Beta-lactam antibiotics account for the majority of antibiotics used worldwide. Resistance by beta-lactamase expression is a serious and growing threat. The typical workflow in a clinical microbiology laboratory leading to identification of antibiotic resistant organisms consists of 1) sample plating and mixed growth, 2) pathogen isolation and growth, 3) identification of the organism by biochemical tests or  Matrix Assisted Laser Desorption Ionization Time of Flight (MALDI-TOF), and finally 4) observed growth in antibiotic containing media to determine antibiotic susceptibility/resistance patterns. This workflow requires 36 to 72 hours, involves multiple manual steps, and may not detect inducible resistance. The evolution and spread of antibiotic resistance among human pathogens represents a serious public health threat. Faster identification of the presence of antibiotic resistant organisms is a key component in the effort to reduce the spread of antibiotic resistance, as evidenced by the inclusion of diagnostic development in the CDC’s national strategy to combat antibiotic resistance. Given the clinical challenges that beta-lactamase expressing pathogens present, there is a clear need for faster identification to both enable effective treatment and to enact isolation precautions preventing further spread of resistant organisms Normal 0 false false false EN-US X-NONE X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin-top:0in; mso-para-margin-right:0in; mso-para-margin-bottom:8.0pt; mso-para-margin-left:0in; line-height:107%; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri",sans-serif; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;}

It has been shown that intensive BP lowering results in higher blood creatinine, which is typically indicative of decreased kidney function, thereby causing physicians concern that the patient is suffering from kidney damage. However, an increase in blood creatinine levels may also be due to changes in blood flow, a hemodynamic effect that is benign to the patient. Sodium glucose transporter 2 (SGLT2) inhibitors are a relatively new class of drugs for treating type 2 diabetes, which have been shown to result in lower risk for progression to dialysis in long-term follow-up. However, when patients first begin a therapeutic regimen of SGLT2 inhibitors, they typically experience an acute change in blood flow to the kidney, which results in a rise in serum creatinine. This causes concerns to practitioners that the drug may be harming the kidneys, rather than being beneficial long term. While some patients may indeed experience intrinsic kidney damage due to marked reductions in blood flow, resulting in cessation of SGLT2 inhibitor therapy and the benefit associated therewith, there is currently no way to differentiate between these two patterns of creatinine change. Thus, a need exists for diagnostic test to differentiate intrinsic kidney damage from hemodynamic changes in patients taking SGLT2 inhibitors for diabetes mellitus.

Currently, patients suffering from diseased and injured organs can be treated with transplanted organs; however, there is a severe shortage of donor organs.  In the United States alone, more than 114,000 people are on transplant waiting lists and have a probability of less than 35 percent of receiving an organ transplant within five years of being added to the list.  Many of the organs in question are branched epithelial organs. Tissue engineering has long held promise for building new organs to functional replace the ones in patients with organ injuries or end-stage organ failure.  However, one major obstacle that remains is the construction of complex 3D functional vascularized epithelial tissues (e.g. lung, kidney, pancreas with both exocrine and endocrine function, breast, and salivary gland, prostate).  Many solutions have been proposed, including bioprinting and assembly of cells around extracellular scaffolds of existing organs, but the complex three-dimensional physiology of branched organs cannot be reproduced.  Importantly, a very promising area of organ-tissue engineering is the production of vascularized proto-organs or biological tissues to analyze organ toxicity from drugs and environmental toxins.  Engineered tissues may offer more accurate predictions of the side effects of potential therapeutic agents because they contain human cells. 

End stage renal disease (ESRD) affects approximately 400,000 individuals in the United States alone, and this number continues to increase rapidly.  While dialysis provides life-saving treatment to patients with ESRD and/or can bridge the time between kidney failure and the receipt of a transplant, only 78% of patients are reported to survive the first year of dialysis and the 10-year survival rate is only 9%.  With over 60,000 people waiting for kidney transplants, the improvement in short-term allograft survival has shifted attention to the two major remaining challenges in kidney transplantation: the shortage of organs and the lack of improvement in the rate of allograft failure after the first post-transplant year.  To address the shortage of donor organs, a variety of tissue-engineering strategies are being pursued, including the extracorporeal renal tubule assist device, the transplantation of renal primordia, the injection of stem-like cells into diseased kidneys and the in vitro engineering of kidneys.  The engineering of a kidney-like tissue from cells with appropriate 3D spatial relationships of nephrons has yet to be achieved.

End-stage renal disease (ESRD) affects almost 350,000 people living in the United States with an incidence that has increased by over 50 percent in the past decade.  The two current treatment modalities for ESRD, dialysis and transplantation, both have significant limitations. Patients on dialysis have an extremely high mortality rate, approaching 20 percent per year. Although patient survival is markedly improved with renal transplantation, the number of renal transplants is severely limited by the short supply of available organs and many patients die while awaiting transplantation of a kidney allograft. Recently, several alternative modalities have been proposed  including augmentation of traditional hemodialysis with a "renal assist device," xenotranplantation of whole developing kidney rudiments into adults, and the generation of histocompatible renal tissue using nuclear transplantation techniques.

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