Tuning Supramolecular Chirality in Iodinated Amphiphilic Peptides Through Tripeptide Linker Editing.

Protease-cleavable supramolecular oligopeptide nanofilaments are promising materials for targeted therapeutics and diagnostics. In these systems, single amino acid substitutions can have profound effects on the supramolecular structure and consequent proteolytic degradation, which are critical parameters for their intended applications. Herein, we describe changes to the self-assembly and proteolytic cleavage of iodine containing sequences for future translation into matrix metalloprotease (MMP-9)-activated supramolecular radio-imaging probes.

MMP-responsive nanomaterials.

Matrix metalloproteinases (MMP) are enzymes that degrade the extracellular matrix and regulate essential normal cell behaviors. Inhibition of these enzymes has been a strategy for anti-cancer therapy since the 1990s, but with limited success. A new type of MMP-targeting strategy exploits the innate selective hydrolytic activity and consequent catalytic signal amplification of the proteinases, rather than inhibiting it.

Leveraging a Dual Variable Domain Immunoglobulin to Create a Site-Specifically Modified Radioimmunoconjugate.

Site-specifically modified radioimmunoconjugates exhibit superior and behavior compared to analogues synthesized via traditional stochastic methods. However, the development of approaches to site-specific bioconjugation that combine high levels of selectivity, simple reaction conditions, and clinical translatability remains a challenge. Herein, we describe a novel solution to this problem: the use of dual-variable domain immunoglobulins (DVD-IgG).

The Impact of Tyrosine Iodination on the Aggregation and Cleavage Kinetics of MMP-9-Responsive Peptide Sequences.

Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed by exposure to these enzymes. With the ultimate goal of developing radio-iodinated peptides as supramolecular building blocks for MMP-sensitive tools for nuclear imaging and therapy, we designed three MMP-9-responsive peptides containing either tyrosine or iodotyrosine to assess the impact of iodotyrosine introduction to the peptide structure and cleavage kinetics.

Peptide-based scaffolds for the culture and maintenance of primary human hepatocytes.

We report here the use of a nanofibrous hydrogel as a 3D scaffold for the culture and maintenance of functional primary human hepatocytes. The system is based on the cooperative assembly of a fiber-forming peptide component, fluorenylmethyloxycarbonyl-diphenylalanine (Fmoc-FF), and the integrin-binding functional peptide ligand, Fmoc-arginine-glycine-aspartic acid (Fmoc-RGD) into a nanofibrous gel at physiological pH. This Fmoc-FF/RGD hydrogel was formulated to provide a biomimetic microenvironment with some critical features such as mechanical properties and nanofiber morphology, which were optimized to support hepatocyte culture.

A brief overview of metal complexes as nuclear imaging agents.

Metallic radionuclides have been instrumental in the field of nuclear imaging for over half a century. While recent years have played witness to a dramatic rise in the use of radiometals as labels for chelator-bearing biomolecules, imaging agents based solely on coordination compounds of radiometals have long played a critical role in the discipline as well. In this work, we seek to provide a brief overview of metal complex-based radiopharmaceuticals for positron emission tomography (PET) and single photon emission computed tomography (SPECT).

Switchable Hydrolase Based on Reversible Formation of Supramolecular Catalytic Site Using a Self-Assembling Peptide.

The reversible regulation of catalytic activity is a feature found in natural enzymes which is not commonly observed in artificial catalytic systems. Here, we fabricate an artificial hydrolase with pH-switchable activity, achieved by introducing a catalytic histidine residue at the terminus of a pH-responsive peptide. The peptide exhibits a conformational transition from random coil to β-sheet by changing the pH from acidic to alkaline.

Inhibition of renalase expression and signaling has antitumor activity in pancreatic cancer.

An essential feature of cancer is dysregulation of cell senescence and death. Renalase, a recently discovered secreted flavoprotein, provides cytoprotection against ischemic and toxic cellular injury by signaling through the PI3K-AKT and MAPK pathways. Here we show that renalase expression is increased in pancreatic cancer tissue and that it functions as a growth factor.

Health aspects of the pre-departure phase of migration.

In the second article in a six-part series on Migration & Health, Brian Gushulak and Douglas MacPherson discuss the pre-departure phase of migration and the specific health risks and policy needs associated with this phase.

The visiting friends or relatives traveler in the 21st century: time for a new definition.

Background: Travelers visiting friends or relatives (VFR travelers) are a group identified with an increased risk of travel-related illness. Changes in global mobility, travel patterns, and inter-regional travel led to reappraisal of the classic definition of the term VFR.

Methods: The peer-reviewed literature was accessed through electronic searchable sites (PubMed/Medline, ProMED, GeoSentinel, TropNetEurop, Eurosurveillance) using standard search strategies for the literature related to visiting friends/relatives, determinants of health, and travel.

Travel case scenarios as a demonstration of risk assessment of VFR travelers: introduction to criteria and evidence-based definition and framework.

Background: Travel-associated health risks need to be balanced against the positive opportunities associated with interregional travel. As the perceived and real spectrum of health risks related to international travel increase both quantitatively and qualitatively, the need for more discriminating tools in clinical assessment for the purpose of mitigation, public health management, and research are needed. One group of international travelers identified as having increased risk of poor travel-related health outcomes are those who travel with the specific intent of visiting friends or relatives (VFR travelers).

Population mobility, globalization, and antimicrobial drug resistance.

Population mobility is a main factor in globalization of public health threats and risks, specifically distribution of antimicrobial drug-resistant organisms. Drug resistance is a major risk in healthcare settings and is emerging as a problem in community-acquired infections. Traditional health policy approaches have focused on diseases of global public health significance such as tuberculosis, yellow fever, and cholera; however, new diseases and resistant organisms challenge existing approaches.

Online communication as a potential travel medicine research tool: analysis of messages posted on the TravelMed listserv.

Background: Access to the Internet and electronic mail has created opportunities for online discussion that can facilitate medical education and clinical problem solving. Research into the use of these information technologies is increasing and the analysis of these tools can support and guide the activities of professional organizations, including educational endeavors.

Objective: The initial objective was to analyze patterns of information exchange on the International Society of Travel Medicine's (ISTM) travel health electronic mailing list related to a specific area of society interest.

Arrest and detention in international travellers.

Systematic published reviews of national arrests of travellers abroad are rare. The pattern of arrest during international travel has implications for travellers and those involved in providing traveller services. There are also consequences for travellers who are arrested and detained abroad.

Syphilis in immigrants and the Canadian immigration medical examination.

Background: Immigrants to Canada must undergo screening for syphilis. This study presents the results of syphilis screening from 2000 to 2004 and describes its impact on Canadian syphilis reporting and epidemiology. The study identifies migrant groups at risk of syphilis disease.

Health and foreign policy: influences of migration and population mobility.

International interest in the relationship between globalization and health is growing, and this relationship is increasingly figuring in foreign policy discussions. Although many globalizing processes are known to affect health, migration stands out as an integral part of globalization, and links between migration and health are well documented. Numerous historical interconnections exist between population mobility and global public health, but since the 1990s new attention to emerging and re-emerging infectious diseases has promoted discussion of this topic.

Death and international travel--the Canadian experience: 1996 to 2004.

Background: Death during international travel concerns several levels of the travel industry. In addition to the immediate effects for the traveler, their family and friends, the nature of travel-related mortality has important implications for pretravel health advisors and providers of medical care services.

Methods: The Consular Affairs Bureau, Foreign Affairs Canada provides information and assistance to Canadian civilians abroad.

Emerging pediatric HIV epidemic related to migration.

In 2002, Canada introduced routine, mandatory HIV antibody screening for all residency applicants, including selected children. We report screening results from January 2002 to February 2005. Thirty-six pediatric HIV cases were detected (14/100,000 applicants); 94% of infected children were eligible to arrive in Canada.

The basic principles of migration health: population mobility and gaps in disease prevalence.

Currently, migrants and other mobile individuals, such as migrant workers and asylum seekers, are an expanding global population of growing social, demographic and political importance. Disparities often exist between a migrant population's place of origin and its destination, particularly with relation to health determinants. The effects of those disparities can be observed at both individual and population levels.

Evaluation of yellow fever vaccination centers in Canada.

Background: Health Canada regulates the designation of yellow fever vaccination centers (YFVCs) in Canada to ensure a national standard in the safe, effective, and appropriate use of yellow fever vaccine for Canadian travelers. The process for the designation of YFVC has evolved over the years, particularly with the development and implementation of specific criteria for designation. Standardized site visits in 1999 to 2001 demonstrated that noncompliance with the criteria jeopardized the objectives of the federal program.

Globalization of infectious diseases: the impact of migration.

With up to 2% of the world's population living outside of their country of birth, the potential impact of population mobility on health and on use of health services of migrant host nations is increasing in its importance. The drivers of mobility, the process of the international movement, and the back-and-forth transitioning between differential risk environments has significance for the management of infectious diseases in migrant receiving areas. The management issues are broad, high-level, and cross-cutting, including policy decisions on managing the migration process for skilled-labor requirements, population demographic and biometric characteristics, and family reunification; to program issues encompassing health care professional education, training, and maintenance of competence; communication of global events of public health significance; development of management guidelines, particularly for nonendemic diseases; access to diagnostic and therapeutic interventions for exotic or rare clinical presentations; and monitoring of health service use and health outcomes in both the migrant and local populations.

Implementation of the Canadian contingency plan for a case of suspected viral hemorrhagic fever.

Objective: To describe the implementation of the Canadian contingency plan for viral hemorrhagic fever (VHF) in response to a suspected case.

Setting: A 300-bed, tertiary-care, university-affiliated hospital.

Participants: A 32-year-old Congolese woman admitted to the hospital with suspected VHF in February 2001.