The incidence rate of treated end-stage renal disease in the united states is 180 per million and continues to rise at a rate of 7.8% per year. Arteriovenous hemodialysis access (AV access) creation and maintenance are two of the most difficult issues associated with the management of patients on hemodialysis. The 1-year complication rate of a primary prosthetic AV access for hemodialysis ranges from 33% to 99%. Various investigators report on patency and complications of AV access. However, it is rather difficult to compare outcomes because of the wide variety of access materials, configurations, locations, risk factors, and quality of inflow and outflow vessels. Although there have been reporting standards for dialysis access endovascular interventions and for central venous access placement, standards regarding surgical access placement and its revision are lacking. The "Dialysis Outcome Quality Initiative," published by the National Kidney Foundation, provides recommendations for optimal clinical practices aimed at improving dialysis outcome and patient survival. This reporting standards document is not meant to be a "practice guidelines" or "best practices" document. Rather, the purpose of this document is to provide standardized definitions related to AV access procedures and to recommend reporting standards for patency and complications, to be used by surgeons, nephrologists, and interventional radiologists, that will permit meaningful comparisons among AV access procedures. The terms, definitions, and categories featured in this article have been approved by the Committee on Reporting Standards of the Society for Vascular Surgery and the American Association for Vascular Surgery and should be observed in preparing manuscripts on AV accesses for submission to the Journal Of Vascular Surgery.

Development of a highly effective vaccine or antibodies for prevention and ultimately elimination of malaria is urgently needed. Here, we report the isolation of a number of human monoclonal antibodies (mAbs) directed against the Plasmodium falciparum (Pf) circumsporozoite protein (CSP) from several subjects immunized with an attenuated whole sporozoite (SPZ) vaccine (Sanaria® PfSPZ Vaccine). Passive transfer of one of these antibodies, mAb CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection. Stoichiometry and affinity of mAb CIS43 for PfCSP indicate two sequential multivalent binding events to six sites: the first 7-fold higher affinity binding event is to a unique “junctional” epitope positioned between the N-terminus and the central repeat domain of PfCSP. Moreover, mAb CIS43 prevented proteolytic cleavage of PfCSP on PfSPZ. Crystal structures of the CIS43 fragment antigen binding (Fab) in complex with the junctional epitope determined the molecular interactions of binding, revealed the epitope’s conformational flexibility, and defined NPN as the structural repeat motif. The demonstration that mAb CIS43 is highly effective for passive prevention of malaria has potential application for use in travelers, military personnel and elimination campaigns and identifies a new and conserved site of vulnerability on PfCSP for next generation rational vaccine design.

The unique relapsing nature of Plasmodium vivax infection is a major barrier to malaria eradication. Upon infection, dormant liver-stage forms, hypnozoites, linger for weeks to months and then relapse to cause recurrent blood-stage infection. Very little is known about hypnozoite biology; definitive biomarkers are lacking and in vitro platforms that support phenotypic studies are needed. Here, we recapitulate the entire liver stage of P. vivax in vitro, using a multiwell format that incorporates micropatterned primary human hepatocyte co-cultures (MPCCs). MPCCs feature key aspects of P. vivax biology, including establishment of persistent small forms and growing schizonts, merosome release, and subsequent infection of reticulocytes. We find that the small forms exhibit previously described hallmarks of hypnozoites, and we pilot MPCCs as a tool for testing candidate anti-hypnozoite drugs. Finally, we employ a hybrid capture strategy and RNA sequencing to describe the hypnozoite transcriptome and gain insight into its biology.

The rupture of vulnerable atherosclerotic plaque accounts for the majority of clinically significant acute cardiovascular events. Because stability of these culprit lesions is directly related to chemical and morphological composition, Raman spectroscopy may be a useful technique for their study. Recent developments in optical fiber probe technology have allowed for the real-time in vivo Raman spectroscopic characterization of human atherosclerotic plaque demonstrated in this work. We spectroscopically examine 74 sites during carotid endarterectomy and femoral artery bypass surgeries. Of these, 34 are surgically biopsied and examined histologically. Excellent signal-to-noise ratio spectra are obtained in only 1 s and fit with an established model, demonstrating accurate tissue characterization. We also report the first evidence that Raman spectroscopy has the potential to identify vulnerable plaque, achieving a sensitivity and specificity of 79 and 85%, respectively. These initial findings indicate that Raman spectroscopy has the potential to be a clinically relevant diagnostic tool for studying cardiovascular disease.

Primaquine (PQ) is an essential antimalarial drug but despite being developed over 70 years ago, its mode of action is unclear. Here, we demonstrate that hydroxylated-PQ metabolites (OH-PQm) are responsible for efficacy against liver and sexual transmission stages of Plasmodium falciparum . The antimalarial activity of PQ against liver stages depends on host CYP2D6 status, whilst OH-PQm display direct, CYP2D6-independent, activity. PQ requires hepatic metabolism to exert activity against gametocyte stages. OH-PQm exert modest antimalarial efficacy against parasite gametocytes; however, potency is enhanced ca.1000 fold in the presence of cytochrome P450 NADPH:oxidoreductase (CPR) from the liver and bone marrow. Enhancement of OH-PQm efficacy is due to the direct reduction of quinoneimine metabolites by CPR with the concomitant and excessive generation of H 2 O 2 , leading to parasite killing. This detailed understanding of the mechanism paves the way to rationally re-designed 8-aminoquinolines with improved pharmacological profiles.

Arm veins are an easily accessible autologous conduit of sufficient length to reach the midtibial level. Excellent patency rates allow durable limb salvage in otherwise difficult circumstances. Vein configuration and splicing do not affect patency rates, but vein quality and repeat operations do. Angioscopy is a valuable adjunct to upgrade graft quality. The contralateral saphenous should be saved for subsequent contralateral revascularization or coronary artery bypass grafting.

Dorsalis pedis arterial bypass is an effective limb salvage procedure with long-term durability comparable to distal vein grafts placed into more proximal arteries.

Local drug delivery depots have significant clinical utility, but there is currently no noninvasive technique to refill these systems once their payload is exhausted. Inspired by the ability of nanotherapeutics to target specific tissues, we hypothesized that bloodborne drug payloads could be modified to home to and refill hydrogel drug delivery systems. To address this possibility, hydrogels were modified with oligodeoxynucleotides (ODNs) that provide a target for drug payloads in the form of free alginate strands carrying complementary ODNs. Coupling ODNs to alginate strands led to specific binding to complementary-ODN-carrying alginate gels in vitro and to injected gels in vivo. When coupled to a drug payload, sequencetargeted refilling of a delivery depot consisting of intratumor hydrogels completely abrogated tumor growth. These results suggest a new paradigm for nanotherapeutic drug delivery, and this concept is expected to have applications in refilling drug depots in cancer therapy, wound healing, and drug-eluting vascular grafts and stents.nanoparticle | targeting | DNA nanotechnology | controlled release | biomaterials