This article summarizes available literature regarding the utilization of probiotic and synbiotics in liver transplant (LTX) recipients, reviewing efficacy in both decreasing infectious complications and immunomodulation, as well as exploring safety concerns. Data suggest that the use of probiotics containing Lactobacillus spp, either alone or in combination with prebiotics (referred to as synbiotics), may be effective in reducing infectious complications after LTX, a major contributor to graft loss, hospital length of stay, and mortality. Literature evaluating the use of probiotics to induce tolerance, reduce rejection, and prevent damage associated with ischemia-reperfusion injury is limited to animal models but compelling, as it suggests the use of probiotics may augment deleterious immune-mediated processes in this population. While the benefits of probiotics should be weighed against potential risks, these concerns are largely theoretical in the LTX recipient, with the majority of evidence extrapolated from case reports in other immunosuppressed populations. Based on available literature, it may be prudent to avoid products containing Saccharomyces sp, as these were not used in the efficacy studies, and the majority of the adverse event reporting stems from the use of products containing this organism. Further evaluation of the safety and efficacy of probiotic therapy is warranted. Studies specifically designed to elucidate the optimal product and initiation scenario and delineate safety in this population are needed to allow expanded use of this inexpensive, relatively nontoxic, and potentially beneficial therapeutic option after LTX.

Prophylaxis failure with HD-A was mostly limited to mild viremia; however, it was associated with significantly reduced long-term graft survival, likely reflecting the negative impact of CMV viremia.

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Mitogen-activated protein kinases-interacting kinases 1 and 2 (MNK1 and MNK2) are Ser/Thr kinases belongs to the group of Ca 2þ /calmodulin-dependent kinases (CaMK) that phosphorylate Eukaryotic initiation factor 4E (eIF4E) [Luc Furic.,et. al., PNAS, 2010, 107 (32):14134-14139] on Ser-209. Overexpression of eIF4E has been associated with tumoregenicity and studies have indicated that eIF4E phosphorylation is oncogenic [Jinqiang Hou. et. al., Oncotarget, 2012, 3:118-131]. Therefore, Mnk1/2 inhibitors could be effective therapeutic agents for the treatment of cancers driven by an overexpression of phosphorylated eIF4E. In the current study we have carried out molecular docking combined with molecular dynamics simulations to study the interaction between ligand and Mnk1/2 kinase catalytic domains. Three dimensional structures of both Mnk1 and Mnk2 were built using comparative modeling methods. A series of Mnk kinase inhibitors were docked to the ensemble of representative structures extracted from a clustering analysis of the MD simulations. The predicted bound conformations were further studied in explicit solvent by MD simulations. Our combined computation approach identified key residues that are important for the protein -inhibitor interactions, provides detailed understanding of the mechanism of these kinds of inhibitors and will be useful for the rational design of Mnk inhibitors. Reperfusion injuries can cause severe damage in hypoxic tissue after the blockage of oxygen supply has been relieved. The condition frequently occurs after ischemic events or surgery and is caused by a combination of inflammation and the generation of harmful reactive oxygen species (ROS). In an effort to gain access to agents capable of combating the damaging effects of ROS, we developed compounds with dual properties capable of preventing the generation of ROS and of absorbing ROS already formed. By combining two beneficial properties in a single molecule, we expected these compounds to be more flexible and effective than those that feature only one of the two activities. Based on the scaffolds of the natural products chalcone and caffeic acid phenethyl ester (CAPE), we synthesized and tested a selection of compounds capable of inhibiting the enzyme xanthine oxidase (XO), a major source of ROS production, and of absorbing radicals. Assays employed in this study measured inhibitory potency against XO activity, radical scavenging ability, and the capacity to increase cell viability under oxidative stress. In addition, computational docking was performed to elucidate XO/inhibitor interactions at the molecular level. Structureactivity relationships were established that identified correlations between molecular structure and the two bioactivities under investigation and that can guide the future synthesis of materials with improved properties.

Introduction The American Heart Association recommends implementation of integrated transition of care programs to manage patients following hospitalization for acute decompensated heart failure (ADHF). At our site, a Nurse Practitioner (NP) has been historically responsible for seeing patients post discharge in the Heart Failure Access Clinic (HFAC). Whether the addition of a clinical pharmacy specialist (CPS) to co-manage patients at the HFAC clinic leads to improved outcomes is not known. Therefore, we conducted a pilot study to assess the feasibility and potential benefits of this integrated approach. Objective We evaluated 30-day heart failure readmission, emergency department (ED) visits, and all-cause mortality in post-discharge patients who were seen in our integrated CPS and NP pilot HFAC clinic. The clinic process and CPS interventions were also assessed. Methods Patients who were discharged from the hospital for ADHF were eligible for the pilot study if they had at least mild LV systolic dysfunction (LVEF ≤50%). In the integrated HFAC clinic, the NP determined patients’ volume and perfusion status, implemented a flexible diuretic plan, and set parameters for patients contacting the HF team. Responsibility for medication reconciliation, neurohormonal medication education, and dose optimization was shifted to the CPS. Descriptive statistics were used as appropriate. Results Between 11/18/2019 and 3/10/2020, 24 visits were conducted in the integrated clinic. Our patients were predominantly Caucasian (88%), male (96%), and elderly (mean age: 70 ± 12 years). Most patients (75%) had LVEF ≤40%. The 30-day post-discharge readmission rate was 2/24 (8%), while both ED visits and all-cause mortality rates were 0%. Historically, veterans at our NP led HFAC clinic have had a 30-day readmission rate of 15.8% (data from 2019). The average time to appointment was 12 ± 8 days post-discharge with 25% patients seen within 7 days. The mean duration of the CPS visit was 36 minutes; the NP visit was 41 minutes (n=12). The CPS noted medication discrepancies in 14/24 (58%), alerted other providers for medication issue follow-up in 10/24 (42%), and identified HF inappropriate medications in 3/24 (13%). HF medications were titrated by the CPS in 13/24 (54%), and 16/24 (67%) patients were scheduled with CPS for ongoing medication dose titration. One patient (4%) was referred for tobacco treatment. Conclusions Early analysis indicates that the integrated HFAC leads to high-quality patient care as evidenced by a very low 30-day hospital readmission rate without ED visits or fatality. These outcomes compare favorably to our institution's 30-day readmission rate observed prior to implementation of this pilot project. Potential benefits of adding a CPS as a provider to our HFAC include medication reconciliation and education, identification of harmful drugs, and timely medication titration. Further anal...

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