytosis; however, the role of other surface receptors in this process is unclear. We describe the convergence of an HS-dependent pathway with the C-end rule (CendR) mechanism that enables peptide ligation with neuropilin-1 (NRP1), a cell surface receptor known to be involved in angiogenesis and vascular permeability.

Biotags Based on Surface-Enhanced Raman Can Be as Bright as Fluorescence Tags.

Surface enhanced Raman spectroscopy (SERS) is a powerful analytical technique that has been proposed as a substitute for fluorescence for biological imaging and detection but is not yet commercially utilized. The reason lies primarily in the lower intensity and poor reproducibility of most metal nanoparticle-based tags as compared to their fluorescence-based counterparts. Here, using a technique that scrupulously preserves the same number of dye molecules in both the SERS and fluorescence measurements, we show that SERS-based biotags (SBTs) with highly reproducible optical properties can be nanoengineered such that their brightness is at least equal to that of fluorescence-based tags.

Light-activated RNA interference in human embryonic stem cells.

We describe a near infrared (NIR) light-activated gene silencing method in undifferentiated human embryonic stem cell (hESC) using a plasmonic hollow gold nanoshell (HGN) as the siRNA carrier. Our modular biotin-streptavidin coupling strategy enables positively charged TAT-peptide to coat oligonucleotides-saturated nanoparticles as a stable colloid formation. TAT-peptide coated nanoparticles with dense siRNA loading show efficient penetration into a wide variety of hESC cell lines.

A tumor-penetrating peptide enhances circulation-independent targeting of peritoneal carcinomatosis.

Peritoneal carcinomatosis is a major source of morbidity and mortality in patients with advanced abdominal neoplasms. Intraperitoneal chemotherapy (IPC) is an area of intense interest given its efficacy in ovarian cancer. However, IPC suffers from poor drug penetration into peritoneal tumors.

Rapid identification by surface-enhanced Raman spectroscopy of cancer cells at low concentrations flowing in a microfluidic channel.

Reliable identification and collection of cells from bodily fluids is of growing interest for monitoring patient response to therapy and for early detection of disease or its recurrence. We describe a detection platform that combines microfluidics with surface-enhanced Raman spectroscopy (SERS) for the identification of individual mammalian cells continuously flowing in a microfluidics channel. A mixture of cancerous and noncancerous prostate cells was incubated with SERS biotags (SBTs) developed and synthesized by us, then injected into a flow-focused microfluidic channel, which forces the cells into a single file.