Association Between Vancomycin Area Under the Curve and Nephrotoxicity: a single center, retrospective cohort study in a veteran population.

Background: It is unclear which vancomycin area under the curve (AUC) values are most associated with risk for acute kidney injury (AKI).

Methods: This retrospective cohort study was undertaken to determine if vancomycin AUC >550 is associated with a higher rate of AKI than an AUC <550. Patients treated with vancomycin for at least 4 days at the VA St.

Experience with Liposomal Amphotericin B in Outpatient Parenteral Antimicrobial Therapy.

Outpatient parenteral antimicrobial therapy (OPAT) is a safe, effective, and convenient treatment strategy for patients receiving intravenous antimicrobials in the outpatient setting; however, data are limited describing the use and safety of liposomal amphotericin B (L-AMB). Records of patients receiving L-AMB OPAT between 1/1/2015 and 7/31/2018 were retrospectively reviewed. The primary objective was to describe the OPAT patient population discharged on L-AMB and evaluate factors associated with readmission and adverse events (AEs).

Rapidly-customizable, scalable 3D-printed wireless optogenetic probes for versatile applications in neuroscience.

Optogenetics is an advanced neuroscience technique that enables the dissection of neural circuitry with high spatiotemporal precision. Recent advances in materials and microfabrication techniques have enabled minimally invasive and biocompatible optical neural probes, thereby facilitating optogenetic research. However, conventional fabrication techniques rely on cleanroom facilities, which are not easily accessible and are expensive to use, making the overall manufacturing process inconvenient and costly.

Ontogenetic Oxycodone Exposure Affects Early Life Communicative Behaviors, Sensorimotor Reflexes, and Weight Trajectory in Mice.

Nationwide, opioid misuse among pregnant women has risen four-fold from 1999 to 2014, with commensurate increase in neonates hospitalized for neonatal abstinence syndrome (NAS). NAS occurs when a fetus exposed to opioids goes into rapid withdrawal after birth. NAS treatment via continued post-natal opioid exposure has been suggested to worsen neurodevelopmental outcomes.

Pain, negative affective states and opioid-based analgesics: Safer pain therapies to dampen addiction.

Across centuries and civilizations opioids have been used to relieve pain. In our modern societies, opioid-based analgesics remain one of the most efficient treatments for acute pain. However, the long-term use of opioids can lead to the development of analgesic tolerance, opioid-induced hyperalgesia, opioid use disorders, and overdose, which can ultimately produce respiratory depressant effects with fatal consequences.

Combretastatin A-4 sulfur-containing heterocyclic derivatives: Synthesis, antiproliferative activities and molecular docking studies.

Combretastatin A-4 inspired heterocyclic derivatives were synthesized and evaluated for their biological activities on tubulin polymerization and cell proliferation. Among the 19 described sulfur-containing compounds, derivatives (Z)-4h and (Z)-4j exhibited interesting in cellulo tubulin polymerization inhibition and antiproliferative activities with IC values for six different cell lines between 8 and 27 nM. Furthermore, in silico docking studies within the colchicine/CA-4 binding site of tubulin were carried out to understand the interactions of our products with the protein target.

Novel synthesis of benzotriazolyl alkyl esters: an unprecedented CH insertion.

We have developed a novel method for the synthesis of benzotriazolyl alkyl esters (BAEs) from -acylbenzotriazoles and dichloromethane (DCM) under mild conditions. This reaction is one of few examples to show the use of DCM as a C-1 surrogate in carbon-heteroatom bond formation and to highlight the versatility of using DCM as a methylene building block.

Post-Dialysis Parenteral Antimicrobial Therapy in Patients Receiving Intermittent High-Flux Hemodialysis.

Patients with end-stage renal disease (ESRD) requiring intermittent hemodialysis (IHD) are at increased risk of infection, which represents a leading cause of mortality in this population. The use of additional vascular access devices such as peripherally inserted central catheters to treat such infections should be minimized in patients with ESRD requiring IHD in order to mitigate complications such as infection and thrombosis and to maintain venous patency for hemodialysis access. Intravenous antimicrobial dosing following IHD has the advantages of avoiding additional access devices and providing convenience for patients and providers.

Think Big, Start Small: How Nanomedicine Could Alleviate the Burden of Rare CNS Diseases.

The complexity and organization of the central nervous system (CNS) is widely modulated by the presence of the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), which both act as biochemical, dynamic obstacles impeding any type of undesirable exogenous exchanges. The disruption of these barriers is usually associated with the development of neuropathologies which can be the consequence of genetic disorders, local antigenic invasions, or autoimmune diseases. These disorders can take the shape of rare CNS-related diseases (other than Alzheimer's and Parkinson's) which a exhibit relatively low or moderate prevalence and could be part of a potential line of treatments from current nanotargeted therapies.

Racial Disparities in Readmissions Following Initial Hospitalization for Sepsis.

Objectives: To assess whether Black race is associated with a higher rate of all-cause readmission compared with White race following community-onset sepsis.

Design: Retrospective cohort study.

Setting: One-thousand three-hundred bed urban academic medical centers.

Controlling opioid receptor functional selectivity by targeting distinct subpockets of the orthosteric site.

Controlling receptor functional selectivity profiles for opioid receptors is a promising approach for discovering safer analgesics; however, the structural determinants conferring functional selectivity are not well understood. Here, we used crystal structures of opioid receptors, including the recently solved active state kappa opioid complex with , to rationally design novel mixed mu (MOR) and kappa (KOR) opioid receptor agonists with reduced arrestin signaling. Analysis of structure-activity relationships for new analogs points to a region between transmembrane 5 (TM5) and extracellular loop (ECL2) as key for modulation of arrestin recruitment to both MOR and KOR.

Rimegepant: acute treatment for migraine headaches.

Migraine headache treatment is quickly evolving. There have been three new acute migraine treatment options (i.e.

Pomegranate bioactive constituents target multiple oncogenic and oncosuppressive signaling for cancer prevention and intervention.

Cancer remains to be the second highest cause of mortality in our society, falling just short of heart disease. Despite major advancement in cancer therapy over the past decade, momentum has been gaining for an alternative approach of using naturally-occurring and dietary agents for cancer prevention and management. Research on pomegranate (Punica granatum L.

Pneumococal community-acquired pneumonia in the intensive care unit: Azithromycin remains protective despite macrolide resistance.

Background: Streptococcus pneumoniae (SP) remains the leading pathogen in community-acquired pneumonia (CAP). Despite the increasing prevalence of macrolide resistance in SP, guidelines recommend the use of macrolides as part of a combination regiment for intensive care unit (ICU) patients with CAP. We sought to describe if macrolide resistance effects outcomes in SP CAP in the ICU and if macrolides remain associated with a mortality advantage in an era of greater resistance.

Targeting E-selectin to Tackle Cancer Using Uproleselan.

E-selectin is a vascular adhesion molecule expressed mainly on endothelium, and its primary role is to facilitate leukocyte cell trafficking by recognizing ligand surface proteins. E-selectin gained a new role since it was demonstrated to be involved in cancer cell trafficking, stem-like properties and therapy resistance. Therefore, being expressed in the tumor microenvironment, E-selectin can potentially be used to eradicate cancer.

Evaluation of the safety and tolerability of spironolactone in patients with heart failure and chronic kidney disease.

Background: Spironolactone reduces morbidity and mortality in patients with heart failure (HF) with reduced ejection fraction (EF) and decreases hospitalizations in HF with preserved EF. To minimize the risk of hyperkalemia, patients must have an estimated glomerular filtration rate (eGFR) > 30 mL/min/1.73 m and potassium < 5.

Nosocomial Infection.

Objective: The first 70 years of critical care can be considered a period of "industrial revolution-like" advancement in terms of progressing the understanding and care of critical illness. Unfortunately, like the industrial revolution's impact on the environment, advancing ICU care of increasingly elderly, immunosuppressed, and debilitated individuals has resulted in a greater overall burden and complexity of nosocomial infections within modern ICUs. Given the rapid evolution of nosocomial infections, the authors provide an updated review.

Kratom Alkaloids, Natural and Semi-Synthetic, Show Less Physical Dependence and Ameliorate Opioid Withdrawal.

Chronic administration of opioids produces physical dependence and opioid-induced hyperalgesia. Users claim the Thai traditional tea "kratom" and component alkaloid mitragynine ameliorate opioid withdrawal without increased sensitivity to pain. Testing these claims, we assessed the combined kratom alkaloid extract (KAE) and two individual alkaloids, mitragynine (MG) and the analog mitragynine pseudoindoxyl (MP), evaluating their ability to produce physical dependence and induce hyperalgesia after chronic administration, and as treatments for withdrawal in morphine-dependent subjects.

The mixed kappa and delta opioid receptor agonist, MP1104, attenuates chemotherapy-induced neuropathic pain.

Effective treatments for chronic pain without abuse liability are urgently needed. One in 5 adults suffer chronic pain and half of these patients report inefficient treatment. Mu opioid receptor agonists (MOP), including oxycodone, tramadol and morphine, are often prescribed to treat chronic pain, however, use of drugs targeting MOP can lead to drug dependency, tolerance and overdose deaths.

Adherence rates and outcomes for 17-hydroxyprogesterone caproate use in women with a previous history of preterm birth.

Background: Progesterone has been used for preventing preterm birth with mixed results. The American College of Obstetricians and Gynecologists and Society for Maternal-Fetal Medicine recommended the use of 17-hydroxyprogesterone caproate for risk reduction of recurrent spontaneous preterm birth based on the results of a multicenter, randomized trial in the United States. However, recent literature lacks consensus for efficacy in the American population.

Tumor microenvironment-targeted nanoparticles loaded with bortezomib and ROCK inhibitor improve efficacy in multiple myeloma.

Drug resistance and dose-limiting toxicities are significant barriers for treatment of multiple myeloma (MM). Bone marrow microenvironment (BMME) plays a major role in drug resistance in MM. Drug delivery with targeted nanoparticles have been shown to improve specificity and efficacy and reduce toxicity.

Synthesis and Pharmacology of a Novel μ-δ Opioid Receptor Heteromer-Selective Agonist Based on the Carfentanyl Template.

In this work, we studied a series of carfentanyl amide-based opioid derivatives targeting the mu opioid receptor (μOR) and the delta opioid receptor (δOR) heteromer as a credible novel target in pain management therapy. We identified a lead compound named that exhibits high G-protein activity at μ-δ heteromers compared to the homomeric δOR or μOR and low β-arrestin2 recruitment activity at all three. Furthermore, exhibits distinct signaling profile, as compared to the previously identified agonist targeting μ-δ heteromers, CYM51010.

The bad expert.

We focus on two cases in which participants narrate and perform a new culture of expertise by constructing a bad expert, a reviled or dangerous figure of scientific credibility gone wrong. We show that a key mechanism in the construction of expertise cultures is the use of antithesis performances, which are performances of scientific and professional credibility that rely on telling stories about a scientific enemy or ostracized Other. By performing the antithesis of the bad expert, actors help generate turning points in expertise, allowing new cultures of expertise to emerge.

Predictors of Student Failure or Poor Performance on Advanced Pharmacy Practice Experiences.

To determine factors predictive of student failure or poor performance on advanced pharmacy practice experiences (APPEs) at a single pharmacy program. This retrospective cohort evaluated students entering the Doctor of Pharmacy (PharmD) program from 2012-2014 at St. Louis College of Pharmacy.