In Peritoneal Dialysis, Is There Sufficient Evidence to Make “PD First” Therapy?

Since its introduction more than 3 decades ago, the use of peritoneal dialysis (PD) has increased greatly due to its simplicity, convenience, and low cost. Advances in technique, antibiotic prophylaxis, and the introduction of newer solutions have improved survival, quality of life, and reduced rate of complications with PD. In Hong Kong, approximately 80% end-stage renal disease (ESRD) patients perform PD; in others, that is, Canada, Australia, and New Zealand, 20%–30% patients use PD. However, in the United States, the annual rate of prevalent patients receiving PD has reduced to 8% from its peak of 15% in mid-1980s. PD as the initial modality is being offered to far less patients than hemodialysis (HD), resulting in the current annual incidence rate of less than 10% in USA. There are many reasons preventing the PD first initiative including the increased numbers of in-center hemodialysis units, physician comfort with the modality, perceived superiority of HD, risk of peritonitis, achieving adequate clearances, and reimbursement incentives to providers. Patient fatigue, membrane failure, and catheter problems are other reasons which discourage PD utilization. In this paper, we discuss the available evidence and provide rationale to support PD as the initial renal replacement modality for ESRD patients

Mycophenolate mofetil: safety and efficacy in the prophylaxis of acute kidney transplantation rejection

Mycophenolate mofetil (MMF), a prodrug of mycophenolic acid (MPA), is an inhibitor of inosine monophosphate dehydrogenase (IMPDH). It preferentially inhibits denovo pathway of guanosine nucleotide synthesis in T and B-lymphocytes and prevents their proliferation, thereby suppresses both cell mediated and humoral immune responses. Clinical trials in kidney transplant recipients have shown the efficacy of MMF in reducing the incidence and severity of acute rejection episodes. It also improves long term graft function as well as graft and patient survival in kidney transplant recipients. MMF is useful as a component of toxicity sparing regimens to reduce or avoid exposure of steroids or calcineurin inhibitor (CNI). Enteric-coated mycophenolate sodium (EC-MPS) can be used as an alternative immunosuppressive agent in kidney transplant recipients with efficacy and safety profile similar to MMF

Binding of Beta-site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE1) Inhibitor Aminoquinoline (68K) for Possible Treatment of Alzheimer\u27s Disease

Alzheimer’s Disease (AD), affecting approximately 24 million people worldwide, is characterized by the formation of amyloid-β plaques within the brain. Alzheimer’s research has been focused on limiting amyloid-β production through developing inhibitors for the enzymes needed within the amyloid cascade. This project focuses on the aminoquinoline class of inhibitors, of which 68K (PDB: 5i3Y) is the most effective because of its strong Kd and IC50 values. The students of the Honors Protein Modeling class at Nova Southeastern University modeled the interaction between Beta-site Amyloid Precursor Protein Cleaving Enzyme 1 (BACE-1) and 68K. Using Jmol a model was developed, and 3D printed to show how the inhibitor (68K) fit into the enzyme’s active site. This model highlights important aspects of the interactions between the ligand and the BACE-1 enzyme. 68K has strong interactions with 32 amino acid residues in BACE1, some of which are intertwined with one another. For example, BACE-1’s residues Val69, Pro70, and Tyr71 are known collectively as “the flap”. “The flap” is a β-hairpin loop structure that is positioned directly over BACE-1’s catalytic dyad, a group of amino acids within the active site of the enzyme. “The flap” is also responsible for regulating access to the enzyme’s catalytic dyad (Asp 32 and Asp 228) by a given substrate (or inhibitor). Researchers found the inhibitor 68K to have interactions with the flap which maximizes the strength of the interaction with BACE-1 residues, thus minimizing the distance between the inhibitor’s various functional groups and accommodating their specific polarities. Being able to visualize the protein structure using a 3D model aids in the understanding of how the ligand inhibits this enzyme leading to the progression of AD.https://nsuworks.nova.edu/protein_modeling_reports/1011/thumbnail.jp

Blue photon management by inhouse grown ZnO:Al cathode for enhanced photostability in polymer solar cells

We report the improvement in photostability of P3HT:PC60BM based bulk heterojunction solar cells deposited on Al-doped ZnO as a cathode layer replacing ITO as regularly used TCO in cells with N-I-P configuration. We experimentally and theoretically demonstrate that use of thicker ZnO:Al as cathode can successfully cut down the rate of photodegradation in short circuit current by ~40% and open circuit voltage by ~30% compared to the control device made on ITO based cathode. This effective reduction in photodegradation is understood to be coming from the absorption of ultraviolet and blue photon in the cathode layer itself. The loss in short circuit current due to the loss of blue photon in EQE is compensated by higher FF (lower series resistance) due to thicker ZnO:Al layer resulting in final device efficiency almost uncompromised with added benefit of reduced photo degradation. The experimental results are supported with optical simulations which show more absorption in the short wavelength region for the thicker ZnO films, compared to ITO films, deposited on glass substrates. This work also proposes using ZnO:Al cathode as a template for random textured front surface to potentially increase short circuit current by increase in photon absorption in active layer matrix by light scattering techniques. Our results provide an inexpensive pathway for improving the stability of organic photovoltaics without compromising the device performance